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Executive Summary: The 2025 British Society for Rheumatology guideline for the treatment of axial spondyloarthritis with biologic and targeted synthetic DMARDs
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Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Adults and Adolescents with Cystic Fibrosis and at Least One F508del Allele: A Phase 3, Open-Label Extension Study
No full textRATIONALE: Clinical and real-world studies show elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is efficacious and safe in people with cystic fibrosis (CF) ≥12 years of age with at least one F508del allele. OBJECTIVES: Given the potential for life-long ELX/TEZ/IVA use, long-term safety and efficacy of ELX/TEZ/IVA was assessed. METHODS: In this phase 3, open-label, single-arm extension study, participants with F508del-minimal function genotypes (from 24-week parent study 445-102 [n = 399]) or with the F508del-F508del genotype (from 4-week parent study 445-103 [n = 107]) received ELX/TEZ/IVA (ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 hours) over 192 weeks. MEASUREMENTS AND MAIN RESULTS: Primary endpoint was safety and tolerability. Mean exposure to ELX/TEZ/IVA was 172.6 weeks. Most participants had adverse events classified as mild (12.8%) or moderate (60.7%) in severity. Eighteen participants (3.6%) had adverse events that led to treatment discontinuation. After starting ELX/TEZ/IVA, participants had consistent increases in percent predicted FEV(1) (ppFEV(1)), Cystic Fibrosis Questionnaire-Revised respiratory domain score, and body mass index, with decreases in sweat chloride concentration and pulmonary exacerbations rates; these improvements were maintained through 192 weeks. The mean annualized rate of change in ppFEV(1) was 0.02 percentage points (95% CI, -0.14 to 0.19) after initiation of ELX/TEZ/IVA. CONCLUSIONS: During this 192-week open label extension study, the longest clinical study of a CFTR modulator to date, ELX/TEZ/IVA remained generally safe and well-tolerated. Participants had sustained improvements in lung function, respiratory symptoms, CFTR function, pulmonary exacerbation rates, and nutritional status. The estimated annualized rate of change in ppFEV(1) suggests no evidence of pulmonary function loss across the study population over the 4-year treatment period. These results confirm the favorable long-term safety profile and durable disease-modifying clinical benefits of ELX/TEZ/IVA in adolescents and adults with CF. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT03525574.CC BY 4.0 (Creative Commons Attribution
Delayed traumatic subcutaneous emphysema: a case report
No full textBACKGROUND: Subcutaneous emphysema is a common, usually benign, and self-limiting complication of traumatic chest wall injury. In a minority of thoracic injuries, pneumothoraces can result in extensive subcutaneous emphysema and subsequent airway obstruction if air tracks along tissue planes within the neck. Furthermore, patients may have a delay to presentation following chest-wall injury and can rapidly decline. Hence, we discuss a case of delayed traumatic subcutaneous emphysema resulting in airway compromise, without cardiorespiratory compromise from tension pneumothoraces. CASE PRESENTATION: A white British female in her 70s attended the emergency department 24 h after a fall at home with the complaint of right sided chest pain and shortness of breath. On arrival, the patient appeared well, with no sign of compromise. The patient rapidly deteriorated over the course of the next 30 min. Massive crepitus swelling was identified of her upper and lower limbs, head (including palpebral closure), neck, chest, and abdomen. Vocal changes and early airway obstruction features were identified. Prompt recognition of rapidly progressive subcutaneous emphysema with airway compromise, early rapid-sequence induction, chest-drain insertion, and a multidisciplinary team approach ensured a positive outcome, with discharge home after 12 days in hospital. CONCLUSION: Subcutaneous emphysema itself is rarely life-threatening, though it can infrequently manifest as an obstructive airway emergency. Delayed presentations are possible, and the presence of subcutaneous emphysema indicates severe chest-wall injury. Airway protection and treatment of pneumothoraces are critical interventions for these patients.Creative Commons Attribution 4.0 International (CC BY 4.0
Mapping the therapeutic landscape in emergency incisional hernia: a scoping review
No full textPURPOSE: Incisional hernias (IH) represent common complications following abdominal surgeries, with emergency repair associated with increased morbidity and mortality. This scoping review aimed to map the existing literature on emergency incisional hernia repair, identify research gaps, and inform future guideline development. METHODS: A comprehensive literature search was conducted in PubMed MEDLINE and SCOPUS for studies published between January 2000 and August 2024. Articles addressing any aspect of emergency incisional hernia repair in adults were included. Data extraction focused on study characteristics, patient demographics, surgical approaches, and outcomes. RESULTS: Of 801 unique articles identified, 73 met the inclusion criteria. Most were cohort studies (73.97%), with only one randomized trial. The primary areas of interest were repair methods (47.95%), operative outcomes (31.51%), risk assessment (16.44%), and diagnosis (5.48%). Pooled analysis revealed a predominantly female (63%), elderly (mean age 62.3 years), and comorbid patient population. The most frequent study endpoints were readmission (18%), surgical site infection (12%), reoperation (8%), and mortality (4%). Significant heterogeneity was observed in defect characterization and surgical techniques. CONCLUSION: This review highlights a paucity of randomized studies guiding emergency incisional hernia management. Key issues identified include inconsistent definitions of emergency presentation, limited data on hernia characteristics, and a lack of standardized outcome reporting. Future research should focus on developing a unified classification system for emergency incisional hernias, evaluating the role of imaging in decision-making, and conducting comparative studies on various treatment strategies across different clinical scenarios.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.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
Small Bowel Motility Quantified by Cine MRI to Predict Longer-Term Response in Patients with Crohn's Disease Commencing Biological Therapy: The Motility Study
No full textBACKGROUND: Small bowel Crohn's disease (SBCD) is increasingly treated with biological therapies. Predicting response or remission (RoR) for individual patients is difficult and complicates treatment strategy. We aimed to determine if motility magnetic resonance imaging (mMRI) is superior to CRP and fecal calprotectin (FC) for the prediction of RoR at 1 year in patients commencing biologics for SBCD. METHODS: Prospective, multicenter (n = 13) cohort study of patients with active non-stricturing SBCD requiring anti-TNFα or anti-IL-12/23 treatment. We measured mMRI and CRP at baseline and post-induction (visit 2: 12-30 weeks), and FC in a subset. RoR was assessed at 1 year using clinical and structural magnetic resonance enterography parameters. We compared sensitivity, specificity, and area under the receiver operating characteristic curve (ROC-AUC) of changes in mMRI and CRP to predict RoR at 1 year. Secondary outcomes compared mMRI with FC, and prediction of improved quality of life (QoL). RESULTS: Eighty-six participants completed all assessments. Stable or improved mMRI at visit 2 was more sensitive than normalization of CRP for RoR (mMRI:71.0%, 95%CI 52.0-85.8; CRP:45.2%, 95%CI 27.3-64.0%, P = .008) but less specific (mMRI:30.9%, 95%CI 19.1-44.8; CRP:67.3%, 95%CI 53.3-79.3%, P < .001). There was no significant difference in ROC-AUC (mMRI:0.48; CRP:0.53, P = .65). Similar results were obtained for FC. None of mMRI, CRP, or FC predicted patient QoL at 1 year. CONCLUSIONS: Although improved mMRI is more sensitive than CRP and FC to predict RoR at 1 year, it is less specific. No factor predicted patient QoL. Motility MRI remains a marker of disease activity at given timepoints.
Changes in CRP, fecal calprotectin level, or small bowel motility as quantified by MRI do not reliably predict response or remission to biological therapy at 1 year. Motility MRI is a useful marker of active small bowel inflammation.
engThis article is available under the Creative Commons CC-BY-NC license and permits non-commercial 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
Improved Neurodevelopment Following In Utero Sulfonylurea Exposure in a Patient With KCNJ11 Permanent Neonatal Diabetes: Future Implications for Targeted Treatment During Pregnancy
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Widening access to recombinant zoster vaccination in IBD
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
Standardized Measurement of Type 1 Diabetes Polygenic Risk Across Multi-Ancestry Population Cohorts
No full textType 1 diabetes (T1D) polygenic risk scores (PRS) are effective tools for discriminating T1D from other diabetes types and predicting T1D risk, with applications in screening and intervention trials. A previously published T1D Genetic Risk Score 2 (GRS2) is widely adopted, but challenges in standardization and accessibility have hindered broader clinical and research utility. To address this, we introduce GRS2x, a standardized and cross-compatible method for accurate T1D PRS calculation, demonstrating genotyping and reference panel independent performance across diverse datasets. GRS2x as a unified approach facilitates accessible and portable measurement of T1D polygenic risk.This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.Unpublished eprin
Management of severe and fulminant Clostridioides difficile infection in adults
No full textClostridioides difficile (formerly known as Clostridium difficile) is a significant cause of healthcare-associated infection with symptoms ranging from diarrhoea and abdominal pain to pseudomembranous colitis and toxic megacolon. Severe disease can pose a significant morbidity and mortality risk and is to be considered a medical emergency. The emergence of a new C. difficile ribotype with an estimated mortality rate of 20% (ribotype 995) has prompted a re-review of the evidence and guidelines around managing severe C. difficile infections (CDI). International guidance on the management of CDI varies regarding first-line antibiotic choice. Metronidazole is no longer favoured as first line due to concerns around resistance, and vancomycin and fidaxomicin are now recommended as first line options. Antibiotic therapy should be used in conjunction with good supportive measures and early consideration of surgical management. Faecal microbiota transplant can be utilized in recurrent CDI and may be useful in severe disease. Severe CDI is a significant ongoing threat to public health, and further research into effective management is essential to ensure the best possible outcomes for patients.CC BY 4.0 (Creative Commons Attribution
Is there still a role for clindamycin and rifampicin in the treatment of hidradenitis suppurativa: A review of the literature
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