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Comprehensive clinical and molecular characterization with long-term outcomes in 40 patients with congenital hyperinsulinism
No full textPURPOSE: Congenital hyperinsulinism (CHI) represents the most frequent cause of recurrent hypoglycemia in neonates and infants, stemming from defects in the regulatory pathways of insulin secretion from pancreatic beta cells. This study aims to assess the clinical and genetic characteristics of a CHI cohort and to discuss the complexities involved in managing this heterogeneous disorder. METHODS: Forty patients (23 girls) with CHI were included in the study. Data on the diagnosis and treatment of CHI were obtained from the medical records. RESULTS: The median age at diagnosis was 1.4 months (range 0.1-30 months). The mean gestational age was 37.8 ± 2.4 weeks, and the birth weight was 1.1 ± 2.0 SDS. The consanguinity ratio was 35.0%. Median glucose, insulin, and C-peptide concentrations at diagnosis were 34.0 mg/dl (IQR 25.2-41.7), 12.4µU/ml (IQR 4.4-27.1), and 1.5 ng/ml (IQR 0.7-3.8), respectively. Molecular genetic diagnosis could be established in 62.5% (n = 25). Pathogenic variants were predominantly identified in the KATP channel genes (17/25, 68%), with the ABCC8 being the most frequent (n = 15; biallelic: 8, monoallelic: 7). KCNJ11 variants were identified in two (5.0%), GLUD1 variants in three (7.5%), and HADH variants in five patients (12.5%). Pancreatectomy was performed in 10 patients, with a mean age at the time of surgery of 3.9 ± 3.2 months. The genetic etiology was identified in all patients who underwent pancreatectomy, all of whom had defects in the KATP channel. ABCC8 variants were detected in nine (biallelic: 5, monoallelic: 4), while a biallelic variant in the KCNJ11 was identified in one case. CONCLUSION: A molecular genetic diagnosis was identified in approximately two-thirds of our cohort, underscoring the significance of genetic testing in the management of CHI. Ongoing advances in genetic technologies are anticipated to enhance our understanding of the etiopathogenesis of CHI and support the development of more personalized therapeutic strategies. Although the genotype-phenotype correlation remains only partially elucidated, specific genetic variants may provide predictive insights into treatment resistance, thereby informing more targeted treatment approaches.None (all rights reserved under exclusive licence to Springer Nature
What is the impact of longer patient travel distances and times on perioperative outcomes following revision knee replacement: a retrospective observational study using data for England from Hospital Episode Statistics
No full textOBJECTIVES: Patients undergoing revision total knee replacement (RevKR) surgery often have difficulties mobilising and increasingly rely on family support. Evolving practice in England aims to manage these patients in specialised centres with the intention of improving outcomes. This practice will result in longer travel distances and times in this frailer group of patients. We want to examine the types of distances and travel times patients can be expected to travel for this complex orthopaedic surgery and to explore concerns of how these impact patient outcomes. DESIGN: Retrospective observational study from the Hospital Episode Statistics. Multivariable adjusted logistic regression models were used to investigate the relationship between patient travel distances and times with perioperative outcomes. SETTING: Patients presenting to tertiary referral centres between 1 January 2016 and 31 December 2019. A tertiary referral centre was defined as a trust performing >49 revisions in the year prior. PARTICIPANTS: Adult patients undergoing RevKR procedures for any reason between 1 January 2016 ando 31 December 2019. EXPOSURE: The shortest patient level travel distance and time was calculated using the Department of Health Journey Time Statistics using Transport Accessibility and Connectivity Calculator software and Dijkstra's algorithm. MAIN OUTCOME MEASURES: The primary outcome is emergency readmission within 30 days. Secondary outcomes are mortality within 90 days and length of inpatient stay. RESULTS: 6880 patients underwent RevKR at 36 tertiary referral centres. There was a weak correlation between social deprivation and travel distance, with patients from the most deprived areas travelling longer distances. Overall, 30-day readmission was not statistically associated with longer driving distance (OR 1.00 95% CI 0.99 to 1.02) or peak driving times (OR 1.00 95% CI 0.99 to 1.01). CONCLUSIONS: There was no association between increasing travel distance and time on perioperative outcomes for RevKR patients.CC BY 4.0 (Creative Commons Attribution
Impact of rapid genomic testing on clinical outcomes of acutely unwell children presenting with severe epilepsy
No full textAbout 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
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
Severe Asthma Questionnaire (SAQ) and Asthma Control Questionnaire (ACQ) as Early Predictors of Biologic Response in Severe Asthma
No full textBACKGROUND: Biologic therapy in asthma can be life-changing and affect health-related quality of life, but symptoms are rarely used in the assessment of response. AIM: To examine the change in health-related quality of life and asthma control between starting a biologic and assessment of biologic response, assessing whether this change can provide early prediction of eventual clinical response at 12 months. METHODS: A service evaluation of severe asthmatics initiating a biologic at the Royal Devon NHS trust between 2019 and 22. Health-Related Quality of Life (Severe Asthma Questionnaire) and asthma control (Asthma Control Questionnaire-6) was captured at baseline, 8 weeks, 16 weeks and 12 months. Patients were classified as responder or non-responder using NICE Criteria for biologic response. Independent samples t-tests were used to determine statistical difference in change from baseline patient reported outcome measure scores between responder and non-responders. RESULTS: One hundred and eight initiations (103 patients) of biologic therapy were included. At 8 weeks and 16 weeks, responders had greater improvement in Severe Asthma Questionnaire & Severe Asthma Questionnaire Global compared to non-responders (p<0.05). Improvement in Asthma Control Questionnaire only achieved significance between all-responders and non-responders at 16 weeks (p<0.05). CONCLUSION: This study provides evidence of the early and sustained improvement in health-related quality of life and symptoms after starting biologic therapy. The findings support the use of the Severe Asthma Questionnaire and the Asthma Control Questionnaire as per the Core Outcome Measures Sets for Severe Asthma (COMSA). We have shown that health-related quality of life and asthma control can assist earlier assessment of response and non-response to biologics.CC BY 4.0 (Creative Commons Attribution
Conservatively managed non-functioning pituitary macroadenomas-cohort study from the UK Non-functioning Pituitary Adenoma Consortium
No full textOBJECTIVE: Surveillance is often adopted for asymptomatic non-functioning pituitary macroadenomas (macroNFPAs). Due to low-quality evidence, uncertainty remains on optimal frequency of imaging/biochemical monitoring and indications for surgery. We assessed the natural history and outcomes of patients with macroNFPA who had monitoring as initial management choice from the UK NFPA Consortium. DESIGN: This was a multicentre, retrospective, cohort study involving 21 UK endocrine departments. METHODS: Clinical, imaging, and hormonal data of 949 patients followed up between January, 1, 2005 and March, 1, 2022 were analysed. RESULTS: Incidence rate for tumour enlargement was 9.8 per 100 patient-years (95% CI, 8.8-10.8), with cumulative probabilities 1.6%, 8.1%, 18.4%, 29.2%, and 43.6% at 6-month, 1-year, 2-year, 3-year, and 5-year follow-up, respectively; rates were higher in tumours abutting/displacing optic chiasm than those not in contact with it. Amongst macroNFPAs not in contact with optic chiasm showing enlargement within 6 months, none impacted visual fields. In tumours with enlargement and continued monitoring (median 2.6 years), further growth occurred in 60.5% (33.8% probability at 2 years), stability in 35.5%, and shrinkage in 4.0%. Rates of new pituitary hormone deficits were 4.0%-4.9%, mainly driven by tumour enlargement. After transsphenoidal surgery, rates of hypopituitarism reversal were 12%-17% and those of additional anterior pituitary hormone deficits were 12%-15% (permanent vasopressin deficiency 3.5%). CONCLUSIONS: Our data provide evidence for monitoring protocols. MacroNFPAs not in contact with optic chiasm require less frequent imaging, and first follow-up scan can be delayed to 1 year. After first enlargement, variable tumour behaviour can occur. New hypopituitarism in stable tumours is rare, challenging necessity of regular pituitary function assessment.CC BY 4.0 (Creative Commons Attribution
Chronic Kidney Disease Following Cardiac Arrest Manifesting as Dyspnoea and Peripheral Oedema in Cardiovascular Multimorbidity: Case Analysis and Brief Literature Review
No full textBACKGROUND/AIM: Chronic kidney disease (CKD) contributes significantly to morbidity, mortality, and healthcare costs. CKD is not only an independent risk factor for cardiovascular disease (CVD) but also a severe complication for patients with CVD, impacting substantially their prognosis and quality of life. CASE REPORT: A 79-year-old male with a complex medical history, including asthma, hypertension, myocardial infarction, ischaemic heart disease, and recent atrial fibrillation, presented with new-onset exertional breathlessness and peripheral oedema following cardiac arrest and pacemaker insertion. Investigations, including medication reviews conducted shortly after in an outpatient setting, revealed severe renal impairment with creatinine levels at 250 μmol/l (reference range for adult males: 59-104), representing an initial acute kidney injury (AKI) that did not resolve and resulted in the diagnosis of stage 4 CKD (eGFR 25 ml/min/1.73 m(2)). The patient was treated with furosemide, dapagliflozin, and adjusted doses of ramipril and edoxaban. Following treatment, the patient's symptoms ameliorated and renal function slightly improved (eGFR 27 ml/min/1.73 m(2)). CONCLUSION: This case highlights the importance of individualised treatment for patients with CKD alongside complex cardiovascular multi-morbidity. The administration of dapagliflozin and furosemide, together with careful adjustments to ramipril, were instrumental in stabilising the patient's renal function and alleviating symptoms. This case demonstrates how a multifaceted approach, continuous monitoring, and patient education are essential for achieving optimal outcomes in patients with CKD and cardiovascular comorbidities.This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international licenseRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Heart Failure Masked as Pulmonary Embolism in Non-adherent Patient With Atrial Fibrillation: Case Report and Analytical Review of the Literature
No full textBACKGROUND/AIM: Atrial fibrillation (AF) and heart failure (HF) commonly co-occur, significantly increasing morbidity and mortality. Poorly controlled AF can contribute to complications like HF and is associated with conditions, such as stroke and pulmonary embolism (PE). This report involves a man with AF who had persistent respiratory symptoms and left-sided chest pain, initially suspected to be PE, but eventually diagnosed as HF. CASE REPORT: A 43-year-old male experienced increasing breathlessness, cough, and fatigue. Initially suspected to have a respiratory infection, his persistent symptoms raised concern for PE. The patient had a history of AF, unsuccessful cardioversion, and long-term non-adherence to beta blockers. Initial assessment revealed persistent respiratory symptoms and elevated levels of C-reactive protein, D-dimer, N-terminal pro-B-type natriuretic peptide, and Troponin T. Chest X-ray showed pulmonary congestion, and echocardiogram confirmed a severely impaired ejection fraction (EF <20%). While the differential diagnosis included community-acquired pneumonia, PE, and HF, the final diagnosis was worsening AF and HF with reduced EF, not PE. CONCLUSION: PE symptoms can overlap with HF, making careful differential diagnosis essential, particularly in AF patients with elevated D-dimer levels, where false positives necessitate caution. This case underscores the importance of thorough differential diagnosis and clinical judgment before ordering tests to avoid misdiagnosis. Long-term non-adherence to beta blockers exacerbated the patient's symptoms, emphasising the critical role of consistent medication use in managing AF and preventing complications like HF. This case report also highlights the importance of thorough investigations, guideline-based treatments and multidisciplinary care in complex AF-HF cases.This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international licenseRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Safety and efficacy of a novel 'One-Visit, Both-Cataracts' high-volume see-and-treat immediate sequential bilateral cataract surgery service in a public healthcare setting
No full textPURPOSE: To evaluate the safety and efficacy of a novel cataract surgery pathway that combines a See-and-Treat (S&T) model with Immediate Sequential Bilateral Cataract Surgery (ISBCS) at the Nightingale Hospital, Exeter, UK. METHODS: A retrospective observational study was conducted on 102 consecutive patients (204 eyes) who underwent S&T ISBCS between July 2023 and July 2024. Patients were triaged based on referral information and underwent preoperative telephone consultations. On the day of surgery, clinical assessment and bilateral cataract surgery were completed in a single visit. Data collected included patient demographics, intraoperative and postoperative outcomes, and complications. RESULTS: Of the 127 patients listed, 102 (84.3%) completed S&T ISBCS. No intraoperative complications were recorded. Fourteen patients (13.7%) required unplanned postoperative consultations, with most cases being non-sight-threatening and self-resolving. Cystoid macular oedema (CMO) was reported in 2.9% of eyes, with no cases of visual loss or endophthalmitis. CONCLUSION: The S&T ISBCS model demonstrated safety and efficiency in delivering cataract care, with a high one-visit completion rate and low complication rates. This model offers significant time and resource savings whilst maintaining patient safety. It holds potential for broader implementation in healthcare settings facing increased demand for cataract services. Further studies are recommended to assess long-term outcomes and optimise this approach.Open 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
The significance of isolated de novo red patches in the bladder in patients referred with suspected urinary tract cancer: Results from the IDENTIFY study
No full textOBJECTIVES: To assess the contemporary malignancy rate in isolated de novo red patches in the bladder and associated risk factors for better selection of red patch biopsy. PATIENTS: Patients from the IDENTIFY dataset; Patients referred to secondary care with suspected urinary tract cancer and found to have isolated de novo red patches on cystoscopy. METHODS: We reported the unadjusted cancer prevalence in isolated de novo red patches that were biopsied; multivariable logistic regression was used to explore cancer-associated risk factors including age, sex, smoking, type of haematuria, LUTS, UTIs and a suspicious-looking red patch (as reported by the cystoscopist). Sub-analysis of these by clinical role and experience was performed. RESULTS: A total of 1110 patients with isolated de novo red patches were included. 41.5% (n = 461) were biopsied, with a malignancy rate of 12.8% (59/461), which was significantly higher in suspicious versus non-suspicious red patches (19.1% vs. 2.81%, p < 0.01). There was a significant association between bladder cancer and age (OR 1.04, 95% CI 1.01-1.07, p = 0.01), smoking history (OR 2.62, 95% CI 1.09-6.27, p = 0.03) and suspicious-looking patch (OR 6.50, 95% CI 2.47-17.1, p < 0.01). The majority of malignancies were in over 60-year-olds. Malignancy rates in suspicious versus non-suspicious red patches did not differ significantly between clinical roles or experiences.Limitations included subjectivity in classifying a suspicious patch and selection bias as not all patches were biopsied. CONCLUSIONS: Many patients still undergo unnecessary biopsies under general anaesthetic for isolated de novo red patches. Clinicians should consider the patient's age, smoking status and how suspicious-looking the patch is, before deciding on surveillance versus biopsy to improve cancer diagnostic yield.This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits 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