Knowledge translation in Anglo-American paramedicine: a scoping review

OBJECTIVE: To map what is currently known about knowledge translation (KT) in Anglo-American paramedicine. The review focuses on reported barriers and facilitators to the implementation of new knowledge, and the use of models, theories and frameworks to guide implementation practice. DESIGN: Scoping review reported as per both the Joanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews reporting guidelines. DATA SOURCES: CINAHL (EBSCO Host) and Medline (OVID interface) were searched from January 2000 to May 2023. Reference lists of all included papers were reviewed, and several key professional journals were hand-searched. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Primary sources that focused on KT models, theories or frameworks, or barriers and facilitators to KT implementation, involving paramedics or Emergency Medical Technicians (Paramedic in America) working in an out-of-hospital, Anglo-American Emergency Medical Service (EMS) system were eligible for inclusion. DATA EXTRACTION AND SYNTHESIS: One reviewer used a data extraction template developed for this review and 10% of the papers were checked by the second author. Findings were summarised in tables and synthesised both quantitatively and qualitatively. RESULTS: The search yielded 1268 primary sources, of which 48 were included in the review. Thirty-two papers examining KT interventions and 16 papers examining the barriers and facilitators to KT were found. Only one randomised controlled trial was found, and only one paper made explicit use of any KT framework. Overall, eight themes describing barriers and facilitators to KT arose from the qualitative literature, with clinicians' perception of the evidence being the dominant theme. All 32 papers describing KT interventions included some form of educational intervention. CONCLUSIONS: Overall, there is little depth and breadth in the literature, with many papers focusing on trauma and airway management. There are large gaps in the evidence surrounding the use of KT theories and frameworks in Anglo-American EMS. Further research is needed to identify appropriate KT models and frameworks that are contextualised to EMS to ensure that paramedic-led research finds its way to the clinicians needing to use it.This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial.This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial

Correction: HELLO: a protocol for a cluster randomized controlled trial to enhance interpersonal relationships and team cohesion among ICU healthcare professionals

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Impact of rapid genomic testing on clinical outcomes of acutely unwell children presenting with severe epilepsy

About 30% of epilepsy patients remain unresponsive to standard antiseizure treatment. Increasing evidence suggests that genetic epilepsies may respond better to targeted management. In this study, we therefore evaluate the therapeutic benefits of rapid genetic testing in children with severe epilepsy. METHODS: the clinical data of patients with epilepsy referred for rapid whole-exome sequencing were systematically collected at two large paediatric/neurogenetic centres (Birmingham/Oxford) in the United Kingdom over 3 years (2019-2022), with follow-up at 12 months post-diagnosis. The demographics, diagnostic yield, management by gene function and seizure group (SZ-seizures only or SZ+ seizures with co-morbidities) were explored. RESULTS: among the 106 eligible patients, the age at testing ranged from 0 to 16 years with a median of 7 months. Underserved ethnic groups, e.g., British Asians and Black British, were well-represented. Thirty-nine genes affecting 49 patients were identified, giving an overall diagnostic yield of 46%, which was further enhanced to 51% (31/61) in the SZ+ group. Twenty percent of genes identified affect ion channels and patients were more likely to present early (<6 months old) and respond to a gene-directed treatment (p = 0.004483). Seizures secondary to metabolic disorders responded to bespoke therapy. A fifth (22/106) of tested patients and 45% (22/49) of those diagnosed had their management impacted. At the 12-month follow-up, 9/15 (60%) patients remained seizure-free following gene-targeted management. CONCLUSION: this study demonstrates high diagnostic yield and significant therapeutic benefit from rapid genetic testing in patients with epilepsy. The gene function categories were statistically significant predictors of management change.CC BY 4.0 (Creative Commons Attribution

UK clinical practice guidelines for the management of patients with constitutional POT1 pathogenic variants

Constitutional or germline pathogenic variants (GPVs) in protection of telomeres 1 (POT1) are associated with a variety of tumours resulting in the recognition of POT1-tumour predisposition syndrome (POT1-TPDS). These tumours may include cutaneous melanoma, angiosarcoma, haematological malignancy and brain tumours. Due to the rarity of POT1 GPVs and limited available data, the overall lifetime cancer risks for individuals with POT1-TPDS are unclear. Furthermore, there is scant evidence to support the role of surveillance in early cancer detection in this patient group. A recent international publication suggested a surveillance protocol similar to that used in Li-Fraumeni Syndrome (LFS) could be offered to POT1 pathogenic variant carriers, particularly where there are LFS-like features. However, current evidence for POT1-TPDS is not supportive of an equivalent lifetime cancer risk. Given the inclusion of POT1 in the National Test Directory in England and the need for UK-based guidance, an expert group undertook a literature review to assess the phenotypic spectrum of POT1-TPDS and to provide lifetime risk estimates of POT1-associated cancers. The available evidence was shared with a small working group of experts that included clinical geneticists, dermatologists, sarcoma specialists, haematologists and radiologists to cover all aspects of the cancers most commonly associated with POT1-TPDS. Following structured expert group discussions, we achieved consensus on best practice recommendations for a POT1-TPDS UK management protocol.CC BY 4.0 (Creative Commons Attribution

Meta-Analysis of Cardiovascular Efficacy of Empagliflozin Versus Dapagliflozin in Type 2 Diabetes: Unveiling Key Insights

The favorable safety profile of sodium-glucose cotransporter 2 inhibitors, notably empagliflozin and dapagliflozin, makes them a suitable treatment option for type 2 diabetes. However, the comparative cardiovascular (CV) benefits of empagliflozin versus dapagliflozin require further investigation. A comprehensive search of electronic databases was conducted from inception till November 7, 2024. Studies reporting CV outcomes of empagliflozin and dapagliflozin were included in the meta-analysis. The random-effects model was used to pool the risk ratio (RR) along with the corresponding 95% confidence intervals (CIs) for all outcomes. We pooled 8 studies with a total of 428,940 participants. The evaluation of pooled results demonstrated that empagliflozin was associated with a nonsignificant association in reducing all-cause death (RR: 0.91, 95% CI: 0.68-1.20), CV death (RR: 1.12, 95% CI: 0.81-1.55), major adverse cardiovascular events (RR: 1.03, 95% CI: 0.86-1.23), myocardial infarction (RR: 1.01, 95% CI: 0.84-1.22), stroke (RR: 0.90, 95% CI: 0.79-1.04), and heart failure-related events (RR: 1.07, 95% CI: 0.87-1.32). This study does not suggest a clear CV benefit of using empagliflozin over dapagliflozin, or vice versa, as an add-on therapy for type 2 diabetes. If both medications have similar safety profiles, differences in their costs are likely to impact their cost-effectiveness in CV risk reduction.Unknow

Interleukin-1β Stimulates Matrix Metalloproteinase 10 Secretion: A Possible Mechanism in Trophoblast-Dependent Spiral Artery Remodeling

Maternal uterine spiral arteries (SpA) undergo significant structural changes in early pregnancy, resulting in increased blood flow to the developing fetus. Endothelial cells (EC) and vascular smooth muscle cells (VSMC) are lost from the SpA wall and are replaced by trophoblasts. We have previously shown that matrix metalloproteinase 10 (MMP-10) and Heparin binding-EGF like growth factor (HB-EGF) gene expression is increased in a 3D EC/VSMC co-culture system in response to trophoblast secreted factors. This study investigated trophoblast mediated MMP-10 and HB-EGF expression and determined if there was a relationship between the secretion of MMP-10 and the release of soluble HB-EGF (sHB-EGF) from EC. MMP-10 was widely expressed in first trimester decidual tissue including trophoblast, and EC, but not VSMC. MMP-10 expression was significantly lower in decidual tissue from pregnancies at increased risk of developing pre-eclampsia compared to low-risk pregnancies. In vitro, SGHEC-7 cells, a human EC line, but not SGHVMC-9, a human VSMC cell line, secreted MMP-10 in response to trophoblast conditioned medium (TCM). TCM contains several growth factors and cytokines, but only interleukin-1β (IL1β) significantly stimulated MMP-10 secretion by SGHEC-7 cells. Interleukin-1 receptor antagonist (IL-1Ra) significantly inhibited TCM-induced MMP-10 secretion. Interrogation of intracellular pathways established the involvement of MEK and JNK in TCM and IL-1β stimulated MMP-10 secretion. Although IL-1β also significantly increased sHB-EGF, inhibition of MMP-10 activity using a broad spectrum MMP inhibitor had no effect on sHB-EGF. Western blot analysis indicated that MMP-10 secreted by EC in response to IL-1β stimulation was the enzymatically inactive pro form.CC BY 4.0 (Creative Commons Attribution

Higher surgeon volume reduces early failure in first time revision of non-infected total knee arthroplasty: An analysis using data from the United Kingdom National Joint Registry

PURPOSE: Revision total knee replacement (RevKR) is an increasingly common procedure. It is hypothesised that higher surgical volume is linked to lower levels of adverse outcomes. The aim was to estimate the association of surgical volume on patient outcomes following first single-stage RevKR for non-infected indications. METHODS: This population-based cohort study used data from the United Kingdom National Joint Registry, Hospital Episode Statistics and National Patient Reported Outcome Measures. Patients undergoing procedures between 1 January 2009 and 30 June 2019 were included. The primary outcome measure was re-revision within 2 years; chosen to reflect the quality of the surgical provision. Fixed effect multivariable regression models were used to examine the association between surgeon and surgical unit annual caseload and the risk of adverse outcomes. RESULTS: A total of 8695 patients underwent first time single stage revision for aseptic loosening, instability, or malalignment across 389 surgical units and 1204 surgeons. Following adjustment for age, gender, ASA grade, year of surgery and operation funder, higher surgeon volume was associated with a lower risk of re-revision at 2 years. The risk of re-revision decreased amongst surgeons performing ≥9 annual revisions (OR 0.77, 95% CI 0.62-0.95, p-value = 0.02) compared to those performing <9 annual revisions. CONCLUSIONS: Annual surgeon case volume of ≥9 first single-stage RevKR for non-infected indications is independently associated with reductions in early re-revision. This evidence supports the setting of minimum volume targets to improve outcomes for patients. LEVEL OF EVIDENCE: Level III, retrospective cohort study of prospectively collected data.CC BY 4.0 (Creative Commons Attribution

Understanding Infection, Viral Exacerbation and Respiratory Symptoms at Admission-Longitudinal (UNIVERSAL) study: a prospective observational cohort study protocol

BACKGROUND: Respiratory viral infections (RVIs) are a significant cause of morbidity and hospital admission worldwide. However, the management of most viral infection-associated diseases remains primarily supportive. The recent COVID-19 pandemic has underscored the urgent need for a deeper understanding of RVIs to improve patient outcomes and develop effective treatment strategies. The Understanding Infection, Viral Exacerbation and Respiratory Symptoms at Admission-Longitudinal Study is an observational study which addresses this need by investigating the heterogeneity of RVIs in hospitalised adults, aiming to identify clinical and biological predictors of adverse outcomes. This study aims to bridge critical knowledge gaps in the clinical course and the economic impact of RVIs by characterising the phenotypic diversity of these infections and their recovery patterns following hospital admission and thus assisting with the optimal design of future interventional studies. METHODS AND ANALYSIS: This prospective longitudinal observational study (V.6, 20 September 2023) will be conducted across multiple UK secondary care sites from August 2022 onwards, with an aim to enrol 1000 participants testing positive for RVI. Adults admitted with respiratory symptoms who test positive for RVIs via the BioFire® FilmArray® System or other validated diagnostic PCR tests will be enrolled. The data collected include patient demographics, clinical history, comorbidities and symptoms experienced prior to, during and after hospitalisation with follow-up after discharge at weeks 1, 2, 4, 8, 12 and 26. In addition, biological samples are collected at multiple time points during the hospital stay. The primary endpoints are to study the impact of different RVIs and identify predictors of disease progression and length of stay. Secondary endpoints include time to recovery and healthcare cost. Exploratory endpoints focus on biomarker profiles associated with virus type and clinical outcomes. ETHICS AND DISSEMINATION: The study protocol received ethical approval from the relevant committees (English Ethics Reference Number: 22/WM/0119; Scottish Ethics Reference Number: 22-SS-0101, 20/09/2023). For patients who lack the capacity to consent, the study complies with the Mental Capacity Act 2005, using a consultee process where a family member, carer or an independent clinician may provide assent on behalf of the patient. Data from all the study centres will be analysed together and disseminated through peer-reviewed journals, conference presentations and workshops. The study group will ensure that participants and their families are informed of the study findings promptly and in an accessible format. TRIAL REGISTRATION NUMBER: ISRCTN49183956.CC BY 4.0 (Creative Commons Attribution

Directed acyclic graphs to minimise bias and optimise causal inference in SNAP-3: an observational cohort study of frailty, multimorbidity, and delirium in older surgical patients

BACKGROUND: The 3rd Sprint National Anaesthesia Project (SNAP-3) aims to describe the impact of frailty, multimorbidity, and delirium, and their management, on outcomes after surgery within the older surgical population. Causal diagrams, such as directed acyclic graphs (DAGs), are a useful tool for visually representing relationships between variables and for clarifying the causal assumptions underlying a chosen statistical model. METHODS: A description of how the SNAP-3 cohort study's DAGs were developed is provided. DAGs have been created for the exposure-outcome relationships between frailty, multimorbidity, and delirium (as an exposure) with postoperative outcomes (length of hospital stay, delirium, morbidity, mortality). DAGs were created following the approach of 'Evidence synthesis for constructing directed acyclic graphs', and revised after independent clinical expert input. RESULTS: DAGs provide visual representations of assumptions made, and provide an objective approach to appropriate statistical adjustments. Key nodes within all the DAGs included age, dementia, genetic predisposition, hearing and visual impairment, length of stay, malignancy, operative severity, polypharmacy, postoperative perioperative medicine service, preoperative clinic review, sex, social deprivation, urgency, with delirium, frailty, multimorbidity, interaction, morbidity acting as exposures, or outcomes in certain DAGs. CONCLUSIONS: DAGs provide a transparent framework for statistical decision-making in observational research. We provide an overview of DAGs using the SNAP-3 DAGs as examples to explain fundamental concepts for developing and using causal diagrams. This overview acknowledges the complexities of exploring clinical relationships and the assumptions that are necessary, providing an opportunity for critique of the relationships described and refinements for future studies.CC BY‑NC‑ND 4.0 (open access

The 2025 British Society for Rheumatology guideline for the treatment of axial spondyloarthritis with biologic and targeted synthetic DMARDs

CC BY‑NC‑ND 4.0 (open access