Influenza is a major global health concern, responsible for up to 650 000 respiratory-related deaths annually. Although influenza is often perceived as mild in healthy adults, it can cause severe outcomes in high-risk groups, such as older adults, young children, pregnant women and those with underlying medical conditions. Various clinical, sociodemographic and environmental factors influence the progression to severe outcomes, whereas resilience factors, such as vaccination, may reduce risks. Despite growing research, the evidence base regarding risk and resilience is spread across many different aspects of the literature. This umbrella review will synthesise evidence from existing systematic reviews and meta-analyses to identify key risk and resilience factors associated with the progression of influenza to severe outcomes in the general population.
This umbrella review follows the Joanna Briggs Institute (JBI) and Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will include systematic reviews and meta-analyses reporting host-related risk or resilience factors for severe influenza outcomes. Four databases (EMBASE, Scopus, Medline and CINAHL) will be searched for English-language publications. Study quality will be assessed using AMSTAR 2, and the body of evidence will be evaluated using Grading of Recommendations Assessment, Development and Evaluation. Due to heterogeneity, findings will be analysed narratively. Risk and resilience factors will be grouped into demographic, clinical, behavioural, social and psychological domains.
No ethical approval is required. The completed review will be shared through peer-reviewed journals and conference presentations.
CRD420250644475.
Limited evidence exists regarding the effectiveness of learning approaches in supporting interprofessional wound care education transnationally. The aim of this pilot study was to explore the feasibility and preliminary impact of an international, online interprofessional masterclass in supporting baccalaureate health students' learning about wound care. Data were collected using multiple methods including quantitative survey, qualitative focus groups, and interviews with baccalaureate nursing, pharmacy, dietetics, podiatry and paramedicine students from two universities based in Australia and Northern Ireland. A retrospective pre-test design was used. A survey retrospectively assessed students' self-reported confidence and understanding before and after the masterclass, while qualitative methods explored students' experiences of interprofessional learning and wound care. Self-reported improvements in students' understanding of wound assessment and management, as well as heightened awareness of interprofessional contributions to patient care indicated the potential value of this interprofessional and international collaboration in supporting wound care education. Qualitative analysis identified four themes: recognising a wound is a person's wound; comparing international healthcare practices; fostering learner engagement; interprofessional recognition, acknowledgment, and understanding of each profession's roles, contributions and expertise. This pilot study has highlighted key issues to be addressed in future research examining the impact of a collaborative online international initiative on baccalaureate students' interprofessional learning about wound care.
Severe mental disorders are associated with increased risk of metabolic dysfunction. Identifying those subgroups at higher risk may help to inform more effective early intervention. The objective of this study was to compare metabolic profiles across three proposed pathophysiological subtypes of common mood disorders (‘hyperarousal-anxious depression’, ‘circadian-bipolar spectrum’ and ‘neurodevelopmental-psychosis’).
751 young people (aged 16–25 years; mean age 19.67±2.69) were recruited from early intervention mental health services between 2004 and 2024 and assigned to two mood disorder subgroups (hyperarousal-anxious depression (n=656) and circadian-bipolar spectrum (n=95)). We conducted cross-sectional assessments and between-group comparisons of metabolic and immune risk factors. Immune-metabolic markers included body mass index (BMI), fasting glucose (FG), fasting insulin, Homeostasis Model Assessment-Insulin Resistance (HOMA2-IR), C reactive protein and blood lipids.
Individuals in the circadian-bipolar spectrum subgroup had significantly elevated FG (F=5.75, p=0.04), HOMA2-IR (F=4.86, p=0.03) and triglycerides (F=4.98, p=0.03) as compared with those in the hyperarousal-anxious depression subgroup. As the larger hyperarousal-anxious depression subgroup is the most generic type, and weight gain is also a characteristic of the circadian-bipolar subgroup, we then differentiated those with the hyperarousal-anxious subtype on the basis of low versus high BMI (2 vs ≥25 kg/m2, respectively). The ‘circadian-bipolar’ group had higher FG, FI and HOMA2-IR than those in the hyperarousal-anxious-depression group with low BMI.
Circadian disturbance may be driving increased rates of metabolic dysfunction among youth with emerging mood disorders, while increased BMI also remains a key determinant. Implications for assessment and early interventions are discussed.
To explore the influences of workplace bullying experiences, witnessing workplace bullying and bystander types on Speaking up for patient safety (SUPS) among hospital nurses.
Cross-sectional study.
A survey was conducted in September 2021 using a structured questionnaire about workplace bullying experiences, witnessing workplace bullying, bystander types, and SUPS. The questionnaire was administered to 200 bedside nurses from two tertiary university hospitals in South Korea.
One hundred and ninety-nine responses were analysed. A hierarchical regression model, incorporating organisational factors, workplace bullying experiences, witnessing workplace bullying, and bystander types explained approximately 44.0% of the variance in nurses' SUPS. Witnessing workplace bullying and the perpetrator-facilitating bystander negatively influenced SUPS, whereas victim-defending bystander had a positive influence on SUPS.
Findings suggest that witnessing workplace bullying and the bystander types of nurses working on patient care units are more impactful on nurses' SUPS than individual experiences of bullying. Notably, the victim-defending and perpetrator-facilitating bystander types were identified as key factors influencing SUPS.
Nurse managers should understand the roles of witnesses and bystanders working on a patient care unit, and how these roles may extend beyond traditional views of perpetrators and victims. Developing strategies to support and effectively manage witnesses and bystanders working on patient care units may promote positive SUPS behaviours among clinical nurses.
What problem did the study address?
Speaking up for patient safety (SUPS) in clinical settings is critical in maintaining and enhancing patient safety. However, a negative work environment, such as one that promotes workplace bullying may hinder nurses' willingness to engage in SUPS. Because many nurses involved in workplace bullying may be witnesses or bystanders rather than direct perpetrators or victims of such situations, this study explored the potential influences of workplace bullying, including the roles of witnesses and bystanders, on SUPS. What were the main findings?
SUPS was influenced more by witnessing workplace bullying and specific bystander types, namely victim-defending and perpetrator-facilitating bystanders, than by workplace bullying experiences. Where and on whom will the research have an impact?
These findings highlight the importance of addressing the roles of witnesses and bystanders in workplace bullying. Nurse managers should broaden their focus beyond perpetrators and victims to include the roles and views of all nursing staff within a department. By effectively managing witnesses and bystander types, they can foster an environment that enhances SUPS behaviours among nurses.
This study adhered to STROBE guidelines.
No Patient or Public Contribution.
To synthesise evidence on nurses' roles in long-term care settings and map their interactions.
Systematic review with network analysis.
Thematic synthesis was used to identify nurses' roles, and network analysis mapped their interactions across domains.
Six databases—Cumulative Index to Nursing and Allied Health Literature, PubMed, Embase, Cochrane Library, Research Information Sharing Service and Database of Periodical Information Academic—were searched for peer-reviewed articles from 2014 to 2024. The Mixed Methods Appraisal Tool assessed study quality.
Fifteen studies were included. Nurses' roles spanned six domains: collaboration, education, leadership, resident-centred care, quality improvement and resource management. Network analysis revealed collaboration and leadership as the most central, each with a degree centrality of five, acting as bridges across domains. Three thematic clusters emerged: collaboration and resource management focused on operational teamwork; leadership and quality improvement centred on systemic care enhancements; and education and resident-centered care emphasised training and resident-focused care. A technological competence gap was identified, alongside barriers like staffing shortages and role ambiguity.
Nurses' interconnected roles are critical for resident-centered care; however, they require systemic support to address barriers and technological gaps.
Enhanced interprofessional training, leadership development and digital skill integration can improve care quality and nurse well-being in long-term care settings.
This study addressed the complexity of nurses' roles in long-term care and their structural interactions, finding collaboration and leadership as pivotal with three role clusters and a technological gap, impacting long-term care nurses, educators and policymakers to inform workforce strategies.
This study adhered to the PRISMA 2020 guidelines and was preregistered in PROSPERO (CRD42024588422).
This study did not include patient or public involvement in its design, conduct or reporting.
PROSPERO: CRD42024588422
Chronic caregiving stress accelerates biological aging, reflecting disease risk and mortality; however, the underlying mechanisms are poorly understood. Epigenetic clocks, which can be estimated from levels of DNA methylation in a subset of cytosine-phosphate-guanine loci in the genome, have been proposed as a promising biological age estimator. The objectives of this scoping review are to systematically scope the literature on the effects of stress on biological ageing measured by epigenetic clocks in family caregivers of patients diagnosed with cancer.
This review will be conducted following Joanna Briggs Institute methodology based on Arksey and O’Malley’s and Levac et al’s framework and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for scoping reviews. Studies will be included if (1) the studies focus on unpaid family caregivers of patients diagnosed with cancer; (2) caregivers are adults (≥18 years of age) and (3) the study measured epigenetic clocks. The search will encompass literature and peer-reviewed literature in PubMed/MEDLINE (National Library of Medicine), Embase (Elsevier), Cochrane CENTRAL (Wiley & Sons), Web of Science: Core Collection (Clarivate Analytics), CINAHL (EBSCOhost) and PsycInfo (American Psychological Association).
Since the scoping review methodology focuses on published literature, this study does not require ethical approval. We will publish our findings in a peer-reviewed journal and plan to disseminate our work in conferences and scientific meetings.
Open Science Framework (https://doi.org/10.17605/OSF.IO/KW7RT).
Relational continuity of care (RCC) refers to the sustained therapeutic relationship between a patient and a clinician, which fosters trust, enhances communication and facilitates the accumulation of knowledge about the patient. RCC is associated with enhanced patient outcomes, reduced hospital admissions, lower mortality rates, decreased healthcare costs and improved patient experience. Despite these benefits, reorganisations within the NHS and workforce challenges have led to an increased reliance on multidisciplinary and part-time working, resulting in fragmented care and a decline in RCC. Our study aims to explore who needs RCC, under what circumstances, to what extent and why, with the goal of informing optimal implementation strategies.
We will conduct a realist review to develop an evidence-based programme theory explaining the mechanisms underlying RCC, the populations that benefit most, the contextual factors influencing RCC and effective care models. Following Pawson’s five iterative stages, we will: (1) Locate existing theories, (2) Search for relevant evidence, (3) Select appropriate articles, (4) Extract and organise data and (5) Synthesise findings to draw conclusions. A stakeholder advisory group, comprising policymakers, healthcare professionals, public contributors and patients, will be engaged throughout the process. We will adhere to Realist And Meta-narrative Evidence Synthesis: Evolving Standards (RAMESES) for realist reviews to ensure methodological rigor.
Our findings will inform practical, evidence-based recommendations for optimising RCC within general practice. Outputs will include peer-reviewed publications, conference presentations, plain English summaries, social media infographics, a short video and end-of-study events. Collaborations with stakeholders and public involvement will ensure both accessibility and impact. Ethical approval is not required for this review.
To investigate the impact of parenting stress in both fathers and mothers on the quality of life (QoL) of children with down syndrome (DS) and the mediating effect of family adaptation.
This cross-sectional study was conducted between April 2023 and August 2023.
A total of 106 father–mother dyads of children with DS aged 2–12 years in South Korea were included. The parents independently completed questionnaires assessing parenting stress, family adaptation, and their children's QoL. The Actor–Partner Interdependence Mediation Model was used for the dyadic analysis.
The direct effect of parenting stress on children's QoL was not significant; however, the indirect effect of family adaptation was significant. Fathers' parenting stress indirectly influenced their children's QoL through their own and their mothers' family adaptations. Conversely, mothers' parenting stress indirectly influenced their children's QoL through their own family adaptation, although the mediating effect of fathers was not statistically significant.
Higher family adaptation in both fathers and mothers was associated with an improved QoL in children with DS. The pathways through which parents influenced their children's QoL differed but were interdependent. Therefore, dyadic interventions aimed at improving family adaptation in both fathers and mothers may help improve the QoL of children with DS.
This is the first study to examine parental influence on children's QoL based on dyadic interactions among fathers, mothers, and children with DS. This study highlights the importance of assessing and promoting fathers' and mothers' levels of family adaptation to improve the QoL of children with DS. Nurses should consider effective dyadic interventions for families that include both parents to maximise improvements in the QoL of children with DS.
No patient or public contributions.
This study adhered to the STROBE guidelines for cross-sectional studies.
Although flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression can accurately rule out myelodysplastic neoplasms (MDS), it lacks reliability and efficiency due to the practical limitations of laboratory-developed liquid reagent-based assays. This study aimed to quantify the agreement and comparative discriminatory accuracy between a single-use flow cytometric lyophilised reagent tube (BD Lyotube Stain 468) and its laboratory-developed liquid reagent counterpart.
Cross-sectional diagnostic accuracy study of two index tests against a reference diagnosis.
A university hospital in France.
Consecutive adult patients with an indication for bone marrow aspiration due to suspected MDS and unexplained peripheral blood cytopenia.
MDS confirmed by cytomorphological evaluation of the bone marrow aspirate performed in duplicate by experienced haematopathologists blinded to the index test.
Of 103 participants enrolled between July 2020 and August 2021, 37 had MDS (prevalence, 36%). The median intra-individual robust coefficient of variation (RCV) for myeloperoxidase expression was 30.9% using the BD Lyotube Stain 468 and 31.2% using the laboratory-developed liquid reagent assay, with an intraclass correlation coefficient of 0.94 (95% CI 0.91 to 0.96). The areas under the receiver operating characteristic curves were 0.83 (95% CI 0.74 to 0.90) and 0.82 (95% CI 0.73 to 0.89), respectively. Using a prespecified threshold of 30.0%, the corresponding sensitivity estimates were 89% (95% CI 75% to 97%) and 95% (95% CI 82% to 99%).
BD Lyotube Stain 468 performs as well as its laboratory-developed liquid reagent counterpart for the quantification of myeloperoxidase expression by peripheral blood neutrophils. It may obviate the need for invasive bone marrow aspiration in up to 40% of patients with suspected MDS.
by Catherine Park, Namhee Kim, Miji Kim, Chang Won Won, Beom-Chan Lee
Falls are a critical concern in older adults with cognitive frailty (CF). However, previous studies have not fully examined whether machine learning models can predict falls in older individuals with CF. The 2-year longitudinal data set from the Korean Frailty and Aging Cohort Study and machine learning approach were utilized to predict fall risk. We analyzed multidimensional health data, including demographics, clinical conditions, as well as the physical and psychological health factors of 443 older adults with CF identified out of 2,404 older adults. For fall risk prediction, we developed a machine learning framework incorporating logistic regression, bootstrapping, and recursive feature elimination. Statistical analysis revealed significant differences between the non-faller and faller groups for nine clinical conditions as well as physical and psychological variables. Using nine significant variables, our machine-learning-based model demonstrated good predictive performance with an area under the curve (AUC) exceeding 80%. Furthermore, our machine learning framework identified four optimal variables: the number of Fried physical frailty (PF) phenotypes, PF-Mobility scores, scores from the Korean version of the Short Geriatric Depression Scale, and scores from SARC-F (consisting of five components: strength, assistance with walking, rising from a chair, climbing stairs, and experiencing falls). It demonstrated excellent predictive performance, with an AUC, sensitivity, specificity, and accuracy exceeding 95%. These variables reflect the critical association between physical and psychological health and fall risk. These findings underscore the importance of integrating multidimensional health data with machine learning methodologies to accurately predict fall risk in older adults with CF, design targeted interventions, and enable healthcare professionals to implement strategies to reduce and prevent such falls.Patients with metastatic oncogene-driven non-small cell lung cancer (NSCLC) are experiencing longer and uncertain trajectories of life-limiting illness due to advances in precision medicine. These advanced cancer survivors face new challenges related to living with uncertainty and desire more support to maximize their health and quality of life. Therefore, we developed a population-specific, blended palliative and survivorship care intervention to address the supportive care needs of patients recently diagnosed with advanced lung cancer and who are receiving targeted therapy for NSCLC with EGFR, ALK, ROS1 or RET driver mutations.
This study is a single-site, non-blinded pilot randomised controlled trial of an intervention for patients with metastatic oncogene-driven NSCLC, Patient-centred, Optimal Integration of Survivorship and palliative carE (POISE) versus usual care. POISE consists of a brief series of structured visits with a trained palliative care clinician to address coping with uncertainty, increase prognostic awareness and promote healthy lifestyle behaviours. We will recruit 60 patients from the Massachusetts General Hospital Cancer Center. Patients will be randomised into a 1:1 ratio to the intervention arm or the usual care arm. Patients randomised to the intervention arm will complete four 60 min virtual or in-person visits with a palliative care physician. The usual care arm will receive standard oncology care. Patients in both arms will complete survey assessments at enrolment, 12 weeks and 20 weeks after enrolment, and patients in the intervention group will complete an exit interview. The primary outcome measure of this trial is feasibility, which will be defined by ≥60% enrolment among eligible patients, ≥70% completion of all sessions for participants in the intervention arm and ≥70% completion of all surveys for all study participants. Exploratory outcomes include acceptability, emotional coping with prognosis, self-efficacy for chronic disease management, prognostic awareness, quality of life, anxiety, depression, intolerance of uncertainty and documentation of goals and values discussions in the electronic health record.
This study was approved by the Dana-Farber/Harvard Cancer Center’s institutional review board (protocol 20-722). The protocol is reported in accordance with the Standard Protocol Items: Recommendations for Interventional Trials guidelines, and the study will be reported in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials.
Infertility resulting from cancer treatment is known to be a major factor that reduces the quality of life of young cancer survivors. However, discussions and decision-making about fertility preservation before cancer treatment have been insufficient owing to barriers in the clinical field. In addition, selecting a fertility preservation option requires a complex decision-making process that considers not only medical information but also the patient’s values and preferences. Hence, an environment that more easily supports patient decision-making about fertility preservation needs to be created. Therefore, this protocol will develop and test a web-based decision aid (DA) for fertility preservation among young patients with cancer, considering patient preferences and values, evaluate acceptability and usability of the developed DA and assess its effectiveness.
This protocol outlines the development of a web-based DA for fertility preservation targeting females of reproductive age diagnosed with cancer. It includes alpha testing to evaluate the usability and acceptability of the DA, as well as beta testing to assess its effectiveness outside of clinical settings, both based on an online survey. The web-based DA for fertility preservation consists of three modules: 1) an information collection module, 2) an option suggestion module and 3) a value communication module. The information collection module collects information essential to select appropriate fertility preservation options. The option suggestion module returns all applicable fertility preservation options based on the patient’s characteristics, which are essential for determining the appropriate option, such as menarche status and desire for pregnancy. The value communication module provides information on the extent to which each fertility preservation option satisfies the patient’s values and preferences. After the development of the DA, a small group of young patients with cancer (n=10) and health providers (n=5) will be asked to use this web-based DA for fertility preservation and assess the acceptability and usability of this DA based on a survey (alpha-testing). By reflecting the feedback of acceptability and usability testing, the DA will be updated for improvement, and clinical field testing (beta-testing pilot trial) will be performed using the updated DA. Beta-testing will be conducted on young patients with cancer (aged 18–40 years) before they receive any curative cancer treatment (n=32). These patients with cancer will be randomly allocated to the DA group (intervention group) or the usual care group (control group). The DA group will use the web-based DA before treatment, and the control group will not have access to the web-based DA and will be asked to decide whether to consult a fertility preservation specialist. The primary outcome of the beta testing will be the level of decisional conflict, and the secondary outcomes will include knowledge, decision self-efficacy, decision readiness, depression severity, quality of life, counselling on fertility preservation and decision-making about fertility preservation. Outcomes, including decisional conflict, knowledge, decision self-efficacy, quality of life and depression severity, will be measured before the intervention (T0), 1 week after the intervention (T1) and 1 month after the intervention (T2). The readiness for decision-making will be assessed at T1 for the intervention group only. Counselling on fertility preservation and decision-making about fertility preservation will be assessed once after testing (T2) for both the intervention and control groups.
The study will be conducted in accordance with ethical standards and was approved by the Institutional Review Board at the National Cancer Centre, Korea (IRB No. NCC2024-0050). All study participants will provide written informed consent before participation. The results generated from this study will be presented at conferences or scientific meetings and disseminated through publication in a peer-reviewed journal.
NCT07038174 (beta-testing phase).
The global burden of chronic immune-mediated inflammatory diseases (IMIDs) is increasing, and rising prevalence rates significantly affect socioeconomic factors and quality of life. Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), along with ankylosing spondylitis (AS), are prominent chronic IMIDs that share overlapping pathophysiological mechanisms. Recent research has highlighted the importance of the gut microbiota in the pathogenesis of these diseases, suggesting that shared microbial dysbiosis may contribute to their development. Comprehensive research focusing on the gut and oral microbial characteristics and environmental factors is essential to elucidate the fundamental pathophysiology and develop personalised management strategies for IBD and AS. In-depth analyses and insights based on multiomics approaches are required to achieve these objectives.
This protocol describes a nationwide prospective observational study of CD, UC and AS in a Korean population. Over 5 years, we aim to recruit at least 900 patients with IBD and 200 first-degree relatives (FDRs), 500 patients with AS and 200 of their FDRs, and 2244 healthy controls. We will systematically collect clinical data and biological samples, including saliva, stool, blood and tissue biopsies, for integrative multiomics analyses focusing primarily on the microbiome. Highly advanced full-length 16S ribosomal RNA gene sequencing and shotgun metagenomics will be used to characterise the microbial composition of saliva and stool samples. Quantitative microbiome profiling will be used to address the pathological, physiological and ecological differences between microbial groups that may be masked by their relative abundance. Metabolomic analyses will be conducted on saliva, stool and plasma samples to assess functional metabolic profiles. Culturomics will be used to isolate, identify and characterise the diversity of microbial species, including rare or previously unrecognised species, to provide a comprehensive understanding of the microbiota associated with these diseases.
Ethical approval was obtained from the Ethics Committee of Kyung Hee University Hospital, Hanyang University Hospital, Kangbuk Samsung Hospital, Yeungnam University Hospital, Kyungpook National University Hospital, Chonnam National University Hospital, Wonkwang University Hospital, Catholic University Daejeon St. Mary’s Hospital, Soon Chun Hyang University Hospital Cheonan, Chung-Ang University Hospital, Inje University Haeundae Paik Hospital, Dankook University Hospital, Hanyang University Guri Hospital, Kyung Hee University Hospital at Gangdong, Chung-Ang University Gwangmyeong Hospital and Keimyung University Dongsan Hospital. Our research team will provide detailed information about the study, including an information sheet explaining its aims and procedures, prior to enrolment. Prospective participants will be informed that they have the right to withdraw from the study at any time, without penalty. Participants will be assured of the anonymity and confidentiality of any data they provide throughout the study, using participant numbers and the storage of sensitive data in locked cabinets. Participants will be enrolled in the study only after providing written informed consent to the research staff. The results of this study will be disseminated to healthcare and academic professionals through publications in peer-reviewed journals and presentations at international conferences.
This prospective observational study is registered at ClinicalTrials.gov ((ID: NCT06124833, data first posted: 9 November 2023); (ID:
To explore surrogate decision-making practices regarding end-of-life care for people with dementia in Korean long-term care hospitals from the perspective of healthcare providers.
A qualitative descriptive study.
The data were collected through individual semi-structured interviews with 24 healthcare providers (physicians, oriental medicine doctors, registered nurses and social workers) involved in dementia end-of-life care in their current long-term care hospitals in South Korea. The data were analysed using a conventional content analytic technique.
The analysis yielded three categories and nine subcategories describing surrogate decision-making practices regarding end-of-life care for people with dementia: (a) typical circumstances of end-of-life care planning, (b) expected roles of key personnel and related challenges and (c) important considerations. Participants discussed available treatment options within long-term care hospitals and the potential transfers to acute care hospitals during admission and periods of health decline. Physicians typically led such end-of-life care planning, with nurses playing a supportive role and family members making the final decisions. However, they faced challenges in performing their roles. In end-of-life care discussions, participants weighed the patients' autonomy and best interests alongside family members' interests and other external concerns such as potential lawsuits and insufficient medical resources.
Surrogate decision-making regarding end-of-life care in the context of dementia within long-term care hospitals is considerably complex and challenging for healthcare providers, requiring multifaceted institution-sensitive support.
The study findings suggest the need for targeted education and training to enhance healthcare providers' competencies in end-of-life care discussions, advance care planning and the development of policies and regulations supporting end-of-life care-related practices within long-term care hospitals.
This study was reported in accordance with the COREQ checklist.
No patient or public contribution.
by Jun Sang Yoo, Jae Hyun Choi, Jae Young Park, Jeong Yun Song, Jun Young Chang, Dong-Wha Kang, Sun U. Kwon, Hang Jin Jo, Bum Joon Kim
BackgroundLipohyalinotic degeneration (LD) and branch atheromatous disease (BAD) can contribute to subcortical infarctions in the lenticulostriate artery (LSA) territory. This study aimed to identify the association between the proximal and distal middle cerebral artery (MCA) diameter ratio and the two different pathomechanisms of LSA infarction.
MethodsPatients with acute LSA infarctions categorized as small vessel occlusive disease were included. Demographic and clinical data, along with MCA geometrical variables, were collected. LD and BAD were differentiated based on the length of the infarction diameter and number of axial slices. The proximal/distal M1 diameter ratio was calculated. MCA geometrics between LD and BAD were compared. Independent factors associated with LD were investigated. Computational fluid dynamics (CFD) analysis was used to evaluate hemodynamic parameters.
ResultsA total of 117 patients were included, of whom 64 (54.7%) and 53 (45.3%) were classified as BAD and LD, respectively. LD was associated with hypertension and favorable prognosis. MCA geometric variables revealed that LD had a higher proximal/distal M1 diameter ratio, indicating a potential distinguishing factor. Multivariate analysis confirmed the independent association between LD and the proximal/distal M1 diameter ratio. The proximal/distal M1 diameter ratio also showed a positive correlation with the number of ipsilesional lacunes. CFD analysis showed that the LD model had faster, greater blood influx into LSAs and higher wall shear stress and pressure gradient compared with the BAD model.
ConclusionsThis study suggests MCA geometry, particularly the proximal/distal M1 diameter ratio, may serve as an independent factor for identifying LD.
by Nicole K. Polinski, Jukka Puoliväli, Leena Rauhala, Taina-Kaisa Stenius, Timo Bragge, Teija Parkkari, Anna-Maija Penttinen, Yi Chen, Omar S. Mabrouk, Kelly E. Glajch, Warren D. Hirst, Michael Perkinton, Terina N. Martinez, Mark A. Frasier
Alpha-synuclein (aSyn) is linked to Parkinson’s disease (PD) through SNCA genetic mutations, phosphorylated aSyn in Lewy bodies and Lewy neurites, and most recently through evidence of aSyn aggregation in patient spinal fluid using the aSyn seed amplification assay. Therefore, understanding the biology of this protein and developing therapeutic interventions targeting pathological processing of aSyn are a key area of focus for novel treatments to slow or stop PD. Reliable preclinical models are imperative for these efforts. To this end, we developed a novel model using CRISPR/Cas9 to humanize the regions surrounding the naturally occurring threonine 53 amino acid in the Sprague Dawley rat to generate a humanized A53T aSyn rat model (aSyn A53T KI). We also generated an Snca knockout (aSyn KO) line to pair with the humanized A53T aSyn rat line to confirm that phenotypes were not due to loss of endogenous rat aSyn protein. A systematic phenotyping study was performed on these lines, assessing PD-related pathology and phenotypes at multiple timepoints. The aSyn KO rat line was profiled at 6 and 12 months of age, revealing successful aSyn protein knockout. The aSyn A53T KI model was profiled at 4, 8, 12, and 18 months of age for motor and non-motor phenotypes, nigrostriatal degeneration, and brain pathology. We confirmed the aSyn A53T KI rat expresses human aSyn while lacking endogenous rat aSyn. Motor function and non-motor function remain largely unaffected in this model, and no overt nigrostriatal degeneration or brain pathology are observed up to 18 months of age. Although the aSyn A53T KI rat lacks the ability to model PD pathology and phenotypes at baseline, it is an ideal model for investigating the impact of exogenous synuclein aggregates or environmental triggers on human aSyn in an in vivo model system.While digital technologies can increase the availability and access to evidence-based interventions, little is known about how users engage with them and the mechanisms associated with effective outcomes. Process evaluations are an important component in understanding the aforementioned factors. The ‘SPARX-UK’ study is a randomised controlled pilot and feasibility trial evaluating personalised human-supported (from an ‘eCoach’) vs a self-directed computerised cognitive behavioural therapy intervention (cCBT), called SPARX (Smart, Positive, Active, Realistic, X-factor thoughts), aimed at adolescents with mild to moderate depression. We are comparing supported vs self-directed delivery of SPARX to establish which format should be used in a proposed definitive trial of SPARX. The control is a waitlist group. We will conduct a process evaluation alongside the trial to determine how the intervention is implemented and provide context for interpreting the feasibility trial outcomes. We will also look at the acceptability of SPARX and how users engage with the intervention. This protocol paper describes the rationale, aims and methodology of the SPARX-UK trial process evaluation.
The process evaluation will use a mixed-methods design following the UK Medical Research Council’s 2015 guidelines, comprising quantitative and qualitative data collection. This will include analysing data usage of participants in the intervention arms; purposively sampled, semi-structured interviews of adolescents, parents/guardians, eCoaches and clinicians/practitioners from the SPARX-UK trial; and analysis of qualitative comments from a survey from those who dropped out early from the trial. Quantitative data will be analysed descriptively. We will use thematic analysis in a framework approach to analyse qualitative data. Quantitative and qualitative data will be mixed and integrated to provide an understanding of how the intervention was implemented and how adolescents interacted with the intervention. This process evaluation will explore the experiences of adolescent participants, parents/guardians, eCoaches and clinicians/practitioners in relation to a complex digital intervention.
Ethical approval was granted by the National Health Service (NHS) Health Research Authority South West - Cornwall & Plymouth Research Ethics Committee (Ethics Ref: 22/SW/0149).
Contextualising how the intervention was implemented, and the variations in uptake and engagement, will help us to understand the trial findings in greater depth. The findings from this process evaluation will also inform the decision about whether and how to proceed with a full randomised controlled trial, as well as the development of more effective interventions which can be personalised more precisely via varying levels of human support. We plan to publish the findings of the process evaluation and the wider project in peer-reviewed journals, as well as disseminate via academic conferences.
ISRCTN: ISRCTN15124804. Registered on 16 January 2023,
by Tremaine B. Williams, Pearman Parker, Milan Bimali, Maryam Y. Garza, Alisha Crump, Taiquitha Robins, Emel Seker, Ava Storey, Allison Purvis, Mya Tolbert, Anthony Drake, Taren Massey Swindle, Kevin Wayne Sexton
African Americans experience approximately 2.5 times more heart failure hospitalizations than Caucasians and the complexity of heart failure requires registered nurses to work in collaboration with other types of healthcare professionals. The purpose of this study was to identify care team configurations associated with long lengths of hospital stay in African Americans with heart failure hospitalizations and the related effect of the presence of registered nurses on their length of hospital stay. This study analyzed electronic health record data on the heart failure hospitalizations of 2,274 African American patients. Binomial logistic regression identified the association between specific care team configurations and length of stay among subgroups of African American patients. Of the significant team configurations, a Kruskal-Wallis H test and linear regression further assessed the team composition and the specific change in days associated with a one-unit change in the number of registered nurses on a patient’s care team. Six team configurations were associated with a long length of stay among all African Americans regardless of age, sex, rurality, heart failure severity, and overall health severity. The configurations only differed significantly in the proportion of registered nurses with respect to other care team roles. An increase in one additional registered nurse on a care delivery team was associated with an increase in length of stay of 8.4 hours (i.e., 504 minutes). Identifying the full range of social and technical care delivery tasks performed by RNs, and controlling for their effect on length of stay, may be a key strategy for reducing length of stay and explaining why these six configurations and RNs are associated with long LOS. The identification of these models can be used to support decision-making that optimizes the availability of patient access to high-quality care (e.g., clinical staffing and supplies).Several studies suggested that short-term variations in out-of-hospital cardiac arrest (OHCA) might be associated with the day of the week and holidays. However, most existing findings were based on Western countries, outdated data (the 1990s or 2000s) and analytical methods that could not control potential confounders.
Case time-series design.
The national OHCA surveillance (a population-level surveillance system operated by the Korea Disease Control and Prevention Agency) from 2015 to 2019.
A total of 89 164 cardiac-origin OHCA cases.
Not applicable.
Cardiac-origin OHCA incidents (primary) and fatality of the OHCA incidents (secondary).
We found that Mondays (relative risk (RR): 1.019 with 95% CI: 1.009 to 1.029) and Sunday (RR: 1.015 with 95% CI: 1.005 to 1.025) had the highest risk of OHCA incidence compared with other weekdays. Holidays showed a higher association with increased OHCA risks than non-holidays. Higher RRs were observed on Christmas (RR: 1.096 with 95% CI: 1.063 to 1.129) and Lunar New Year’s Day (RR: 1.082 with 95% CI: 1.060 to 1.104) compared with non-holidays. These patterns by the day of the week and holidays were heterogeneous by age, sex and urbanicity level.
This study provides epidemiological evidence of the association of the day of the week and holidays with OHCA incidents in South Korea, using national surveillance data and state-of-the-science statistical methods. Our findings could contribute to the implications for more targeted action plans and public health resource mobilisation against OHCA.