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British Thyroid Association Survey of Graves' Disease Management in the UK
No full textBACKGROUND: Recent years have seen changes and uncertainties in evidence and guideline recommendations in Graves' disease treatment. To understand the impact of these developments on current practice, we undertook a survey of Graves' disease management in the United Kingdom and compared this to other national and international surveys. METHOD: Members of the British Thyroid Association, the UK Society for Endocrinology and regional endocrinology networks, were invited by e-mail to complete a 15-min online survey (October 2022 to March 2023). RESULTS: Out of 158 eligible respondents, 99% were endocrinologists. For a 40-year-old female with a first presentation of Graves' hyperthyroidism, TSH-receptor antibodies (TRAb) were requested at diagnosis and at follow-up by 95% and 76%, respectively. Isotope scans and ultrasound were rarely requested (< 5%). Majority (95%) would treat with antithyroid drugs (ATD), predominantly Carbimazole (CMZ), while radioactive iodine (RAI) was preferred for recurrent disease (81%). Common reasons for avoiding RAI were thyroid eye disease, pregnancy intention, or contact with young children whereas biochemical severity, goitre, or male sex did not influence decision to use RAI. Propylthiouracil (PTU) was preferred in preconception and early pregnancy, but after the first-trimester, 50% would continue PTU while 50% switch back to CMZ. CONCLUSIONS: The survey confirms a growing application of TRAbs, both for diagnostic and prognostic purposes. ATDs remain the preferred first-line therapy for Graves' disease, which is consistent with global trends but contrary to National Institute of Health and Care Excellence (NICE) guidance. Further studies are required to explore the clinical and pragmatic determinants of current treatment approaches.CC BY 4.0 Internationa
A qualitative exploration of stressors in anaesthesia training in the UK and mechanisms to improve resident wellbeing
No full textINTRODUCTION: High levels of stress and burnout have been identified among resident anaesthetists in UK training programmes. Factors involving clinical roles, workplace culture and training are known stressors, but in-depth research investigating how to improve wellbeing is limited. METHODS: We used a qualitative design in two phases with participants from across the UK. Phase 1 involved semi-structured interviews of resident anaesthetists in the 2nd-5th years of training, and educational stakeholders. Phase 2 involved additional participants in two focus groups, one each for residents and stakeholders. Interviews and focus groups were conducted online, audio-recorded and transcribed for thematic analysis using a framework approach. RESULTS: We interviewed 52 participants in phase 1, comprising resident anaesthetists from England, Wales and Scotland and key educational stakeholders. A further 11 resident anaesthetists and stakeholders participated in the phase 2 focus groups. We identified four overarching themes contributing to stress: clinical work; non-clinical work; structure of training; and workplace culture. We also identified supportive features at individual, local, regional and national levels. Stress and burnout were commonplace, particularly during demanding periods of training. Balancing non-clinical commitments alongside busy workloads was difficult. Clinically, intensive care medicine and obstetrics generated the most stress. Frequent rotations and long commutes increased stress, impacting on working and family relationships. Curriculum changes, examinations and competition for higher training posts caused stress and poor morale. Proposed mechanisms to improve wellbeing include: peer-to-peer support; request-based rotas; adoption of 'lead employers'; decreasing rotation frequency and commuting distances; access to less than full-time working and professional support; and adapting the structure of training to improve the stability of the resident anaesthetist workforce. DISCUSSION: Attention to the factors identified as contributing to stress could improve resident anaesthetists' wellbeing through changes to policy and practice at local, regional and national levels, for which we make research-informed recommendations.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.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
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
No full textAIMS: 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
Zonal Characteristics of Collagen Ultrastructure and Responses to Mechanical Loading in Articular Cartilage
No full textThe biomechanical properties of articular cartilage arise from a complex bioenvironment comprising hierarchically organised collagen networks within the extracellular matrix (ECM) that interact with the proteoglycan-rich interstitial fluid. This network features a depth-dependent fibril organisation across different zones. Understanding how collagen fibrils respond to external loading is key to elucidating the mechanisms behind lesion formation and managing degenerative conditions like osteoarthritis. This study employs polarisation-resolved second harmonic generation (pSHG) microscopy to quantify the ultrastructural organisation of collagen fibrils and their spatial gradient along the depth of bone-cartilage explants under a close-to-in vivo condition. By combining with in-situ loading, we examined the responses of collagen fibrils by quantifying changes in their principal orientation and degree of alignment. The spatial gradient and heterogeneity of collagen organisation were captured at high resolution (1 μm) along the longitudinal plane of explants (0.5 mm by 2 mm). Zone-specific ultrastructural characteristics were quantified to aid in defining zonal borders, revealing consistent zonal proportions with varying overall thicknesses. Under compression, the transitional zone exhibited the most significant re-organisation of collagen fibrils. It initially allowed large deformation through the re-orientation of fibrils, which then tightened fibril alignment to prevent excessive deformation, indicating a dynamic adaptation mechanism in response to increasing strain levels. Our results provide comprehensive, zone-specific baselines of cartilage ultrastructure and micromechanics, crucial for investigating the onset and progression of degenerative conditions, setting therapeutic intervention targets, and guiding cartilage repair and regeneration efforts. STATEMENT OF SIGNIFICANCE: Achieved unprecedented quantification of the spatial gradient and heterogeneity of collagen ultrastructural organisation at a high resolution (1 μm) along the full depth of the longitudinal plane of osteochondral explants (0.5 mm by 2 mm) under close-to-in vivo condition. Suggested new anatomical landmarks based on ultrastructural features for determining zonal borders and found consistent zonal proportions in explants with different overall thicknesses. Demonstrated that collagen fibrils initially respond by reorienting themselves at low strain levels, playing a significant role in cartilage deformation, particularly within the transitional zone. At higher strain levels, more collagen fibrils re-aligned, indicating a dynamic shift in the response mechanism at varying strain levels.This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted 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
Improved Neurodevelopment Following In Utero Sulfonylurea Exposure in a Patient With KCNJ11 Permanent Neonatal Diabetes: Future Implications for Targeted Treatment During Pregnancy
No full textJournal 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
Elucidating the clinical and genetic spectrum of inositol polyphosphate phosphatase INPP4A-related neurodevelopmental disorder
No full textPURPOSE: Biallelic INPP4A variants have recently been associated with severe neurodevelopmental disease in single-case reports. Here, we expand and elucidate the clinical-genetic spectrum and provide a pathomechanistic explanation for genotype-phenotype correlations. METHODS: Clinical and genomic investigations of 30 individuals were undertaken alongside molecular and in silico modelling and translation reinitiation studies. RESULTS: We characterize a clinically variable disorder with cardinal features, including global developmental delay, severe-profound intellectual disability, microcephaly, limb weakness, cerebellar signs, and short stature. A more severe presentation associated with biallelic INPP4A variants downstream of exon 4 has additional features of (ponto)cerebellar hypoplasia, reduced cerebral volume, peripheral spasticity, contractures, intractable seizures, and cortical visual impairment. Our studies identify the likely pathomechanism of this genotype-phenotype correlation entailing translational reinitiation in exon 4 resulting in an N-terminal truncated INPP4A protein retaining partial functionality, associated with less severe disease. We also identified identical reinitiation site conservation in Inpp4a(-/-) mouse models displaying similar genotype-phenotype correlation. Additionally, we show fibroblasts from a single affected individual exhibit disrupted endocytic trafficking pathways, indicating the potential biological basis of the condition. CONCLUSION: Our studies comprehensively characterize INPP4A-related neurodevelopmental disorder and suggest genotype-specific clinical assessment guidelines. We propose that the potential mechanistic basis of observed genotype-phenotype correlations entails exon 4 translation reinitiation.This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).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
Comprehensive clinical and molecular characterization with long-term outcomes in 40 patients with congenital hyperinsulinism
No full textPURPOSE: Congenital hyperinsulinism (CHI) represents the most frequent cause of recurrent hypoglycemia in neonates and infants, stemming from defects in the regulatory pathways of insulin secretion from pancreatic beta cells. This study aims to assess the clinical and genetic characteristics of a CHI cohort and to discuss the complexities involved in managing this heterogeneous disorder. METHODS: Forty patients (23 girls) with CHI were included in the study. Data on the diagnosis and treatment of CHI were obtained from the medical records. RESULTS: The median age at diagnosis was 1.4 months (range 0.1-30 months). The mean gestational age was 37.8 ± 2.4 weeks, and the birth weight was 1.1 ± 2.0 SDS. The consanguinity ratio was 35.0%. Median glucose, insulin, and C-peptide concentrations at diagnosis were 34.0 mg/dl (IQR 25.2-41.7), 12.4µU/ml (IQR 4.4-27.1), and 1.5 ng/ml (IQR 0.7-3.8), respectively. Molecular genetic diagnosis could be established in 62.5% (n = 25). Pathogenic variants were predominantly identified in the KATP channel genes (17/25, 68%), with the ABCC8 being the most frequent (n = 15; biallelic: 8, monoallelic: 7). KCNJ11 variants were identified in two (5.0%), GLUD1 variants in three (7.5%), and HADH variants in five patients (12.5%). Pancreatectomy was performed in 10 patients, with a mean age at the time of surgery of 3.9 ± 3.2 months. The genetic etiology was identified in all patients who underwent pancreatectomy, all of whom had defects in the KATP channel. ABCC8 variants were detected in nine (biallelic: 5, monoallelic: 4), while a biallelic variant in the KCNJ11 was identified in one case. CONCLUSION: A molecular genetic diagnosis was identified in approximately two-thirds of our cohort, underscoring the significance of genetic testing in the management of CHI. Ongoing advances in genetic technologies are anticipated to enhance our understanding of the etiopathogenesis of CHI and support the development of more personalized therapeutic strategies. Although the genotype-phenotype correlation remains only partially elucidated, specific genetic variants may provide predictive insights into treatment resistance, thereby informing more targeted treatment approaches.None (all rights reserved under exclusive licence to Springer Nature
How do we avoid over-treating skin cancer in people with severe frailty and limited life expectancy?
No full textAll rights reserve
What is the impact of longer patient travel distances and times on perioperative outcomes following revision knee replacement: a retrospective observational study using data for England from Hospital Episode Statistics
No full textOBJECTIVES: Patients undergoing revision total knee replacement (RevKR) surgery often have difficulties mobilising and increasingly rely on family support. Evolving practice in England aims to manage these patients in specialised centres with the intention of improving outcomes. This practice will result in longer travel distances and times in this frailer group of patients. We want to examine the types of distances and travel times patients can be expected to travel for this complex orthopaedic surgery and to explore concerns of how these impact patient outcomes. DESIGN: Retrospective observational study from the Hospital Episode Statistics. Multivariable adjusted logistic regression models were used to investigate the relationship between patient travel distances and times with perioperative outcomes. SETTING: Patients presenting to tertiary referral centres between 1 January 2016 and 31 December 2019. A tertiary referral centre was defined as a trust performing >49 revisions in the year prior. PARTICIPANTS: Adult patients undergoing RevKR procedures for any reason between 1 January 2016 ando 31 December 2019. EXPOSURE: The shortest patient level travel distance and time was calculated using the Department of Health Journey Time Statistics using Transport Accessibility and Connectivity Calculator software and Dijkstra's algorithm. MAIN OUTCOME MEASURES: The primary outcome is emergency readmission within 30 days. Secondary outcomes are mortality within 90 days and length of inpatient stay. RESULTS: 6880 patients underwent RevKR at 36 tertiary referral centres. There was a weak correlation between social deprivation and travel distance, with patients from the most deprived areas travelling longer distances. Overall, 30-day readmission was not statistically associated with longer driving distance (OR 1.00 95% CI 0.99 to 1.02) or peak driving times (OR 1.00 95% CI 0.99 to 1.01). CONCLUSIONS: There was no association between increasing travel distance and time on perioperative outcomes for RevKR patients.CC BY 4.0 (Creative Commons Attribution
Is there still a role for clindamycin and rifampicin in the treatment of hidradenitis suppurativa: A review of the literature
No full textCC BY 4.0 (Creative Commons Attribution