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Hoy — Marzo 4th 2026Tus fuentes RSS

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.

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.

Proton Nuclear Magnetic Resonance With Time‐Frequency Analysis: A Potential Diagnostic Approach for Keloids

ABSTRACT

Keloids are chronic fibroproliferative skin disorders with high recurrence rates and limited treatment options, yet reliable diagnostic biomarkers are lacking. Current classification systems rely heavily on clinical observation, underscoring the need for objective, noninvasive tools. In this exploratory study, serum-based 1H nuclear magnetic resonance (NMR) measurement combined with short-time Fourier transform (STFT) for time-frequency analysis was performed, followed by principal component analysis (PCA), to investigate potential patient subgroups. Serum samples from 29 patients were analysed and PC1 scores suggested two potential patient subgroups. Retrospective analysis showed that these subgroups differed primarily in keloid aetiology: one group predominantly included cases arising from unclear or minimal causes (e.g., acne, folliculitis), whereas the other comprised cases following clear traumatic events (e.g., surgery). Although most clinical variables showed no significant differences, significant differences in aetiology and Japan Scar Workshop Scar Scale (JSS) scores support the biological relevance of this separation of subgroups. These findings suggest that the time-frequency features of NMR signals from serum samples capture systemic characteristics associated with keloid pathophysiology. If validated in larger cohorts, this approach may serve as a noninvasive adjunct to clinical assessment and lay the foundation for objective patient stratification and precision-guided treatment strategies.

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Applications of artificial intelligence for real-world evidence generation: a protocol for a living scoping review

Por: Oikonomidi · T. · Raad · H. · Diaz-Decaro · J. · Li · H. · Y Smith · M. · Rivera · D. R. · Liu · W. · Soriano Gabarro · M. · Bennett · D. · Mack · C. D. · Teltsch · D. Y. · Gerber · J. E. · Bray · B. · Dickinson · H. · Jani · M. · Naidoo · N.
Introduction

Artificial intelligence (AI) is rapidly evolving, offering an expanding suite of capabilities that go beyond the traditional focus on prediction and classification. Generative AI (GenAI) and agentic AI could create transformative practices to support real-world evidence (RWE) generation for health research by streamlining studies, accelerating insights and improving decision-making. However, there is no published overview available describing the range of applications in RWE generation. This review aims to describe where and how genAI and agentic AI are applied across the domains of healthcare research tasks for RWE generation. Additionally, to map applications by tasks and methods across the product lifecycle continuum, and to identify emerging gaps and opportunities.

Methods and analysis

This Living Scoping Review (LSR) will include studies reporting an application and/or evaluation of genAI or agentic AI applied to one or more RWE generation research tasks. Searches will be conducted in Embase, MEDLINE and additional sources (eg, grey literature). Citations will be independently screened by two human senior reviewers for a substantive training dataset and a commercially available screening algorithm (Robot Screener) will complete screening with a human reviewer. The LSR will include reports of studies (primary or reviews) describing and/or evaluating the application of any genAI model for RWE generation in healthcare, in English, published from 1 January 2025 to the date of search. Data will be extracted from all studies included in the LSR by one independent senior reviewer using a piloted template, with 10% quality check by a second senior reviewer. Descriptive statistics will be used to summarise the applications of genAI per RWE research task, and the results of genAI evaluations. Thematic analysis will be used to describe genAI application patterns, trends, gaps and opportunities. The LSR protocol and reports will be updated annually, and findings will be published on a publicly available website (eg, ISPE—the International Society for Pharmacoepidemiology).

Ethics and dissemination

Ethical approval is not required due to use of previously published data. Planned dissemination includes peer-reviewed publication, presentation and short summaries.

Mental health impact of the COVID-19 pandemic on frontline healthcare workers in Ethiopia: a scoping review of associated mental health risk and protective factors

Por: Draebel · T. A. · Birhanu · Z. · Lien · L. · Soerensen · J. B. · Andersen · L. S. · Terefe Tucho · G. · Mekonnen · H.
Objectives

The mental health impacts of COVID-19 on frontline healthcare workers have been reported globally; however, there is limited evidence from low-income countries such as Ethiopia. We reviewed the literature to understand how COVID-19 impacted the mental health of frontline healthcare workers, including the associated risk and protective factors.

Design

A scoping review of peer-reviewed research was conducted between 2020–2025 to explore the mental health and well-being of frontline healthcare workers in Ethiopia during COVID-19. The process adhered to the guidelines for data extraction outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Our search identified 35 studies, of which 29 studies were included in the final synthesis.

Data sources

Three online databases, PubMed, Web of Science and PsycInfo, were systematically searched for data.

Eligibility criteria

Studies were considered for inclusion in the review if they focused on mental health conditions and psychosocial well-being among healthcare workers during COVID-19 in Ethiopia. Studies were only included if published in English and excluded if they were conference abstracts, case studies, reviews, commentaries, contained incomplete data or lacked variables of interest.

Data extraction and synthesis

Data extraction was conducted manually by two reviewers by using a data extraction sheet created in Excel.

Results

Most frontline healthcare workers experienced symptoms of insomnia, psychological distress, stress, anxiety, post-traumatic stress disorder and depression during COVID-19. Female frontline healthcare workers, nurses, midwives and laboratory technicians reported higher rates of adverse mental health outcomes. Our results found that being married, living together with a spouse and having a high educational level were risk factors for adverse mental health outcomes.

Conclusion

The mental health and well-being of frontline healthcare workers is at risk during a global health crisis; however, there is a limited understanding of how to protect the mental health of frontline healthcare workers in low-income countries, such as Ethiopia, at such a critical time. Additional research is needed to better inform mental health preparedness interventions for frontline healthcare workers in these contexts, particularly given predictions of another pandemic occurring within the next decade.

Cohort profile: Sub-cohort study on the second phase of the Chiba Study of Mother and Child Health (C-MACH), Japan

Purpose

The second phase of the Chiba Study of Mother and Child Health (C-MACH) was initiated to investigate how environmental exposures from the fetal period to early childhood influence maternal and child health outcomes. The sub-cohort focuses specifically on detailed assessments of indoor environmental factors and neighbourhood-built and social environments. By integrating environmental metrics with biological, behavioural and sociodemographic data, the study aims to elucidate their role in the development of allergies, neurodevelopmental disorders and other non-communicable diseases in early life.

Participants

Between June 2021 and April 2023, 505 pregnant women were enrolled in the second phase of the C-MACH main study. Of these, 298 participants consented to join the sub-cohort study, including 258 in the sleep and physical activity monitoring option (Option 1) and 148 in the indoor allergen exposure sub-study (Option 2). The study includes biological sampling, environmental monitoring and repeated questionnaire surveys. At baseline, 253 live births were recorded from 251 pregnancies.

Findings to date

Of the 298 women, 272 completed early pregnancy questionnaires. The mean maternal age was 33.1 years (SD 4.6); 97.8% were married. University-level education was reported by 51.0% of mothers and 53.7% of fathers. Most households had an annual income of 6 to

Future plans

Longitudinal follow-up will continue until the children reach age 15. Future analyses will examine associations between environmental exposures and allergic, developmental, endocrine/metabolic and obesity-related outcomes.

Genetic, lifestyle and environmental influences on health: a Finnish biobank recall study protocol (BioRecall)

Por: Sillanpää · E. · Föhr · T. · Kurtti · E. · Aittola · K. · Mäkelä · J. · Southerington · T. · Lakka · T. A. · Jokela · T. · Ahtiainen · M. · Laakkonen · E. · Rantakokko · M. · Ravi · S.
Introduction

Non-communicable diseases are the leading causes of premature mortality worldwide. Both genetic predispositions and environmental exposures affect disease risk. While biobanks have increased understanding of genetic predictors of these diseases, environmental influences are expected to have a greater impact on disease development. Individuals also create their own environments and lifestyles based on genetically regulated preferences, leading to gene–environment interactions that require large datasets to study. Finnish biobanks typically lack sufficient lifestyle and environmental data, which limits their use. We present a protocol for a biobank-recall study (BioRecall) to collect data on lifestyle and environmental exposures and combine these findings with genotypes, biological samples and clinical outcomes.

Methods and analysis

All previously genotyped donors from the Central Finland Biobank who have been diagnosed with type 2 diabetes and have consented to recall will be invited to participate in the pilot study. The preliminary feasibility assessment reveals that there are 1580 suitable candidates. Participants will complete an electronic questionnaire on a secure online platform. The questionnaire includes validated questions on lifestyles, anthropometrics, weight loss history, health, symptoms, work characteristics, emotional states and residential environments. Postcode information will facilitate the addition of spatial environmental data. Genotype and related clinical data will be provided in the study in accordance with the Finnish Biobank Act and combined with questionnaire data.

Ethics and dissemination

The Human Sciences Ethics Committee of the University of Jyväskylä delivered a favourable statement regarding the study protocol (1671/13.00.04.00/2023). Central Finland Biobank approved the research plan (no: BB24-0333-A01). The data collected will be returned to the Central Finland Biobank for research purposes with the participants’ consent. Permission for data usage can then be applied through standard protocols of the Fingenious service (https://site.fingenious.fi/en/). If successful, the study will be expanded to other donors and Finnish biobanks.

Left atrial appendage closure versus direct oral anticoagulants after pulmonary vein isolation for atrial fibrillation: protocol for a multicentre, prospective, randomised, non-inferiority trial (PROMOTE study)

Por: Shen · L. · Jiang · L. · Hao · Z. · Chu · H. · Wang · X. · Ning · Z. · Zhang · J. · Yang · B. · Xu · Y. · Fang · R. · Kong · L. · Zhang · X. · He · Q. · Zhang · Z. · Zhang · T. · Du · C. · Wu · Y. · Zhao · D. · Huang · H. · Ma · W. · Liang · Z. · Pan · X. · Wang · C. · Miao · Y. · Shen · L. · He · B.
Introduction

Atrial fibrillation (AF), with a prevalence of 1–2%, is the most common cardiac arrhythmia. AF is associated with a fivefold increased risk of cardioembolic events; approximately 20% of all strokes are caused by AF. Pulmonary vein isolation (PVI) has become the first-line treatment for AF. However, PVI cannot eliminate the residual stroke risk. Current guidelines recommend that anticoagulation be continued in this specific group of patients, regardless of the presence or absence of AF. In this large AF population post-PVI, who are considered to be in an earlier stage of AF, it is unknown whether left atrial appendage closure (LAAC) offers an alternative to direct oral anticoagulant (DOAC) therapy.

Methods and analysis

The trial will be a prospective, randomised, multicentre non-inferiority study comparing two treatment strategies in AF patients after atrial ablation. Patients will be randomly assigned to either percutaneous LAAC (group A) or DOAC treatment (group B) in a 1:1 ratio; both sequential and concomitant planned ablation with or without LAAC are accepted. Randomisation will be conducted using web-based randomisation software. A total of 1012 participants (506 patients per group) will be enrolled. The primary effectiveness measure will be the occurrence of any of the specified events within 24 months after randomisation: stroke/transient ischaemic attack/systemic thromboembolism, cerebral haemorrhage, other major haemorrhages (Bleeding Academic Research Consortium ≥2), cardiovascular mortality and all-cause mortality.

Ethics and dissemination

The study was approved by the Ethical Review Board of Shanghai Chest Hospital, China (KS(Y)20287). Written informed consent will be obtained from all participants. The trial will follow the Declaration of Helsinki and Good Clinical Practice. Confidentiality will be maintained with anonymised, securely stored data. Findings will be disseminated through peer-reviewed publications and conferences.

Trial registration number

ChiCTR2000036538.

Factors Associated With Newly Graduated Nurses' Work Engagement: Systematic Review of Quantitative Studies

ABSTRACT

Aim

To describe the factors associated with work engagement in newly graduated nurses.

Design

Systematic review of original quantitative studies according to Joanna Briggs Institute guidelines.

Methods

The systematic review utilised PEO inclusion criteria. Original peer-reviewed quantitative studies were identified. Two researchers independently conducted a screening of study eligibility based on title, abstract, and full text. The JBI critical appraisal tool for analytical cross-sectional studies was employed to perform a rigorous methodological quality assessment. The data was extracted, tabulated, and then analysed narratively.

Data Sources

The literature search was conducted in November 2023 by screening four databases: Scopus, CINAHL (Ebsco), ProQuest, and Ovid Medline.

Results

The review included 19 articles, presenting an overview of factors associated with newly graduated nurses' work engagement. Factors were classified into seven categories explaining supportive workplace, transition and orientation to workplace, competence and career development in nursing practice, personal and psychological characteristics, work environment characteristics, stress and challenges in a work environment, and satisfaction with work.

Conclusions

To support newly graduated nurses' work engagement, nurse leaders should provide a supportive working environment and focus on new nurses' effective support systems in the workplace. Their abilities to develop and educate themselves need to be prioritised to enhance their knowledge and skills in nursing. Additionally, organisations should have policies and procedures to ensure quality orientation, and units need to implement transition and mentorship programmes.

Implications for the Profession and/or Patient Care

This research could be valuable to health care when wanting to develop and improve work engagement, especially among newly graduated nurses. The economic significance of nurses' work engagement is evident, as the cost of nurse turnover is considerable. Reducing nurse turnover and improving retention relies on understanding the factors influencing nurses' decisions to leave the organisation and the profession.

Impact

What problem did the study address? The global shortage of nurses, worsened by newly qualified nurses leaving the health sector, necessitates understanding factors influencing their work engagement; The factors associated with newly graduated nurses' work engagement were supportive work environment, transition and orientation to work, success and career development in nursing, personal and psychological characteristics, characteristics of the work environment, stress and challenges in the work environment, and job satisfaction. Where and on whom will the research have an impact? The results can be used by health care organisations to plan the preceptorship/mentoring programmes of new nurses. Identifying and understanding the factors associated with the retention of newly qualified nurses can help to attract and retain nurses and to promote the adaptation and integration of new nurses into healthcare organisations.

Reporting Method

The YNEPR author checklist has been completed and implemented during this systematic review process. Also, the Prisma 2020 checklist has been used.

Patient or Public Contribution

No patient or public contribution: systematic review.

Trial Registration

PROSPERO number: CRD42023408705 (https://www.crd.york.ac.uk/PROSPERO/)

Essential newborn care practices and determinants in Ethiopia: a multilevel analysis of national survey data

Por: Mekonnen · T. S. · Delie · A. M. · Hailu · M. · Mehari · M. G. · Bizuneh · G. K. · Mengistie · B. A.
Objectives

To assess the prevalence and determinants of essential newborn care (ENC) practices among Ethiopian mothers using the 2023 Performance Monitoring for Action (PMA) dataset.

Design

A cross-sectional analysis of the nationally representative 2023 PMA Ethiopia survey.

Participants

A total of 1933 mothers with complete data on ENC practices were included.

Setting

Ethiopia, using a multi-stage stratified cluster sample.

Primary outcome measures

ENC, defined as the adoption of at least four of five WHO-recommended practices: immediate drying, delayed bathing, skin-to-skin contact, clean cord care and early initiation of breastfeeding.

Results

Overall, 32.1% (95% CI 28.1% to 36.0%) of mothers practised at least four ENC components. Coverage was highest for immediate drying (95.4%) and delayed bathing (87.3%), but lower for skin-to-skin contact (53.6%) and clean cord care (64.5%). Health facility delivery showed a strong association with higher ENC practice (adjusted OR (AOR)=106.00; 95% CI 46.14 to 243.54). Mothers who were spouses, rather than household heads, had higher odds of practising ENC (AOR=2.88; 95% CI 1.20 to 6.89) and those mothers with parity two or three had higher odds of practising ENC compared with first-time mothers (AOR=2.00; 95% CI 1.33 to 3.02 and AOR=3.39; 95% CI 1.76 to 6.53, respectively). Lack of postnatal care attendance was negatively associated with ENC (AOR=0.56; 95% CI 0.37 to 0.85). Regional disparities were observed, with mothers in the Southern Nations, Nationalities and Peoples’ region being significantly less likely to practise ENC compared with those in Addis Ababa (AOR=0.31; 95% CI 0.15 to 0.64). All results are based on weighted data to ensure national representativeness.

Conclusion

The prevalence of ENC practices remains low in Ethiopia. Health facility delivery, maternal role in the household, parity and region of residence were significant predictors of ENC practice. Strengthening facility-based delivery, promoting maternal empowerment and addressing regional disparities are essential to improving newborn health outcomes in the country and achieving Sustainable Development Goal 3.

Combined determinants of adverse birth outcomes in Ethiopia: an application of ecological model using Demographic and Health Survey data

Por: Kusheta · S. · Mekonnen · W.
Background

Studies of determinants of adverse birth outcomes (ABOs) were conducted in Ethiopia; however, there is a lack of a single study considering the factors operating at multiple levels (individual, interpersonal, organisational, environmental and policy levels). Therefore, this study identified combined determinants of ABOs at all levels in Ethiopia by analysing the Demographic and Health Survey data guided by the Ecological model, considering that birth outcomes are shaped by the interaction between a mother’s environment and her biological and psychological health.

Objective

This study aims to identify combined determinants of ABOs at all levels in Ethiopia by analysing the Demographic and Health Survey data guided by the Ecological model.

Design

A cross-sectional study design based on interviewer-administered questionnaires was used for the respective Demographic and Health Surveys.

Setting

We used data from the 2016 Ethiopian and Demographic Health Survey, a stochastically national representative study with inclusive information on ABOs, to examine how various levels of influence from individual behaviours to environmental-level factors are affecting birth outcomes.

Participants

An effective number of 11 023 live births within the 5 years preceding the survey.

Main outcome measure

ABOs, including low birth weight and preterm birth. Multivariable multilevel mixed-effects logistic regression was used to identify determinants of ABOs through five hierarchical models in Stata V.14. Model I was the null model; models II, III, IV and V sequentially included intrapersonal, interpersonal, organisational and environmental variables, respectively. Statistical significance was determined using ORs with 95% CIs at p

Results

The weighted prevalence of ABOs in Ethiopia is 27.0% (95% CI 25.7% to 28.3%). The final model of the multivariable multilevel mixed-effects logistic regression identified several predictors of ABOs at the intrapersonal or individual level, including maternal age of 15–24 completed years (adjusted OR (AOR)=1.24, 95% CI 1.02 to 1.51); poorest (AOR=1.41, 95% CI 1.01 to 2.00), poorer (AOR=1.42, 95% CI 1.02 to 2.01) and middle wealth quintiles (AOR=1.45, 95% CI 1.02 to 2.06); first-born twin (AOR=2.61, 95% CI 1.31 to 5.21) and second-born twin (AOR=4.05, 95% CI 2.16 to 7.61); and female childbirth (AOR=1.41, 95% CI 1.22 to 1.63). On the other hand, intimate partner physical violence (AOR=1.19, 95% CI 1.07 to 1.34) was the only factor associated with ABOs at the interpersonal level; cluster altitudes of 180–1500 m (AOR=1.28, 95% CI 1.05 to 1.55) and 2501–3455 m (AOR=1.51, 95% CI 1.15 to 1.99) were found to be an exposure of ABOs at the environmental level.

Conclusions

The prevalence of ABOs in Ethiopia is high. Factors associated with ABOs at the individual level include maternal age, wealth quintile, twin birth and female birth. In contrast, exposure variables at the interpersonal level comprise intimate partner violence, and those at the environmental level include cluster altitude. To improve ABOs and consequently reduce neonatal mortality, maternal and child health investment and future studies should act at all levels.

Multiarm multistage randomised controlled trial of inflammatory signal inhibitors (MATIS) for patients hospitalised with COVID-19 pneumonia during the UK pandemic

Por: Hazell · L. · Pillay · C. · Cornelius · V. · Phillips · R. · Charania · A. · Wason · J. · Cherlin · S. · Savic · S. · Whittington · A. · Neelakantan · P. · Collini · P. · Cook · L. · Willicome · M. · Milojkovic · D. · Kon · O. M. · Youngstein · T. · Innes · A. · Thursz · M. · Cooke · G. S.
Objectives

To determine the safety and efficacy of ruxolitinib (RUX) and fostamatinib (FOS) compared with standard of care (SOC) in patients requiring hospital admission for the treatment of COVID-19 pneumonia.

Design

Adaptive multiarm, multistage, randomised, open-label trial (three arm, two stage).

Setting

Five hospitals in England between October 2020 and September 2022.

Participants

Hospitalised patients (≥18 years) with COVID-19 pneumonia defined by a modified WHO COVID-19 severity grade of 3 or 4.

Interventions

Participants were randomly assigned 1:1:1 to receive RUX (10 mg two times per day for 7 days then 5 mg two times per day for 7 days), FOS (150 mg two times per day for 7 days then 100 mg two times per day for 7 days) or SOC.

Main outcome measures

Primary outcome was development of severe COVID-19 pneumonia (modified WHO severity grade≥5) within 14 days of randomisation. Secondary outcomes included mortality, invasive and non-invasive ventilation, venous thromboembolism, duration of hospital stay, readmissions, inflammatory markers and serious adverse events (SAEs).

Results

At stage 1, 181 patients were randomised, with 4 assessed as ineligible post randomisation. FOS was stopped early for futility with 16 participants (27.6%, n=58) developing severe COVID-19 pneumonia compared with 15 (25.0%, n=60) in the SOC arm (adjusted odds ratio (aOR) compared with SOC: 1.12; 95% CI 0.49 to 2.58; p=0.608). RUX progressed to stage 2 but the trial was stopped early due to slow recruitment. At the final analysis, 10 participants (16.1%, n=62) developed severe COVID-19 pneumonia in the RUX arm compared with 15 (24.6%, n=61) in the SOC arm (aOR: 0.63; 95% CI 0.25 to 1.57; p=0.161). Four (7.4%) participants in the FOS arm, none in the RUX arm and three (5.5%) in the SOC arm died within 14 days of randomisation. Infections were the most frequently reported SAE and were numerically higher in the FOS (10, 17.2%) and RUX (10, 16.1%) arms compared with SOC (7, 11.5%). Two unexpected serious adverse reactions occurred in the RUX arm only.

Conclusions

We found no evidence that FOS was superior to SOC for the treatment of COVID-19 pneumonia in patients requiring hospital admission. Due to early stopping, the trial was underpowered to establish RUX’s effect in this population. Further study is needed.

Trial registration number

NCT04581954; EUDRA-CT: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001750-22/GB.

Comparative Effectiveness of Acupoint Stimulation Therapies for Cancer‐Related Fatigue: A Network Meta‐Analysis

ABSTRACT

Aim

This study aimed to evaluate and rank the effectiveness of various acupoint stimulation therapies in alleviating cancer-related fatigue (CRF), a pervasive and distressing symptom among cancer patients.

Background

CRF severely compromises patients' quality of life across treatment and survivorship stages. Despite growing interest in nonpharmacological interventions, comparative evidence on the efficacy of acupoint stimulation therapies remains limited.

Methods

A systematic review and network meta-analysis of 28 randomized controlled trials (RCTs) involving 2370 participants was conducted. Databases searched included MEDLINE, CINAHL, Embase, Cochrane, Web of Science, and Airiti Library. Interventions included acupuncture, acupressure, oil acupressure, moxibustion, and transcutaneous electrical acupoint stimulation (TEAS). Standardized mean differences (SMDs) were calculated using a random-effects model. Surface Under the Cumulative Ranking Curve (SUCRA) was used to rank therapies.

Findings

Oil acupressure (SUCRA: 73.6%), relaxing acupressure (73.4%), and acupuncture (72.7%) were the most effective interventions. Both professionally administered and self-administered therapies significantly reduced CRF, with no major differences in efficacy. Subgroup analyses revealed consistent effectiveness across cancer types, particularly breast and lung cancer, and treatment stages.

Conclusions

Acupoint stimulation therapies, especially acupressure and acupuncture, effectively reduce CRF and are suitable for integration into routine cancer care. Self-administered acupressure offers a practical, low-cost alternative, especially in resource-limited settings. Standardization of protocols and long-term studies are warranted to guide clinical implementation.

Trial Registration

The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42024556455)

A systematic review of the scope and impact of rural primary healthcare innovations using digital health technology

Por: MacAskill · W. · Gill · P. · Woloszczuk · C. · Alam · K. · Wallis · K. · McGrail · M. R. · Kondalsamy-Chennakesavan · S. · Nasir · B. F.
Objectives

Digital technology in primary healthcare service delivery can enhance accessibility, service delivery and health outcomes in rural populations. The objective of this systematic review is to review and synthesise the scope and impact of digital health technology innovations within rural primary healthcare settings.

Design

Systematic review.

Data sources

Articles published on PubMed, PsycINFO, Cochrane Central, SCOPUS, Web of Science, EMBASE and CINAHL between January 2013 and October 2025 were searched using key search terms.

Eligibility criteria

Patient, intervention, context, outcome model criteria guided article eligibility. Included articles were undertaken in rural populations, used digital health technology for treatment or management, explored the impact of digital health technology on rural primary healthcare and reported on healthcare outcomes. Included articles were in the English language and presented peer-reviewed primary research.

Data extraction and synthesis

Extraction was performed using a bespoke standardised template by multiple reviewers. Quality assessment was undertaken using the Mixed Methods Appraisal Tool. Descriptive analysis and conventional inductive content analysis were applied to quantitative and qualitative data, respectively. The review is written in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols statement guidelines.

Results

66 studies were included in the review. Most studies were conducted in the USA (n=26). Most studies focused on adult patient populations, with limited representation of Indigenous (In=3) and paediatric populations (n=2). Telemedicine/telehealth interventions using audio, video or both were the most common (n=36). Remote patient monitoring or point-of-care testing was integrated into 21 studies. Physical health conditions, particularly diabetes (n=17), cardiovascular diseases (n=11) and general primary healthcare concerns (n=13) were commonly reported. Others reported on areas including mental health, hypertension, obesity and pregnancy care.

Conventional inductive content analysis identified key themes: cost and time effectiveness, quality healthcare provision, consumer acceptance from both patients and practitioners, and healthcare service provider perspectives. Uptake barriers included staff workload and patient non-compliance, while facilitators encompassed process standardisation and practitioner acceptance and endorsement. Consumer acceptance was linked to satisfaction, willingness to engage and improved health outcomes and well-being.

Conclusions

Digital health interventions in rural primary healthcare offer significant potential to improve healthcare delivery, reduce costs and enhance patient access, satisfaction and health outcomes. However, careful consideration of factors such as feasibility, consumer and practitioner acceptance, and recognition of limitations is crucial for successful implementation. The review underscores the importance of flexible policies to support emerging digital healthcare solutions, including the integration of artificial intelligence. Overall, digital health interventions offer a promising avenue to improve healthcare outcomes in rural areas and should be prioritised for government funding and investment.

PROSPERO registration number

CRD42023477233.

Comparison of remimazolam versus propofol under deep sedation for elderly patients during prostate biopsy: a protocol for a randomised controlled trial

Por: Fukano · K. · Fukuda · Y. · Chiba · Y. · Kondo · S. · Sawada · I. · Miyazawa · K. · Otsuka · Y. · Iizuka · Y. · Shiotsuka · J. · Sanui · M.
Introduction

With the rapid increase in the ageing population, the use of procedural sedation and analgesia (PSA) for diagnostic procedures such as prostate biopsy in older adults is increasing. However, elderly patients are particularly susceptible to respiratory depression during PSA testing and have a significantly higher risk of hypoxaemia during procedures requiring deep sedation. Although propofol combined with fentanyl is commonly used, it frequently causes hypoxaemia and apnoea. Remimazolam, a novel ultrashort-acting benzodiazepine, may be a safer alternative with less respiratory compromise; however, the supporting evidence remains limited. This study aims to assess whether remimazolam combined with fentanyl reduces the incidence of respiratory depression compared with propofol combined with fentanyl in elderly patients undergoing prostate biopsy under deep sedation requiring immobility.

Methods and analysis

This is a single-centre, participant and assessor-blinded (with pragmatic blinding of participants), parallel-group, superiority randomised controlled trial conducted at the Jichi Medical University Saitama Medical Centre, Japan. Eligible participants are men aged ≥70 years who are scheduled to undergo prostate biopsy under intravenous sedation. Participants will be randomised in a 1:1 ratio to receive either remimazolam or propofol, each administered in combination with fentanyl at a fixed effect-site concentration. The primary outcome is the incidence of severe apnoea (≥1 min). The primary analysis will follow the intention-to-treat principle, implemented practically as a full analysis set analysed using a complete case approach. Sensitivity analyses will include a per-protocol analysis and multiple imputations of missing data. A subgroup analysis of patients aged ≥75 years was performed.

Ethics and dissemination

This study was approved by the Jichi Medical University Central Clinical Research Ethics Committee (approval number: 24JMU001S-2) and was registered with the Japan Registry of Clinical Trials on 11 November 2024. Written informed consent was obtained from all participants before enrolment. These findings will be disseminated through publications in peer-reviewed journals and presentations at scientific conferences.

Trial registration number

jRCTs031240478.

Healthcare Professionals' Perceptions of Artificial Intelligence in Healthcare—A Systematic Review of Qualitative Studies

ABSTRACT

Aim

To identify the experiences and perceptions of healthcare professionals on artificial intelligence in healthcare.

Design

Systematic literature review of qualitative studies and meta-aggregation.

Data Sources

CINAHL, PubMed, Scopus, Medic and ProQuest were systematically searched on December 9, 2024.

Results

Twenty-six studies were included in the review, of which 25 were analysed using meta-aggregation, and the results of one study were reported narratively. A total of 185 findings were identified from the included studies that addressed the research question. These findings were aggregated into 33 categories and then into five synthesised findings as follows: (1) Perceived benefits of AI in healthcare; (2) Perceived impact of AI on professional roles and workforce dynamics; (3) Perceived impacts of AI in communication and interaction; (4) Perceived challenges of AI related to technical, financial and systemic factors; (5) Perceived ethical, cultural and regulatory considerations regarding the use of AI.

Conclusion

While AI holds significant potential to enhance efficiency and improve patient outcomes, it is essential to address the concerns raised by healthcare professionals regarding workforce dynamics, communication and ethical considerations.

Implications for the Profession

The results can inform and support the implementation of AI in healthcare and the development of AI-related education and training to meet the demands of future healthcare work.

Reporting Method

The review was conducted and reported in accordance with the PRISMA guidelines.

Patient or Public Contribution

None.

Trial Registration

PROSPERO (CRD1073200)

Feasibility of a mobile application-based geriatric assessment and communication support intervention for older adults with cancer: protocol for a pilot randomised controlled trial (MAPLE2 pilot)

Por: Matsuoka · A. · Konishi · Y. · Boku · N. · Takashima · A. · Okusaka · T. · Mori · K. · Akechi · T. · Tsubata · Y. · Majima · Y. · Uchitomi · Y. · Nagashima · F. · Fujimori · M.
Introduction

Older adults with cancer have ageing-related vulnerabilities that influence their treatment tolerance and decision-making. In our previous randomised controlled trial (MAPLE), integrating geriatric assessment (GA) with communication support using a question prompt list (QPL), delivered by trained intervention providers, facilitated patient–oncologist communication, increased implementation of GA-guided management (GAM) and improved patient outcomes. However, its widespread adoption has been limited by the need for trained personnel and dedicated time. To enhance scalability and sustainability, we developed a mobile application-based intervention to deliver GAM and communication support. This MAPLE2 study aims to evaluate the feasibility of the intervention using this mobile application-based GA and QPL among older adults with cancer.

Methods and analysis

This multicentre, open-label, pilot randomised controlled trial will be conducted at two academic hospitals in Japan. Patients aged≥70 years with solid cancer or lymphoma initiating or changing systemic therapy will undergo baseline GA. Patients with any GA impairment will be randomised to receive either (1) a mobile application-based intervention providing feedback of GA summary with tailored GAM recommendations and QPL or (2) usual care. The primary endpoint is the proportion of participants who complete all of the following interventions using the mobile application: (1) self-administered GA, (2) receipt of the tailored GAM recommendations and QPL and (3) confirmation that their oncologists review the tailored GAM recommendations and QPL at subsequent visits. Forty participants are planned to be enrolled.

Ethics and dissemination

The study has been approved by the Institutional Review Board of the National Cancer Center, Japan (approval number: 2025-089). Written informed consent will be obtained from all participants. Results will be presented at academic conferences and published in peer-reviewed journals.

Trial status

Recruitment has been initiated from 8 September 2025 and is planned to be completed by 31 August 2026, with a follow-up period by 31 August 2027.

Trial registration number

UMIN000058887

Innovation Competence in Healthcare: Individual, Environmental and Organisational Factors—A Mixed‐Method Systematic Review

ABSTRACT

Aims

To identify healthcare professionals' experiences of innovation competence and the factors associated with it; and to examine the instruments developed to assess innovation competence and its associated factors among healthcare professionals.

Design

A mixed-methods systematic review.

Methods

Researchers independently screened original studies by title and abstract (n = 2996) and then full text (n = 189). Eighteen studies were included: 16 quantitative and two qualitative. Qualitative data were analysed using inductive content analysis, and quantitative data were tabulated and synthesised narratively.

Data Sources

The review followed the Joanna Briggs Institute Mixed Methods Systematic Review methodology. Searches were conducted in Scopus, CINAHL, Ovid Medline, ProQuest, Web of Science, PsycArticles, and Medic. Articles published in English or Finnish with no date restrictions were included. The search covered records from database inception to August 2024.

Results

From qualitative studies, we identified three categories describing experiences of innovation competence: Competences for Innovation in Healthcare, Application and Impact of Innovation in Healthcare, and Challenges and Strategies for Implementing Innovation. Quantitative studies identified three conceptual domains: Individual Capacities in Innovation, Innovation-related Competence Behaviours, and Social and Organisational Enablers. Four categories of factors associated with innovation competence emerged: sociodemographic, career-related, organisational, and academic factors.

Conclusions

Healthcare professionals' innovation competence is a multifaceted construct encompassing individual abilities, behavioural expressions, and social and organisational engagement. A systematic and multilevel approach that targets both personal attributes and organisational enablers is needed to strengthen competence. Enhancing innovation competence can improve the healthcare sector's ability to respond to complex challenges and sustain innovation capacity.

Impact

Findings inform the development of education programmes and leadership strategies to enhance innovation competence among healthcare professionals, supporting innovation implementation in healthcare organisations.

Patient or Public Contribution

No patient or public involvement was included in this study.

Trial Registration

PROSPERO: CRD42024614551

Impact of storage conditions on the stability and biological efficacy of <i>trans</i>-arachidin-1 and <i>trans</i>-arachidin-3

by Ploy Khongrungjarat, Chonnikan Tothong, Chanyanut Pankaew, Suchada Phimsen, Nopawit Khamto, Nutthamon Kijchalao, Warissara Wongkham, Piyathida Wongkham, Wipaporn Chuaymaung, Adsadayu Thonnondang, Apinun Limmongkon

Prenylated stilbenoids, particularly trans-arachidin-1 (Ara-1) and trans-arachidin-3 (Ara-3), have gained attention for their notable bioactivities and potential health-promoting properties. This study presents the first comprehensive investigation into the stability and biological efficacy of these compounds in both peanut hairy root culture crude extracts (PCE) and partially purified fractions derived from elicited peanut hairy root cultures. PCE stored at –20 °C and 4 °C maintained higher antioxidant capacity, total phenolic content compared to samples stored at room temperature. In cytotoxicity assays using SW480 colon cancer cells, the extract stored at –20 °C retained bioactivity with only minor changes in IC₅₀ values over three months, demonstrating superior stability under frozen conditions. Over a six-month period, partially purified fractions of Ara-1 and Ara-3 showed a time-dependent decline in compound content. However, Ara-3 maintained strong cytotoxicity against KKU-100 cholangiocarcinoma cells, while Ara-1 exhibited a significant loss in activity. These findings demonstrate that low-temperature storage, particularly at –20 °C, is crucial for preserving the chemical integrity and bioactivity of stilbenoid-rich extracts. The study underscores the importance of optimizing storage conditions to ensure consistent bioactivity, supporting the potential application of these compounds in the development of stable and effective pharmaceutical or nutraceutical products.

Evaluating the PATHFAST TB LAM Ag assay as a treatment monitoring tool for pulmonary tuberculosis: protocol for a prospective longitudinal study in Nairobi, Kenya

Por: Takaizumi · Y. · Kinoti · J. · Hikone · M. · Orina · F. · Meme · H. · Ong'ango · J. R. · Muriithi · B. · Mueni · E. · Kaneko · S. · MacLean · E. L.-H. · Sato · S. · Saito · N.
Background

Treatment failure remains a major challenge in tuberculosis (TB) management. Rapid and objective assessment of treatment response is essential, as existing tools have limited accuracy and slow turnaround times. The PATHFAST TB LAM Ag assay (PATHFAST-LAM), an automated chemiluminescent enzyme immunoassay, was developed to quantify lipoarabinomannan (LAM) in sputum within 1 hour. Previous studies have shown a strong correlation between sputum LAM concentration and culture-based bacterial load. However, its clinical utility for predicting poor outcomes during treatment has not been prospectively evaluated.

Methods and analysis

We will conduct a prospective longitudinal study enrolling newly diagnosed, bacteriologically confirmed patients with pulmonary TB at Rhodes Chest Clinic and Mbagathi County Referral Hospital in Nairobi, Kenya. We will follow participants throughout the 6-month treatment course, attempting to collect sputum weekly during weeks 1–4, biweekly during weeks 5–12 and monthly during months 3–6. We will measure LAM concentrations at these time points using the PATHFAST-LAM assay. The primary outcome is to assess whether changes in sputum LAM concentration during the intensive phase (baseline to week 4 and/or week 8) predict a composite poor outcome, defined as positive sputum culture at month 6, treatment failure, death during treatment or relapse within 3 months after treatment completion. The primary endpoint is the area under the curve from the receiver operating characteristic analysis, representing the predictive performance of changes in sputum LAM concentration for the composite poor outcome. We will identify the optimal cut-off value for LAM change and estimate sensitivity and specificity with 95% CIs using 2x2 tables. We will apply an adaptive design that allows sample-size re-estimation after interim analysis.

Ethics and dissemination

The study was approved by the Kenya Medical Research Institute (KEMRI/SERU/CRDR/124/5241) and Nagasaki University (250619327). Findings will be disseminated through peer-reviewed publications and scientific meetings.

Trial registration number

NCT07157904.

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