by Gunnhild Helmsdal, Marnar Fríðheim Kristiansen, Eyðbjørg Klemmentsen Gaard, Barbara Joensen Eysturoy, Pál Weihe, Eina Hansen Eliasen, Maria Skaalum Petersen
BackgroundSix years since the emergence of SARS-CoV-2, the newer variants of the virus continue to have long-term health effects.
ObjectivesThe aim of the study was to investigate persistent symptoms, cognitive impairment, and clinical and paraclinical predictors of long COVID in individuals infected during the Omicron wave.
MethodsWe conducted a clinical case-control study including participants with persistent symptoms up to 13 months after confirmed SARS-CoV-2 Omicron infection (long COVID or LC group) and antibody-verified never-infected controls (NI group).
ResultsA total symptom score based on a 24-item questionnaire was strongly associated with increased odds of long COVID (adjusted odds ratio (aOR) 1.21, 95% CI 1.13–1.30, p Conclusions
One year after Omicron infection, a subset of people continue to experience a substantial symptom burden, particularly fatigue, cognitive impairment, and mental well-being, and a higher frequency of intercurrent infections.
by Agatha Ribeiro Kalthof, Nikolas Dresch Ferreira, Caio Mateus Silva, Iuri Cordeiro Valadão, Iguaracy Pinheiro de Sousa, Ester Riserio Matos Bertoldi, Vanessa Morais Lima, Lauro Thiago Turaca, Ana Beatriz Ruiz Afonso Barbosa, Miriam Helena Fonseca-Alaniz, Jean-Paul Concordet, Elida Adalgisa Neri, Jose E. Krieger
Generating mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) remains a major obstacle to accurate disease modeling and cardiac repair. As the transcription factor Irx3 is a key determinant of ventricular conduction system fate in mice, we hypothesized that suppressing IRX3 expression accelerates human working cardiomyocyte differentiation. Here, we demonstrate that depleting IRX3 enhances hiPSC-CM differentiation. IRX3-knockout (KO) hiPSCs generated a greater number of cardiomyocytes with elevated expression of TNNI1 and CX43. Notably, IRX3-KO cardiomyocytes exhibited improved electrophysiological properties, more uniform mitochondrial distribution, better sarcomere organization, and enhanced intercellular connectivity. We observed that IRX3 expression peaks during the early stages of cardiomyocyte differentiation, whereas IRX3-KO cardiac progenitors have increased expression of GATA4, NKX2–5, and TBX5, as well as enhanced cell proliferation. These integrative analyses indicate that IRX3 influences cardiomyocyte differentiation by modulating the gene regulatory networks driven by GATA4, NKX2–5, and TBX5, providing functional evidence linking gene regulatory networks to the structural and electrophysiological development of cardiomyocytes. Collectively, these findings identify IRX3 as a key regulator of early cardiac commitment and highlight the potential of IRX3 suppression to enhance the molecular and functional phenotype of hiPSC-derived cardiomyocytes.by Atala Jongo, Edwin Lugazia, Salehe Mrutu, Amina Abillah Omari, Hassani Msanga, Ansbert Sweetbert Ndebea, Felix Paul Amani
BackgroundSepsis continues to pose a significant global health challenge, particularly in low- and middle-income countries, which face a disproportionate burden of sepsis and sepsis-related deaths. The estimated prevalence of sepsis and sepsis-related mortality is higher in intensive care units than in hospitals overall. The burden can be higher in tertiary referral centers that receive patients from different regions.This study aimed to determine the prevalence of sepsis, its outcomes, and the factors associated with these outcomes among adult patients admitted to the Intensive Care Unit (ICU) of the Muhimbili National Hospital (MNH) in Tanzania.
MethodologyThis prospective cohort study was conducted over a period of six months from May 16 to November 16, 2023, at MNH. A total of 248 patients were admitted during the study period and screened for sepsis on admission or for the development of sepsis during their ICU stay. Sepsis was defined according to the Sepsis-3 criteria as a suspected infection with a Sequential Organ Failure Assessment (SOFA) score ≥2 within 24 h of ICU admission. Proportions were used for descriptive statistics, and modified Poisson regression analysis was used to identify independent predictors of mortality at a 95% confidence interval, with P Results
The prevalence of sepsis was 41.5%. The respiratory system was the most common source of infection (32%), and 22.3% of patients had more than one infection site. The ICU mortality rate was 55.3%, with 35% of patients developing systemic complications during their ICU stay.Factors independently associated with mortality included multiple comorbidities (aPR 3.35, 95% confidence interval [CI], 1.20–9.32; p = 0.021) and a higher SOFA score (aPR 7.08, 95% CI 3.48–14.4; p Conclusion
This study revealed a high prevalence of sepsis and sepsis-related mortality in the ICU. A high SOFA score and multiple complications were independent predictors of mortality. Early initiation of antibiotic therapy was an independent predictor of survival. This underscores the importance of early treatment, close monitoring, and aggressive management in patients with predictors of poor outcome.
Asthma, chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are prevalent chronic respiratory diseases associated with increased comorbidity, mortality and healthcare costs. Physical activity and exercise are widely recommended as part of treatment for these conditions, yet the specific effects of Nordic walking (NW) remain underexplored. The aims of this randomised controlled trial (RCT) are to improve physical fitness, functional capacity and respiratory health and increase regular physical activity and quality of life of older adults with asthma and/or COPD and/or OSA through a supervised 3-month group-based NW intervention combined with resistance, balance and mobility training.
This single-blinded, parallel-group RCT will recruit 100 adults aged 55–80 years diagnosed with asthma and/or COPD and/or OSA in the Northern Savo region of Finland. Participants will be randomly allocated to either an intervention group or a control group.
The intervention group will participate in a 12-week supervised exercise programme consisting of progressive NW sessions twice per week and resistance, balance and mobility training once per week. The primary outcome is a change in cardiorespiratory endurance. Secondary outcomes include functional capacity, physical activity level, spirometry parameters and quality of life. The control group will continue their usual physical activity and receive physical activity guidance after 12 weeks. Measurements were conducted at baseline, three and 9 months. Data will be analysed according to the intention-to-treat principle. Group differences over time will be examined using appropriate parametric or non-parametric methods depending on data distribution.
Ethical approval was obtained from the Regional Medical Research Ethics Committee of Eastern Finland Collaborative Area (892/13.00/2023). Findings will be disseminated through publications in peer-reviewed journals and presentations at scientific conferences.
The trial is registered at ISRCTN12097135, registration date: 7 June 2024.
The Mental health care: Adverse Sequelae of COVID-19 study aimed to (1) compare the consequences of the COVID-19 pandemic for mental health services and people with pre-existing mental health conditions (MHCs) in six low- and middle-income countries and (2) identify good practice to mitigate these impacts.
An observational study, using a mixed-methods convergent design triangulating data from (1) semistructured interviews or focus groups and/or a self-completed survey, (2) routine service utilisation data, (3) local grey literature and (4) expert consultation.
The study was conducted in Chile, Ethiopia, Georgia, Nigeria, South Africa and Sri Lanka.
121 key informants.
We found clear evidence in all sites that the pandemic exacerbated pre-existing disadvantages experienced by people with MHCs and led to a deterioration in the availability and quality of care, especially psychosocial care. Alongside increased vulnerability to COVID-19, people with MHCs faced additional barriers to accessing prevention and treatment interventions compared with the general population. To varying extents, sites showed accelerated implementation of digital technologies, but with evidence of worsening inequities in access. In sites where primary care-based mental healthcare was more developed or prioritised, systems seemed more resilient and adaptive.
Our findings have the following implications. First, these mental health service reductions are clear examples of ‘structural stigma’, namely policy level decisions in healthcare which place a low priority upon services for people with MHCs. Second, integration of mental healthcare into all general healthcare settings is key to ensuring accessibility and parity of physical and mental healthcare. Third, digital innovations should be designed to strengthen and not fragment health systems. We discuss these findings in terms of anticipating such challenges for future pandemics and preparing layers of resilience.
People with severe mental illness (SMI) engage in less physical activity (PA) and more sedentary behaviour (SB) than the general population, contributing to poorer physical health outcomes in this population. Therefore, the aim of this study was to evaluate the feasibility of a multi-component behaviour change intervention called Walking fOR Health (WORtH), delivered by community mental health teams, aimed at increasing PA and reducing SB compared with a one-off education session in people with SMI.
Feasibility randomised controlled trial (RCT).
Study recruitment and intervention delivery took place within four community mental health teams in the UK and Ireland.
Eligible participants had a diagnosis of a SMI and no contraindications to participating in physical activity. Fifty-four participants (25 male, 29 female; mean age 51.6 years) were recruited.
Participants were randomised to the 13-week WORtH intervention, comprising education, activity tracking and health coaching or an education-only control.
Feasibility outcomes included recruitment, retention, adherence and acceptability. Clinical outcomes included device-measured (Axivity AX3) and self-reported PA and SB, body anthropometry, physical function and mental well-being.
This feasibility study met 90% target recruitment and 94% of participants provided follow-up data. Adherence to allocated intervention and engagement with all core intervention components was >80%. Qualitative feedback indicated high levels of satisfaction. Valid device-measured moderate-vigorous PA (MVPA), the intended primary outcome for a definitive trial, was obtained from 90% of participants at baseline and 75% of participants at post-intervention. Point estimates indicated a mean increase of 8.6 min/day of MVPA in the intervention group (baseline 54.7 min/day (95% CI 39.5 to 70.0); follow-up 63.3 min/day (95% CI 50.1 to 76.4)) and of 1.0 min/day in the control group (baseline 42.1 min/day (95% CI 24.6 to 59.6); follow-up 43.1 min/day (95% CI 29.6 to 56.5)).
The results of this study support the feasibility of the WORtH intervention in adults with SMI, and findings will be used to optimise the design of a definitive RCT.
To assess the prevalence of workplace violence (WPV) against clinical nursing students during internships and quantify the prevalence of different types of violence, such as physical, verbal and sexual.
Systematic review and meta-analysis.
Eligible cross-sectional studies that reported WPV prevalence among clinical nursing students were included. Two researchers independently screened literature and extracted data. The Joanna Briggs Institute tool was used to evaluate bias risk. Pooled prevalence rates, heterogeneity and publication bias were examined.
A comprehensive search was conducted across eight databases, from the inception of each database to 31 March 2025.
A total of 16 cross-sectional studies from eight countries involving 8037 nursing students were included in the analysis, with 11 studies (n = 5550) contributing to the overall pooled estimate. Using a random-effects model, the pooled prevalence of WPV of any type was found to be 40%, with substantial heterogeneity. Verbal violence emerged as the most prevalent subtype (47%), followed by sexual violence (12%) and physical violence (10%). Significant publication bias was detected for both physical and sexual violence, indicating a potential underestimation of the true prevalence.
This systematic review indicated that WPV is a significant occupational hazard encountered by clinical nursing students across diverse international contexts represented during internships.
These findings highlight the urgent need for educational and healthcare institutions and policymakers to implement coordinated measures, such as enhanced preventive training, comprehensive reporting and support systems and a zero tolerance safety culture to protect the future nursing workforce.
This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
This study did not include patient or public involvement in its design, conduct or reporting.
The research protocol was registered with PROSPERO (CRD420251027354).
Cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC) is a treatment for peritonitis carcinomatosa. These procedures often involve significant blood and fluid loss, leading to hyperdynamic circulation and vasodilation, necessitating intraoperative fluids and vasoconstrictors such as catecholamines. Excessive fluid administration to counteract vasodilation can cause intraoperative fluid overload, which is linked to increased postoperative complications. Vasopressin has emerged as a potential alternative to catecholamines, restoring vascular tone via non-adrenergic pathways and supporting perfusion pressure, potentially reducing the need for compensatory fluids solely administered to compensate for vasodilation. We hypothesise that compared with norepinephrine, vasopressin reduces cumulative intraoperative fluid administration during CRS-HIPEC within a goal-directed fluid therapy (GDFT) protocol, ultimately leading to a lowering of postoperative complications.
HiPress is a two-centre, two-arm randomised clinical trial with blinding of both patients and outcome assessors. A total of 70 adult patients undergoing CRS-HIPEC will be included. Patients will be randomised to receive either continuous low-dose argipressin or continuous low-dose norepinephrine. Both groups will receive standardised GDFT during the procedure. The primary endpoint is cumulative intraoperative fluid administration (mL). Secondary endpoints include direct fluid-related outcomes (eg, cumulative intraoperative fluid (ml/kg/hour), postoperative fluid balance until day five and ultrasound-assessed pulmonary oedema and venous congestion) and indirect fluid-associated outcomes (eg, quality of recovery, surgical and abdominal complications, acute kidney injury (AKI), pulmonary complications, length of ICU and hospital stay and 30-day mortality).
The study is enrolling patients since February 2025. The trial is approved by the Medical Research Ethics Committee (hereinafter: MREC) NedMec, The Netherlands (Ref: D-25-500202). Results of the trial will be published in an international peer-reviewed journal and announced at national and international scientific meetings.
Clinical Trials Information System (CTIS): European Union clinical trials register (EUCT) number: 2024–5 13 598-33-00
In 2017, Lifeline Nehemiah Projects in Sierra Leone launched 2YoungLives, a mentoring initiative for vulnerable pregnant adolescents, including those living with disabilities. Drawing from the social model of disability, we aimed to investigate the exacerbated disabling barriers which prevent these girls and their babies from accessing available healthcare and develop comprehensive solutions to improve their access.
Qualitative methods were used in this study.
Participants were invited to participate in face-to-face interviews in one district in Sierra Leone.
Six pregnant or postnatal adolescents living with disability, alongside four caregivers and five stakeholders from various organisations participated in semi-structured interviews employing thematic analysis.
We identified four key themes: (1) discrimination and financial barriers within the healthcare system, despite laws ensuring free healthcare for persons living with disabilities, (2) societal stigma manifested through abandonment by families and inadequate support, (3) lack of understanding of disability issues, particularly of those with intellectual impairments, leading to stigmatisation and exclusion, and (4) infrastructural limitations which hinder accessibility to essential services, with many facilities remaining non-compliant with disability regulations.
Adolescent girls living with disability during pregnancy and after birth in Sierra Leone face barriers to accessing healthcare, including caregiver ignorance, lack of autonomy, disabling services, social stigma and ineffective policy implementation, despite existing supportive laws. These findings keep those women who are arguably the most vulnerable, adolescent and living with a disability, from accessing perinatal healthcare, exacerbating their risk and that of their babies. Solutions include the need to enforce disability-inclusive policies and infrastructure adaptations, awareness and training for healthcare providers and community advocacy to break down social stigma.
Objetivo: Analizar y clarificar el concepto de conocimientos de automanejo en personas con enfermedades crónicas, identificando sus atributos definitorios, antecedentes y consecuencias, a fin de construir una definición conceptual y operacional aplicable a la práctica e investigación en enfermería. Metodología: Se utilizó la metodología de análisis de concepto en sus ocho pasos, se realizó una revisión exhaustiva de la literatura científica, teoría e institucional publicada entre 2015 y 2025 en bases de datos confiables. La información obtenida fue organizada, depurada y analizada mediante el software Rayyan®. Los resultados se presentan con base a los ocho pasos. Resultados: el análisis permitió identificar tres dimensiones que definen el concepto: 1) cognitivo: que es la comprensión y dominio de la información en salud; 2) procedimental: que es la aplicación práctica del conocimiento y 3) reflexiva-contextual: que es la integración del conocimiento con experiencias y toma de decisiones. Los antecedentes se relacionan con el diagnóstico de enfermedades crónica, la alfabetización en salud y el apoyo del sistema de salud. Las consecuencias se asocian con una mayor adherencia al tratamiento, control clínico, autoeficacia y calidad de vida. Conclusiones: el conocimiento de automanejo en personas con enfermedades crónicas se define como un proceso cognitivo, procedimental y reflexivo, a través del cual la persona adquiere, comprende y aplica información relevante sobre su enfermedad para la toma de decisiones informadas y sostenibles. Su clarificación conceptual aporta una base sólida para el desarrollo de intervenciones en salud e instrumentos de medición.
ABSTRACT
Objective: To analyze and clarify the concept of self-management knowledge in people with chronic diseases, identifying its defining attributes, background, and consequences, to construct a conceptual and operational definition applicable to nursing practice and research. Methodology: The eight-step concept analysis methodology was used, and exhaustive review of the scientific, theoretical, and institutional literature published between 2015 and 2025 in reliable databases was conducted. The information obtained was organized, refined, and analyzed using Rayyan® software. The results are presented based on the eight steps. Results: The analysis identified three dimensions that define the concept: 1) cognitive: understanding and mastery of health information; 2) procedural: practical application of knowledge; and 3) reflective-contextual: integration of knowledge with experiences and decision-making. The background relates to the diagnosis of chronic diseases, health literacy, and health system support. The consequences are associated with greater adherence to treatment, clinical control, self-efficacy, and quality of life. Conclusions: Self-management knowledge in people with chronic diseases is defined as a cognitive, procedural, and reflective process through which individuals acquire, understand, and apply relevant information about their disease to make informed and sustainable decisions. Its conceptual clarification provides a solid basis for the development of health interventions and measurement instruments.
by Ika Saptarini, Sri Masyeni, Alida Roswita Harahap, Astuti Giantini, Pringgodigdo Nugroho, Agus Handito, Harimat Hendarwan, Adityo Susilo, Sotianingsih Haryanto, Desi Fitriani, R. Tedjo Sasmono, Erni Juwita Nelwan
BackgroundDengue virus (DENV) infection can manifest as dengue fever (DF) or dengue hemorrhagic fever (DHF), although DHF often becomes clinically apparent around defervescence. How complement components and other immune responses evolve over the course of illness from the febrile to recovery phase remains incompletely defined. This study characterized circulating complement activation and immune mediators in DF and DHF using paired febrile and early-recovery samples.
MethodsWe conducted a multicenter prospective cohort study at five hospitals in Indonesia between November 2024 and October 2025. Patients with laboratory-confirmed dengue were classified as DF or DHF. Plasma concentrations of PTX3, C5a, IL-6, IL-10, IL-8, and CXCL10 were quantified in paired febrile and early recovery phase samples. Between-group differences, within-patient changes between the two time points, and correlations among immune mediators were assessed using appropriate statistical methods.
ResultsWe included 110 confirmed dengue cases in the analysis. PTX3 and IL-10 levels were significantly higher in DHF than in DF during early recovery, whereas no mediator differed significantly between severity groups during the febrile phase. Across phases, C5a increased significantly from febrile to early recovery in DHF but not in DF, whereas PTX3 decreased significantly in DF but not in DHF. Correlations among mediators were generally weak to moderate, with a reproducible PTX3–IL-10–CXCL10 module observed across both phases.
ConclusionThe measured mediators did not distinguish DF from DHF during the febrile phase, but differences emerged in early recovery, with higher PTX3 and IL-10 in DHF. Across phases, C5a increased significantly from febrile to early recovery in DHF, whereas PTX3 decreased significantly only in DF. A PTX3–IL-10–CXCL10 module was observed at both time points. Together, these patterns suggest that within-patient changes around defervescence or in the early recovery may be informative and warrant evaluation in larger, prospectively timed cohorts.
Beta Glucans (β-glucans) are naturally occurring polysaccharides that have positive effects on healing in acute and chronic wounds. This study aimed to identify how β-glucans modulate macrophage polarisation and inflammation to aid the healing response. Flow cytometry was used to assess the effect of β-glucan on human monocytes during differentiation into M0, M1 and M2 macrophages. Subsequently, a murine full-thickness excisional wound healing model was conducted where wounds were treated with either β-glucan hydrogel or vehicle, at the time of wounding. The wounds were analysed to determine the rate of wound closure, the effect on inflammation, and matrix deposition. β-glucan promoted differentiation of monocytes to M0 macrophages but inhibited differentiation of M0 macrophages to pro-inflammatory M1 macrophages with no effect on M2 macrophage formation. In vivo, treatment of excisional wounds with β-glucan hydrogel accelerated healing with an earlier, more resolved inflammatory phase containing greater numbers of M2 macrophages and fewer neutrophils within the wound. No statistically significant effect on matrix deposition was observed. β-glucans modulate macrophage differentiation and accelerate healing in excisional wounds with no adverse effect on matrix formation. β-glucans are a potential therapeutic approach for treatment of hard-to-heal wounds in humans.
Although implementing evidence-based interventions has been shown to improve the quality of care, there is limited evidence evaluating how these interventions are implemented. In intensive care settings, the use of evidence-based protocols, guidelines and care bundles has been associated with enhanced care quality and reduced burden on patients.
To identify and map existing evidence on the evaluation of evidence-based intervention implementation in adults' intensive care.
A scoping review was conducted by including original published and unpublished studies in English and Finnish.
The studies were retrieved from five databases (CINAHL, Scopus, Ovid Medline, Medic ja Mednar) from January 2000 to December 2024. The data search was performed on 29 November 2022 and updated on 10 December 2024. The results were synthesized and presented in a tabular and descriptive form.
A total of 19 studies were included in the review. These studies evaluated the implementation of evidence-based interventions, focusing on nurse and patient outcomes. Nurse outcomes included measures such as compliance, knowledge and self-confidence. Patient outcomes included indicators such as body temperature, blood glucose, incidence of pressure ulcers and length of stay.
The evaluation of evidence-based intervention implementation does not consistently extend to the evaluation of the entire implementation process. More consistent research reporting would improve disseminating the evidence. The evaluation implementation makes it possible to show the impact of nurse and patient outcomes. The evaluation results can reveal the success of the implementation. Further research on evaluation implementation, development of systematic and comprehensive evaluation implementation methods, or evaluation matrix is needed.
The review will be useful for nursing professionals in planning evidence of implementation, developing or researching evaluation implementation. Promoting evaluation of evidence-based intervention implementation in Nursing can improve the quality of patient care, improve disseminating evidence and uniformities of care practice.
What Problem Did the Study Address? There is limited evidence of evaluation of evidence-based interventions of implementation. Evaluating evidence-based implementation is important to ensure the quality of patient care and patient safety.
What Were the Main Findings? Evaluation of implementation of evidence-based interventions focused on nurse and patient outcomes. Evaluation of the entire implementation process was not identified, and implementation strategies were not evaluated.
Where and on Whom Will the Research Have an Impact? Evidence-based practice implementation in nursing for researchers, developers, nursing leaders and clinical nursing practitioners who implement and evaluate evidence-based practice implementation.
PRISMA 2020 statement.
No Patient of Public Contribution: This study did not include patient or public involvement in its design, conduct or reporting.