Type 1 diabetes presenting in adults: Trends, diagnostic challenges and unique features

Type 1 diabetes (T1D) has been historically regarded as a childhood-onset disease; however, recent epidemiological data indicate that adult-onset T1D accounts for a substantial proportion of cases worldwide. There is evidence that adult-onset T1D is associated with the classic T1D triad of elevated genetic risk, the presence of islet-specific autoantibodies and progression to severe insulin deficiency. In this article, we review our understanding of the commonalities and differences between childhood and adult-onset T1D, and we highlight significant knowledge gaps in our understanding of the diagnosis, incidence, trajectory and treatment of adult-onset T1D. Compared to children, adults presenting with T1D exhibit differences in genetic risk, immunologic profiles and metabolic outcomes, including differences in the type and number of autoantibodies present, genetic associations and total genetic burden, rates of C-peptide decline, the persistence of C-peptide in long-duration disease and glycaemic control. In addition, obesity and metabolic syndrome are increasingly common in adults, which not only blurs the clinical distinction of adult-onset T1D from type 2 diabetes (T2D) but also likely contributes to differences in metabolic outcomes and rates of progression. Because T2D is so prevalent in the adult population, adult-onset T1D is misclassified as T2D in at least one in three cases, leading to delays in appropriate treatment. Current diagnostic tools, including autoantibody testing and C-peptide measurement, are underutilised or lack specificity in distinguishing adult-onset T1D from atypical T2D. Additionally, the impact of different responses to disease-modifying therapy between adults and children is unclear. Addressing these knowledge gaps requires expanded epidemiological studies, diverse patient registries and refined classification criteria to improve early detection and treatment strategies. A deeper understanding of adult-onset T1D will be critical to reduce the burden of misdiagnosis, lead to earlier diagnosis and treatment and optimise population-based screening approaches in this under-recognised population. PLAIN LANGUAGE SUMMARY: Type 1 diabetes (T1D) is an autoimmune disease that causes metabolic and nutritional complications due to the destruction of insulin-producing pancreatic β cells. T1D was formerly known as juvenile diabetes" because it was assumed that most cases occurred in childhood; however, recent epidemiological data show that nearly half of all T1D cases are diagnosed in adulthood. Despite the high prevalence of adult-onset T1D, there are challenges with correctly diagnosing T1D in adulthood, and significant knowledge gaps remain regarding the incidence, trajectory, and treatment of adult-onset T1D. In this article, we summarize the current understanding of commonalities and differences between childhood and adult-onset T1D. Particularly, we highlight age-related differences in genetic risk, immunologic profiles, and metabolic outcomes and complications. Finally, we highlight key gaps in our understanding of adult-onset T1D that need to be addressed to reduce the burden of misdiagnosis and allow for better screening and treatment of T1D in adulthood."CC BY 4.0 Internationa

Mapping the therapeutic landscape in emergency incisional hernia: a scoping review

PURPOSE: 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

Usability testing a web application to support evidence-based commissioning decisions for implementing mobile stroke units

Commissioning of innovations in healthcare is a complex socio-technical process, ideally informed by high quality evidence. However, evidence is not always prepared and presented in a format usable for commissioning decisions. Agile methodology, combined with qualitative co-design, were used to develop a digital web application incorporating machine learning models of stroke outcomes to inform commissioning decisions for the implementation of mobile stroke units (MSUs) in England, followed by usability testing using think aloud methodology. Sixteen stakeholders involved in developing consensus on model parameters and pathways participated with data thematically analysed. Required improvements to the web application were identified and novel insights into the complexity of context-specific commissioning decisions were generated, which also informed participants' views on the viability of MSUs. This study provides empirical evidence in support of developing innovative and accessible digital dissemination methods to engage with commissioning processes and prospectively understand commissioning challenges.CC BY 4.0 (Creative Commons Attribution

Experiences of the Management of Uncertainty Amongst Musculoskeletal First Contact Practitioners Working in Primary Care

AIM: To develop a deeper understanding of strategies used to manage uncertainty by Musculoskeletal First Contact Practitioners (MSK FCPs), including barriers to and facilitators for these strategies. BACKGROUND: MSK FCP services provide patients with an alternative to seeing their GP regarding MSK complaints. Research suggests that the role demands different skills and attributes from traditional physiotherapy roles, including the ability to deal with greater clinical uncertainty. There is a lack of research evaluating the strategies FCPs find most helpful for managing uncertainty. METHOD: A qualitative study using semi-structured online interviews. Participants were recruited using convenience sampling. Data was analysed using Braun & Clarke's reflexive approach to thematic analysis. The research was underpinned by a theoretical framework of hermeneutic phenomenology. FINDINGS: Nine participants were recruited. Three main themes were developed: (1) Being comfortable with being uncomfortable; (2) Teamwork makes the dream work and (3) Navigating uncertainty with patients. CONCLUSION: This study provides further insight into how FCPs manage uncertainty. Management of uncertainty was influenced by many factors, including: clinician experience, patient complexity and wider medical knowledge, fear of over-medicalising patients, communication and consultation styles and having protected non-clinical time. Recommendations for clinical practice include: consideration of the challenges facing FCPs, and what support is needed to maintain staff retention, health and wellbeing; consideration of how FCPs might best approach meeting the needs of an ageing population and supporting change in health and wellness behaviour. The key to successful management of uncertainty was having a supportive team which encouraged open non-judgemental discussions about uncertainty.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. Click on the 'Additional link' above to access the full-text

The effect of minimum volume recommendations on surgeon activity for first revision total knee replacement: an analysis of 2009-2019 United Kingdom National Joint Registry data

AIMS: The aim of this study was to investigate changes in first time revision knee replacement (RevKR) volumes following the publication of a report identifying low surgeon volumes in England. As a secondary aim we sought to investigate the rate of accrual of volumes for early career surgeons. METHODS: This population-based cohort study used data from the United Kingdom National Joint Registry. Patients undergoing first time RevKR between 1st January 2009 and 31 December 2019. Annual revision volumes for each surgeon were calculated and trends in surgeon volumes plotted as medians and bootstrapped 95% confidence intervals. Data before and after the report was compared. The rate of accrual of experience for new surgeons inclusive of both first-time revisions and re-revisions was calculated and adjusted for unit volume. RESULTS: A total of 21,067 patients were included. Over the whole study period, 123/1433 (8.58%) of surgeons achieved a mean annual volume of 15 or more revisions. Temporal trends in surgeon revision volumes observed an increase for non-acute indications. New surgeons in lower volume units have 42% lower chance of reaching 15 operations per year compared to those in the highest volume units (HR 0.52; 95% CI 0.33 to 0.83). CONCLUSIONS: We observed an increase in surgeon volumes following the report in first time non acute RevKRs. New RevKR surgeons were more likely to achieve and maintain revision volume targets in higher volume centres, this supports the drive for dual consultant operating and prospective revision knee consultants being appointed to highest volume units.CC BY 4.0 Internationa

UK corneal surgeons' attitudes towards splitting donor corneas between multiple recipients

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

Treatment options to support the elimination of hepatitis C: an open-label, factorial, randomised controlled non-inferiority trial

BACKGROUND: WHO recommends treating hepatitis C infection with one of three antiviral combinations for 8-12 weeks. No randomised trials have compared these regimens, and high cure rates might be achievable with shorter durations of therapy. We aimed to compare sofosbuvir-daclatasvir with sofosbuvir-velpatasvir, and to evaluate potential novel treatment strategies. METHODS: We conducted a multi-arm, open-label, randomised controlled non-inferiority trial in two public hospitals in Viet Nam. Adults (aged ≥18 years) with chronic hepatitis C infection and mild-to-moderate liver fibrosis were eligible. Recruitment was stratified by centre and viral genotype (1-5 vs 6) with 1:1 random allocation to an oral fixed-dose combination of sofosbuvir 400 mg plus daclatasvir 60 mg (sofosbuvir-daclatasvir) or sofosbuvir 400 mg plus velpatasvir 100 mg (sofosbuvir-velpatasvir). Participants were simultaneously factorially randomly assigned to one of four treatment strategies: 12 weeks' standard of care (SOC); 4 weeks' therapy with four weekly PEGylated interferon alfa-2a subcutaneous injections; induction and maintenance therapy with 2 weeks' standard therapy followed by 10 weeks' therapy 5 days a week; and response-guided therapy (RGT) for 4, 8, or 12 weeks determined by viral load on day 7. The primary outcome was sustained virological response (SVR) 12 weeks after treatment completion, analysed in all evaluable participants regardless of actual treatment received. We chose a 5% non-inferiority margin for the drug comparison, and a 10% non-inferiority margin for the treatment strategy comparisons. Safety was assessed in all randomised participants. This trial is registered with ISRCTN, 61522291, and is completed. FINDINGS: Between June 19, 2020, and May 10, 2023, 624 participants were randomised (470 [75%] were male and 154 [25%] were female). 296 (47%) had genotype 6 and 328 (53%) had genotypes 1-5. The primary outcome was assessable in 609 (98%) participants. SVR occurred in 294 (97%) of 302 participants in the sofosbuvir-daclatasvir group and 292 (95%) of 307 participants in the sofosbuvir-velpatasvir group (risk difference 2·2%, 90% credible interval [CrI] -0·2 to 4·8, within the 5% non-inferiority margin; 93% probability that sofosbuvir-daclatasvir is superior to sofosbuvir-velpatasvir). SVR occurred in 148 (99%) of 150 in the SOC group, 143 (94%) of 152 in the 4-week antiviral plus interferon group (-4·5%, 90% CrI -8·3 to -1·3), 151 (99%) of 152 in the induction-maintenance group (0·6%, -1·1 to 2·7), and 144 (93%) of 155 in the RGT group (-5·7%, -9·6 to -2·3); all risk differences were within the 10% non-inferiority margin. Serious adverse events were rare (11 [4%] of 313 participants in the sofosbuvir-velpatasvir group vs six [2%] of 311 in the sofosbuvir-daclatasvir group; risk difference -1·6% [95% CrI -4·2 to 0·8]) with no evidence of differences between regimens or strategies, but adverse reactions were very common in the 4-week antiviral plus interferon group compared with the other treatment strategies (risk difference vs SOC group, 66·8% [59·2 to 74·0]; p<0·0001). INTERPRETATION: Sofosbuvir-daclatasvir was non-inferior to sofosbuvir-velpatasvir. High efficacy was seen with novel strategies, which might help to inform approaches to treatment for harder-to-reach populations. FUNDING: Wellcome Trust.CC BY 4.0 (Creative Commons Attribution

Oxidative-Stress-Mediated Epigenetic Dysregulation in Spermatogenesis: Implications for Male Infertility and Offspring Health

Male reproductive health is governed by an intricate interplay of genetic, epigenetic, and environmental factors. Epigenetic mechanisms-encompassing DNA methylation, histone modifications, and non-coding RNA activity-are crucial both for spermatogenesis and sperm maturation. However, oxidative stress, driven by excessive reactive oxygen species, disrupts these processes, leading to impaired sperm function and male infertility. This disruption extends to epigenetic modifications, resulting in abnormal gene expression and chromatin remodeling that compromise genomic integrity and fertilization potential. Importantly, oxidative-stress-induced epigenetic alterations can be inherited, affecting the health and fertility of offspring and future generations. This review investigates how oxidative stress influences epigenetic regulation in male reproduction by modifying DNA methylation, histone modifications, and non-coding RNAs, ultimately compromising spermatogenesis. Additionally, it discusses the transgenerational implications of these epigenetic disruptions and their potential role in hereditary infertility and disease predisposition. Understanding these mechanisms is vital for developing therapeutic strategies that mitigate oxidative damage and restore epigenetic homeostasis in the male germline. By integrating insights from molecular, clinical, and transgenerational research, this work emphasizes the need for targeted interventions to enhance male reproductive health and prevent adverse outcomes in progeny. Furthermore, elucidating the dose-response relationships between oxidative stress and epigenetic changes remains a critical research priority, informing personalized diagnostics and therapeutic interventions. In this context, future studies should adopt standardized markers of oxidative damage, robust clinical trials, and multi-omic approaches to capture the complexity of epigenetic regulation in spermatogenesis. Such rigorous investigations will ultimately reduce the risk of transgenerational disorders and optimize reproductive health outcomes.Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://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

Anticoagulation Timing in Acute Stroke With Atrial Fibrillation According to Chronic Kidney Disease: The OPTIMAS Trial

INTRODUCTION: Patients with chronic kidney disease (CKD) are at increased risk of ischemic stroke (IS) and intracerebral hemorrhage, so the safety and efficacy of early direct oral anticoagulant (DOAC) initiation in those with CKD are of interest. METHODS: OPTIMAS was a multicenter, randomized, parallel-group, open-label trial with blinded outcome assessment, recruiting patients with IS and atrial fibrillation from 100 UK hospitals between 2019 and 2024. Participants were randomized 1:1, stratified by stroke severity, to early (within 4 days of onset) or delayed (at days 7-14) DOAC initiation. CKD was defined as a past medical history of known CKD, collected according to trial protocol as part of the case report form. For this prespecified subgroup analysis, the trial cohorts were classified according to the presence or absence of CKD. Whether CKD modified the treatment effect of early DOAC initiation was determined by fitting mixed effects logistic regression models with interaction terms between CKD and treatment group. The primary outcome was a composite outcome of recurrent IS, symptomatic intracranial hemorrhage, and systemic arterial embolism. Key secondary outcomes included the individual components of the primary outcome and all-cause mortality. RESULTS: We included 3601 patients (mean age, 78±10 years; 45% female), 543 with CKD. There were 116 primary outcome events: 97 (3.2%) in the normal kidney function group and 19 (3.5%) in the CKD group. There was no difference between early and delayed DOAC initiation for the primary outcome in either the normal kidney function group (odds ratio, 1.01 [95% CI, 0.67-1.51]) or the CKD group (odds ratio, 0.90 [95% CI, 0.36-2.25]; P(interaction)=0.822). Similarly, for the secondary outcomes, we detected no modification of the treatment effect according to CKD (P(interaction) values of 0.637, 0.386, and 0.107 for IS, symptomatic intracranial hemorrhage, and all-cause mortality, respectively). CONCLUSIONS: Our findings suggest that CKD does not modify the effects of early versus delayed DOAC initiation after acute IS. Based on these results, early DOAC initiation should not be withheld in patients with CKD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03759938.CC BY 4.0 (Creative Commons Attribution

A multimodal approach to reduce the incidence of peripheral venous cannula bacteraemias and improve patient safety

BACKGROUND: 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