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Maternal plasma cortisol's effect on offspring birth weight: a Mendelian Randomisation study
No full textBACKGROUND: Observational studies and randomized controlled trials have found evidence that higher maternal circulating cortisol levels in pregnancy are associated with lower offspring birth weight. However, it is possible that the observational associations are due to residual confounding. METHODS: We performed two-sample Mendelian Randomisation (MR) using a single genetic variant (rs9989237) associated with morning plasma cortisol (GWAS; sample 1; N = 25,314). The association between this maternal genetic variant and offspring birth weight, adjusted for fetal genotype, was obtained from the published EGG Consortium and UK Biobank meta-analysis (GWAS; sample 2; N = up to 406,063) and a Wald ratio was used to estimate the causal effect. We also performed an alternative analysis using all GWAS reported cortisol variants that takes account of linkage disequilibrium. We also tested the genetic variant's effect on pregnancy cortisol and performed PheWas to search for potential pleiotropic effects. RESULTS: The estimated effect of maternal circulating cortisol on birth weight was a 50 gram (95% CI, -109 to 10) lower birth weight per 1 SD higher log-transformed maternal circulating cortisol levels, using a single variant. The alternative analysis gave similar results (-33 grams (95% CI, -77 to 11)). The effect of the cortisol variant on pregnancy cortisol was 2-fold weaker than in the original GWAS, and evidence was found of pleiotropy. CONCLUSIONS: Our findings provide some evidence that higher maternal morning plasma cortisol causes lower birth weight. Identification of more independent genetic instruments for morning plasma cortisol are necessary to explore the potential bias identified.published versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Carbon footprint of hospital laundry: a life-cycle assessment
No full textOBJECTIVES: To assess greenhouse gas (GHG) emissions from a regional hospital laundry unit, and model ways in which these can be reduced. DESIGN: A cradle to grave process-based attributional life-cycle assessment. SETTING: A large hospital laundry unit supplying hospitals in Southwest England. POPULATION: All laundry processed through the unit in 2020-21 and 2021-22 financial years. PRIMARY OUTCOME MEASURE: The mean carbon footprint of processing one laundry item, expressed as in terms of the global warming potential over 100 years, as carbon dioxide equivalents (CO(2)e). RESULTS: Average annual laundry unit GHG emissions were 2947 t CO(2)e. Average GHG emissions were 0.225 kg CO(2)e per item-use and 0.5080 kg CO(2)e/kg of laundry. Natural gas use contributed 75.7% of on-site GHG emissions. Boiler electrification using national grid electricity for 2020-2022 would have increased GHG emissions by 9.1%, however by 2030 this would reduce annual emissions by 31.9% based on the national grid decarbonisation trend. Per-item transport-related GHG emissions reduce substantially when heavy goods vehicles are filled at =50% payload capacity. Single-use laundry item alternatives cause significantly higher per-use GHG emissions, even if reusable laundry were transported long distances and incinerated at the end of its lifetime. CONCLUSIONS: The laundry unit has a large carbon footprint, however the per-item GHG emissions are modest and significantly lower than using single-use alternatives. Future electrification of boilers and optimal delivery vehicle loading can reduce the GHG emissions per laundry item.Published version, accepted version, submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Chromosome 20p11.2 deletions cause congenital hyperinsulinism via the loss of FOXA2 or its regulatory elements
No full textPersistent congenital hyperinsulinism (HI) is a rare genetically heterogeneous condition characterised by dysregulated insulin secretion leading to life-threatening hypoglycaemia. For up to 50% of affected individuals screening of the known HI genes does not identify a disease-causing variant. Large deletions have previously been used to identify novel regulatory regions causing HI. Here, we used genome sequencing to search for novel large (>1 Mb) deletions in 180 probands with HI of unknown cause and replicated our findings in a large cohort of 883 genetically unsolved individuals with HI using off-target copy number variant calling from targeted gene panels. We identified overlapping heterozygous deletions in five individuals (range 3-8 Mb) spanning chromosome 20p11.2. The pancreatic beta-cell transcription factor gene, FOXA2, a known cause of HI was deleted in two of the five individuals. In the remaining three, we found a minimal deleted region of 2.4 Mb adjacent to FOXA2 that encompasses multiple non-coding regulatory elements that are in conformational contact with FOXA2. Our data suggests that the deletions in these three children may cause disease through the dysregulation of FOXA2 expression. These findings provide new insights into the regulation of FOXA2 in the beta-cell and confirm an aetiological role for chromosome 20p11.2 deletions in syndromic HI.Accepted version (6 month embargo), submitted versionRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Assessing the feasibility and acceptability of a hands-on surgical robotics workshop for medical students and early-career doctors
No full textDespite the increased adoption of robotic surgery across various specialities, medical students and early-career doctors have limited exposure. This study aims to assess the feasibility and acceptability of a hands-on surgical robotics workshop for those early-career medics. 26 participants with minimal prior exposure to robotic surgery attended a workshop using the Versius(©) robotic surgical system and Virtual Reality simulation platforms. We analysed pre-workshop registration form and post-workshop feedback form utilising mixed quantitative and qualitative approach. Pre-workshop registration revealed motivations and barriers to attending surgical robotics courses. Post-workshop evaluations showed significant improvements in self-assessment scores, familiarity with robotic surgery, and confidence in using the technology. All participants expressed a strong enthusiasm for greater access to robotic surgery education and 84% of participants strongly agreed this workshop increased their interests in surgical specialities. The study also highlighted the perceived ease of use of robotic systems compared to laparoscopic instruments and explored the potential of virtual reality in surgical training. Further efforts are needed for better integration of robotic surgery training into medical curricula to prepare future surgeons for the evolving surgical landscape.Not hel
Group A beta-haemolytic streptococcal infection in children
No full textUnknownRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Real-world effectiveness of upadacitinib in Crohn's disease: a UK multicentre retrospective cohort study
No full textBACKGROUND: Upadacitinib is a Janus kinase inhibitor, which has recently been approved for treating Crohn's disease. There are limited real-world studies on the outcomes of upadacitinib in Crohn's disease. OBJECTIVE: Our aim was to evaluate the outcomes of upadacitinib in a real-world Crohn's disease cohort. METHODS: We conducted a retrospective, multicentre, cohort study over a 2-year period across National Health Service (NHS) Lothian and Royal Devon University Healthcare NHS Foundation Trust. The primary outcome was treatment persistence at week 24. Secondary endpoints were corticosteroid-free clinical remission (Harvey-Bradshaw Index (HBI)<5) and biomarker remission (C-reactive protein (CRP)=5 mg/L and faecal calprotectin (FCAL)<250 µg/g) at 12, 24 and 52 weeks. We recorded adverse events. RESULTS: 135 patients commenced upadacitinib as of the 1 January 2024, of which 93 patients with active Crohn's disease were included with a minimum of 12 weeks follow-up. The median follow-up time was 25 weeks (IQR 15-42 weeks). 82% of the cohort had exposure to at least two classes of advanced therapies, and 52% had exposure to at least three classes of advanced therapies. Treatment persistence was 87.1% at week 12, 81.7% at week 24 and 62.8% at week 52. Rates of clinical remission were 64% (42/66), 48% (22/46) and 38% (8/21) at weeks 12, 24 and 52, respectively. Significant reductions in HBI, CRP and FCAL were observed during follow-up. 14% (13/91) had a hospitalisation due to Crohn's disease. Adverse events occurred in 40% (37/93) of the cohort, of which 12% (11/93) were serious. CONCLUSION: Upadacitinib was effective in a real-world, highly refractory, Crohn's disease cohort with good persistence.Published version (12 month embargo), accepted version (12 month embargo)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
New AI model for neoplasia detection and characterisation in inflammatory bowel disease
No full textPublished version, accepted version, submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
First Contact Physiotherapy: A 4-Year Service Evaluation of UK Primary Care Data
No full textBACKGROUND: The First Contact Physiotherapist (FCP) role offers patients direct access to musculoskeletal (MSK) specialists in primary care settings and is designed to reduce GP workload while providing high-quality care. Despite positive early evaluations of FCP services, there remains a need for up-to-date assessments of their impact. AIM: To evaluate the FCP model of care implemented in an NHS Primary Care Network (PCN) against pre-defined service objectives. METHOD: A service evaluation was conducted using data from April 2020 to March 2024. Key performance indicators were based on national FCP evaluation criteria. Data included appointment utilisation, wait times, referral patterns, patient and staff satisfaction surveys, and audit results from clinical data. RESULTS: Over 4 years, 12,185 patients were seen. Of these, 69% of patients were seen as true first contacts. The majority of patients (86.4%) were managed within primary care, with a referral rate of 8.5% to outpatient physiotherapy and 5.1% to orthopaedics. Patient satisfaction was high, with 82% rating their FCP experience as excellent or outstanding. DISCUSSION: The FCP service successfully met its objectives by reducing GP workload and providing effective care. However, there was an increase in outpatient physiotherapy referrals over the 4-year period. Staff satisfaction was generally positive, though some highlighted concerns about appointment duration and workload. CONCLUSION: This evaluation demonstrates that FCP services provide a viable solution for managing MSK conditions in primary care. Future research should explore the most effective MSK service delivery models and incorporate digital solutions for comprehensive outcome and experience measures.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 PARTNER trial of neoadjuvant olaparib with chemotherapy in triple-negative breast cancer
No full textPARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer(1,2), who were germline BRCA1 and BRCA2 wild type(3). Here we report the results of the trial. Patients (n = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin-paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery. The primary end point was pathologic complete response (pCR)(4), and secondary end points included event-free survival (EFS) and overall survival (OS)(5). pCR was achieved in 51% of patients in the research arm and 52% in the control arm (P = 0.753). Estimated EFS at 36 months in the research and control arms was 80% and 79% (log-rank P > 0.9), respectively; OS was 90% and 87.2% (log-rank P = 0.8), respectively. In patients with pCR, estimated EFS at 36 months was 90%, and in those with non-pCR it was 70% (log-rank P < 0.001), and OS was 96% and 83% (log-rank P < 0.001), respectively. Neoadjuvant olaparib did not improve pCR rates, EFS or OS when added to carboplatin-paclitaxel and anthracycline-based chemotherapy in patients with triple-negative breast cancer who were germline BRCA1 and BRCA2 wild type. ClinicalTrials.gov ID: NCT03150576 .Accepted version (6 month embargo), submitted versionRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Has the energy poverty crisis fuelled a rise in hot water bottle burn injuries within the United Kingdom?
No full textINTRODUCTION: There are an estimated 10 million hot water bottles (HWB) currently in use within the United Kingdom (UK), and HWB related burn injuries represent a significant resource burden to UK Burns Services. These injuries can be caused through a variety of mechanisms including scalds sustained when filling the bottle or scalds from leaking or rupture. The fuel poverty crisis started in February 2022 leading to an estimated six-fold increase in alternative sources of heating, in particular hot water bottles. In this study, we wish to understand the impact that this may have had upon burn injuries sustained by these products. METHODS: All hot water bottle (HWB)-related injuries sustained January 2014 - February 2023 were retrieved from the UK International Burn Injury Database (IBID). Data were collected on patient demographics, injury mechanism, anatomical location, and clinical outcomes. The data were collated and analysed; statistical analysis was performed using R StudioTM. Patient levelling costs were also incorporated to enable translation of these data into healthcare costs. RESULTS: A total of 5944 HWB-related burn injuries were recorded in the IBID database in England and Wales, from 2014 to 2023, with a mean of 594 (SD 146.2) burn injuries annually, costing an estimated £ 12.7 million. There were 423 burn injuries sustained from HWB in winter 2022 compared to 295 in winter 2021, representing a 43.4 % increase over one year, with a corresponding increase of 43.1 % in the number of patients managed in an outpatient setting. The largest increase in burn incidence between winter 2021 and winter 2022 was seen in children (0-16 years old) and older adults (greater than 65 years old) with a rise of 60.3 % (n = 41) and 68.5 % (n = 37) respectively. CONCLUSION: Our epidemiological study on hot water bottle (HWB)-related burn injuries within the United Kingdom has shown that the dramatic rise in fuel prices, which sparked the fuel poverty crises, has coincided with a 43.4 % increase in HWB burns incidence on the health service in that year alone. This alarming rise in HWB-related injuries highlights the continued need for targeted public awareness campaigns to ensure a safe and proper use of these devices.Not hel