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Hoy — Marzo 4th 2026Tus fuentes RSS

Effect of prehabilitation before total knee replacement on postoperative patient-reported joint awareness, enablement and knee function: protocol for the PROTEKT randomised controlled trial

Por: Ljung · M. · Gustafsson · K. · Kvist · J.
Introduction

Knee osteoarthritis (OA) causes pain, reduced function and disability and may require total knee replacement (TKR). Although TKR is effective, up to 20% of patients remain dissatisfied, partly due to poor preoperative function and unrealistic expectations. Long waiting times for surgery may worsen patients’ function, yet preoperative physiotherapy is rarely offered. Prehabilitation—exercise and education before surgery—could improve postoperative recovery, but current evidence is limited. This trial investigates whether adding prehabilitation to standard care before TKR improves postoperative patient-reported joint awareness, enablement and knee function.

Methods and analysis

This multicentre, randomised controlled parallel-group trial is planned to be conducted within two specialised orthopaedic outpatient rehabilitation units in the southeast healthcare region of Sweden. Eligible patients (40–85 years, awaiting unilateral TKR) are randomised 1:1, stratified by age (≤67, >67 years), to either 8 weeks of prehabilitation—comprising two times per week supervised exercise therapy (strength, range of motion and balance) and education—in addition to standard care, or to standard care alone. Standard care consists of self-care, a single standardised preoperative education session and standardised postoperative rehabilitation. Assessments are conducted at baseline, post-intervention, 1 week pre-surgery and 6, 12 and 52 weeks post-surgery. A total of 110 patients will be recruited to the trial. Primary outcomes are joint awareness (Forgotten Joint Score-12) and patient enablement (modified Patient Enablement Instrument-2). Secondary outcomes are patient satisfaction (5-category Likert scale), the Knee injury and Osteoarthritis Outcome Score, the EuroQol 5 Dimension 3 Level questionnaire, the International Physical Activity Questionnaire—short form, objective function and accelerometer-based physical activity. Analyses will follow intention-to-treat and per-protocol principles. Between-group and within-group differences will be tested using t-tests or non-parametric equivalents, and linear mixed models or generalised linear models. Multiple linear regression and logistic regression will be used to analyse predictor variables for the primary outcomes. Sensitivity analyses will be performed to quantify the magnitude of missing data from patients lost to follow-up.

Ethics and dissemination

The trial has received ethical approval from the Swedish Ethical Review Authority (reg. no.2023-05120-01) and complies with the Declaration of Helsinki. Signed informed consent is collected for all patients before entering the trial. Results will be submitted for publication in a peer-reviewed journal and presented at international/national conferences. The findings may improve future clinical guidelines and care pathways for patients undergoing TKR.

Trial registration number

NCT06290336.

Understanding integrated mental healthcare for people experiencing forced migration: a realist review protocol

Por: Clark · N. · Argüelles Bullon · A. · Huq · M. · Mukumbang · F. C.
Introduction

Forced migrants (i.e., asylum seekers and refugees) experience greater mental health disparities and inequities in care. Mental health services and systems lack clear policy on integrated mental healthcare. Understanding the causal mechanisms of integrated mental health for migrants can promote a resilient and adaptive health and social care system. However, to achieve a functional mental health service integration, there is a need to understand how and why mental health system integration works and under what health systems conditions. The purpose of this realist review protocol will be to outline a process for refining an initial programme theory (IPT), developed through deliberative dialogues with key interest groups in British Columbia, Canada, and to test the IPT against the global evidence base.

Methods and analysis

A realist review is an interpretive methodological approach to synthesising the literature based on the realist philosophy of science. Realist reviews are pragmatic approaches to theory development because they involve the participation of real-world actors or people who work within complex systems. Realist reviews are particularly useful for synthesising complex knowledge. We plan to conduct a seven-step review process, with iteration between each step. Steps 1–3 have already been completed in our previous work and included the development of an IPT, which will be refined systematically by exploring the global literature and consulting with an international advisory group. These will be used iteratively to identify, test and refine the programme theory. The quality of included literature will be appraised using the relevance, richness and rigour criteria and the realist quality appraisal tool, TAPUPASM (transparency, accessibility, propriety, utility, purposiveness, accuracy, specificity and modified objectivity). Steps 4–7 will include data extraction and realist analysis through retroductive theorising using the ICAMO (intervention, context, actor, mechanism and outcome) heuristic to help distinguish actors and resources from contexts, mechanisms and outcomes.

Ethics and dissemination

Ethics approval for the deliberative dialogue interviews that inform this realist review and IPT were obtained by the University of British Columbia (ref: REB Number: H22-03195). Study recruitment occurred between 21 November 2023 and 16 January 2024. All participants provided informed consent to take part in deliberative dialogues and to have their interviews audio recorded and transcribed for the purpose of this research. We will disseminate results of the review through academic papers, conference presentations and through iterative interest group workshops and discussions.

PROSPERO registration number

CRD42024580083.

Assessment of health-related quality of life, cognitive, physical and psychological impairments in critically ill adults after status epilepticus (POSEIDON 2): protocol for a multicentre longitudinal study

Por: Legriel · S. · Bernard · C. · Sboui · G. · Sigaud · F. · Lascarrou · J.-B. · Mayenco-Cardenal · N. · Chelly · J. · Bruel · C. · Mongardon · N. · Marzouk · M. · Quenot · J.-P. · Hugues · R. · Schnell · D. · Beuret · P. · Bailly · P. · Lesieur · O. · Argaud · L. · Chambon · R. · Jacq · G.
Introduction

Status epilepticus (SE) in adults is a serious neurological emergency that can lead to high morbidity and mortality rates. Although functional outcomes are often assessed using general scoring systems, limited data on health-related quality of life (HRQoL) in patients admitted to intensive care units (ICUs) are still limited. Furthermore, comprehensive evaluations of patient-reported physical, cognitive, mental health and psychological outcomes are lacking in this population. POSEIDON 2 aims to assess HRQoL and cognitive, physical and psychological impairments at 3 and 12 months after ICU discharge following SE and quantify caregiver burden.

Methods and analysis

POSEIDON 2 is a prospective, multicentre, longitudinal study conducted in 19 French ICUs. The study combines data from the SE ICTAL Registry with data from patients who survived admission to the ICU for SE, who will be recruited for the study. The study also includes patient-reported outcome (PRO) data collected 3 (M3) and 12 (M12) months after discharge from the ICU using validated instruments. The Zarit scale will be used to measure the burden on caregivers at M3 and M12. The primary endpoint is the prevalence of overall HRQOL impairment at M3 and M12, as defined by dichotomous scores on the physical and mental components of the 36-Item Short Form Health Survey compared with those of the general population. Secondary endpoints include domain-specific impairments, such as cognitive function, dependence, mental health and patient experiences. The sample size has been calculated based on an estimated prevalence of 75% for HRQoL impairment, with a planned sample size of 140 patients.

Ethics and dissemination

The POSEIDON 2 study protocol received ethical approval from the ethics committee ‘Comité de Protection des Personnes Ouest VI’ on 5 October 2023 (#2023-A01223-42). The study is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice and the regulatory requirements of France. Written informed consent is obtained from participants, who are able to decline participation or withdraw from the study at any time. Findings will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences.

Trial registration number

NCT06100978.

The Barriers and Facilitators Healthcare Professionals' Experience When Assessing the Cutaneous Manifestations of Chronic Venous Insufficiency and Peripheral Arterial Disease in People With Dark Skin Tones: A Qualitative Descriptive Study

ABSTRACT

Recognising peripheral arterial disease and chronic venous insufficiency early and managing them appropriately improves patient outcomes and prevents ulceration. However, few studies consider the influence patient skin tone has on this assessment. The study aimed to explore the experiences of healthcare professionals when assessing the cutaneous manifestations of chronic venous insufficiency and peripheral arterial disease in people with dark skin tones. We conducted semi-structured online interviews with healthcare professionals working in the United Kingdom between July and December 2023. The ‘theoretical domains framework of behaviour change’ (TDF) guided the interview schedule and data analysis. 24 healthcare professionals were interviewed (18 nurses, 5 doctors, 1 physiotherapist) with an average experience of 15 years (IQR 9.75–21.75 years). We found the environmental context domain best explains clinical behaviour, which included effective teamworking, referral pathways and training, and adequate lighting. Environmental factors also influenced other aspects of the TDF such as skill development, focus and concentration, and belief about capabilities. Some participants also found personal challenges in asking questions exploring patients' behaviour and skin care practices as they did not want to cause offence. Findings will inform the development of interventions to support lower limb assessment in those with dark skin tones.

Intensive Care Unit Nurses' Perceptions of Work Environments: A Cross‐Sectional Study From Five European Counties

ABSTRACT

Aim

To explore intensive care nurses' perceptions of their work environments at the unit and organisational levels according to the American Association of Critical Care Nurses standards, their impact on care quality, national differences, and demographic associations.

Design

Cross-sectional study using a survey design.

Methods

Study conducted between January 2021 and April 2022, using a convenience sample of intensive care unit nurses across Cyprus, Spain, Croatia, and Poland, Romania. The Critical Elements of a Healthy Work Environment Scale (CEHWES) developed by the American Association of Critical Care Nurses and cross-culturally adapted by the authors was used, which included four sections, including sociodemographic data and a total of 50 questions. The core section of the tool comprised 16 questions using Likert-type response (1—strongly disagree—4 strongly agree). Perception of fulfilment of healthy work environment standards was calculated using the aforementioned Likert-type scale.

Results

A total of 1183 nurses participated reporting moderate perception of fulfilment of the standards, with mean scores ranging from 2.6 to 2.8. Skilled communication and effective decision making were the highest rated. 56% (n = 662) reported awareness of some standards and while 25.8% (n = 305) reported full or significant implementation in their unit. Significant differences related to the perception of all standards were observed across countries. Implementation of the standards was significantly associated with higher quality of care having better perception when standards were fully implemented.

Conclusions

This study shows moderate perception of healthy work environment standards among intensive care nurses. Country differences highlight the need for more awareness, training, and further implementation of the standards, which is linked to better care quality.

Implications for the Profession

Work environment still need to improve and needs to be prioritised by organisations, considering local and national particularities. Having a measuring tool available in multiple languages facilitates comparisons and getting a global picture.

Impact

The questionnaire used is validated in different languages, allowing results to be compared with other countries. Novel data from countries that were poorly investigated is now available. More evidence points out the need to prioritise work environment for maintaining quality in patient care.

Reporting Method

The study has been reported following the STROBE checklist.

Patient or Public Contribution

This study did not include patient or public involvement in its design, conduct, or reporting.

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.

Nurses' Perceptions of Reasons for Missed Nursing Care in Hospitals: A Qualitative Systematic Review

ABSTRACT

Aim

To identify and synthesise qualitative evidence on nurses' perceptions of reasons for missed nursing care in hospitals.

Design

Systematic review of qualitative evidence.

Methods

An extensive search of all relevant databases was conducted. Study selection, quality assessment, data extraction and meta-aggregation were performed independently by two reviewers according to the JBI guidelines for systematic reviews of qualitative evidence. Confidence in the findings was assessed using the ConQual approach.

Data Sources

The electronic databases CINAHL, PubMed, Embase, PsychInfo, and Scopus were searched in January 2024 and repeated in May 2025.

Results

Thirty-one studies from hospital settings worldwide were included following critical appraisal, with overall quality rated moderate to high. The studies contributed 168 findings, which were organised into 10 categories and three synthesised findings: Organisational and system-level factors influencing missed nursing care, Teamwork and cultural factors influencing missed nursing care, and Individual nurse- and patient-related factors influencing missed nursing care.

Conclusions

Reasons for missed nursing care represent an interplay of systemic, organisational, and individual factors within complex resource-constrained contexts.

Implications for the Profession and/or Patient Care

Healthcare organisations are recommended to implement system-level interventions, rather than relying solely on behaviour-focused solutions. Healthcare leaders should ensure flexible staffing, strong managerial support, and adequate resources to enable fundamental care. Building collaborative, interprofessional cultures that value relational and fundamental care as well as technical tasks is essential, together with education and mentorship that support nurses' decision-making, resilience, and clinical competence.

Impact

Hospital leaders, policymakers, and nurse managers can use the recommendations to reduce missed nursing care and promote a safe person-centred practice. Implementing systemic changes will improve nurses' working conditions and capacity to deliver comprehensive care, ultimately enhancing patient satisfaction and outcomes.

Reporting Method

The ‘enhancing transparency in reporting the synthesis of qualitative research statement’.

Patient or Public Contribution

No patient or public involvement.

Trial and Protocol Registration

The review is registered in the International Prospective Register of Systematic Reviews. PROSPERO CRD42023438198 (https://www.crd.york.ac.uk/PROSPERO/search)

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Response of mid-lactation primiparous Holstein cows to the supplementation of rumen-protected methionine during the summer

by Caio R. Monteiro, Victor Augusto de Oliveira, Rabeche Schmith, João Pedro A. Rezende, Tales L. Resende, João A. Negrão, Marina A. C. Danés

This study aimed to evaluate the effects of rumen-protected methionine (RPM) supplementation on productive and physiological responses of primiparous Holstein cows during summer. We hypothesized that RPM supplementation would maintain or improve milk yield and composition due to beneficial physiological, redox, and inflammatory responses in cows exposed to summer heat. The trial was conducted in a randomized block design during nine weeks in Brazil using 80 primiparous cows (182 ± 64 DIM; 42.9 ± 4.7 kg/d milk). Cows were blocked by milk yield and DIM and assigned to a control diet (CON; no added RPM) or the same diet supplemented with RPM (Mepron®, Evonik) at 0.75 g/kg diet dry matter, targeting 20 g/cow/day (product contains 62% metabolizable methionine) to the average cow. Milk yield and composition, vaginal temperature, respiratory rate, and plasma samples were collected in weeks 3, 6, and 9. Data were analyzed using mixed models including treatment, week, and their interaction as fixed effects, and block and cow as random effects. Cows were maintained under naturally occurring summer conditions. Environmental monitoring during weeks 3, 6, and 9 indicated elevated temperature–humidity index (THI) values, with values remaining above the heat-stress threshold (THI > 68) for 68.3% of the monitored hours (mean THI = 70.6; range 61.0–84.4). Overall (least squares mean across weeks 3, 6, and 9), RPM increased milk yield by 2.0 kg/d (44.9 vs. 42.9 kg/d), protein yield by 50 g/d (1,464 vs. 1,414 g/d), lactose yield by 108 g/d (2,109 vs. 2,001 g/d), and total solids yield by 176 g/d (5,331 vs. 5,155 g/d). Lactose concentration was lower in RPM (4.71 vs. 4.76%). Fat yield was unaffected, but a treatment × week interaction was observed for fat content. Milk fatty acid (FA) profile was unchanged, although treatment × week interactions were observed for individual fatty acids (C16:0, C18:0, C18:1, and preformed FA). Plasma glucose was lower, and insulin was higher in RPM than in CON cows (39.3 vs. 43.2 mg/dL and 0.52 vs. 0.35 ng/mL, respectively). Antioxidant capacity improved, with RPM cows having greater ferric reducing antioxidant power (32.9 vs. 28.5 µM) and lower malondialdehyde (2.48 vs. 2.78 nmol/mL). Other biochemical, inflammatory, and immune markers were unaffected. Respiratory rate was slightly higher in RPM than in CON cows (55 vs. 50 breaths/min). Mean vaginal temperature did not differ between treatments; however, a treatment × time × hour interaction was observed. Supplementation with RPM improved milk and solids yield, and enhanced antioxidant capacity and insulin levels, supporting its use to improve metabolic resilience under warm conditions.

The association between epicardial adipose tissue thickness and diabetes mellitus, hyperlipidemia, hepatosteatosis, pancreatic steatosis and pancreatitis

by Ece Zengin, Aybuke Ucgun, Mehmet Emir Çevik, Sehnaz Evrimler, Ihsaniye Suer Dogan

Background

Epicardial adipose tissue (EAT) is associated with cardiometabolic disorders such as diabetes mellitus (DM), hyperlipidemia, and nonalcoholic fatty liver disease. However, its potential relationship with pancreatic steatosis and pancreatitis remains unclear, and existing studies offer inconsistent findings. Therefore, a clearer understanding of whether EAT reflects broader systemic ectopic fat burden or inflammatory processes is needed.This study evaluated the relationships between EAT thickness and DM, hyperlipidemia, hepatosteatosis, pancreatic steatosis, and pancreatitis.

Methods

This retrospective, single-center study included 200 patients who underwent abdominal CT between 2022 and 2024. EAT thickness was measured at the mid-RCA and LAD levels, and subcutaneous fat was measured at the umbilical level. Liver and pancreatic steatosis were assessed with CT or MRI. Demographic and clinical data (age, gender, LDL cholesterol, diabetes, and history of pancreatitis) were collected. Mann-Whitney U, Spearman correlation, and logistic regression were used in analyses; p  Results

Of the 200 patients, 31.4% had diabetes, 42% had hepatosteatosis, and 73.5% had a history of pancreatitis. EAT and subcutaneous fat were significantly higher in women at all levels (p  Conclusions

EAT thickness is significantly associated with DM, LDL cholesterol, pancreatitis history, and age, supporting its role as a potential imaging biomarker of cardiometabolic risk. These findings suggest that EAT may serve as an imaging marker of broader metabolic and inflammatory burden, supporting its relevance for cardiometabolic risk assessment.

Spatial heterogeneity and spatially varying determinants of childhood stunting in Northern Rwanda: A cross-sectional study to inform targeted interventions

by Clarisse Kagoyire, Albert Ndagijimana, Gilbert Nduwayezu, Jean Nepo Utumatwishima, Jean Pierre Mpatswenumugabo, Marie Anne Mukasafari, Diane Rinda, Vedaste Ndahindwa, Kristina Elfving, Gunilla Krantz, Torbjörn Lind, Ali Mansourian, Renée Båge, Ewa Wredle, Elias Nyandwi, Aline Umubyeyi, Jean Baptiste Ndahetuye, Petter Pilesjö

Despite national progress, stunting remains prevalent in specific regions of Rwanda, highlighting the limitations of coarse-resolution data for effective mapping and intervention planning. This study explored optimal spatial resolution and analytical approach to capture localised dynamics and the multifactorial nature of stunting. A cross-sectional, population-based study was conducted in the Northern Province of Rwanda, focusing on children aged 1–36 months. Data were collected using structured questionnaires covering socio-demographic, economic, health, childcare, livestock factors and anthropometric measurements. Environmental characteristics were obtained from national datasets, while household geographic coordinates were captured using a customized mobile geodata platform (emGeo). After data cleaning, predictors were analysed using univariable and multivariable logistic regression as well as geographically weighted logistic regression (GWLR) to account for spatial heterogeneity. Among 601 children, stunting prevalence was 27% (boys 33.8%; girls 20.9%). GWLR improved model fit, increasing adjusted deviance explained from 34% to 39%. Significant predictors included child age (adjusted OR = 2.46; 95% CI: 1.78–3.39), male sex (OR = 2.83; 95% CI: 1.65–4.86), birthweight (OR = 0.71; 95% CI: 0.54–0.94), maternal autonomy (ability to refuse sexual intercourse; OR = 0.48; 95% CI: 0.27–0.86), inconsistent maternal social support (OR = 2.30; 95% CI: 1.20–4.42), household electricity access (OR = 0.48; 95% CI: 0.27–0.84) and handwashing facilities (OR = 0.21; 95% CI: 0.07–0.67). GWLR revealed substantial spatial heterogeneity in these factors, delineating areas where each factor matters most. This household-level, spatially explicit analysis reveals localised risk patterns often masked by aggregated national data. Prioritising context-specific interventions (such as electrification, hygiene promotion, and enhanced maternal social support), can enhance effectiveness. The proposed analytical workflow provides a model for addressing persistent stunting in other resource-limited settings.

Evaluation of usability and acceptability of a Peruvian telemental health service for early assessment among vulnerable occupational workers: Mixed-method study with a user-centered design approach

by Jimmy Andreyvan Cainamarks-Alejandro, Liliana Cruz-Ausejo, Miguel Angel Burgos-Flores, Jaime Rosales-Rimache, Jonh Astete-Cornejo, David Villarreal-Zegarra

Background

The COVID-19 pandemic marked an increase in depressive, anxiety, and post-traumatic stress disorder symptoms, more specifically among healthcare workers, teachers, and police officers. These workers face external and occupational factors which had a significant impact on mental health, significant increase in workload and direct exposure to the virus, shortage of personnel protective equipment, and instances of abuse, including discrimination. Mental health care in primary care requires a process of early identification and timely referral of complex cases. Telehealth emerges as an effective alternative for addressing challenges in mental health care, although its implementation encounters obstacles.

Objective

To design a telehealth service that facilitates screening, initial management, and timely referral for mental health diagnoses in workers with prior SARS-CoV-2 infection, and to evaluate usability, acceptability, and user satisfaction.

Methods

Mixed-method study with a user-centered design approach involving key external and internal service users in three sequential stages (pre-design, co-design, and post-design). The study phases lasted 6 months, involving a total of 23 participants in the pre-design phase (contextual inquiry and preparation and training), 12 participants in the co-design phase (framing the issue, generative design, and sharing design), and in the post-design phase, 4 participants were involved in service implementation, and 81 participants—drawn from the subgroup of 134 users who received psychoeducation—were included in the efficacy assessment.

Results

The proposal included the development and evaluation of a service model guide and a telehealth software platform. First, the participants took part in a series of workshops (Pre-design, Co-design) where they provided ideas for meeting the product requirements, based on the Design Thinking methodology framework. The telehealth service model was named TelePsico CENSOPAS. It comprised four processes: a) Service promotion; b) User pre-identification; c) Appointment management; d) Psychoeducation counseling and referral. The Telehealth platform was designed through three cycles of an iterative process and integrated a proprietary development platform with third-party service technologies for communication support and information exchange. During post-design, the pilot test involved 698 screened patients; 193 were identified with mental health risks, and 134 of them received psychoeducation sessions. In addition to user acceptance, the usability score of the platform was 86.1 ± 16.9 SD, satisfaction dimensions of the service was 45.1 ± 7.2 SD for satisfaction with care processes, and 36.7 ± 5.2 SD satisfaction with psychological care.

Conclusion

The proposal for mental health telehealth services and its supporting platform was successfully developed and accepted by both internal and external users, particularly within well-structured occupational health services in workplaces serving vulnerable occupational groups. In addition, it achieved higher satisfaction and usability scores than Peru’s outpatient care services. These findings support the replicability of user-centered design frameworks—such as design thinking—within the occupational health sphere.

Effects of tacrolimus treatment on the gut microbiota and metabolites in liver transplant recipients

by Guohui Wang, Lu Liu, Hanshu Zhang, Panpan Mao, Saijuan Lu, Xiaofang Zhang, Xingde Li, Cangsang Song

Background

Liver transplantation (LT) is an effective treatment for patients with end-stage liver disease. In recent years, more and more evidence has supported the association between gut microbiota dysbiosis and the pathogenesis and progression of liver diseases.

Methods

The study included 36 patients who received tacrolimus treatment after liver transplantation. Patients were stratified into subgroups according to three key variables: tacrolimus treatment duration, whole-blood tacrolimus concentration, and tacrolimus concentration-to-dose (C/D) ratio. Fecal samples and whole-blood specimens were collected from all participants. The Illumina HiSeq X platform was used to detect the gut metagenome, analyzing the composition and characteristics of the gut microbiota. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology was employed to detect metabolites of the gut microbiota, revealing their metabolic profiles.

Results

As the duration of tacrolimus use increased, the diversity of the gut microbiota also increased, and the abundance of Escherichia coli_D and Bacteroides stercoris rose. Additionally, the abundance of Brunovirus and Uetakevirus tended to decrease. The abundance of gene functions related to chemical carcinogenesis and bacterial invasion of epithelial cells significantly decreased. In the gut microbiota metabolites, 16 substances like Astragaloside A and Acetyl-L-carnitine significantly increased, while 108 substances like Capsaicin and TLK significantly decreased. Within a certain range, as the concentration of tacrolimus in whole blood increased, the diversity of the gut microbiota increased. The abundance of Phocaeicola and Klebsiella increased, and the abundance of Peduovirus among viruses also rose. However, excessively high concentrations may lead to a decrease in the diversity of the gut microbiota and a decrease in the abundance of Phocaeicola. With respect to the C/D ratio, increased ratios were linked to significantly higher levels of 57 fecal metabolites (e.g., PC 34:2, 5-Methyl-2’-deoxycytidine), whereas 13 metabolites (e.g., FAHFA 2:0/16:0) showed substantial declines.

Conclusions

Tacrolimus treatment is associated with distinct alterations in gut microbiota and metabolites among LT recipients. These findings provide a preliminary framework for future investigations aimed at optimizing immunosuppressive regimens, although their clinical translational potential requires validation in larger-scale, prospective cohort studies.

Attenuating effects of inflammatory pathway by prolonged left ventricular unloading after myocardial infarction in male rats

by Jingwen Gao, Yasushige Shingu, Ryota Azuma, Satoru Wakasa

Background

Inflammatory response plays a pivotal role in myocardial injury and post-infarction remodeling after acute myocardial infarction (AMI). Mechanical unloading (UL) of the left ventricle (LV) has been proposed as a potential therapeutic strategy to preserve cardiac function; however, its effects on myocardial inflammation remain incompletely understood.

Methods

We employed a rat model of partial UL using heterotopic heart-lung transplantation following AMI. RNA sequencing (RNA-seq) was performed to evaluate transcriptomic changes, with a specific focus on inflammatory pathways in the non-infarcted remote area. Immune cell abundance was estimated using deconvolution analysis (QUANTISEQ). Quantitative PCR was performed to analyze some inflammatory cytokines, and macrophage polarization was evaluated by immunohistochemistry.

Results

AMI significantly impaired cardiac function, which was mitigated by UL. RNA-seq analysis revealed marked activation of inflammatory pathways and identified several hub genes involved in cytokine signaling following AMI, while these transcriptional changes were not significantly altered in UL groups after AMI. Immune cell profiling demonstrated an increase in M2 macrophages after AMI, while UL preserved M2 macrophage levels. Histological analysis further supported UL’s modulatory effect on macrophage polarization. Pro-inflammatory cytokines TNFα and IL1β were upregulated after AMI but showed attenuation with UL.

Conclusion

Partial UL potentially attenuates cardiac functional deterioration after AMI while exerting substantial effects on inflammatory gene expression and macrophage polarization. These findings suggest that the cardioprotective effects of UL may be correlated with the modulation of inflammatory pathways in the remote area after AMI.

Interventions to improve functionality among paediatric patients with oncological diagnosis: a systematic review and meta-analysis protocol

Por: Holanda · K. M. · Vivas Costa · J. · Pereira · W. M. G. · Barbosa · A. S. · Martinez-Silveira · M. · Garcia-Hermoso · A. · Guerra · P. H. · Bezerra · I. N. · Barbosa Filho · V.
Introduction

Cancer is the leading cause of death and morbidity among children and adolescents worldwide. Functionality-based interventions are relevant among children and adolescents with an oncological diagnosis, whence studies summarising evidence on this topic are needed. This systematic review will summarise evidence on the effect of interventions to improve functionality indicators among paediatric patients diagnosed with cancer.

Methods and analysis

This protocol will follow Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA)-Protocols reporting guidelines. The systematic review will be conducted according to the Cochrane Handbook and PRISMA 2020. Studies will be searched in MEDLINE (PubMed), Embase, Web of Science, CENTRAL, LILACS and PEDro. Additional searches will include Google Scholar, reference lists of included studies, relevant reviews and trial registries. Studies will be included if they implement a functionality-based intervention. They must evaluate effects among paediatric patients with an oncological diagnosis. Secondary outcomes will include health-related quality of life. There will be no limits to language or year of publication, and articles published in peer-reviewed journals will be accepted. Only randomised controlled trials will be included. Risk of bias will be assessed using the Cochrane Risk of Bias Tool 2. Two independent reviewers will select studies, extract data and assess risk of bias. A narrative synthesis and meta-analysis will be conducted if studies are clinically and methodologically homogeneous. Statistical heterogeneity will be assessed using Higgins’ inconsistency test (I²). Meta-analysis may estimate combined effects using random-effects and the inverse variance method. The R statistical software will be used. The certainty of evidence will be evaluated for each outcome using the Grading of Recommendations Assessment, Development and Evaluation system.

Ethics and dissemination

This study used data from previously published studies, thus waiving submission to an Ethics Committee. Scientific dissemination strategies will include publication in peer-reviewed journals, conference presentations and workshops for the public.

PROSPERO registration number

CRD42024462833.

Exploring stress and coping among black women in early midlife with elevated blood pressure in a safety-net health system: a qualitative focus group protocol

Por: Sprague · B. N. · Beverly · A. R.
Introduction

Black women in early midlife experience disproportionate exposure to stress and elevated cardiovascular risk, including hypertension. Despite this, few stress management interventions are designed with and for this population. This study aims to explore the lived experiences of stress and coping among black women in early midlife with elevated blood pressure to inform the codesign of a culturally relevant, multilevel stress management intervention.

Methods and analysis

We will conduct one-time, semistructured focus groups with black women aged 35–50 who have elevated blood pressure, recruited from a large safety-net health system. Data will be analysed using a constructivist grounded theory approach, with inductive theme development supported by line-by-line, focused and theoretical coding. The Social Determinants of Cardiovascular Disease framework will serve as a sensitising guide to multilevel contextual factors rather than a prescriptive coding structure. An artificial intelligence (AI)-assisted analytic component will complement human-led analysis by supporting preliminary theme exploration and enhancing transparency.

Ethics and dissemination

Approved by the Indiana University Institutional Review Board (Protocol #21785). All participants will provide written informed consent. Findings will be shared via peer-reviewed publications, conference presentations and lay summaries for stakeholders.

How public health practitioners in the UK are using parental guidance on talking to children about weight: a qualitative study

Por: Brockman · R. · Gillison · F. · Grey · E. B. · Jago · R. · MacArthur · G. J. · Gutteridge · C. · Langford · R.
Objective

To understand how public health practitioners (PHPs) are using parental guidance on talking to children in their work with parents. In 2021, evidence-based guidance was produced for parents of young children to facilitate these conversations, but it is unclear how this guidance is being promoted to parents or used by PHPs.

Design

Qualitative study, consisting of in-depth, semistructured interviews.

Setting

Local authority, National Health Service or other healthy weight service providers in the UK.

Participants

Participants were PHPs working on children’s healthier lifestyles programmes in the UK as part of the UK’s National Child Measurement Programme (NCMP). Invitations to participate were distributed via the Department of Health and Social Care and regional and national networks.

Results

24 participants were interviewed. Practice varied between organisations with the guidance being used in NCMP letters to parents, in follow-up phone calls with parents and in training NCMP staff and other health or education professionals. Participants valued the evidence-based guidance and its compassionate tone, feeling it gave them and parents, confidence in addressing a sensitive topic. Some felt it was too lengthy for parents with learning disabilities or low literacy levels. Others identified a need for similar guidance for older children. Though helpful, participants acknowledged the guidance was only one small part of a necessary systems-wide approach to promoting healthy weight.

Conclusions

The guidance is a useful tool but needs systematic promotion to increase use and effectiveness. Further work is warranted to develop adapted versions for other populations.

Mechanisms of SGLT inhibitor action and physiological mediators: systematic review and protocol for the MOSAIC collaborative meta-analysis

Por: Kugathasan · L. · Nardone · M. · Muskiet · M. · Diaz Martinez · J. P. · Lovblom · L. E. · Orchanian-Cheff · A. · Nielsen · S. · Rotbain · V. · Kazup · A. · Cersosimo · E. · Gullaksen · S. · Vernstrom · L. · van Baar · M. J. B. · van Bommel · E. · Kannenkeril · D. · Scholtes · R. · Hesp
Introduction

Sodium-glucose cotransporter (SGLT) inhibitors have shown substantial benefit in reducing cardiovascular and kidney events across diverse clinical populations, but the underlying physiological mechanisms remain unclear. However, existing mechanistic studies on renal and cardiovascular haemodynamics show variability in design, have limited statistical power and yield inconsistent outcomes, thus limiting the ability to draw generalisable conclusions. To address this gap, we conducted a systematic review and proposed the first meta-analysis to aggregate individual participant-level data from mechanistic studies to identify consistent physiological patterns and enhance understanding of the therapeutic effects of SGLT inhibition.

Methods and analysis

Gold-standard measured glomerular filtration rate (mGFR) was selected as the primary outcome for this systematic review, which aimed to identify all completed mechanistic studies investigating the effects of SGLT inhibition. Electronic databases including Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews; and Cochrane Central Register of Controlled Trials were searched using a detailed search strategy. In total, 24 studies (n=1296) were identified. This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Key variables including demographics, medical history, concomitant medications, vital signs, mGFR, renal haemodynamics, urine and plasma biochemistry, tubular sodium handling, echocardiography, cardiac output monitoring, arterial stiffness and fluid volume will be extracted. A one-stage individual participant data meta-analysis under a Bayesian framework will be conducted, using hierarchical models to simultaneously analyse data from all eligible studies. The risk of bias due to missing results will be assessed. Sensitivity analyses and subgroup evaluations will be incorporated to explore sources of heterogeneity and assess robustness of findings.

Ethics and dissemination

Ethics approval was obtained from University Health Network, Toronto, Canada. Findings from the Mechanisms of SGLT Inhibitor Action and Physiological Mediators (MOSAIC) meta-analysis will be published in peer-reviewed journals and results will be disseminated at scientific conferences.

PROSPERO registration number

CRD420251001413.

Transmission dynamics and control of tuberculosis in high-altitude regions: a modelling study in Xizang, China

Por: Li · M. · Zheng · R. · Guo · L. · Wu · Y. · Dong · J. · Jiang · H. · Song · D. · Cui · Z. · Li · C.
Objectives

To estimate tuberculosis (TB) incidence trends in the high-altitude Xizang, China, and to explore the key intervention strategies on achieving the WHO 2030 TB control target.

Design

We developed a susceptible–exposed–infectious–recovered transmission model using routinely reported TB surveillance data from 2004 to 2022. Scenario-based simulations were conducted to project future TB incidence under alternative intervention strategies. Model assumptions are as follows: (1) a stable population, (2) lifelong vaccine-induced immunity, (3) infectiousness of active TB cases, (4) relapse risk after recovery and (5) homogeneous mixing within the population.

Setting

Seven prefectures of Xizang Autonomous Region on the Tibetan Plateau, China.

Participants

An estimated population of approximately 3 million individuals residing in Xizang.

Interventions

We assessed the epidemiological impact of four interventions implemented independently: increasing vaccine efficacy rate, reducing transmission rates of susceptible individuals, decreasing progression rate from latent TB infection to active disease and reducing relapse rate among successfully treated patients, compared with continuation of current control measures.

Results

The estimated basic reproduction number (R0 ) for TB in Xizang was 0.39 (95% CI 0.21 to 0.71) in the absence of additional interventions, which was the highest among all regions of China. Model simulations indicated that all four evaluated interventions were each likely to reduce TB incidence, but only reducing the latent-to-active TB progression had a substantial effect. A 50% reduction in the progression rate was predicted to lower TB incidence from 66.56 (62.00–70.11) to 40.54 (37.15–43.77) cases per 100 000 population, meeting the WHO 2030 TB control target.

Conclusion

Targeted management of individuals with latent TB infection should be strengthened to substantially reduce TB transmission in high-altitude areas.

Exploring potential pathogenesis mechanisms of onchocerciasis-associated epilepsy through cerebrospinal fluid analysis of children with complex febrile seizures: a pilot study in Aketi, Democratic Republic of the Congo

Por: Kungu Gbulu · R. · De Wilde · B. · Lubbers · C. · Falay · D. S. · Siewe Fodjo · J. N. · Colebunders · R.
Introduction

Onchocerciasis, commonly known as river blindness, is a parasitic disease caused by Onchocerca volvulus affecting millions predominantly in sub-Saharan Africa. Robust epidemiological evidence points to a clinical relationship between onchocerciasis and epilepsy, a condition termed onchocerciasis-associated epilepsy (OAE). Despite extensive research and various successful elimination programmes over the past decades, the pathogenesis of OAE is still unknown. Current hypotheses propose that O. volvulus microfilaria, their excretory-secretory products or the newly discovered filarial O. volvulus RNA virus 1 (OVRV1) virus may traverse the blood-brain barrier, triggering seizures or immune responses that result in neurological damage. However, direct evidence of microfilaria or their DNA in cerebrospinal fluid (CSF) or brain tissue remains elusive, likely due to immune-mediated parasite clearance. Additionally, investigations into the potential neurotoxicity of these novel filarial viruses have yet to be pioneered.

Methods and analysis

This prospective cohort study will involve 100 ivermectin-naïve children aged 2–5 years, recruited from rural communities in the Aketi health zone, located in the Democratic Republic of Congo. This region is known to be an onchocerciasis-endemic area with a high prevalence and transmission of OAE, despite years of community-directed treatment with ivermectin. Lumbar punctures (LP) will be performed in children presenting with complex febrile seizures according to WHO’s paediatric guidelines. CSF samples will be examined for white blood cells, protein levels, glycorrhachia, microfilaria, OVRV1 and O. volvulus biomarkers. Children will be followed annually, monitoring the development of epilepsy and O. volvulus infection. This approach aims to elucidate the presence of O. volvulus and OVRV1 in the brain and their role in the pathogenesis of epileptic seizures and the myriad of clinical symptoms observed in OAE.

Ethics and dissemination

The protocol has been approved by the Ethics Committee of the University of Kisangani (UNIKIS/CE/KGB/001/2025) and the University of Antwerp (project ID 7323-Edge n/a-BUN B3002025000078). Written informed consent will be obtained from all parents and/or legal guardians of children for whom an LP is considered. Findings will be disseminated at national and international levels via meetings and peer-reviewed open-source publications. Study data will be stored in an open repository.

Trial registration number

Pan African Clinical Trials Registry (PACTR202507670131109).

Psychological Outcomes of Family Members Related to a Loved One's Resuscitation in the Emergency Department: A Cross‐Sectional Study

ABSTRACT

Aims

This study aimed to assess the psychological outcomes of family members of patients who were resuscitated in the Emergency Department (ED) and analyse factors associated with these outcomes.

Design

This study utilised a cross-sectional design

Methods

Data were collected using a self-reported questionnaire sent to family members of patients who had undergone resuscitation in the ED from February 2024 to January 2025. Instruments for data collection included The Impact of Event Scale-Revised (IES-R), the short version of The Depression, Anxiety and Stress Scale–21 items (DASS-21), the Multicultural Quality of Life Index (MQLI) and questions related to demographic variables and the resuscitation event.

Results

A total of 106 family members completed the questionnaire. Of this, 64.2% (n = 68) reported witnessing the resuscitation attempt, and 35.8% (n = 38) did not witness the event. Family members who witnessed the resuscitation displayed more symptoms of post-traumatic stress disorder (PTSD), measured by the IES-R, compared to those who did not witness the event. A statistically significant negative correlation was found between the IES-R and the MQLI scores, indicating that higher PTSD symptoms correlate with lower quality of life (QoL) ratings.

Conclusion

The findings of this study indicated that witnessing the resuscitation of a loved one in the ED is associated with increased PTSD symptoms.

Implications for Health Professionals and Patient Care

Patients' and family members' cultural and religious needs should be acknowledged by the health care providers. Study findings indicate that family members prefer to be with the patient during the patient's resuscitation. However, without adequate support from hospital staff, this experience may cause adverse psychological effects. Strategies to support family members during and after resuscitation should be developed and integrated into the management of in-hospital resuscitation.

Reporting Method

This study followed the STROBE guidelines.

Patient or Public Contribution

No patient or public contribution.

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