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Ear splinting for ear anomalies in infants. Is it worth doing and have we missed the boat? A prospective, cohort study
No full textINTRODUCTION: Ear deformities can cause distress to children as they age, especially with ear deformity surgery not routinely available through the NHS. Ear splinting is a non-surgical method that can obviate the need for surgery; however, it is believed that it can only be provided in the first few weeks of life. There is also little evidence in the literature regarding caregiver-reported outcomes of appearance and adherence. METHOD: Over a 5-year period (2018-2023), pre- and post-splinting questionnaires were provided to caregivers of infants who underwent ear splinting for treatment of congenital ear deformities. Caregiver-reported outcomes assessed the appearance of different anatomical areas of the ear, ease of use, complications and referral pathways. RESULTS: In total, 123 participants were recruited. Following ear splinting, there was a significant improvement in the ratings of appearance (p<0.001), shape (p<0.001) and projection (p<0.001) of the ear. Caregiver ratings of anatomical regions of the pinna also showed significant improvements for the helical rim (p<0.001) and scaphoid fossa (p<0.001). A small number of caregivers encountered difficulty using the splints (5%), which included application of the splints and keeping them clean and dry. Excellent results were reported regardless of age, with the oldest child being one year old, but the duration of splinting positively correlated with age (p<0.05). CONCLUSIONS: Ear splinting showed high satisfaction rates in outcomes and adherence, with a low complication rate. It is still preferable to start ear splinting early, but good results were still being found up to one year of age in this study.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
Disparity in endoscopic localisation of early distal colorectal cancers: a retrospective cohort analysis from a single institution
No full textBACKGROUND: Accurate staging of distal colorectal cancers is paramount in guiding neoadjuvant therapy, peri-operative, and ostomy planning. Early colonic lesions can be difficult to visualise on computed tomography (CT) scans, with tumour location solely deduced via endoscopy with the potential for introducing error. We aimed to address the paucity in literature in this area and assessed the accuracy of radiological and endoscopic localisation of distal colorectal cancers. METHODS: Retrospective analysis of an electronic database of patients at a large District General Hospital (DGH) diagnosed with distal colorectal cancer between January 2014 to January 2023 was performed. Patient demographics, investigations, endoscopic, and operative findings were analysed. Outcomes were assessed to determine disparities between pre-operative endoscopy and final tumour location. RESULTS: A total of 212 patients were endoscopically diagnosed with distal sigmoid tumour. Of these, 207 (97.6%) had a CT scan performed with 25.1% (52/207) lesions not being identified on this imaging modality with the remainder (74.9%; 155/207) being reported as visible. 38.2% (79/207) of tumours were in the sigmoid colon, 17.4% (36/207) rectosigmoid, and 19.3% (40/207) in the rectum. Pre-operative magnetic resonance imaging (MRI) was performed in 42.5% (90/212) of cases showing 84 tumours: 6.0% (5/84) sigmoid colon, 9.5% (8/84) rectosigmoid and 83.3% (70/84) rectal cancers (upper: 34, mid-rectum: 26, low: 10), with one anal cancer. 42.3% (22/52) of patients with non-visible lesions on CT had MRI scans: 68.2% (15/22) had rectal cancer (upper: 10, mid-rectum: 4, low: 1). Of the 30 where MRI was not performed, 46.7% (14) had sigmoid cancer, 16.7% (5) rectosigmoid, and 33.3% (10) rectal intraoperatively. Overall, 30.7% (65/212) of patients reported as having a distal sigmoid lesion endoscopically in fact had rectal cancer intra-operatively (rectosigmoid lesions excluded). CONCLUSION: Endoscopic localisation of distal colorectal tumours can be unreliable for accurate staging and operative planning. A pre-operative MRI scan should be considered in such instances, and particularly for non-visible lesions on CT scan. This may improve peri-operative planning, staging accuracy and patient outcomes.Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, 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 you modified the licensed material.Not hel
Distribution of age at natural menopause, age at menarche, menstrual cycle length, height and BMI in BRCA1 and BRCA2 pathogenic variant carriers and non-carriers: results from EMBRACE
No full textBACKGROUND: Carriers of germline pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are at higher risk of developing breast and ovarian cancer than the general population. It is unclear if these PVs influence other breast or ovarian cancer risk factors, including age at menopause (ANM), age at menarche (AAM), menstrual cycle length, BMI or height. There is a biological rationale for associations between BRCA1 and BRCA2 PVs and reproductive traits, for example involving DNA damage and repair mechanisms. The evidence for or against such associations is limited. METHODS: We used data on 3,046 BRCA1 and 3,264 BRCA2 PV carriers, and 2,857 non-carrier female relatives of PV carriers from the Epidemiological Study of Familial Breast Cancer (EMBRACE). Associations between ANM and PV carrier status was evaluated using linear regression models allowing for censoring. AAM, menstrual cycle length, BMI, and height in carriers and non-carriers were compared using linear and multinomial logistic regression. Analyses were adjusted for potential confounders, and weighted analyses carried out to account for non-random sampling with respect to cancer status. RESULTS: No statistically significant difference in ANM between carriers and non-carriers was observed in analyses accounting for censoring. Linear regression effect sizes for ANM were -0.002 (95%CI: -0.401, 0.397) and -0.172 (95%CI: -0.531, 0.188), for BRCA1 and BRCA2 PV carriers respectively, compared with non-carrier women. The distributions of AAM, menstrual cycle length and BMI were similar between PV carriers and non-carriers, but BRCA1 PV carriers were slightly taller on average than non-carriers (0.5 cm difference, p = 0.003). CONCLUSION: Information on the distribution of cancer risk factors in PV carriers is needed for incorporating these factors into multifactorial cancer risk prediction algorithms. Contrary to previous reports, we found no evidence that BRCA1 or BRCA2 PV are associated with hormonal or anthropometric factors, except for a weak association with height. We highlight methodological considerations and data limitations inherent in studies aiming to address this question.CC BY 4.0 Internationa
Body composition, maximal fitness, and submaximal exercise function in people with interstitial lung disease
No full textBACKGROUND: Cardiopulmonary exercise testing (CPET) is feasible, valid, reliable, and clinically useful in interstitial lung disease (ILD). However, maximal CPET values are often presented relative to body mass, whereas fat-free mass (FFM) may better reflect metabolically active muscle during exercise. Moreover, despite the value of maximal parameters, people with ILD do not always exercise maximally and therefore clinically relevant submaximal parameters must be identified. Therefore, this study assessed peak oxygen uptake (VO(2peak)) relative to FFM, identifying the validity of common scaling techniques; as well as characterising the oxygen uptake efficiency slope (OUES) and plateau (OUEP) as possible submaximal parameters. METHODS: Participants with ILD underwent assessment of body composition and CPET via cycle ergometry during a single study visit. To determined effectiveness of scaling for body size, both body mass and FFM were scaled using ratio-standard (X/Y) and allometric (X/Y(b)) techniques. Pearsons's correlations determined agreement between OUES, OUEP, and parameters of lung function. Cohens kappa (κ) assessed agreement between OUES, OUEP and VO(2peak). RESULTS: A total of 24 participants (7 female; 69.8 ± 7.5 years; 17 with idiopathic pulmonary fibrosis) with ILD completed the study. Maximal exercise parameters did not require allometric scaling, and when scaled to FFM, it was shown that women have a significantly higher VO(2peak) than men (p = 0.044). Results also indicated that OUEP was significantly and positively correlated with DL(CO) (r = 0.719, p < 0.001), and held moderate agreement with VO(2peak) (κ = 0.50, p < 0.01). CONCLUSION: This study identified that ratio-standard scaling is sufficient in removing residual effects of body size from VO(2peak), and that VO(2peak) is higher in women when FFM is considered. Encouragingly, this study also identified OUEP as a possible alternative submaximal marker in people with ILD, and thus warrants further examination.CC BY 4.0 Internationa
Post-colonoscopy pancreatitis: a case report and a systematic review of the literature
No full textBACKGROUND: Colonoscopy represents a commonly performed endoscopic procedure for the study of large bowel. Even though, colonoscopy is considered a safe and well-tolerated procedure, in the literature, it has also been related with in a few cases of acute pancreatitis. METHODS: A systematic PubMed and Scopus search was conducted, a propos of a case report. RESULTS: Twelve patients were included from 11 case reports. The mean age of the patients was 57.4 years (range: 25 - 84). None of the included patients had a history of cholelithiasis or alcoholism. The principal indication for colonoscopy was cancer/polyp surveillance (7 out of 12, 58.3%). Polypectomy was performed in 9 patients (75%). In 4 out of 12 cases (33.3%) the procedure of colonoscopy was characterised as difficult and external manipulation was necessitated. The mean onset of symptoms was 8 hours after colonoscopy (range: 2 - >24). Hospitalization was necessary in 9 out of 12 patients (75%). Regarding the location of the pancreatitis, body/tail (3 out of 12, 25%), body (4 out of 12, 33.3%) and tail (4 out of 12, 33.3%) were most affected. The median duration of symptoms was 7 days (range: 3-12). No complications were reported. The mean follow-up period of the included patients was 15 months (range: 3-36). No fatalities were reported. CONCLUSION: Post-colonoscopy pancreatitis is an extremely rare complication of colonoscopy. After having excluded a surgical emergency, acute pancreatitis should be taken into consideration, especially when endoscopy is technically challenging. Conservative management is indicated in these cases, while no serious sequels have been reported in the literature.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
Assessing artificial intelligence in breast screening with stratified results on 306 839 mammograms across geographic regions, age, breast density and ethnicity: A Retrospective Investigation Evaluating Screening (ARIES) study
No full textOBJECTIVES: Evaluate an Artificial Intelligence (AI) system in breast screening through stratified results across age, breast density, ethnicity and screening centres, from different UK regions. METHODS: A large-scale retrospective study evaluating two variations of using AI as an independent second reader in double reading was executed. Stratifications were conducted for clinical and operational metrics. Data from 306 839 mammography cases screened between 2017 and 2021 were used and included three different UK regions.The impact on safety and effectiveness was assessed using clinical metrics: cancer detection rate and positive predictive value, stratified according to age, breast density and ethnicity. Operational impact was assessed through reading workload and recall rate, measured overall and per centre.Non-inferiority was tested for AI workflows compared with human double reading, and when passed, superiority was tested. AI interval cancer (IC) flag rate was assessed to estimate additional cancer detection opportunity with AI that cannot be assessed retrospectively. RESULTS: The AI workflows passed non-inferiority or superiority tests for every metric across all subgroups, with workload savings between 38.3% and 43.7%. The AI standalone flagged 41.2% of ICs overall, ranging between 33.3% and 46.8% across subgroups, with the highest detection rate for dense breasts. DISCUSSION: Human double reading and AI workflows showed the same performance disparities across subgroups. The AI integrations maintained or improved performance at all metrics for all subgroups while achieving significant workload reduction. Moreover, complementing these integrations with AI as an additional reader can improve cancer detection. CONCLUSION: The granularity of assessment showed that screening with the AI-system integrations was as safe as standard double reading across heterogeneous populations.CC BY 4.0 (Creative Commons Attribution
Discovery of a DNA methylation profile in individuals with Sifrim-Hitz-Weiss syndrome
No full textPathogenic heterozygous variants in CHD4 cause Sifrim-Hitz-Weiss syndrome, a neurodevelopmental disorder associated with brain anomalies, heart defects, macrocephaly, hypogonadism, and additional features with variable expressivity. Most individuals have non-recurrent missense variants, complicating variant interpretation. A few were reported with truncating variants, and their role in disease is unclear. DNA methylation episignatures have emerged as highly accurate diagnostic biomarkers in a growing number of rare diseases. We aimed to study evidence for the existence of a CHD4-related DNA methylation episignature. We collected blood DNA samples and/or clinical information from 39 individuals with CHD4 variants, including missense and truncating variants. Genomic DNA methylation analysis was performed on 28 samples. We identified a sensitive and specific DNA methylation episignature in samples with pathogenic missense variants within the ATPase/helicase domain. The same episignature was observed in a family with variable expressivity, a de novo variant near the PHD domain, variants of uncertain significance within the ATPase/helicase domain, and a sample with compound heterozygous variants. DNA methylation data revealed higher percentages of shared probes with BAFopathies, CHD8, and the terminal ADNP variants encoding a protein known to form the ChAHP complex with CHD4. Truncating variants, as well as a sample with a recurrent pathogenic missense variant, exhibited DNA methylation profiles distinct from the ATPase/helicase domain episignature. These DNA methylation differences, together with the distinct clinical features observed in those individuals, provide preliminary evidence for clinical and molecular sub-types in the CHD4-related disorder.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
Usability testing a web application to support evidence-based commissioning decisions for implementing mobile stroke units
No full textCommissioning 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
A UK multicentre cohort study of clinical outcomes of proximal femoral replacement for nononcological conditions : the EndoProsthetic Replacement for nonOncological conditions (EPRO) study
No full textAIMS: This study aims to determine the outcomes of proximal femoral replacement (PFR) for nononcological conditions. METHODS: This was a multicentre retrospective cohort study across six UK centres. The primary outcome was the local complication rate. Secondary outcomes were blood transfusions, critical care requirements, return to baseline mobility and residence status, systemic complications, reoperations, and mortality rates. Implant survival analysis was performed using Kaplan-Meier methodology with local complication as the endpoint, and was compared by surgical indication, stem length, and construct stem ratio (CSR). RESULTS: There were 230 PFRs in 226 patients with a median age of 76.0 years (IQR 66.9 to 83.7). Indications were periprosthetic femoral fracture (n = 62; 27%), infected revision arthroplasty (n = 55; 24%), chronic/failed trauma (n = 41; 18%), aseptic revision arthroplasty (n = 38; 17%), acute trauma (n = 33; 14%), and complex primary arthroplasty (n = 1; 0.5%). Median follow-up was 4.2 years (IQR 1.9 to 7.2). The local complication rate was 27% (n = 62). The most common local complications were dislocation (n = 27; 12%) and periprosthetic joint infection (n = 22; 10%). Blood transfusion was required in 86 patients (37%). Overall, 90 patients (39%) required critical care facilities. A return to baseline mobility and residence was observed in 127 (55%) and 200 (87%) patients, respectively. The six-month systemic complication rate was 9% (n = 21) and the reoperation rate was 21% (n = 48). The 30-day and one-year mortality rates were 2% (n = 4) and 8% (n = 19), respectively. The two-year implant survival rate was 78.0% (SE 2.8). Survival rates did not differ significantly by surgical indication, stem length, or CSR. CONCLUSION: This is the largest study of PFR for nononcological conditions. Due to high local complication and reoperation rates, it should be considered a salvage option for complex hip reconstruction and patients should be counselled appropriately.All rights reserve
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