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☐ ☆ ✇ PLOS ONE Medicine&Health

Integrating sequence-based GWAS and comparative genomic analysis reveals conservation and species-specificity of putative functional variants influencing tail length and tail abnormalities in pigs and sheep

by Xuying Zhang, Johanna Mainzer, Isabella Giambra, Tong Yin, Petra Engel, Hannah Hümmelchen, Henrik Wagner, Axel Wehrend, Christiane Egerer, Katharina Gerhards, Gerald Reiner, Sven König

Long tails trigger tail biting in pigs and increase the risk of flystrike infections in sheep. Tail docking has been a common management practice in both species for decades, but increasingly conflicts with legal animal welfare guidelines. Sustainable solutions require breeding strategies targeting shorter tails. In consequence, the aims were to conduct whole-genome sequencing (WGS)-based genome-wide association studies (GWAS) and comparative genomic analyses (CGA) to explore functional elements influencing tail traits. Phenotypically divergent experimental populations of pigs and sheep were established through unified selection and mating experiments. Tail traits included tail length (TL) measured at birth, and tail abnormalities (TA) assessed radiographically at 14 weeks of age. WGS-based GWAS identified a significant locus on SSC18 in pigs and suggestive loci for TL in both species, which, together with previously reported loci for TA, were further analyzed by CGA. The genomic windows of the significant locus on SSC18 in pigs and the TL GWAS locus on OAR4 in sheep were found to be conserved, harboring six common genes with predicted functional variants. These variants were jointly associated with TL (Plm) in both species in linear regression models adjusted for sex, age of the dam, body length, and body weight. In other GWAS locus windows (±1 Mb), species-specific TL candidate genes were identified in sheep (HOXB13, MUC5B, EPB41L3, MTCL1, PIEZO2, MPPE1, and LOXHD1) and in pigs (KNL1, DISP2, SPRED1, TGFB2, and HAND1), each harboring associated putative functional variants. For TA, sheep-specific candidates (PGM2, LRRC66, CRACD, LOC105601916, and SH2D4B) and pig-specific candidates (MYOT, TMCO6, and PCDHAC2) were revealed using logistic regression models (Pglm). GO analyses of candidate genes predicted shared biological processes between sheep and pigs, whereas pathway analyses indicated that common carbohydrate metabolism pathways, along with species-specific immune and inflammatory signaling, and pig-specific TGF-β signaling and endochondral ossification, may contribute to tail length variation and abnormalities. These findings provided deeper insights into the genetic basis of differential embryonic tail morphogenesis and perinatal tail development across species.
☐ ☆ ✇ PLOS ONE Medicine&Health

COVID-19 knowledge, attitudes, and practices among people vulnerable to HIV in Uganda: A cross-sectional cohort analysis

by Job Kasule, Julius L. Tonzel, Natalie Burns, Tyler Hamby, Roger Ying, Grace Mirembe, Immaculate Nakabuye, Hannah Kibuuka, Margaret Yacovone, Betty Mwesigwa, Trevor A. Crowell, for the Multinational Observational Cohort of HIV and other Infections (MOCHI) Study Group

Background

People with behavioral vulnerability to HIV face barriers to healthcare engagement that may impede uptake of non-pharmaceutical and other interventions to prevent COVID-19. Understanding COVID-19 knowledge, attitudes, and practices in this population can inform disease prevention efforts during future pandemics.

Materials and methods

From October 2022 to September 2024, we enrolled participants aged 14–55 years without HIV who endorsed recent sexually transmitted infection, injection drug use, transactional sex, condomless sex, and/or anal sex with male partners. At enrollment, we collected socio-behavioral data, including assessments of COVID-19 knowledge, attitudes, and practices. Robust Poisson regression with purposeful variable selection was used to estimate prevalence ratios with 95% confidence intervals for factors associated with COVID-19 preventive practices.

Results

Among 418 participants, 228 (56.9%) were female, the median age was 21 years (interquartile range 19−24), and 362 (84.9%) reported sex work. Knowledge about SARS-CoV-2 transmission routes was high (95.4%) but lower for the consequences of genetic variants (48.5%−69.7%) and possibility for asymptomatic infection or transmission (66.7%−80.8%). Handwashing was practiced by 90.8% of participants in the preceding month, whereas mask-wearing (76.5%), avoiding symptomatic people (73.7%), and any history of COVID-19 vaccination (46.9%) were less prevalent. Males were more likely to report avoiding symptomatic people (adjusted prevalence ratio 1.16 [95% confidence interval 1.03–1.31]) and COVID-19 vaccination (1.30 [1.05–1.60]). Enrollment during the BQ.1/BQ.1.1 Omicron wave was associated with less mask-wearing (0.81 [0.67–0.99]) but more vaccination (1.59 [1.29–1.95]).

Discussion

We observed variable COVID-19 knowledge and attitudes among Ugandan adolescents and adults with little impact on COVID-19 preventive practices. Efforts to address suboptimal uptake of disease preventive practices during this and future disease outbreaks will require more than just improving knowledge.

☐ ☆ ✇ PLOS ONE Medicine&Health

Simulation of phased alerting of community first responders for cardiac arrest

by Pieter L. van den Berg, Shane G. Henderson, Hemeng Li, Bridget Dicker, Caroline J. Jagtenberg

Background

Community First Responders (CFRs) are commonly used for out-of-hospital cardiac arrests, and advanced systems send so-called phased alerts: notifications with built-in time delays. The policy that defines these delays affects both response times and volunteer fatigue.

Methods

We compare alert policies by Monte Carlo Simulation, estimating patient survival, coverage, number of alerts and redundant CFR arrivals. In the simulation, acceptance probabilities and response delays are bootstrapped from 29,307 rows of historical data covering all GoodSAM alerts in New Zealand between 1-12-2017 and 30-11-2020. We simulate distances between the patient and CFRs by assuming that CFRs are located uniformly at random in a 1-km circle around the patient, for different CFR densities. Our simulated CFRs travel with a distance-dependent speed that was estimated by linear regression on observed speeds among those responders in the above-mentioned data set that eventually reached the patient.

Results

The alerting policy has a large impact on the four metrics above, and the best choice depends on volunteer density. For each volunteer density, we are able to identify a policy that improves GoodSAM New Zealand’s current policy on all four metrics. For example, when there are 30 volunteers within 1 km from the patient, sending out alerts to 7 volunteers and replacing each volunteer that rejects by a new one, is expected to save 10 additional lives per year compared to the current policy, without increasing volunteer fatigue. Our results also shed light on polices that would improve one metric while worsening another, for example, when there are 10 volunteers within 1 km from the patient, dispatching them all immediately increases our survival estimate by 11% compared to the current policy, with the downside of also increasing the redundant arrivals by 137%.

Conclusions

Monte Carlo simulation can help CFR system managers identify a good policy before implementing it in practice. We recommend balancing survival and volunteer fatigue, aiming to ultimately further improve a CFR system’s effectiveness.

☐ ☆ ✇ PLOS ONE Medicine&Health

Adoption and implementation of teleaudiology as a telehealth model in Jordan and Arab countries: A cross-sectional survey

Por: Hala M. AlOmari · Hanady Bani Hani · Telda Alkhateeb · Dua’ Qutaishat — Marzo 3rd 2026 at 15:00

by Hala M. AlOmari, Hanady Bani Hani, Telda Alkhateeb, Dua’ Qutaishat

Background and objectives

Telehealth is the provision of healthcare services remotely via telecommunications technology. The implementation, clinical applications, and perceived effectiveness of telehealth among audiologists across the Arab region, particularly following its accelerated adoption due to the COVID-19 pandemic was investigated.

Materials and methods

A cross-sectional survey was conducted between April and June 2024 among 194 audiologists from multiple countries. A non-probability purposive sampling approach was implemented. The respondents were grouped into providers and non-providers of telehealth services. The questionnaire collected data on demographics, service delivery models, telehealth applications, training background, and perceived challenges. Descriptive and inferential analyses were performed to identify predictors of teleaudiology adoption.

Results

46.9% of the sample reported providing telehealth services. Many of them (69.2%) indicated that they began offering telehealth services following the COVID-19 pandemic. Synchronous delivery was commonly utilised. Younger professionals and those employed in public institutions were more likely to engage in remote service delivery (p Conclusions

The audiologists’ reported perceptions and experiences indicate that teleaudiology remains limited in clinical diagnostic service delivery. Broader integration of teleaudiology practices may benefit from enhanced professional training, the development of standardised guidelines, and investment in technological infrastructure to support access to remote hearing healthcare.

☐ ☆ ✇ PLOS ONE Medicine&Health

Protocol for a systematic review and meta-analysis of pharmacological and non-pharmacological interventions for chronic pain management in chronic kidney disease

by Chi Peng Chan, Babaniji Omosule, Courtney Lightfoot, Ellesha A. Smith, Ffion Curtis, James O. Burton, Paul Gardner, Sarah Jasat, Sherna F. Adenwalla, Jyoti Baharani, Daniel S. March

Background

Chronic pain affects up to 60% of people with chronic kidney disease (CKD), yet remains under-recognised and under-treated. Pain management in this population is complicated by altered drug pharmacokinetics, polypharmacy, and the potential nephrotoxicity of conventional analgesics. Despite the high prevalence and significant impact on quality of life, evidence-based guidance specific to pain management in CKD remains limited.

Objectives

This systematic review aims to evaluate the effectiveness and safety of both pharmacological and non-pharmacological interventions in reducing chronic pain intensity among people with CKD on dialysis, not on dialysis, and kidney transplant recipients, across all stages of CKD.

Methods

The primary outcome is the effectiveness of interventions in reducing chronic pain intensity as assessed by pain assessment tools. We will conduct a comprehensive search of MEDLINE, Embase, CINAHL, Web of Science, and ClinicalTrials.gov from their inception to the present date to identify studies for chronic pain management in people living with CKD. Study screening will be conducted independently by two reviewers. One reviewer will extract data from each study, with a second reviewer cross-checking for accuracy and completeness. Data will be extracted on study characteristics, participant demographics, intervention components, pain outcomes, and adverse events. The certainty of evidence will be evaluated independently by two reviewers using the GRADE approach. Where applicable, data will be combined in meta-analyses using random-effects models. Additionally, a network meta-analysis will be performed if enough studies are available.

Expected results

This review will synthesise the current evidence for pain management strategies in CKD, by evaluating effectiveness of interventions among people receiving different renal replacement therapy modalities with varying pain and disease phenotypes. Findings will highlight the comparative effectiveness of various interventions while considering their safety profiles specific to the CKD context. The review will identify gaps in the literature and provide recommendations for clinical practice and future research.

Significance

This review seeks to deliver a thorough evaluation of pain management strategies for people living with CKD. This systematic review is supported by the UK Kidney Association (UKKA), and findings will inform the upcoming UKKA guideline on symptoms management in people with CKD, alongside the other symptoms including itch, fatigue, and gastrointestinal symptoms. This review will aid clinicians in making well-informed decisions regarding pain management strategies, ensuring a balance between effectiveness and the specific risks associated with CKD.

☐ ☆ ✇ PLOS ONE Medicine&Health

Exploring the relationship between mental health and urban green space soundscapes: A scoping review

by Elham Ahmadi, Sophia Baierl, Stephan Voss, Ida Asenkerschbaumer, Ursula Berndt, Leonie Bernhard, Anita Hennig, Anna-Lena Würfele, Michaela Coenen

Urban soundscapes, particularly those experienced in green spaces, have been increasingly recognized as factors that influence human mental health. This scoping review explores the existing literature on soundscapes within urban green spaces and their associated mental health outcomes. It aims to classify the methodologies used in this domain, identify mental health outcomes related to urban green space soundscapes, and examine specific soundscape elements and their correlations with mental health. A systematic search of peer-reviewed studies was conducted. After screening titles, abstracts, and full texts, 22 studies met the inclusion criteria. Diverse methodological approaches were identified, with an emphasis on quantitative multi-method designs. Commonly studied mental health outcomes include stress reduction, mood enhancement, perceived restorativeness, and cognitive restoration. Standardized psychometric tools, such as the Perceived Stress Scale (PSS-14), Positive and Negative Affect Schedule (PANAS) and Perceived Restorativeness Soundscape Scale (PRSS) are frequently used as outcome measures. Natural soundscape elements such as birdsong, water sounds, and rustling leaves had a positive association with relaxation and perceived mental restoration throughout all studies, while mechanical sounds, such as traffic noise were linked to adverse mental health outcomes. These findings highlight that natural soundscapes in urban green spaces have a potential positive relationship with mental health by reducing stress and enhancing mood. However, the cross-sectional design and methodological heterogeneity of the included studies limit causal interpretation. Future research should explore multi-sensory experiences and examine soundscapes in diverse urban contexts to provide more robust insights into their relationship with mental health. The practical implications suggest that urban planners should prioritize integrating natural sound elements into urban areas to improve mental health. The study protocol of this scoping review had been registered at OSF (osf.io/4r7gd).
☐ ☆ ✇ PLOS ONE Medicine&Health

Computational frameworks for automated detection and quantification of paroxysmal sympathetic hyperactivity among traumatic brain injury patients

by Xiangxiang Kong, Lujie Karen Chen, Sancharee Hom Chowdhurry, Ryan B. Felix, Shiming Yang, Peter Hu, Neeraj Badjatia, Jamie Erin Podell

Paroxysmal sympathetic hyperactivity (PSH) is a syndrome that occurs in a large subset of critically ill traumatic brain injury (TBI) patients and is associated with complications and poor recovery. PSH is defined by recurrent episodic vital sign elevations in the appropriate clinical context. However, standard diagnostic criteria rely heavily on subjective judgment, leading to challenges and delays in recognition, monitoring, and management. The objective of this study was to develop automated PSH detection and quantification tools that exclusively utilize objective bedside continuous vital sign data. Using a cohort of 221 critically ill acute TBI patients with at least 14 days of continuous physiologic data (of which 107 were clinically diagnosed with PSH) we developed a high-resolution clinical feature scale based on established PSH-Assessment Measure criteria and two artificial intelligence-based episode detection models including an expert system approach and a machine learning model approach, using a clinician-annotated case example as ground truth. For the episode detection methods, PSH was quantified as the number, duration, and overall temporal burden of detected episodes. To evaluate performance, we compared quantifications across PSH cases and controls and explored precision and recall. All three methods demonstrated initial face validity to delineate PSH cases from non-PSH TBI controls. Future optimization and implementation of the described computational frameworks with real-time patient data could improve the standard monitoring and management of this challenging clinical syndrome.
☐ ☆ ✇ PLOS ONE Medicine&Health

“The system is a bit broken…” a qualitative exploration of barriers in the pathway for diagnosing Developmental Coordination Disorder

by Lucy H. Eddy, Nat K. Merrick, Cara E. Staniforth, Jade L. Jukes, Liam J. B. Hill, Mark Mon-Williams, Farid Bardid, Rebecca Murray

Background

Approximately 5% of children are affected by a neurodevelopmental disorder of their sensorimotor skills. DSM-V and ICD-10, the two most widely used diagnostic systems, define this diagnostically as ‘Developmental Coordination Disorder’ (DCD) or ‘Specific Developmental Disorder of Motor Function’ (SDDMF), respectively. A diagnosis of DCD has been found to have a detrimental impact on a range of outcomes (e.g., health and education). It is therefore crucial that these children receive timely intervention. This is reliant, however, on effective assessment and support pathways. Research has shown there is great parental dissatisfaction, but there has been limited research exploring a clinical and education perspective. This study therefore aimed to understand barriers and facilitators for clinical and education practitioners in the pathway in a diverse district in the UK (Bradford).

Methods

Semi-structured interviews were completed with stakeholders across the pathway to identify barriers and facilitators to assessing, diagnosing, and supporting children with sensorimotor skill difficulties. Theoretical thematic analysis aligned to the Capability, Opportunity, Motivation model of Behaviour change (COM-B) was used to analyse the qualitative data.

Results

Interviews revealed many barriers in the DCD pathway related to capability (confusing terminology, inconsistent knowledge, inappropriate referrals), opportunity (resource constraints, DCD being considered low priority, and disconnected services), and motivation (overlapping job roles, a desire to consider those with difficulties not eligible for a diagnosis). No facilitators were consistently identified across interviews.

Conclusion

Families face multiple barriers to obtaining a diagnosis for their child through existing clinical pathways for assessment and support. These findings are unlikely to be unique to Bradford, due to international research highlighting these issues via parental interviews. These findings therefore may reflect challenges both nationally and internationally within DCD pathways. There is an urgent need for: (i) clear communication across different services (with consistency in terminology), and (ii) a more collaborative and integrated approach to assessment, diagnosis, and support in order to help these children thrive.

☐ ☆ ✇ PLOS ONE Medicine&Health

Mental health help-seeking intentions among health workers in the east coast of peninsular Malaysia: Perceived barriers and predictive factors

by Muhammad Syafiq Kunyahamu, Aziah Daud, Ijlal Syamim Mohd Basri, Tengku Alina Tengku Ismail, Mohd Faiz Md Tahir

Introduction

Mental health problems among health workers are a growing concern globally, including in Malaysia. Despite the availability of mental health services, some health workers do not seek professional help. This study aims to determine the level of health workers’ intention to seek professional help, examine the barriers they perceive, and identify predictors of mental health help-seeking intention.

Methods

This cross-sectional study involved 470 health workers in the East Coast region of Peninsular Malaysia. Data was collected using a self-administered questionnaire. Linear regression analysis was employed to identify the predictors of professional help-seeking intention.

Results

The mean score for mental health help-seeking intention was 4.90 (SD = 1.03). Perceived need for help positively predicted help-seeking intention (B = 0.532, p  Conclusions

This study highlights the roles of the perceived need for help and perceived stigma barriers in predicting health workers’ help-seeking intentions, offering a basis for targeted interventions and policies to enhance mental health support within Malaysian healthcare settings.

☐ ☆ ✇ PLOS ONE Medicine&Health

Exploratory study on the impact of <i>Ganoderma australe</i> extract on gut microbiota and immune gene expression in honey bees exposed to <i>Vairimorpha ceranae</i>

by Sarah Zuern, Bella Romero, Carlos Spichiger, Leandro Ortiz, Alejandro Jerez, Esteban Basoalto, Max Emil Schön, Sigisfredo Garnica

The microsporidium Vairimorpha (Nosema) ceranae is an emerging threat to honey bees (Apis mellifera), known to disrupt gut microbiota and suppress immune responses, potentially contributing to colony losses. Fungal extracts have recently gained interest as sources of bioactive compounds with antimicrobial and immunomodulatory potential. In this study, we explored the effects of different dietary supplements—sugar syrup, HiveAlive™, and a novel Ganoderma australe extract (GanoBee)—on gut bacterial composition and immune-related gene expression in honey bees subjected to experimental exposure to V. ceranae 1 x 104 spores per bee. The GanoBee diet altered the gut microbiota, notably reducing the relative abundance of Rhizobiaceae (Bartonella apis) and increasing Frischella compared to other treatments. While alpha diversity was not significantly affected by diet or exposure to V. ceranae, beta diversity differed significantly in bees fed with GanoBee. Additionally, the expression of the antimicrobial peptide genes abaecin and hymenoptaecin was elevated in both exposed and unexposed bees fed with GanoBee, depending on the sampling day. However, the establishment of V. ceranae infection appeared limited, likely due to low spore viability, and mortality in control bees was higher than expected. The low Vairimorpha ceranae infection levels observed in this study are likely attributable to reduced spore viability caused by storage conditions and/or suboptimal environmental conditions within the laboratory cages. Post hoc analyses indicated that the high viscosity of GanoBee-supplemented diets likely contributed to the elevated bee mortality observed, underscoring a critical limitation of the experimental design related to diet formulation and delivery method. These physical factors complicate the interpretation of treatment efficacy and highlight the importance of optimizing feeding protocols to avoid confounding effects. Despite these constraints, GanoBee demonstrated promising potential as a modulator of gut microbiota composition and immune-related gene expression, supporting the need for further research under improved and carefully controlled experimental conditions.
☐ ☆ ✇ PLOS ONE Medicine&Health

Methodological review of the design, objectives and sample size of Research for Patient Benefit (RfPB) applications that use an external randomised controlled pilot trial design: A protocol

by Claire L. Chan, Saskia Eddy, Jennie Hejdenberg, Ben Morgan, Heather M. Morgan, Gillian Lancaster, Clare Robinson, Sandra M. Eldridge

Background

The National Institute for Health and Care Research accepts applications for pilot and feasibility studies to their Research for Patient Benefit (RfPB) programme. There has been limited work describing the design practices of these applications and funding status. Knowing some of the qualities which may contribute towards a pilot or feasibility study application successfully gaining funding could help researchers improve the quality of their applications. Therefore, this study describes the protocol for a review looking at the characteristics of funded and non-funded external pilot trial applications. In particular, the primary objective is to describe the planned sample size and sample size justifications.

Methods

The study will be conducted on 100 applications from Competition 31–37 with a randomised feasibility design, identified and given access to us by RfPB where the lead applicant has consented. We will screen these applications to identify the external pilot trials, first looking through the titles and then the full text. Following this, we will extract data on information such as medical area, study design, objective(s), sample size, sample size justification, and funding outcome stage one and two. Validation will be performed on 20% of the data extracted; discrepancies will be resolved by discussion or a third reviewer will decide if there is no consensus. We will use descriptive statistics to summarise quantitative data, and will analyse qualitative data using thematic analysis. Findings will be summarised through discussion with the project contributors to produce a reader-friendly guidance document.

Discussion

This work will provide a more complete picture of RfPB external randomised pilot and feasibility trials. The findings will assist researchers when planning their pilot trials, and could help improve the quality of submitted applications.

Protocol Registration

Open Science Framework protocol registration DOI: https://doi.org/10.17605/OSF.IO/PYKVG.

☐ ☆ ✇ PLOS ONE Medicine&Health

Comprehensive post-marketing safety evaluation of atezolizumab: A disproportionality analysis based on individual case safety reports in the FAERS

Por: Yu Cui · Yuxuan Gao · Na Meng · Xiaojuan Li · Na Zhao · Lili Yu — Marzo 3rd 2026 at 15:00

by Yu Cui, Yuxuan Gao, Na Meng, Xiaojuan Li, Na Zhao, Lili Yu

Atezolizumab is a widely used immune checkpoint inhibitor (ICI) for cancer treatment, and postmarketing testing is important. This study aims to provide a reference for the safe and rational use of drugs in clinical practice by mining and analyzing the adverse event (AE) signals of atezolizumab on the basis of the FDA Adverse Event Reporting System (FAERS). This research extracted AE reports from the second quarter (Q2) of 2016 to Q2 of 2024 from the FAERS. AEs were standardized and classified on the basis of the System Organ Class (SOC) and Preferred Term (PT) from the Medical Dictionary for Regulatory Activities (MedDRA) version 23.0. This study utilized disproportionality analysis (DPA) for signal mining and analysis, including the reporting odds ratio (ROR) method, the Medicines and Healthcare Products Regulatory Agency (MHRA) method, and the Bayesian confidence propagation neural network (BCPNN) method. We obtained a total of 3,124 AE signals and identified 640 PTs and 21 SOCs for atezolizumab. The highest signal intensity was systemic immune activation (n = 15, ROR = 449.20, PRR = 449.07, IC = 8.06), and the most frequently reported AEs were death, pyrexia, infectious pneumonia, anaemia, and febrile neutropenia. The top 100 PTs in terms of signal intensity involved a total of 16 SOCs, including those associated with endocrine disorders; respiratory, thoracic and mediastinal disorders; and renal and urinary disorders. This study revealed that AEs in the endocrine, respiratory and urinary systems need to be monitored in clinical practice.
☐ ☆ ✇ PLOS ONE Medicine&Health

Self-efficacy mediates the relationship between grit and life satisfaction in a sample of employed university students resident in the United Arab Emirates

Por: Ektha Benny · Zahir Vally — Marzo 3rd 2026 at 15:00

by Ektha Benny, Zahir Vally

Balancing academic and professional responsibilities presents unique psychological challenges for employed university students. Most existing literature on this student population has adopted a deficits-approach. However, identifying the strengths inherent in such individuals could offer valuable avenues for informing strategies to reduce their risk of psychological distress. This study examined whether self-efficacy impacts the relationship between grit and life satisfaction among employed university students in the United Arab Emirates (UAE). A cross-sectional study was employed with data collected from 242 employed university students residing in the UAE. Participants completed a self-report survey that comprised of measurements of grit, self-efficacy and life satisfaction. Grit was significantly and positively associated with both life satisfaction and self-efficacy. Additionally, self-efficacy was found to significantly mediate the relationship between grit and life satisfaction in this sample of participants. This study identified grit as a potential factor that could be harnessed to improve life satisfaction, through the mediating role of self-efficacy. These findings hold important implications for informing strategies to promote positive mental health outcomes among employed university students who possess the strength of grit.
☐ ☆ ✇ BMJ Open

Utility of Xpert MTB/RIF using bronchoalveolar lavage samples for the diagnosis of pulmonary tuberculosis in negative or sputum-scarce adults: a systematic review and meta-analysis protocol

Por: Sabella-Jimenez · V. L. · Sabella-Jimenez · V. · Estupinan-Bohorquez · A. F. · Acosta-Reyes · J. — Marzo 3rd 2026 at 13:40
Introduction

Tuberculosis is the leading cause of death globally from a single infectious agent. Early diagnosis is critical to reducing morbimortality. In cases of negative smear microscopy or limited sputum production, bronchoalveolar lavage (BAL) samples offer an alternative for diagnosis. Culture, the gold standard, requires a high bacterial load, extensive infrastructure and is time-consuming. Xpert MTB/RIF provides faster results with a higher cost. Previous systematic reviews present substantial limitations, including significant heterogeneity. Therefore, the diagnostic utility of Xpert MTB/RIF using BAL samples in adults with negative or scant sputum for pulmonary tuberculosis (PTB) needs to be reassessed.

Methods and analysis

A systematic search of MEDLINE, Embase, LILACS and Web of Science will be conducted without language or publication date restriction. Cross-sectional diagnostic studies of negative or sputum-scarce adults with presumptive PTB who underwent bronchoscopy to obtain samples for Xpert MTB/RIF and culture will be included. Screening and data extraction will be performed independently. Methodological quality will be assessed using the QUADAS-2 tool. A bivariate hierarchical random-effects model will synthesise sensitivity and specificity. Meta-analysis will be performed using Meta-DiSc 2.0. Heterogeneity will be assessed using I2 and Cochrane thresholds. Subgroup analyses will be performed based on study design, population differences, country, culture method and risk of bias. Publication bias will be investigated using a funnel plot. The certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. There was no patient or public involvement in the development of the systematic review protocol.

Ethics and dissemination

Ethical approval is not required as this study will use publicly available data. Findings will be disseminated through peer-reviewed publication.

PROSPERO registration number

CRD42025639440.

☐ ☆ ✇ BMJ Open

Comparative effectiveness and safety of digital health delivery models for pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: a protocol for systematic review and network meta-analysis of randomised controlled trials

Por: Xu · L. · Chen · X. · Yang · C. · Feng · M. · Wu · Y. — Marzo 3rd 2026 at 13:40
Introduction

Chronic obstructive pulmonary disease (COPD) affects approximately 480 million individuals globally and is projected to reach 600 million by 2050, representing a substantial burden on healthcare systems and patient quality of life. Pulmonary rehabilitation is a cornerstone intervention for COPD management, delivering clinically meaningful improvements in exercise capacity, health-related quality of life and dyspnoea. Despite strong guideline recommendations and established efficacy, only 2%–4% of eligible patients with COPD access traditional centre-based pulmonary rehabilitation due to geographical barriers, transportation difficulties, scheduling conflicts and limited healthcare resources. Digital health technologies offer promising alternatives to overcome these access barriers while potentially maintaining therapeutic benefits. Various digital delivery models have emerged, including video-based telerehabilitation, virtual reality platforms, mobile health applications and web-based programmes. However, their comparative effectiveness remains unclear, limiting evidence-based clinical decision making. This systematic review and network meta-analysis will aim to compare and rank the effectiveness and safety of different digital health delivery models for pulmonary rehabilitation in patients with COPD, providing evidence to inform optimal intervention selection in clinical practice.

Methods and analysis

We will conduct a systematic review and Bayesian network meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Network Meta-Analyses guidelines. Comprehensive searches will be performed across five electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, CINAHL) from inception to January 2026, without language restrictions. Eligible studies will include randomised controlled trials comparing digital health delivery models for pulmonary rehabilitation in adults with COPD. Digital health interventions will be categorised into four distinct delivery models: video-based telerehabilitation, virtual reality rehabilitation, mobile health rehabilitation and web-based platform rehabilitation. Interventions combining multiple modalities will be categorised according to the predominant component based on intervention frequency, duration and primary therapeutic mechanism. Two independent reviewers will perform study selection, data extraction and risk of bias assessment using the Cochrane Risk of Bias 2 tool. The primary outcome will be change in 6 min walk distance. Key secondary outcomes will include disease-specific quality of life measures, dyspnoea severity, hospitalisation rates, exacerbation frequency, intervention adherence and adverse events. A Bayesian random-effects network meta-analysis will be conducted, calculating mean differences or ORs with 95% credible intervals. Treatment rankings will be estimated using surface under the cumulative ranking curve probabilities. Evidence certainty will be assessed using the Confidence in Network Meta-Analysis framework. Planned subgroup analyses will explore potential effect modifiers including disease severity, intervention duration, supervision mode and technological features.

Ethics and dissemination

As this systematic review will use data from previously published studies, formal ethical approval is not required. Findings will be disseminated through peer-reviewed publication, presentations at relevant scientific conferences and communication to healthcare providers, policymakers and patient advocacy organisations.

PROSPERO registration number

CRD420251268701.

☐ ☆ ✇ BMJ Open

Pragmatic, open-label, multicentre, randomised controlled trial to guide initial therapy for immune checkpoint inhibitor-induced inflammatory arthritis comparing standard of care (prednisolone) to adalimumab without glucocorticoids: REACT trial protocol

Por: Fisher · B. A. · Rowe · A. · Hodson · C. · Wilkhu · M. · Williams · E. · Turner · E. · Allard · A. · Blake · T. · Bombardieri · M. · Cope · A. P. · Dubey · S. · Mankia · K. · Malley · T. · Moore · O. · Payne · M. · Plummer · R. · Tilby · M. · Tillett · T. · Wong · E. · Wu · Y. · Filer · A. · Pra — Marzo 3rd 2026 at 13:40
Introduction

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment through targeted disruption of the physiological pathways that maintain tissue tolerance, but which are co-opted by cancers to evade immunosurveillance. Thus, the resultant T-cell activity often causes immune-related adverse events including immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA). ICI-IA results in functional impairment that frequently persists, even after ICI discontinuation, with substantial quality-of-life impacts for cancer survivors.

A high-quality body of evidence to guide ICI-IA management remains an unmet need. Pharmacological treatment may be prolonged, typically begins with non-specific immunosuppression, including systemic steroids, and is usually only rationalised to more targeted therapy in resistant cases. Moreover, retrospective data suggest the high dose glucocorticoids sometimes used in new-onset ICI-IA may be associated with worse cancer outcomes.

Tumour necrosis factor (TNF) inhibition strategies are well established with excellent efficacy and safety profiles in ‘spontaneous’ inflammatory arthritides including rheumatoid and psoriatic arthritis. Mechanistic evidence from ex vivo and murine studies also supports the utility of anti-TNF therapy for steroid-refractory cases of ICI-IA. Although good clinical responses have been reported in this setting, the REACT trial (REmission induction of Arthritis caused by Cancer ImmunoTherapy) aims to provide randomised and robust clinical evidence for deploying targeted therapy earlier in ICI-IA management. It will test whether up-front anti-TNF therapy can more effectively and quickly control symptoms, reduce glucocorticoid exposure, prevent early ICI discontinuation and increase the frequency of drug-free ICI-IA remission.

Methods and analysis

REACT is a prospective, multicentre, open-label, superiority, two-arm, randomised controlled clinical trial to guide initial therapy for patients with ICI-IA. The trial will compare the current standard of care (initial prednisolone; Arm A) with the anti-TNF drug, adalimumab without glucocorticoids (Arm B).

The primary outcome is glucocorticoid-free arthritis remission rate at 24 weeks where remission is defined as: (i) No use of systemic or intra-articular glucocorticoids (except when used for adrenal insufficiency) within 4 weeks prior to assessment at 24 weeks; and (ii) absence of synovitis on clinical examination.

Ethics and dissemination

The protocol was approved by East Midlands—Leicester South Research Ethics Committee on 31-Oct-2024 (Ref: 24/EM/0202). Participants are required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

Trial registration number

ISRCTN18217497.

☐ ☆ ✇ BMJ Open

Hepatitis B virus infection and its determinants among pregnant women in Ethiopia: protocol for umbrella review of systematic review and meta-analysis 2025

Por: Bekele · M. · Oche · W. O. · Geltore · T. E. · Sileshi · E. · Hadaro · T. S. · Alano · B. A. · Abera · W. — Marzo 3rd 2026 at 13:40
Introduction

Among the five hepatitis viruses, the hepatitis B virus (HBV) is a major cause of serious acute and chronic liver infections worldwide. The major public health impact of HBV infection arises from chronic liver disease, including cirrhosis and hepatocellular carcinoma, which predominantly affects young and middle-aged adults of both sexes. Therefore, preventive interventions focusing on mothers and infants are critical due to vertical and early childhood transmission dynamics.

HBV prevalence largely varies among pregnant women in Ethiopia because of multiple interrelated factors. This umbrella review will consolidate all existing systematic reviews and create a more reliable picture of HBV infection and its determinants among pregnant women in Ethiopia.

Methods and analysis

This umbrella review will be conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses reporting standards. The review will focus on identifying and integrating evidence from eligible systematic reviews and meta-analyses, with methodological quality appraised using the MeaSurement Tool to Assess systematic Reviews instrument. A comprehensive literature search strategy will be developed using relevant Medical Subject Headings alongside free-text keywords. Electronic searches will be conducted in PubMed/MEDLINE, African Journals Online, Web of Science, Scopus and Google Scholar. Statistical heterogeneity among the included reviews will be quantified using the I² statistic. Data management and meta-analytic procedures will be performed using STATA version 17, and effect estimates will be presented with corresponding 95% CIs to determine statistical precision.

Ethics and dissemination

This review uses only published or publicly available data, so ethics approval is not required. Findings will be disseminated via peer-reviewed publications, conference presentations and shared with policymakers, healthcare partners, clinicians and patients to inform policy, enhance education and guide future research.

PROSPERO registration number

PROSPERO (CRD420251118982).

☐ ☆ ✇ BMJ Open

Efficacy of perioperative intravenous lidocaine infusion on postoperative recovery and analgesia in patients undergoing video-assisted thoracoscopic surgery: study protocol for a randomised, double-blind, placebo-controlled trial

Por: Omindo · W. W. · Xiao · Z. · Wang · X. · Fu · L. · Wang · J. · Zhang · R. · Ping · W. · Zhou · B. · Zhang · N. — Marzo 3rd 2026 at 13:40
Introduction

Despite the minimally invasive nature of video-assisted thoracoscopic surgery (VATS), moderate-to-severe postoperative pain remains frequent and impairs recovery. Intravenous lidocaine possesses multimodal analgesic, antihyperalgesic and anti-inflammatory properties that may improve pain control and functional outcomes, but robust evidence in thoracic surgery is lacking. Moreover, its potential to attenuate neuropathic pain, a key component of chronic post-thoracic pain syndromes, has not been adequately investigated. This trial will determine whether continuous perioperative intravenous lidocaine infusion improves recovery, reduces acute pain intensity and prevents the development of neuropathic pain after VATS.

Methods and analysis

This single-centre, randomised, double-blind, placebo-controlled trial will enrol 84 adult patients undergoing elective VATS. Participants will be randomised (1:1) to receive either intravenous lidocaine (bolus 1 mg/kg at induction followed by continuous infusion at 1.5 mg/kg/hour intraoperatively and postoperatively for 24 hours) or matched normal saline postoperatively, with identical intraoperative management in both groups. The primary outcome is the incidence of moderate-to-severe movement-evoked pain at 24 hours postoperatively. Secondary outcomes include pain at 48 and 72 hours, opioid consumption, pulmonary complications, sleep quality, quality of recovery, neurocognitive outcomes and chronic neuropathic pain at 3 months. Analyses will follow the intention-to-treat principle.

Ethics and dissemination

The study protocol was approved by the Institutional Review Board of Tongji Hospital (Reference No. TJ-IRB202509102) and registered in the Chinese Clinical Trial Registry (ChiCTR2500111163). Written informed consent will be obtained from all participants. Results will be submitted to peer-reviewed journals and academic conferences.

Trial registration number

ChiCTR2500111163.

☐ ☆ ✇ BMJ Open

Mapping the evidence on dietary acculturation post-migration among Indian immigrants in Australia, Canada, New Zealand and the UK: a scoping review protocol

Por: Bachani Singh · S. · George · M. S. · Upton · P. · Knight-Agarwal · C. R. — Marzo 3rd 2026 at 13:40
Introduction

Indian immigrants experience significant dietary acculturation post-migration, shifting from traditional diets to more westernised eating patterns influenced by socioeconomic and environmental factors. This transition, often marked by increased processed food consumption and reduced intake of traditional staples, contributes to elevated risks of obesity and type 2 diabetes. Despite the growing Indian diaspora in Australia, Canada, New Zealand and the UK, the evidence on their dietary acculturation remains limited.

Methods and analysis

This review will adopt the Joanna Briggs Institute (JBI) methodology for scoping reviews. A three-step search strategy will be applied across databases including MEDLINE (via PubMed), CINAHL, Scopus and Web of Science. Google Scholar will be used as a supplementary search tool to identify additional relevant studies. The search will include peer-reviewed studies and grey literature published in English between 1 January 2000 and 22 May 2025. First-generation Indian immigrants of all ages will be included, while second-generation immigrants, refugee populations and studies linked to non-communicable disease interventions will be excluded. Screening will be conducted in Covidence by two independent reviewers, with discrepancies resolved by a third reviewer. Data will be extracted using a standard JBI tool, charted in tabular form, and synthesised narratively and thematically.

Ethics and dissemination

As this review will use published and publicly available data, formal ethics approval is not required. Findings will be disseminated through peer-reviewed publication, conference presentations and community engagement.

☐ ☆ ✇ BMJ Open

From mother to child: a protocol paper on the longitudinal effects of a perinatal intervention on maternal self-efficacy and emotion regulation and child outcomes

Por: Montreuil · T. · Skinner · J. · Humez · L. · Gratton · C. · Herba · C. M. · Cote · S. M. — Marzo 3rd 2026 at 13:40
Introduction

Parental psychological challenges and poor well-being are key factors in shaping both the quality of parent-child interactions and child development. Specifically, maternal psychological distress is a central determinant of child development. Elevated levels of distress in mothers are associated with poorer child cognitive, behavioural and social-emotional outcomes, with effects persisting into adolescence and adulthood. While this highlights the critical importance of early prevention and intervention efforts to support parents, postpartum mental healthcare remains limited, despite ongoing and evident needs.

Methods and analysis

This protocol outlines a 2-year longitudinal follow-up study investigating the impact of a secondary perinatal programme (ie, Toi, Moi, Bébé), completed by mothers during pregnancy, and its impact on children’s cognitive and social-emotional functioning at 24 and 48 months. Further, the study aims to explore whether maternal self-efficacy and emotion regulation may serve as potential mediators or moderators of the relationship between programme participation and child development outcomes. The research aims to leverage the Toi, Moi, Bébé programme, by recruiting mother-child dyads (n=250) in which the mothers participated in the programme during pregnancy. Mothers were randomly assigned to complete the parenting well-being intervention either independently or with added telephone support. Participants who consent will be invited to take part in a two-wave follow-up at 24 months (T1) and 48 months postpartum (T2). At both time points, mothers will complete demographic questionnaires and standardised measures assessing maternal well-being (Generalised Anxiety Disorder-7, Edinburgh Postnatal Depression Scale and Perceived Stress Scale), child cognitive functioning (Ages and Stages Questionnaire-3 and MacArthur-Bates Communicative Development Inventory), child social-emotional functioning (Ages and Stages Questionnaire, Social Emotional—second Edition-2 and Child Behaviour Checklist for Ages 1.5–5), maternal emotion regulation (Cognitive Emotion Regulation Questionnaire) and maternal self-efficacy (Parental Cognitions and Conduct Towards the Infant Scale & Me as a Parent Scale). Parents’ perceptions of their parenting experience will be measured using the Parental Reflective Functioning Questionnaire. Mother-child interaction, parenting quality and cognitive stimulation in the home environment will be measured using a brief virtual interview (StimQ2-Toddler) and a naturalistic observation assessment (Parenting Interactions with Children: Checklist of Observations Linked to Outcomes). Using RStudio, linear mixed models will be used to assess the impact of the intervention (online intervention only vs only with telephone support) on child cognitive and social-emotional development at T1 and T2. In parallel, separate models will be conducted to examine associations between maternal emotion regulation and self-efficacy on the child development outcomes at the same timepoints. Exploratory analyses will be conducted to examine potential moderating effects of child sex and group assignment on the associations between maternal emotion regulation and self-efficacy and child developmental (cognitive and socioemotional) outcomes, using causal inference models.

Ethics and dissemination

The current study has been registered, reviewed and approved (MP-37-2025-10894) by the Research Institute of the McGill University Health Centre Research Ethics Board. Findings from this research will be disseminated through peer-reviewed open access publications, and presentations at national and international conferences.

Trial registration number

NCT05110456.

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