Royal Devon and Exeter Research Repository
Not a member yet
4351 research outputs found
Sort by
Albumin versus balanced crystalloid for resuscitation in the treatment of sepsis: A protocol for a randomised controlled feasibility study, ABC-Sepsis""
No full textBACKGROUND: Patients presenting with suspected sepsis to secondary care often require fluid resuscitation to correct hypovolaemia and/or septic shock. Existing evidence signals, but does not demonstrate, a benefit for regimes including albumin over balanced crystalloid alone. However, interventions may be started too late, missing a critical resuscitation window. METHODS: ABC Sepsis is a currently recruiting randomised controlled feasibility trial comparing 5% human albumin solution (HAS) with balanced crystalloid for fluid resuscitation in patients with suspected sepsis. This multicentre trial is recruiting adult patients within 12 hours of presentation to secondary care with suspected community acquired sepsis, with a National Early Warning Score ≥5, who require intravenous fluid resuscitation. Participants are randomised to 5% HAS or balanced crystalloid as the sole resuscitation fluid for the first 6 hours. OBJECTIVES: Primary objectives are feasibility of recruitment to the study and 30-day mortality between groups. Secondary objectives include in-hospital and 90-day mortality, adherence to trial protocol, quality of life measurement and secondary care costs. DISCUSSION: This trial aims to determine the feasibility of conducting a trial to address the current uncertainty around optimal fluid resuscitation of patients with suspected sepsis. Understanding the feasibility of delivering a definitive study will be dependent on how the study team are able to negotiate clinician choice, Emergency Department pressures and participant acceptability, as well as whether any clinical signal of benefit is detected.Accepted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Improving the diagnosis of cancer in patients with non-site-specific symptoms: an evaluation of the suspicions of cancer service
No full textPublished version (12 month embargo), accepted version (12 month embargo)The article is available via Open Access. Click on the 'Additional link' above to access the full-text
FLT3 inhibitors as MRD-guided salvage treatment for molecular failure in FLT3 mutated AML
No full textPatients with FLT3-mutated AML have a high relapse rate and suboptimal outcomes. Many have co-mutations suitable for measurable residual disease (MRD) monitoring by RT-qPCR and those destined to relapse can be identified by high or rising levels of MRD, called molecular failure. This provides a window for pre-emptive intervention, but there is little evidence to guide treatment. The use of FLT3 inhibitors (FLT3i) appears attractive but their use has not yet been evaluated. We identified 56 patients treated with FLT3i at molecular failure. The FLT3 mutation was an ITD in 52, TKD in 7 and both in 3. Over half of patients had previously received midostaurin. Molecular failure occurred at a median 9.2 months from diagnosis and was treated with gilteritinib (n = 38), quizartinib (n = 7) or sorafenib (n = 11). 60% achieved a molecular response, with 45% reaching MRD negativity. Haematological toxicity was low, and 22 patients were bridged directly to allogeneic transplant with another 6 to donor lymphocyte infusion. 2-year overall survival was 80% (95%CI 69-93) and molecular event-free survival 56% (95%CI 44-72). High-sensitivity next-generation sequencing for FLT3-ITD at molecular failure identified patients more likely to benefit. FLT3i monotherapy for molecular failure is a promising strategy which merits evaluation in prospective studies.unknownNot hel
Implementation of flash glucose monitoring in four pediatric diabetes clinics: controlled before and after study to produce real-world evidence of patient benefit
No full textAIMS: To assess the real-world evidence for flash glucose monitoring (Abbott FreeStyle Libre) for children with type 1 diabetes in terms of glucose control, secondary healthcare resources and costs. RESEARCH DESIGN AND METHODS: We conducted a controlled before and after study (approximately 12 months before and after) using routinely collected health record data on children who start using flash monitors and a control population of children with self-monitoring of blood glucose (SMBG). Our population-based sample of eligible individuals using flash monitoring (n=114) and controls (n=80) aged between 4 and 18 years was drawn from four paediatric diabetes clinics (secondary care) in the South West England. Outcome measures included: glycated hemoglobin (HbA1c), frequency of BG tests; frequency of sensor scans; time in recommended glucose range; short-term complications (hypoglycemia, diabetic ketoacidosis and related illness resulting in investigation) and secondary care costs. RESULTS: After adjustment for age, time since diagnosis, deprivation and the test modality (point of care or laboratory), the mean HbA1c reading for controls was 61.2 (mmol/mol) for the period before and 63.9 after. For individuals using flash monitoring, the adjusted mean HbA1c reading was 64.6 for the period before implementation and 63.8 after. Rates of short-term complications were low across all groups in the study. Whereas the 'after' flash monitoring group had substantially higher incremental costs (+£703 vs the flash monitoring 'before' comparison and +£841 vs contemporaneous SMBG controls), these cost differences were driven by primary care prescribing (sensor costs). CONCLUSIONS: There was some indication that flash monitoring might help young people improve the control of their diabetes but for our sample, the difference between finger-prick testing and flash monitoring was not clinically significant (HbA1c improvement <5 mmol/mol). Given the pace of technological change within diabetes, research efforts should now facilitate the real-time analysis of long-term routine data on flash and continuous glucose monitors.Published version, accepted version, submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Intravitreal dexamethasone to manage post endothelial keratoplasty cystoid macular oedema refractory to topical therapy
No full textBACKGROUND/OBJECTIVES: To describe the visual and clinical outcomes of patients with post endothelial keratoplasty (EK) cystoid macular oedema (CMO) refractory to topical treatment with intravitreal sustained-release dexamethasone implant (Ozurdex). SUBJECTS/METHODS: 131 eyes from 111 patients undergoing solitary or combined EK (52 DSAEK (40.0%) and 79 DMEK (60.0%)) at Southend University Hospital between January 2020 and February 2022 with a minimum follow-up of 6 months were evaluated. Patients suspected of having CMO underwent spectral-domain macular optical coherence tomography (SD-OCT) Patients with diabetes were not included in this series. RESULTS: CMO was identified in 5.3% (n = 7) of cases, with 2 of these patients responding to topical corticosteroid treatment. The remaining 5 patients underwent intravitreal dexamethasone implant, with 1 patient requiring repeat implant due to CMO recurrence. All presented within 2 months postoperatively. 4 out of 5 eyes treated with intravitreal dexamethasone achieved a Snellen BCVA ≤6/9.5. 1 patient had an uncontrolled rise in intraocular pressure (IOP) despite maximal medical treatment requiring an urgent PreserFlo Ab-Externo MicroShunt. CONCLUSIONS: The use of intravitreal sustained-release dexamethasone implant in the management of post EK CMO refractory to topical therapy is effective and safe in most cases, but patients should be monitored and treated promptly for any secondary IOP response.Published version, accepted versionSupports Open Acces
E-cigarette side effects in otolaryngology: unveiling the vape mirage
No full textDATA SOURCES: The following databases were searched for publications up to May 2020: Web of Science, EMBASE, CENTRAL, Medline and CINAHL. Additionally, previously published reviews were hand searched. STUDY SELECTION: Clinical studies conducted in English language were considered, encompassing cohorts of more than four vaping individuals who have encountered inadvertent side effects. Both adult and paediatric populations were included. In vitro, animal studies and systematic or literature reviews were excluded from the analysis. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened 1125 studies following deduplication. Two-hundred and eight full-text studies were assessed for eligibility. RESULTS: Thirty-two studies met the inclusion criteria. Diverse study designs were included, comprising of cross-sectional, randomised controlled trials, case-control studies, cohort studies, case series investigations and non-randomised trials. Of note, four studies focused on paediatric patients. Most reported side effects were cough, throat and mouth irritation and intra-oral lesions. CONCLUSIONS: While the direct side effects of e-cigarettes are well-documented, the long-term effects remain uncertain.accepted version (6 months), submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Fragility of Randomized Clinical Trials Using Mesh in Abdominal Wall Reconstruction
No full textThis systematic review evaluates the fragility of randomized clinical trials that used mesh in abdominal wall reconstruction.
eng from Becton Dickinson, WL Gore, AbbVie, and 3M during the conduct of the study and serving as a consultant for Integra LifeSciences, Baxter, WL Gore, Becton Dickinson, and Bard Pharmaceuticals outside the submitted work. Dr Smart reported receiving funding from the National Institute for Health and Care Research and receiving personal fees from Medtronic and WL Gore outside the submitted work. Dr Heniford reported receiving personal fees from WL Gore and Allergan outside the submitted work. No other disclosures were reported.UnknownThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
What defines an incisional hernia as 'complex': results from a Delphi consensus endorsed by the European Hernia Society (EHS)
No full textPublished version, accepted version (12 month embargo), submitted versionRD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Whole blood DNA methylation changes are associated with anti-TNF drug concentration in patients with Crohn's disease
No full textBACKGROUND AND AIMS: Anti-TNF treatment failure in patients with inflammatory bowel disease (IBD) is common and frequently related to low drug concentrations. In order to identify patients who may benefit from dose optimisation at the outset of anti-TNF therapy, we sought to define epigenetic biomarkers in whole blood at baseline associated with anti-TNF drug concentrations at week 14. METHODS: DNA methylation from 1,104 whole blood samples from 385 patients in the Personalised Anti-TNF Therapy in Crohn's disease (PANTS) study were assessed using the Illumina EPIC Beadchip (v1.0) at baseline, weeks 14, 30 and 54. We compared DNA methylation profiles in anti-TNF-treated patients who experienced primary non-response at week 14 and if they were assessed at subsequent time points, were not in remission at week 30 or 54 (infliximab n = 99, adalimumab n = 94), with patients who responded at week 14 and when assessed at subsequent time points, were in remission at week 30 or 54 (infliximab n = 99, adalimumab n = 93). RESULTS: Overall, between baseline and week 14, we observed 4,999 differentially methylated probes (DMPs) annotated to 2376 genes following anti-TNF treatment. Pathway analysis identified 108 significant gene ontology terms enriched in biological processes related to immune system processes and responses.Epigenome-wide association (EWAS) analysis identified 323 DMPs annotated to 210 genes at baseline associated with higher anti-TNF drug concentrations at week 14. Of these, 125 DMPs demonstrated shared associations with other common traits (proportion of shared CpGs compared to DMPs) including body mass index (23.2%), followed by CRP (11.5%), smoking (7.4%), alcohol consumption per day (7.1%) and IBD type (6.8%). EWAS of primary non-response to anti-TNF identified 20 DMPs that were associated with both anti-TNF drug concentration and primary non-response to anti-TNF with a strong correlation of the coefficients (Spearman's rho = -0.94, p < 0.001). CONCLUSION: Baseline DNA methylation profiles may be used as a predictor for anti-TNF drug concentration at week 14 to identify patients who may benefit from dose optimisation at the outset of anti-TNF therapy.Published version, accepted version (12 month embargo), submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Non-randomised feasibility study of training workshops for Talking Therapies service high-intensity therapists to optimise depression and anxiety outcomes for individuals with co-morbid personality difficulties: a study protocol
No full textBACKGROUND: The NHS Talking Therapies for Anxiety and Depression programme ('TTad'; formerly Improving Access to Psychological Therapies 'IAPT') delivers high-intensity cognitive behavioural therapy (CBT) to over 200,000 individuals each year for common mental health problems like depression and anxiety. More than half of these individuals experience comorbid personality difficulties, who show poorer treatment outcomes. TTad therapists report feeling unskilled to work with clients with personality difficulties, and enhancing the training of TTad therapists may lead to improved treatment outcomes for individuals presenting with secondary personality difficulties alongside depression and anxiety. METHODS: This is a pre-post non-randomised mixed-method feasibility study, exploring the feasibility and acceptability of a 1-day training workshop for high-intensity (HI) CBT therapists. The workshop is focused on understanding and assessing personality difficulties and adapting HICBT treatments for anxiety and depression to accommodate client needs. The feasibility and acceptability of the workshop and the evaluation procedures will be investigated. It will be examined to what extent the workshop provision leads to improvements in therapist skills and confidence and explored to what extent the training has the potential to enhance clinical outcomes for this client group. DISCUSSION: This feasibility study will provide data on the acceptability and feasibility of delivering brief therapist training to adapt usual HICBT to optimise care for individuals with secondary personality difficulties seeking treatment in TTad services for a primary problem of depression and/or anxiety. The study will also evaluate proof of concept that such an approach has the potential to improve clinical outcomes for those with secondary personality difficulties and report any possible harms identified. The study will inform the design of a future randomised controlled trial designed to test the effectiveness and cost-effectiveness of the training. TRIAL REGISTRATION: ISRCTN81104604 . Submitted on 6th June 2022. Registration date: 3rd January 2023.Published version, accepted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text