Royal Devon and Exeter Research Repository
Not a member yet
4351 research outputs found
Sort by
Fetal manipulation of maternal metabolism is a critical function of the imprinted Igf2 gene
No full textMaternal-offspring interactions in mammals involve both cooperation and conflict. The fetus has evolved ways to manipulate maternal physiology to enhance placental nutrient transfer, but the mechanisms involved remain unclear. The imprinted Igf2 gene is highly expressed in murine placental endocrine cells. Here, we show that Igf2 deletion in these cells impairs placental endocrine signaling to the mother, without affecting placental morphology. Igf2 controls placental hormone production, including prolactins, and is crucial to establish pregnancy-related insulin resistance and to partition nutrients to the fetus. Consequently, fetuses lacking placental endocrine Igf2 are growth restricted and hypoglycemic. Mechanistically, Igf2 controls protein synthesis and cellular energy homeostasis, actions dependent on the placental endocrine cell type. Igf2 loss also has additional long-lasting effects on offspring metabolism in adulthood. Our study provides compelling evidence for an intrinsic fetal manipulation system operating in placenta that modifies maternal metabolism and fetal resource allocation, with long-term consequences for offspring metabolic health.unknownThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Expert guidelines on exercise and physical activity for people with cystic fibrosis
No full textResearch has shown that there is a lack of confidence and understanding in how to use exercise for managing cystic fibrosis. This editorial discusses the key points of a consensus statement that highlights what is and is not known about the relationship between cystic fibrosis and exercise.Published version, accepted version (6 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
OpenSAFELY NHS Service Restoration Observatory 2: changes in primary care clinical activity in England during the COVID-19 pandemic
No full textBACKGROUND: The COVID-19 pandemic has disrupted healthcare activity across a broad range of clinical services. The NHS stopped non-urgent work in March 2020, later recommending services be restored to near-normal levels before winter where possible. AIM: To describe changes in the volume and variation of coded clinical activity in general practice across six clinical areas: cardiovascular disease, diabetes, mental health, female and reproductive health, screening and related procedures, and processes related to medication. DESIGN AND SETTING: With the approval of NHS England, a cohort study was conducted of 23.8 million patient records in general practice, in situ using OpenSAFELY. METHOD: Common primary care activities were analysed using Clinical Terms Version 3 codes and keyword searches from January 2019 to December 2020, presenting median and deciles of code usage across practices per month. RESULTS: Substantial and widespread changes in clinical activity in primary care were identified since the onset of the COVID-19 pandemic, with generally good recovery by December 2020. A few exceptions showed poor recovery and warrant further investigation, such as mental health (for example, for 'Depression interim review' the median occurrences across practices in December 2020 was down by 41.6% compared with December 2019). CONCLUSION: Granular NHS general practice data at population-scale can be used to monitor disruptions to healthcare services and guide the development of mitigation strategies. The authors are now developing real-time monitoring dashboards for the key measures identified in this study, as well as further studies using primary care data to monitor and mitigate the indirect health impacts of COVID-19 on the NHS.Not permittedThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
How long do ankle arthroplasties last?
No full textDespite the increasing numbers of ankle arthroplasties, there are limited studies on their survival and comparisons between different implants. The primary aim of this study was to determine the failure rates of primary ankle arthroplasties commonly used in the UK. A data linkage study combined National Joint Registry (NJR) data and NHS Digital data. The primary outcome of failure was defined as the removal or exchange of any components of the implanted device. Life tables and Kaplan-Meier survival charts were used to illustrate survivorship. Cox proportional hazards regression models were fitted to compare failure rates between 1 April 2010 and 31 December 2018. Overall, 5,562 primary ankle arthroplasties were recorded in the NJR. Linked data show a one-year survivorship of 98.8% (95% confidence interval (CI) 98.4% to 99.0%), five-year survival in 2,725 patients of 90.2% (95% CI 89.2% to 91.1%), and ten-year survival in 199 patients of 86.2% (95% CI 84.6% to 87.6%). The five-year survival for fixed-bearing implants was 94.3% (95% CI 91.3% to 96.3%) compared to 89.4% (95% CI 88.3% to 90.4%) for mobile-bearing implants. A Cox regression model for all implants with over 100 implantations using the implant with the best survivorship (Infinity) as the reference, only the STAR (hazard ratio (HR) 1.60 (95% CI 0.87 to 2.96)) and INBONE (HR 0.38 (95% CI 0.05 to 2.84)) did not demonstrate worse survival at three and five years. Ankle arthroplasties in the UK have a five-year survival rate of 90.2%, which is lower than recorded on the NJR, because we have shown that approximately one-third of ankle arthroplasty failures are not reported to the NJR. There are statistically significant differences in survival between different implants. Fixed-bearing implants appear to demonstrate higher survivorship than mobile-bearing implants.Accepted version (12 month embargo)The article is available via Open Access. Click on the 'Additional link' above to access the full-text
Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation
No full textFollowing the diagnosis of a paediatric disorder caused by an apparently de novo mutation, a recurrence risk of 1-2% is frequently quoted due to the possibility of parental germline mosaicism; but for any specific couple, this figure is usually incorrect. We present a systematic approach to providing individualized recurrence risk. By combining locus-specific sequencing of multiple tissues to detect occult mosaicism with long-read sequencing to determine the parent-of-origin of the mutation, we show that we can stratify the majority of couples into one of seven discrete categories associated with substantially different risks to future offspring. Among 58 families with a single affected offspring (representing 59 de novo mutations in 49 genes), the recurrence risk for 35 (59%) was decreased below 0.1%, but increased owing to parental mixed mosaicism for 5 (9%)-that could be quantified in semen for paternal cases (recurrence risks of 5.6-12.1%). Implementation of this strategy offers the prospect of driving a major transformation in the practice of genetic counselling.Published version, accepted versionThis article is freely available online. Click on the 'Additional Link' above to access the full-text via the publisher's site
Childhood/adolescent Sydenham's chorea in the UK and Ireland: a BPSU/CAPSS surveillance study
No full textOBJECTIVE: To conduct the first prospective surveillance study of Sydenham's chorea (SC) in the UK and Ireland, and to describe the current paediatric and child psychiatric service-related incidence, presentation and management of SC in children and young people aged 0-16 years. DESIGN: Surveillance study of first presentations of SC reported by paediatricians via the British Paediatric Surveillance Unit (BPSU) and all presentations of SC reported by child and adolescent psychiatrists through the Child and Adolescent Psychiatry Surveillance System (CAPSS). RESULTS: Over 24 months from November 2018, 72 reports were made via BPSU, of which 43 met the surveillance case definition of being eligible cases of suspected or confirmed SC. This translates to an estimated paediatric service-related incidence rate of new SC cases of 0.16 per 100 000 children aged 0-16 per year in the UK. No reports were made via CAPSS over the 18-month reporting period, although over 75% of BPSU cases presented with emotional and/or behavioural symptoms. Almost all cases were prescribed courses of antibiotics of varying duration, and around a quarter of cases (22%) received immunomodulatory treatment. CONCLUSIONS: SC remains a rare condition in the UK and Ireland but has not disappeared. Our findings emphasise the impact that the condition can have on children's functioning and confirm that paediatricians and child psychiatrists should remain vigilant to its presenting features, which commonly include emotional and behavioural symptoms. There is a further need for development of consensus around identification, diagnosis and management across child health settings.Published version, accepted version, 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
Supracondylar elbow fracture management (Supra Man) : a national trainee collaborative evaluation of practice
No full textAIMS: Management of displaced paediatric supracondylar elbow fractures remains widely debated and actual practice is unclear. This national trainee collaboration aimed to evaluate surgical and postoperative management of these injuries across the UK. METHODS: This study was led by the South West Orthopaedic Research Division (SWORD) and performed by the Supra Man Collaborative. Displaced paediatric supracondylar elbow fractures undergoing surgery between 1 January 2019 and 31 December 2019 were retrospectively identified and their anonymized data were collected via Research Electronic Data Capture (REDCap). RESULTS: A total of 972 patients were identified across 41 hospitals. Mean age at injury was 6.3 years (1 to 15), 504 were male (52%), 583 involved the left side (60%), and 538 were Gartland type 3 fractures (55%). Median time from injury to theatre was 16 hours (interquartile range (IQR) 6.6 to 22), 300 patients (31%) underwent surgery on the day of injury, and 91 (9%) underwent surgery between 10:00 pm and 8:00 am. Overall, 910 patients (94%) had Kirschner (K)-wire) fixation and these were left percutaneous in 869 (95%), while 62 patients (6%) had manipulation under anaesthetic (MUA) and casting. Crossed K-wire configuration was used as fixation in 544 cases (59.5%). Overall, 208 of the fixation cases (61%) performed or supervised by a paediatric orthopaedic consultant underwent lateral-only fixation, whereas 153 (27%) of the fixation cases performed or supervised by a non-paediatric orthopaedic consultant used lateral-only fixation. In total, 129 percutaneous wires (16%) were removed in theatre. Of the 341 percutaneous wire fixations performed or supervised by a paediatric orthopaedic consultant, 11 (3%) underwent wire removal in theatre, whereas 118 (22%) of the 528 percutaneous wire fixation cases performed or supervised by a non-paediatric orthopaedic consultant underwent wire removal in theatre. Four MUA patients (6%) and seven K-wire fixation patients (0.8%) required revision surgery within 30 days for displacement. CONCLUSION: The treatment of supracondylar elbow fractures in children varies across the UK. Patient cases where a paediatric orthopaedic consultant was involved had an increased tendency for lateral only K-wire fixation and for wire removal in clinic. Low rates of displacement requiring revision surgery were identified in all fixation configurations.Cite this article: Bone Joint J 2023;105-B(1):82-87.Accepted version (12 month embargo)The article is available via Open Access. Click on the 'Additional link' above to access the full-text
Ultrasound Directed Reduction of Colles' type distal radial fractures in ED (UDiReCT): a feasibility randomised controlled trial
No full textBACKGROUND: There is a high rate of surgical fixation of displaced Colles' type distal radial wrist fractures despite fracture manipulation in the ED. Point-of-care ultrasound has been used to guide ED manipulations but its effect on the quality of fracture reduction or subsequent need for surgical fixation is unknown. This study aims to assess the feasibility of conducting a definitive randomised controlled trial to assess the use of ultrasound to guide these fracture manipulations. METHODS: We conducted a pragmatic randomised controlled feasibility trial in two EDs in England over a 6-month period (7 October 2019 to 6 April 2020). Adult patients with wrist fractures undergoing manipulation in the ED were randomised 1:1 to ultrasound-guided distal radial fracture manipulation or manipulation with sham ultrasound. The primary outcome for this study was trial recruitment rate. Other measures were recorded to assess potential future definitive trial outcomes and feasibility. RESULTS: Of 120 patients meeting inclusion criteria, 48 (40%) were recruited and randomised in the two centres, giving overall recruitment rates of 0.3 and 1.8 participants per week at each site, respectively, and 1 participant per week overall. The most common reason that patients were not included was research staff availability. After 6 weeks, six patients in each group (26% intervention, 24% control) had undergone surgical fixation, with 98% data completeness for this potential definitive trial primary outcome. Randomisation, blinding and data collection processes were effective but there were data limitations in the X-ray assessment of fracture positions. CONCLUSION: A definitive study of a similar design would be feasible within UK ED practice but organisational factors and research staff availability should be considered when estimating the predicted recruitment rate and required sites. 6-week surgical fixation rate was the most reliable outcome measure. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03868696).Published version, accepted version, 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
Editor's choice - September 2023
No full textAccepted version (12 month embargo)RD&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
Enhanced recovery and earlier discharge after colorectal resections - still evolving?
No full textAccepted version (12 month embargo)RD&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