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Characteristics of older patients undergoing surgery in the UK: SNAP-3, a snapshot observational study
No full textBACKGROUND: Frailty and multimorbidity are common in older adults, but the prevalence and interaction of these conditions in surgical patients remain unclear. This study describes the clinical characteristics of a heterogeneous cohort of older UK surgical patients. METHODS: We conducted a prospective observational cohort study during 5 days in March 2022, aiming to recruit all UK patients aged 60 yr and older undergoing surgery, excluding minor procedures (e.g. cataract surgery). Data were collected on patient characteristics, clinical care, frailty, and multimorbidity measures. RESULTS: A total of 7134 patients from 214 NHS hospitals were recruited, with a mean (sd) age of 72.8 (8.1) yr. Of all operations, 69% (95% confidence interval [CI] 67.9-70.1%) were elective, and 34% (95% CI 32.7-34.8%) were day cases. Of the patients, 19% (95% CI 18.3-20.1%) were living with frailty (Clinical Frailty Score ≥5), and 63.1% (95% CI 62.0-64.3%) were living with multimorbidity (count of ≥2 comorbidities). Those living with frailty, multimorbidity, or both were typically older, were from lower socioeconomic backgrounds, and experienced greater polypharmacy and reduced independence. Patients living with frailty were less likely to undergo elective and day-case surgeries. Four out of five (78.8% [1079/1369]) of those who were living with frailty were also living with multimorbidity; 27.1% (1079/3978) of those who were living with multimorbidity were also living with frailty. CONCLUSIONS: In the UK, one in five older patients undergoing surgery is living with frailty, and almost two-thirds of older patients are living with multimorbidity. These data highlight the importance of frailty screening. In addition, they can serve to guide resource allocation and provide comparative estimates for future research.This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.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
UK clinical practice guidelines for the management of patients with constitutional POT1 pathogenic variants
No full textConstitutional 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
Widening Patient Engagement for Rare Disease Drug Trials: The Perspectives of Patients With Idiopathic Pulmonary Fibrosis on Participating in Clinical Drug Trials and Drug Trial Design
No full textBACKGROUND: Research about patient engagement for people with rare diseases has identified how the experiences of some members of the public are overlooked in relation to clinical trial design and trial participation. As part of a knowledge transfer partnership (KTP), the authors were granted access to patient insight reports about the needs of people with idiopathic pulmonary fibrosis (IPF), to inform clinical trial design and marketing strategy. These were contrasted with data from qualitative interviews, informed by and collected from people with IPF and the clinical staff who recruit them to trials. OBJECTIVE: To identify patient and professional perspectives for IPF drug trials to create opportunities for innovation in patient engagement. DESIGN: Ethnography. Qualitative researcher embedded in a pharmaceutical organisation. SETTING AND PARTICIPANTS: International patient insight reports to inform a clinical trial protocol (n = 1) and marketing strategy (n = 6), including the experiences of over 100 patients with IPF. In the United Kingdom, interviews with patients with IPF (n = 32) and the staff who support them clinically and recruit them to trials of new medicines (n = 19) at one specialist interstitial lung disease (ILD) centre. RESULTS: Methodological practices inherent in inpatient insight reports ensured the perspectives of some people with IPF were overlooked. Interviews with a more marginalised population of people with IPF, and the staff who support them, identified that some found trial information confusing, trial practices frustrating and the opportunities to engage in trial design absent. DISCUSSION: Current pharmaceutical practices of working with contract research organisations and patient organisations exclude the perspectives of patients with IPF who do not engage with either. Trial recruitment information needs to be tailored to the needs of individuals, and trial processes need to enable a wider group of patients to participate. CONCLUSIONS: People with IPF want the opportunity to participate in drug trials and trial science. However, methodological rigour and deliberative practices are required to enable a wider group of patients to have a stake in the design and conduct of drug trials for rare diseases. The challenge now is for regulators to mandate such inclusive practices and for pharmaceutical organisations to adopt them. PATIENT OR PUBLIC CONTRIBUTION: A Patient Advisory Group (PAG) comprising six people with IPF gave input on the research protocol and then on the scope and content of the ongoing research. Two patients from international patient organisations served as a Steering Group (SG). Members of these groups provided their interpretations of the study findings and gave insight on their experiences in clinical design and participation.CC BY 4.0 (Creative Commons Attribution
A UK multicentre cohort study of clinical outcomes of proximal femoral replacement for nononcological conditions : the EndoProsthetic Replacement for nonOncological conditions (EPRO) study
No full textAIMS: This study aims to determine the outcomes of proximal femoral replacement (PFR) for nononcological conditions. METHODS: This was a multicentre retrospective cohort study across six UK centres. The primary outcome was the local complication rate. Secondary outcomes were blood transfusions, critical care requirements, return to baseline mobility and residence status, systemic complications, reoperations, and mortality rates. Implant survival analysis was performed using Kaplan-Meier methodology with local complication as the endpoint, and was compared by surgical indication, stem length, and construct stem ratio (CSR). RESULTS: There were 230 PFRs in 226 patients with a median age of 76.0 years (IQR 66.9 to 83.7). Indications were periprosthetic femoral fracture (n = 62; 27%), infected revision arthroplasty (n = 55; 24%), chronic/failed trauma (n = 41; 18%), aseptic revision arthroplasty (n = 38; 17%), acute trauma (n = 33; 14%), and complex primary arthroplasty (n = 1; 0.5%). Median follow-up was 4.2 years (IQR 1.9 to 7.2). The local complication rate was 27% (n = 62). The most common local complications were dislocation (n = 27; 12%) and periprosthetic joint infection (n = 22; 10%). Blood transfusion was required in 86 patients (37%). Overall, 90 patients (39%) required critical care facilities. A return to baseline mobility and residence was observed in 127 (55%) and 200 (87%) patients, respectively. The six-month systemic complication rate was 9% (n = 21) and the reoperation rate was 21% (n = 48). The 30-day and one-year mortality rates were 2% (n = 4) and 8% (n = 19), respectively. The two-year implant survival rate was 78.0% (SE 2.8). Survival rates did not differ significantly by surgical indication, stem length, or CSR. CONCLUSION: This is the largest study of PFR for nononcological conditions. Due to high local complication and reoperation rates, it should be considered a salvage option for complex hip reconstruction and patients should be counselled appropriately.All rights reserve
FUT8 Is a Critical Driver of Prostate Tumour Growth and Can Be Targeted Using Fucosylation Inhibitors
No full textBACKGROUND: An unmet clinical need requires the discovery of new treatments for men facing advanced prostate cancer. Aberrant glycosylation is a universal feature of cancer cells and plays a key role in tumour growth, immune evasion and metastasis. Alterations in tumour glycosylation are closely associated with prostate cancer progression, making glycans promising therapeutic targets. Fucosyltransferase 8 (FUT8) drives core fucosylation by adding α1,6-fucose to the innermost GlcNAc residue on N-glycans. While FUT8 is recognised as a crucial factor in cancer progression, its role in prostate cancer remains poorly understood. METHODS & RESULTS: Here, we demonstrate using multiple independent clinical cohorts that FUT8 is upregulated in high grade and metastatic prostate tumours, and in the blood of prostate cancer patients with aggressive disease. Using novel tools, including PhosL lectin immunofluorescence and N-glycan MALDI mass spectrometry imaging (MALDI-MSI), we find FUT8 underpins the biosynthesis of malignant core fucosylated N-glycans in prostate cancer cells and using both in vitro and in vivo models, we find FUT8 promotes prostate tumour growth, cell motility and invasion. Mechanistically we show FUT8 regulates the expression of genes and signalling pathways linked to prostate cancer progression. Furthermore, we find that fucosylation inhibitors can inhibit the activity of FUT8 in prostate cancer to suppress the growth of prostate tumours. CONCLUSIONS: Our study cements FUT8-mediated core fucosylation as an important driver of prostate cancer progression and suggests targeting FUT8 activity for prostate cancer therapy as an exciting area to explore.CC BY 4.0 (Creative Commons Attribution
Body composition, maximal fitness, and submaximal exercise function in people with interstitial lung disease
No full textBACKGROUND: Cardiopulmonary exercise testing (CPET) is feasible, valid, reliable, and clinically useful in interstitial lung disease (ILD). However, maximal CPET values are often presented relative to body mass, whereas fat-free mass (FFM) may better reflect metabolically active muscle during exercise. Moreover, despite the value of maximal parameters, people with ILD do not always exercise maximally and therefore clinically relevant submaximal parameters must be identified. Therefore, this study assessed peak oxygen uptake (VO(2peak)) relative to FFM, identifying the validity of common scaling techniques; as well as characterising the oxygen uptake efficiency slope (OUES) and plateau (OUEP) as possible submaximal parameters. METHODS: Participants with ILD underwent assessment of body composition and CPET via cycle ergometry during a single study visit. To determined effectiveness of scaling for body size, both body mass and FFM were scaled using ratio-standard (X/Y) and allometric (X/Y(b)) techniques. Pearsons's correlations determined agreement between OUES, OUEP, and parameters of lung function. Cohens kappa (κ) assessed agreement between OUES, OUEP and VO(2peak). RESULTS: A total of 24 participants (7 female; 69.8 ± 7.5 years; 17 with idiopathic pulmonary fibrosis) with ILD completed the study. Maximal exercise parameters did not require allometric scaling, and when scaled to FFM, it was shown that women have a significantly higher VO(2peak) than men (p = 0.044). Results also indicated that OUEP was significantly and positively correlated with DL(CO) (r = 0.719, p < 0.001), and held moderate agreement with VO(2peak) (κ = 0.50, p < 0.01). CONCLUSION: This study identified that ratio-standard scaling is sufficient in removing residual effects of body size from VO(2peak), and that VO(2peak) is higher in women when FFM is considered. Encouragingly, this study also identified OUEP as a possible alternative submaximal marker in people with ILD, and thus warrants further examination.CC BY 4.0 Internationa
Long-term outcomes of Grammont style reverse shoulder arthroplasty at a minimum of 10-year follow-up: A survival analysis
No full textBACKGROUND: Reverse shoulder arthroplasty (RSA) is an established and successful treatment for rotator cuff tear arthropathy. Despite increased popularity, there is a paucity of long-term survivorship data and patient-reported outcome measures. This study aimed to establish the survival at a minimum 10-year follow-up for a Grammont-style reverse shoulder prosthesis. METHODS: A single centre, retrospective case series of 101 primary RSAs in 86 patients, performed between 1999 and 2012 was conducted. The primary outcome measure was all-cause revision. Implant survivorship analysis using the Kaplan-Meier method was conducted. Deaths were censored. Secondary outcomes included up-to-date Oxford Shoulder Score (OSS) in surviving patients, historic OSS scores over time and radiological outcomes. RESULTS: Mean age was 76 years (SD ± 7.29) at time of surgery. The 10-year implant survival was 93.2% (95% confidence interval [CI] 87.8-98.6). The mean OSS was 33 (range 17-48, 95% CI 29.1-36.9) with a minimum of 10-year follow-up (n = 21). Radiographic review showed scapular notching in 79% of implants over 10 years old, but no radiolucency around humeral implants. CONCLUSIONS: The rate of RSA survivorship is high at 93.2% at 10 years. Most patients died with their primary implant in-situ. Functional outcome scores were less predictable over time.All rights reserve
Water-soluble contrast agents in adhesional small bowel obstruction: meta-analysis and PRECIS-2 assessment of trials
No full textBACKGROUND: Adhesional small bowel obstruction is a common presentation to acute general surgical services. Initial management is typically conservative and includes the use of water-soluble contrast agents. Current trials assessing water-soluble contrast agents are limited by sample size and demonstrate contrasting results. The aim of this review was to systematically appraise the use of water-soluble contrast agents in adhesional small bowel obstruction. METHODS: This systematic review and meta-analysis was registered with PROSPERO (CRD42024573136) and conducted in line with PRISMA guidelines. Searches of Medline, Embase and Central databases were undertaken to include randomized clinical trials reporting the use of water-soluble contrast agents in adhesional small bowel obstruction. Searches were last updated on 26 July 2024. The primary outcome was the need for operative intervention. Secondary outcomes included the rate of intestinal ischaemia, the need for bowel resection, and mortality. A random-effects meta-analysis was conducted for outcomes reported in three or more studies. Risk of bias was assessed using the Cochrane Risk-of-Bias tool, and trial methods were appraised using the PRagmatic Explanatory Continuum Indicator Summary (PRECIS-2) tool. RESULTS: In all, 11 randomized controlled trials were included with a median sample size of 88 (range 26-242), nine of which were single-centre studies; only one study used computed tomography imaging to diagnoses adhesional small bowel obstruction. Meta-analysis revealed no significant difference in operative intervention (odds ratio 0.63, 95% confidence interval 0.39 to 1.01; P = 0.053), small bowel ischaemia, small bowel resection, or mortality. Risk of bias raised concerns in several domains. PRECIS-2 assessment showed trials were pragmatic rather than explanatory designs. CONCLUSION: This review does not support the use of therapeutic water-soluble contrast agents in adhesional small bowel obstruction. Further adequately powered trials are needed. Standardization of diagnostic modality and consideration of explanatory designs should be considered.CC BY‑NC‑ND 4.0 (open access
UK corneal surgeons' attitudes towards splitting donor corneas between multiple recipients
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
Large copy number variants are an important cause of congenital hyperinsulinism that should be screened for during routine testing
No full textINTRODUCTION: Congenital hyperinsulinism (HI) is characterized by inappropriate insulin secretion from the pancreatic beta-cells which causes severe hypoglycemia. Copy number variants (CNVs) encompassing multiple genes (contiguous gene CNVs) can cause syndromic forms of HI although they are not typically screened for during routine genetic testing for this condition. We aimed to assess the prevalence of disease-causing contiguous gene CNVs in a cohort of individuals referred for HI genetic testing. METHODS: Our cohort consisted of 3,763 individuals, of which 1,916 had received a genetic diagnosis for their HI and 1,847 were genetically unsolved following routine testing. We screened for 6 different contiguous gene CNVs using next-generation sequencing data from all individuals in the genetically unsolved cohort and searched for patients in our solved cohort who had already been found to have one of these CNVs. RESULTS: We identified a contiguous gene CNV affecting 5 of the 6 genomic loci in 53 probands; 28 from the solved cohort and 25 from the genetically unsolved cohort. Variants on the X chromosome were most common, being detected in 24/53 children. Overall, these variants represented 2.7% (53/1,941) of genetic diagnoses, which is similar to the prevalence of variants in other commonly screened HI genes. DISCUSSION: These results confirm that contiguous gene CNVs are an important cause of HI which should be included in standard gene panel testing processes as this will improve pick-up rates for genetic diagnoses in HI.This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.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