Conectar
Current guideline-recommended antibiotic treatment durations for ventilator-associated pneumonia (VAP) are largely standardised, with limited consideration of individual patient characteristics, pathogens or clinical context. This one-size-fits-all approach risks both overtreatment—promoting antimicrobial resistance and adverse drug events—as well as undertreatment, increasing the likelihood of pneumonia recurrence and sepsis-related complications. There is a critical need for VAP-specific biomarkers to enable individualised treatment strategies. The Ventilator-associated pneumonia Biomarker Evaluation (VIBE) study aims to identify a dynamic alveolar biomarker signature associated with treatment response, with the goal of informing personalised antibiotic duration in future clinical trials.
VIBE is a prospective, observational, case-cohort study of 125 adult patients with VAP in Michigan Medicine University Hospital intensive care units. Study subjects will undergo non-bronchoscopic bronchoalveolar lavage on the day of VAP diagnosis (Day 1) and then on Days 3 and 5. Alveolar biomarkers (quantitative respiratory culture bioburden, alveolar neutrophil percentage and pathogen genomic load assessed via BioFire FilmArray polymerase chain reaction) will be assessed. An expert panel of intensivists, blinded to biomarker data, will adjudicate each patient’s Day 10 outcome as VAP clinical cure (control) or treatment failure (case). Absolute biomarker levels and mean-fold changes in biomarker levels will be compared between groups. Data will be used to derive a composite temporal alveolar biomarker signature predictive of VAP treatment failure.
Ethical approval was obtained from the University of Michigan Institutional Review Board (IRB #HUM00251780). Informed consent will be obtained from all study participants or their legally authorised representatives. Findings will be disseminated through peer-reviewed publications, conferences and feedback into clinical guidelines committees.
by Shiella A. Soetomo, Michael F. Sharp, Wayne Crismani
Synthetic lethality describes a genetic relationship where the loss of two genes results in cell death, but the loss of one of those genes does not. Drugs used for precision oncology can exploit synthetic lethal relationships; the best described are PARP inhibitors which preferentially kill BRCA1-deficient tumours preferentially over BRCA1-proficient cells. New synthetic lethal targets are often discovered using genetic screens, such as CRISPR knockout screens. Here, we present a competitive co-culture assay that can be used to analyse drugs or gene knockouts with synthetic lethal effects. We generated new BRCA1 isogenic cell line pairs from both a triple-negative breast cancer cell line (SUM149) and adapted pre-existing non-cancerous BRCA1 isogenic pair (RPE). Each cell line of the isogenic pair was transformed with its own fluorescent reporter. The two-coloured cell lines of the isogenic pair were then grown together in the same vessel to create a more competitive environment compared to when grown separately. We used four PARP inhibitors to validate the ability to detect synthetic lethality in BRCA1-deficient cancer cells. The readout of the assay was performed by counting the fluorescently coloured cells after drug treatment using flow cytometry. We observed preferential targeting of BRCA1-deficient cells, by PARPi, at relative concentrations that broadly reflect clinical dosing. Further we reveal subtle differences between PARPi resistant lines compared to BRCA1-proficient cells. Here, we demonstrate the validation and potential use of the competitive assay, which could be extended to validating novel genetic relationships and adapted for live cell imaging.To co-produce a prototype intervention to help nurses improve the assessment and care of the sexual health needs of men with inflammatory bowel disease.
Inflammatory bowel disease can have a significant impact on the sexual health and well-being of men, but has largely been neglected in research and clinical guidelines. Men with the disease report that sexual health is not discussed during consultations, while healthcare practitioners describe a lack of confidence to initiate sexual health assessments. At present, no evidence-based tool exists to support nurses in detecting, assessing, and providing care for the sexual health of men with the disease.
A mixed-methods study shaped by phase 1 of the Medical Research Council's framework for the development of complex interventions.
(1) Cross-sectional surveys of (i) men with inflammatory bowel disease, (ii) nurses, and (iii) inflammatory bowel disease services to determine the current state of sexual health provision across the UK National Health Service. (2) Semi-structured interviews with men and the partners of men with IBD and asynchronous focus groups with health professionals to explore appropriate and acceptable ways to provide sexual healthcare. (3) Three consecutive co-production workshops inclusive of men with the disease, healthcare professionals, and stakeholders to formulate a prototype intervention.
This study will create an evidence-based prototype intervention that will provide nurses with the knowledge and skills required to effectively assess the sexual health needs of men with inflammatory bowel disease and provide appropriate, patient-centred care.
The study design was supported by a patient group. The study delivery will be supported by a patient co-investigator and stakeholder group inclusive of men with lived experience of the disease.
This report adheres to the SPIRIT 2013 checklist for standard protocol items for clinical trials.
clinicaltrials.gov ID: NCT06562751
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).Sympathetic dysfunction in skin is well known in diabetic peripheral neuropathy. This produces dry, cracked, peeling skin susceptible to infection and also epidermal microcirculation insufficiency. Impaired autonomic neurovascular control opens dermal arterio-venous anastomoses and shunts microcirculation away from the epidermis and impairs skin oxygenation and nutrition. Few recognise that diabetic neuropathy includes swelling-induced entrapment neuropathy. Multiple peripheral nerves, swollen by the secondary polyol metabolic pathway, suffer local compressions at fibro-osseous tunnels. This includes the C-fibres controlling autonomic functions which constitute most of the nerve axons. No current standard of care therapy addresses the sympathetic-regulated neurovascular impairment of skin microcirculation in diabetes. Epineurolysis surgery for peripheral nerve decompression relieves local axonal compressions and generates recovery of sub-epidermal capillary flow. Clinical and animal diabetes studies have demonstrated objective improvements to epidermal hypoxia, demyelination and axonal histology. Seven surgery studies find an average 1.39% recurrence and zero amputations after prior Risk Class 3 wound healing in a mean of 1.78 years of follow-up. Deficits of electrophysiology, transcutaneous oxygenation and vasa nervorum circulation also improve. Surgically improved microcirculation is physiology-based. Nerve decompression minimises diabetic peripheral neuropathy, avoids initial diabetic foot ulcers, promotes neuropathic diabetic foot ulcer healing and minimises ulcer recurrences and subsequent amputation. The observational studies of these important benefits suggest wide application to the complications of diabetes neuropathy and beg for academic attention to Level 1 EBM confirmation.
The aim of this study was to (i) identify barriers and enablers and (ii) inform mitigating or strengthening strategies for implementing nurse-initiated care protocols at scale in emergency departments (EDs).
Embedded mixed methods.
The study included four clusters with a total 29 EDs in NSW, Australia. Concurrent quantitative and qualitative data were collected via electronic nursing and medical staff surveys and analysed. Barriers and enablers to implementation were identified and mapped to the domains of the Theoretical Domains Framework (TDF). Selection of intervention functions and behaviour change techniques (BCTs) enabled development of implementation strategies.
In total, 847 responses from nursing and medical staff (43%) reported four enablers for use and implementation: (i) knowing or being able to learn to use simple nurse-initiated care; (ii) protocols help staff remember care; (iii) carefully considered education programme with protected time to attend training; and (iv) benefits of nurse-initiated care. Nine barriers were identified: (i) lack of knowledge; (ii) lack of skills to initiate complex care (paediatric patients, high-risk medications and imaging); (iii) risk for inappropriate care from influence of cognitive bias on decision-making; (iv) punitive re-enforcement; (v) protocols that are too limited, complex or lack clarity; (vi) perceived lack of support from medical or management; (vii) perception that tasks are outside nursing role; (viii) concern nurse-initiated care may increase the already high workload of medical and nursing staff; and (ix) context. The barriers and enablers were mapped to nine TDF domains, five intervention functions and 18 BCTs informing implementation using strategies, including an education programme, pre-existing videos, audit and feedback, clinical champions and an implementation plan.
A rigorous, systematic process generated a multifaceted implementation strategy for optimising nurse-initiated care in rural, regional and metropolitan EDs.
Staff wanted safe interventions that did not lead to increased workload. Staff also wanted support from management and medical teams. Common barriers included a lack of knowledge and skill in advanced practice. Clinicians and policymakers can consider these barriers and enablers globally when implementing in the ED and other high-acuity areas. Successful strategies targeting barriers to advanced practice by emergency nurses can be addressed at the local, state and national levels.
Implementation of new clinical practices in the ED is complex and presents challenges. Key barriers and enablers, including those related to initiating care and workloads in the ED were identified in this study. This research broadly impacts ED staff and policymakers globally.
Mixed Methods Reporting in Rehabilitation & Health Sciences (MMR-RHS).
Site senior nurse researchers for each cluster worked closely with site stakeholders, including local consumer groups. Consumer councils were engaged at all the sites. Site visits by the research nurses have been an important strategy for discussing the study with key stakeholders.
Australian and New Zealand Clinical Trial: ACTRN12622001480774p
To evaluate the effects of exergaming on physical frailty in older adults.
Systematic review with meta-analysis.
Six electronic databases were searched for randomised controlled trials evaluating the effects of exergaming on frailty in older adults. Data were synthesised using narrative synthesis and meta-analysis. The risk of bias and the certainty of the evidence were assessed.
CINAHL, Cochrane Library, Embase, PubMed, Web of Science, and China Academic Journal Network Publishing Database were searched from their inception through February 2024.
Five studies (n = 391) were included. Exergaming, which was delivered in 20–36 sessions over 8–12 weeks, resulted in improvements in frailty scores and indices, frailty status, and frailty phenotypes, including exhaustion, low physical activity levels, gait speed, and muscle weakness over time. There was no effect on unintentional weight loss. Meta-analyses showed that the effects of exergaming were not significantly different from those observed in the control groups. The rate of adherence to the intervention of the exergaming group was slightly higher than that of the comparison group (87.3%–87.7% vs. 81.1%–85.4%). The overall risk of bias was high in all studies. The certainty of the evidence was very low.
Exergaming exerts effects on frailty comparable to those of conventional physical exercises. Participants appeared to have better adherence to exergaming. Future studies with robust designs are warranted.
With effects comparable to those of conventional physical exercises, exergaming could be considered in clinical settings to address frailty.
This review addressed the effects of exergaming on frailty instead of physical outcomes. Exergaming was comparable to conventional physical exercises in improving frailty scores and indices, frailty status, and four frailty phenotypes. The findings provide insights to healthcare providers on the design of exergames.
PRISMA guidelines.
PROSPERO number: CRD42023460495.
No Patient or Public Contribution.
by Anja Arner, Andreas Ettinger, Bradley Wayne Blaser, Bettina Schmid, Irmela Jeremias, Nadia Rostam, Vera Binder-Blaser
Acute lymphoblastic leukemia (ALL) is the most common type of malignancy in children. ALL prognosis after initial diagnosis is generally good; however, patients suffering from relapse have a poor outcome. The tumor microenvironment is recognized as an important contributor to relapse, yet the cell-cell interactions involved are complex and difficult to study in traditional experimental models. In the present study, we established an innovative larval zebrafish xenotransplantation model, that allows the analysis of leukemic cells (LCs) within an orthotopic niche using time-lapse microscopic and flow cytometric approaches. LCs homed, engrafted and proliferated within the hematopoietic niche at the time of transplant, the caudal hematopoietic tissue (CHT). A specific dissemination pattern of LCs within the CHT was recorded, as they extravasated over time and formed clusters close to the dorsal aorta. Interactions of LCs with macrophages and endothelial cells could be quantitatively characterized. This zebrafish model will allow the quantitative analysis of LCs in a functional and complex microenvironment, to study mechanisms of niche mediated leukemogenesis, leukemia maintenance and relapse development.The purpose of this study was to generate a conceptual definition and theory of grief for nurses working on the frontlines during the COVID-19 pandemic using grounded theory methodology.
The COVID-19 pandemic has had a negative impact on nurses working on the frontlines. The increasing flow of diagnosed COVID-19 cases, diverse unknowns and demands in the treatment of patients with COVID-19, and depression related to countless deaths can trigger grief experiences.
A mixed methods approach, including the qualitative method of grounded theory and a quantitative 30-question survey, was used in this study.
Eight focus group sessions were conducted with registered nurses working on the frontlines during the pandemic. Sessions were audio recorded and analysed using constant comparative data analysis. Following the interviews, a survey including demographics and self-report inventories was completed by participants. The COREQ checklist was used to assess study quality.
Major concepts that emerged include ‘facing a new reality’, ‘frustrations’, ‘stress’ and ‘coping’. Core concepts were combined into a conceptual definition of grief and a grounded theory of the experience of nurses working on the frontlines during the pandemic. Cross comparisons of qualitative and quantitative findings were made and compared with the literature.
This study provides a better understanding of the grief experience of nurses working on the frontlines during the COVID-19 pandemic. It is necessary to recognise professional grief and develop intervention strategies that lead to grief reconciliation.
Findings provide useful insights for healthcare administrators to provide support and develop interventions to reduce frustrations and stress of frontline registered nurses.
This study design involved registered nurses participating in focus group sessions. Participants detailed their experience working on the frontlines of the COVID-19 pandemic with patients, family and hospital administration.
FreshRSS 