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Evaluation of the management of nasal septal haematoma and abscess - a systematic review
No full textRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
The reliability of clinical assessment of distal radioulnar joint instability among non-United Kingdom European surgeons
No full textClinical assessment of distal radioulnar joint (DRUJ) instability has been shown to be unreliable among experienced hand surgeons in the United Kingdom (UK). The aim of this study was to test the reliability of assessing DRUJ stability in European surgeons outside the UK. Four participants (eight wrists) with four unstable and four stable DRUJs as measured with a proven jig were assessed by 34 surgeons (22 men and 12 women) with a mean age of 43 years (range 29-61). Clinical assessment of DRUJ instability had a sensitivity of 32%, specificity of 88%, a positive predictive value of 72% and a negative predictive value of 56%. Surgeons who had attended a 1-hour workshop on clinical assessment of DRUJ stability the day before the testing were no more reliable at assessing DRUJ instability when compared with those who did not. This further highlights the need for better training with feedback when assessing the DRUJ and the need for objective assessment of DRUJ instability when reported in scientific studies.Level of evidence: V.Published version, accepted 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
Perineural invasion: An independent risk factor for cervical cancer prognosis and a possible pathway for a future targeted treatment?
No full text0Journal 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
Clustering of predicted loss-of-function variants in genes linked with monogenic disease can explain incomplete penetrance
No full textBACKGROUND: Genetic variants that severely alter protein products (e.g. nonsense, frameshift) are often associated with disease. For some genes, these predicted loss-of-function variants (pLoFs) are observed throughout the gene, whilst in others, they occur only at specific locations. We hypothesised that, for genes linked with monogenic diseases that display incomplete penetrance, pLoF variants present in apparently unaffected individuals may be limited to regions where pLoFs are tolerated. To test this, we investigated whether pLoF location could explain instances of incomplete penetrance of variants expected to be pathogenic for Mendelian conditions. METHODS: We used exome sequence data in 454,773 individuals in the UK Biobank (UKB) to investigate the locations of pLoFs in a population cohort. We counted numbers of unique pLoF, missense, and synonymous variants in UKB in each quintile of the coding sequence (CDS) of all protein-coding genes and clustered the variants using Gaussian mixture models. We limited the analyses to genes with = 5 variants of each type (16,473 genes). We compared the locations of pLoFs in UKB with all theoretically possible pLoFs in a transcript, and pathogenic pLoFs from ClinVar, and performed simulations to estimate the false-positive rate of non-uniformly distributed variants. RESULTS: For most genes, all variant classes fell into clusters representing broadly uniform variant distributions, but genes in which haploinsufficiency causes developmental disorders were less likely to have uniform pLoF distribution than other genes (P < 2.2 × 10(-6)). We identified a number of genes, including ARID1B and GATA6, where pLoF variants in the first quarter of the CDS were rescued by the presence of an alternative translation start site and should not be reported as pathogenic. For other genes, such as ODC1, pLoFs were located approximately uniformly across the gene, but pathogenic pLoFs were clustered only at the end, consistent with a gain-of-function disease mechanism. CONCLUSIONS: Our results suggest the potential benefits of localised constraint metrics and that the location of pLoF variants should be considered when interpreting variants.Published version, accepted versionJournal 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
Development of a clinical calculator to aid the identification of MODY in pediatric patients at the time of diabetes diagnosis
No full textMaturity Onset Diabetes of the Young (MODY) is a young-onset, monogenic form of diabetes without needing insulin treatment. Diagnostic testing is expensive. To aid decisions on who to test, we aimed to develop a MODY probability calculator for paediatric cases at the time of diabetes diagnosis, when the existing MODY calculator" cannot be used. Firth logistic regression models were developed on data from 3541 paediatric patients from the Swedish 'Better Diabetes Diagnosis' (BDD) population study (n = 46 (1.3%) MODY (HNF1A, HNF4A, GCK)). Model performance was compared to using islet autoantibody testing. HbA1c, parent with diabetes, and absence of polyuria were significant independent predictors of MODY. The model showed excellent discrimination (c-statistic = 0.963) and calibrated well (Brier score = 0.01). MODY probability > 1.3% (ie. above background prevalence) had similar performance to being negative for all 3 antibodies (positive predictive value (PPV) = 10% v 11% respectively i.e. ~ 1 in 10 positive test rate). Probability > 1.3% and negative for 3 islet autoantibodies narrowed down to 4% of the cohort, and detected 96% of MODY cases (PPV = 31%). This MODY calculator for paediatric patients at time of diabetes diagnosis will help target genetic testing to those most likely to benefit, to get the right diagnosis."Published version, accepted version, submitted versionJournal 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
Challenges in developing and implementing international best practice guidance for intermediate-risk variants in cancer susceptibility genes: APC c.3920T>A p.(Ile1307Lys) as an exemplar
No full textPublished version, accepted version, 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
Stroke survivor views on ambulance redirection as a strategy to increase access to thrombectomy in England
No full textINTRODUCTION: Intravenous thrombolysis and mechanical thrombectomy are effective time-sensitive treatments for selected cases of acute ischaemic stroke. While thrombolysis is widely available, thrombectomy can only be provided at facilities with the necessary equipment and interventionists. Suitable patients admitted to other hospitals require secondary transfer, causing delays to treatment. Pre-hospital ambulance redirection to thrombectomy facilities may improve access but treatment eligibility cannot be confirmed pre-hospital. Some redirected patients would travel further and be displaced without receiving thrombectomy. This study aimed to elicit stroke survivor and carer/relative views about the possible consequences of introducing a conceptual, idealised ambulance redirection pathway. METHODS: Focus groups were undertaken using a topic guide describing four hypothetical ambulance redirection scenarios and their possible consequences: earlier treatment with thrombectomy; delayed diagnosis of non-stroke 'mimic' conditions; delayed thrombolysis treatment; and delayed diagnosis of haemorrhagic stroke. Meetings were audio recorded, transcribed verbatim and data analysed thematically using emergent coding. RESULTS: Fifteen stroke survivors and carers/relatives participated in three focus groups. There was wide acceptance of possible low-risk consequences of ambulance redirection, including extended travel time, being further from home and experiencing longer hospital stays. Participants were more uncertain about higher-risk consequences, including delays in diagnosis/treatment for patients unsuitable for thrombectomy, but remained positive about ambulance redirection overall. Participants rationalised acceptance of higher-risk consequences by recognising that redirected patients would still access appropriate treatment, even if delayed. In addition, acceptance of ambulance redirection would be increased if there were robust clinical evidence showing net benefit over secondary transfer pathways. CONCLUSIONS: Participant views were generally supportive of ambulance redirection to facilitate access to thrombectomy. Further research is needed to demonstrate overall benefit in an NHS context.Published version, 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
Clinical evolution of gallstones following percutaneous cholecystostomy in patients with severe acute calculous cholecystitis: a single-center analysis of 102 cases
No full textBACKGROUND: Percutaneous cholecystostomy (PC) is effective in controlling sepsis in patients with severe acute calculous cholecystitis (ACC). The long-term treatment of this group is still debated. We aimed to assess the clinical evolution of gallstones after severe ACC and the outcomes of laparoscopic cholecystectomy (LC) and conservative management, following PC. METHODS: This was a retrospective analysis of the rate of readmissions due to recurrent biliary disease and all-cause mortality in subjects who underwent a PC for severe ACC. We compared results between patients who underwent interval LC and those who received conservative management. Readmissions and late mortality were assessed using the Kaplan-Meier method and multivariate regression analysis. RESULTS: A total of 102 patients were included, of whom 30 underwent interval LC and 72 PC only. Overall, 51.6% were readmitted with recurrent biliary events and the rate did not differ between groups (P=0.583). The probability of recurrent gallstone events was higher in the first 30 weeks after PC; in the surgical cohort, 77.8% of them developed before LC. Late deaths occurred in 46.2% of patients: 13.3% LC vs. 61.9% conservative (P<0.001). Three years after PC, the estimated survival was 75% LC vs. 38% conservative (P=0.014). High-grade comorbidities and severity of ACC were positive predictors of all-cause mortality (P=0.004 and P=0.027), whereas LC was a negative predictor (P=0.003). CONCLUSIONS: Recurrent biliary events were common following PC for ACC. Interval LC was associated with lower rates of readmissions and all-cause late mortality.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
Clinical features of type 1 diabetes in older adults and the impact of intermittently scanned continuous glucose monitoring: An Association of British Clinical Diabetologists (ABCD) study
No full textAIMS: To evaluate the clinical features and impact of flash glucose monitoring in older adults with type 1 diabetes (T1D) across age groups defined as young-old, middle-old, and old-old. MATERIALS AND METHODS: Clinicians were invited to submit anonymized intermittently scanned continuous glucose monitoring (isCGM) user data to a secure web-based tool within the National Health Service secure network. We collected baseline data before isCGM initiation, such as demographics, glycated haemoglobin (HbA1c) values from the previous 12 months, Gold scores and Diabetes Distress Scale (DDS2) scores. For analysis, people with diabetes were classified as young-old (65-75 years), middle-old (>75-85 years) and old-old (>85 years). We compared baseline clinical characteristics across the age categories using a t test. All the analyses were performed in R 4.1.2. RESULTS: The study involved 1171 people with diabetes in the young-old group, 374 in the middle-old group, and 47 in the old-old group. There were no significant differences in baseline HbA1c and DDS2 scores among the young-old, middle-old, and old-old age groups. However, Gold score increased with age (3.20 [±1.91] in the young-old vs. 3.46 [±1.94] in the middle-old vs. 4.05 [±2.28] in the old-old group; p < 0.0001). This study showed reduced uptake of insulin pumps (p = 0.005) and structured education (Dose Adjustment For Normal Eating [DAFNE] course; p = 0.007) in the middle-old and old-old populations compared to the young-old population with T1D. With median isCGM use of 7 months, there was a significant improvement in HbA1c in the young-old (p < 0.001) and old-old groups, but not in the middle-old group. Diabetes-related distress score (measured by the DDS2) improved in all three age groups (p < 0.001) and Gold score improved (p < 0.001) in the young-old and old-old populations but not in the middle-old population. There was also a significant improvement in resource utilization across the three age categories following the use of is CGM. CONCLUSION: This study demonstrated significant differences in hypoglycaemia awareness and insulin pump use across the older age groups of adults with T1D. The implementation of isCGM demonstrated significant improvements in HbA1c, diabetes-related distress, hypoglycaemia unawareness, and resource utilization in older adults with T1D.Published version, accepted version (12 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
The discontinuation of implantable cardioverter defibrillator shock therapies towards the end of life: consensus guideline from the British Heart Rhythm Society
No full textImplantable cardioverter defibrillators (ICDs) are implanted in increasing numbers of patients with the aim of treating ventricular arrhythmias in high-risk patients and reducing their risk of dying. Individuals are also living longer with these devices. As a result, a greater number of patients with an ICD will deteriorate either with worsening cardiac failure, another non-cardiac condition or general frailty and will have a limited prognosis. Frequently, they will be cared for by non-cardiac teams who may be less familiar with ICDs. Therefore, to ensure the person receives high-quality end-of-life care, they should have the opportunity to consider and discuss the option to deactivate the shock function of their ICD. If the ICD shock therapy is not discontinued, there is an increased risk that, as a person reaches the last days of life, the ICD may deliver multiple, painful shocks that are distressing. There is also a risk that the device may delay the person's natural death, which the person would not have chosen if they had been given the opportunity to discuss discontinuation. The British Heart Rhythm Society has developed a practical guideline to support all healthcare professionals who are caring for patients who have an ICD. This includes descriptions of different device types, ethical and legal aspects, timing and nature of ICD discussions and practical advice regarding how the devices may be deactivated. It aims to promote awareness and timely discussion between professionals and patients and to encourage best practice.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