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Optimising outcomes for adults with cystic fibrosis taking CFTR modulators by individualising care: Personalised data linkage to understand treatment optimisation (PLUTO), a novel clinical framework
No full textJournal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
Executive Summary: The 2025 British Society for Rheumatology guideline for the treatment of axial spondyloarthritis with biologic and targeted synthetic DMARDs
No full textCC BY 4.0 (Creative Commons Attribution
Evaluation of intestinal biopsy tissue preservation methods to facilitate large-scale mucosal microbiota research
No full textBACKGROUND: Large-scale multicentre studies are needed to understand complex relationships between the gut microbiota, health and disease. Interrogating the mucosal microbiota may identify important biology not captured by stool analysis. Gold standard tissue cryopreservation ('flash freezing') limits large-scale study feasibility. We aimed to compare gut microbiota in gold standard and pragmatic mucosal biopsy storage conditions. METHODS: We collected endoscopic recto-sigmoid biopsies from 20 adults with inflammatory bowel disease. Biopsies were preserved using three methods: (i) flash freezing (most proximal and distal biopsy sites); (ii) nucleic acid preservative reagents (QIAGEN Allprotect®, Invitrogen RNAlater™, and Zymo DNA/RNA Shield™); and (iii) formalin fixation with paraffin embedding (FFPE), which is used to preserve tissue for clinical histopathology within healthcare settings. Microbiota were sequenced on the MiSeq platform (V4 region, 16S rRNA gene). FINDINGS: Tissue microbiota were consistent between most proximal and distal tissue suggesting any within-patient variation observed reflected storage condition, not biopsy location. There was no significant difference in alpha-diversity or microbial community profiles of reagent-preserved versus gold standard tissue. FFPE community structure was significantly dissimilar to other tissue samples, driven by differential relative abundance of obligate gut anaerobes; Faecalibacterium, Anaerostipes and Lachnospiraceae. Despite these differences, tissue microbiota grouped by participant regardless of preservation and storage conditions. INTERPRETATION: Preservative reagents offer a convenient alternative to flash freezing tissue in prospective large-scale mucosal microbiota studies. Whilst less comparable, FFPE provides potential for retrospective microbiota studies using historical samples. FUNDING: Medical Research Council (MR/T032162/1) and The Leona M. and Harry B. Helmsley Charitable Trust (G-2002-04255).This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Journal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
Management of post-operative anaemia in patients undergoing surgery for colorectal cancer: a qualitative focus group-based study
No full textBACKGROUND: Optimal management of anaemia following surgery for colorectal cancer remains unclear. Peri-operative anaemia is common in patients undergoing resectional surgery for colorectal cancer. A significant amount of research has been conducted into the management of pre-operative anaemia; however, little work has investigated post-operative anaemia. We intended to investigate the facilitators of and barriers against the standardised correction of post-operative anaemia. These can aid in identifying optimum treatment for patients following surgery for colorectal cancer. METHODS: Four focus groups were held with 29 participants from a multidisciplinary panel of healthcare professionals from two different NHS hospital sites in the UK. The discussions were audio recorded and underwent professional transcription. Transcripts were checked against recordings before undergoing thematic analysis using a realist approach. RESULTS: Four themes were identified. The key barriers to standardised post-operative anaemia correction were a lack of protocoled guidelines or a defined pathway, insufficient education and training, and systemic barriers, such as financial drivers and drug availability. The key facilitator identified was collaboration and communication. DISCUSSION: This study has identified several key barriers and thresholds which can be used in future studies to improve the standardised management of post-operative anaemia.RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Correction: HELLO: a protocol for a cluster randomized controlled trial to enhance interpersonal relationships and team cohesion among ICU healthcare professionals
No full textOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.Journal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
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
No full textBACKGROUND: 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
Meta-Analysis of Cardiovascular Efficacy of Empagliflozin Versus Dapagliflozin in Type 2 Diabetes: Unveiling Key Insights
No full textThe 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
Management of individuals with heterozygous germline pathogenic variants in ATM: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)
No full textPURPOSE: ATM germline pathogenic variants (GPVs) are associated with a moderately increased risk of female breast cancer, pancreatic cancer, and prostate cancer. Resources for managing ATM heterozygotes in clinical practice are limited. METHODS: An international workgroup developed a clinical practice resource to guide management of ATM heterozygotes using peer-reviewed publications and expert opinion. RESULTS: Although ATM is a moderate (intermediate) penetrance gene, cancer risks may be considered as a continuous variable, influenced by family history and other modifiers. ATM GPV heterozygotes should generally be offered enhanced breast surveillance according to their personalized risk estimate and country-specific guidelines and, generally, risk-reducing mastectomy is not recommended. Prostate cancer surveillance should be considered. Pancreatic cancer surveillance should be considered based on assessment of family history, ideally as part of a clinical trial, with existence of country-specific guidelines. For ATM GPV heterozygotes who develop cancer, radiation therapy decisions should not be influenced by the genetic result. Although poly-adenosine diphosphate ribose polymerase inhibitors are licensed for use in metastatic castration-resistant prostate cancer and ATM GPVs, the evidence-base is currently weak. CONCLUSION: Systematic prospective data collection is needed to establish the spectrum of ATM-associated cancer and determine the outlines of surveillance, response to cancer treatment, and survival.RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
A multimodal approach to reduce the incidence of peripheral venous cannula bacteraemias and improve patient safety
No full textBACKGROUND: Incidence of peripheral venous cannula (PVC) bacteraemia have been rising in a trust in the south-west of England, with a 267% increase noted over the 2022/23 financial year compared with the previous year. AIM: To use a multimodal approach to reduce the incidence of PVC bacteraemia and improve patient safety. METHODS: The initiative consisted of an educational poster highlighting the severity of infection associated with PVCs alongside key prevention messages rooted in Trust policy. Teaching sessions, complementing the poster, were delivered by the infection prevention and control team to each clinical area. FINDINGS: The data showed that the provision of further educational resources and wider support resulted in a 54.5% decrease in the incidence of PVC bacteraemia in 2023/24 compared with the previous year. An audit undertaken in the fourth quarter of 2023/24 (January-March) found zero cases of PVC bacteraemia for the first time in 2 years. CONCLUSION: Dedication and collaborative working are vital for securing the success of quality improvement projects. PVC-related bacteraemias and the severity of infection remain an under-acknowledged and under-recognised topic within health care, with further research required.RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
A systematic review of short- compared with standard-length Exeter stems in primary total hip arthroplasty
No full textAIMS: The Exeter femoral stem has a cemented, polished taper-slip design, and an excellent track record. The current range includes short-length options for various offsets, but less is known about the performance of these stems. The aim of this study was to compare the survival of short-length stems with standard-length Exeter stems. METHODS: A systematic review of all studies reporting the use of short-length Exeter stems in primary total hip arthroplasty (THA) was undertaken. Survival data, the indication for revision, and patient-reported outcomes were gathered from observational and randomized studies. Studies based on registry data were analyzed separately. RESULTS: The review included nine studies which covered a total of 2,190 short stems. The mean follow-up was 6.4 years (2 to 12) with an all-cause survival of 95.4%. When revisions due to aseptic acetabular loosening were excluded, the survival was 97.7%. Four stems fractured (0.18%). The mean Oxford Hip Score improved from 18.29 (1.33 to 21.6) preoperatively to 41.59 (32.9 to 43.4) at final follow-up. Three studies used data from national registries. A total of 25,895 short stems (offset ≤ 35.5 mm) were used compared with 336,218 standard-length stems. In these studies, short stems had a hazard ratio (HR) for all-cause survival of 1.19 (95% CI 0.96 to 1.43) with a rate of revision per 1,000 component-years of 0.037 compared with 0.035 for standard-length stems. One study from the New Zealand Joint Registry divided short stems into standard and small offset groups. Standard offset short stems (≥ 37.5 mm) had a 0.84 HR (95% CI 0.38 to 1.88) while small offset short stems (≤ 35.5 mm) had a 1.6 HR compared with standard stems (95% CI 1.3 to 1.98). CONCLUSION: Short Exeter stems perform well and are a safe femoral component in primary THA, according to the current literature. There does not appear to be an increased risk of implant fracture associated with these stems.Not hel