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Publication Dietary management, clinical status and outcome of patients with Citrin deficiency in the UK.(MDPI Publishing, 2020-10-29) Pinto, Alex; Ashmore, Catherine; Batzios, Spyros; Daly, Anne; Dawson, Charlotte; Dixon, Marjorie; Evans, Sharon; Green, Diane; Gribben, Joanna; Hunjan, Inderdip; Jameson, Elisabeth; Newby, Camille; Pierre, Germaine; Rajwal, Sanjay; Robertson, Louise; Santra, Si; Sharrard, Mark; Vara, Roshni; White, Lucy; Wilcox, Gisela; Yilmaz, Ozlem; MacDonald, Anita; Endocrinology; Therapy; Medical and Dental; Dawson, Charlotte; Robertson, LouiseBackground: Little is known about the optimal dietary treatment for citrin deficiency. Our aim is to describe the management of UK citrin deficiency patients. Methods: A longitudinal retrospective review was performed. Data were collected from medical records on presenting signs and symptoms, dietary management and clinical outcome. Results: data were collected on 32 patients from 21 families. 50% were females (16/32). Median age at diagnosis was 4 y (5 days-35 y) with 12 patients diagnosed in the neonatal period with neonatal intrahepatic cholestasis (NICCD), eight later in childhood (FTTDCD) and 12 by family screening based on index cases from five families. No patient had adult-onset type II citrullinemia. The patient age at the time of data collection was a median of 11 y (1-44 y). 91% (29/32) of patients had normal physical and neurological development, 47% (15/32) experienced recurrent unexplained abdominal pain and 9% (3/32) episodes of hypoglycaemia. Siblings had different phenotypes (5 families had > 1 affected patient). Most patients preferred high protein foods, limiting sugar-containing foods. Only 41% (13/32) were prescribed a low CHO, high protein, high fat diet (restriction varied) and two used medium chain triglyceride (MCT) supplements. No patient was prescribed drug therapy. Twenty-five per cent (8/32) of patients were underweight and 41% (13/32) had height <-1 z-scores. Conclusions: patients presented with various phenotypes, symptoms and suboptimal growth. Symptoms and biochemical markers improved with age, but height remained low in some. More research is necessary to assess the effectiveness of dietary approaches in improving clinical outcomes and symptoms in citrin deficiency.Publication Epidemiology and mortality of Cushing's syndrome.(Elsevier, 2021-03-15) Hakami, Osamah A; Ahmed, Shahzada; Karavitaki, Niki; Ear, Nose and Throat; Endocrinology; Medical and Dental; Ahmed, Shahzada; Karavitaki, NikiEndogenous Cushing's syndrome (CS) is a rare endocrine disorder characterised by excess cortisol secretion due to either ACTH-dependent conditions [commonly an ACTH-producing pituitary adenoma (Cushing's disease)] or ACTH-independent causes (with most common aetiology being a benign adrenal adenoma). Overall, the annual incidence of CS ranges between 1.8 and 3.2 cases per million population. Mortality in active CS is elevated compared to the general population, and a number of studies support the view that survival is also compromised even after apparent successful treatment. The main cause of death is cardiovascular disease highlighting the negative impact of cortisol excess on cardiovascular risk factors. Early diagnosis and prompt treatment of the cortisol excess, as well as vigilant monitoring and stringent control of cardiovascular risk factors are key elements for the long-term prognosis of these patients.Publication Evidence-based prescribing of diabetes medications: are we getting closer?(The Lancet, Diabetes & Endocrinology, 2020-01-29) Bellary, Srikanth; Tahrani, Abd A; Barnett, Anthony H; General Medicine; Medical and Dental; Barnett, AnthonyNo abstract availablePublication Exercise-induced hypoglycaemia in type 1 diabetes.(Wiley-Blackwell, 2020-01-09) Cockcroft, E J; Narendran, P; Andrews, R C; Diabetes; Medical and Dental; Narendran, ParthNew findings: What is the topic of this review? Hypoglycaemia is a commonly cited barrier to exercise in type 1 diabetes mellitus (T1D). Knowledge of approaches to prevent or manage exercise-induced hypoglycaemia can support patients to exercise and help clinicians to give advice. This review presents evidence-based strategies to prevent exercise-induced hypoglycaemia in T1D. What advances does it highlight? This review highlights approaches that can be used before, during and after exercise to mitigate the risk of hypoglycaemia. The approaches include the timing of exercise, the type of exercise, adjustments to insulin and carbohydrate, use of novel technology and education. Abstract: Exercise is a key component for the management of type 1 diabetes mellitus (T1D) and is associated with reduced risk of cardiovascular disease, decreased daily insulin requirements and improved quality of life. Owing to these benefits, people with T1D are recommended to undertake regular physical activity, 150 min per week for adults and 60 min per day for children and adolescents. Despite the recommendations, many people do not meet these targets. One of the commonly cited barriers to exercise is fear of hypoglycaemia along with limited knowledge of effective preventative strategies. Hypoglycaemia can be difficult to predict, and symptoms are often masked during exercise or stress of competition. For athletes with T1D, hypoglycaemia can also limit sporting success. Hypoglycaemia before an event increases the risks of hypoglycaemia during competition and can reduce performance. To avoid hypoglycaemia, people with T1D may avoid exercise altogether or consume excessive amounts of carbohydrates, which mitigates many of the health benefits of exercise. Increased understanding of approaches to prevent or manage hypoglycaemia is therefore important to help increase levels of physical activity in people with T1D and to support athletes with T1D to compete at the highest level. This review outlines the prevalence of exercise-related hypoglycaemia, its underlying physiology and the strategies that can be used to prevent and manage exercise-induced hypoglycaemia in T1D. Our hope is that this knowledge will be used by people withPublication Diabetes and frailty: an expert consensus statement on the management of older adults with type 2 Diabetes.(Springer Healthcare, 2021-04-08) Strain, W David; Down, Su; Brown, Pam; Puttanna, Amar; Sinclair, AlanPrognosis and appropriate treatment goals for older adults with diabetes vary greatly according to frailty. It is now recognised that changes may be needed to diabetes management in some older people. Whilst there is clear guidance on the evaluation of frailty and subsequent target setting for people living with frailty, there remains a lack of formal guidance for healthcare professionals in how to achieve these targets. The management of older adults with type 2 diabetes is complicated by comorbidities, shortened life expectancy and exaggerated consequences of adverse effects from treatment. In particular, older adults are more prone to hypoglycaemia and are more vulnerable to its consequences, including falls, fractures, hospitalisation, cardiovascular events and all-cause mortality. Thus, assessment of frailty should be a routine component of a diabetes review for all older adults, and glycaemic targets and therapeutic choices should be modified accordingly. Evidence suggests that over-treatment of older adults with type 2 diabetes is common, with many having had their regimens intensified over preceding years when they were in better health, or during more recent acute hospital admissions when their blood glucose levels might have been atypically high, and nutritional intake may vary. In addition, assistance in taking medications, as often occurs in later life following implementation of community care strategies or admittance to a care home, may dramatically improve treatment adherence, leading to a fall in glycated haemoglobin (HbA1c) levels. As a person with diabetes gets older, simplification, switching or de-escalation of the therapeutic regimen may be necessary, depending on their level of frailty and HbA1c levels. Consideration should be given, in particular, to de-escalation of therapies that may induce hypoglycaemia, such as sulphonylureas and shorter-acting insulins. We discuss the use of available glucose-lowering therapies in older adults and recommend simple glycaemic management algorithms according to their level of frailty.Publication Publication Denosumab, raloxifene, romosozumab and teriparatide to prevent osteoporotic fragility fractures: a systematic review and economic evaluation.(NIHR Journals Library, 2020-06) Davis, Sarah; Simpson, Emma; Hamilton, Jean; James, Marrissa Martyn-St; Rawdin, Andrew; Wong, Ruth; Goka, Edward; Gittoes, Neil; Selby, Peter; Endocrinology; Medical and Dental; Gittoes, NeilBackground: Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. Objectives: The objectives were to evaluate the clinical effectiveness, safety and cost-effectiveness of non-bisphosphonates {denosumab [Prolia®; Amgen Inc., Thousand Oaks, CA, USA], raloxifene [Evista®; Daiichi Sankyo Company, Ltd, Tokyo, Japan], romosozumab [Evenity®; Union Chimique Belge (UCB) S.A. (Brussels, Belgium) and Amgen Inc.] and teriparatide [Forsteo®; Eli Lilly and Company, Indianapolis, IN, USA]}, compared with each other, bisphosphonates or no treatment, for the prevention of fragility fracture. Data sources: For the clinical effectiveness review, nine electronic databases (including MEDLINE, EMBASE and the World Health Organization International Clinical Trials Registry Platform) were searched up to July 2018. Review methods: A systematic review and network meta-analysis of fracture and femoral neck bone mineral density were conducted. A review of published economic analyses was undertaken and a model previously used to evaluate bisphosphonates was adapted. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years for a simulated cohort of patients with heterogeneous characteristics. This was done for each non-bisphosphonate treatment, a strategy of no treatment, and the five bisphosphonate treatments previously evaluated. The model was populated with effectiveness evidence from the systematic review and network meta-analysis. All other parameters were estimated from published sources. An NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture® (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX® (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net monetary benefit was estimated using non-parametric regression. A probabilistic sensitivity analysis and scenario analyses were used to assess uncertainty. Results: Fifty-two randomised controlled trials of non-bisphosphonates were included in the clinical effectiveness systematic review and an additional 51 randomised controlled trials of bisphosphonates were included in the network meta-analysis. All treatments had beneficial effects compared with placebo for vertebral, non-vertebral and hip fractures, with hazard ratios varying from 0.23 to 0.94, depending on treatment and fracture type. The effects on vertebral fractures and the percentage change in bone mineral density were statistically significant for all treatments. The rate of serious adverse events varied across trials (0-33%), with most between-group differences not being statistically significant for comparisons with placebo/no active treatment, non-bisphosphonates or bisphosphonates. The incremental cost-effectiveness ratios were > £20,000 per quality-adjusted life-year for all non-bisphosphonate interventions compared with no treatment across the range of QFracture and FRAX scores expected in the population eligible for fracture risk assessment. The incremental cost-effectiveness ratio for denosumab may fall below £30,000 per quality-adjusted life-year at very high levels of risk or for high-risk patients with specific characteristics. Raloxifene was dominated by no treatment (resulted in fewer quality-adjusted life-years) in most risk categories. Limitations: The incremental cost-effectiveness ratios are uncertain for very high-risk patients. Conclusions: Non-bisphosphonates are effective in preventing fragility fractures, but the incremental cost-effectiveness ratios are generally greater than the commonly applied threshold of £20,000-30,000 per quality-adjusted life-year. Study registration: This study is registered as PROSPERO CRD42018107651. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 29. See the NIHR Journals Library website for further project information.Publication Association of metformin with susceptibility to COVID-19 in people with type 2 diabetes.(Oxford University Press, 2021-04-23) Wang, Jingya; Cooper, Jennifer M; Gokhale, Krishna; Acosta-Mena, Dionisio; Dhalla, Samir; Byne, Nathan; Chandan, Joht Singh; Anand, Astha; Okoth, Kelvin; Subramanian, Anuradhaa; Bangash, Mansoor N; Jackson, Thomas; Zemedikun, Dawit; Taverner, Tom; Hanif, Wasim; Ghosh, Sandip; Narendran, Parth; Toulis, Konstantinos A; Tahrani, Abd A; Surenthirakumaran, Rajendra; Adderley, Nicola J; Haroon, Shamil; Khunti, Kamlesh; Sainsbury, Christopher; Thomas, G Neil; Nirantharakumar, Krishnarajah; Anaesthetics; Diabetes; Medical and Dental; Bangash, Mansoor N; Hanif, Wasim; Narendran, ParthObjective: Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes. Research design and methods: We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF-). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed. Results: There were 29 558 and 10 271 patients in the MF+ and MF- groups, respectively, who met the inclusion criteria. In the propensity score-matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding. Conclusion: Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with.Publication 11-oxygenated estrogens are a novel class of human estrogens but do not contribute to the circulating estrogen pool.(Oxford University Press, 2021-03-01) Barnard, Lise; Schiffer, Lina; Louw du-Toit, Renate; Tamblyn, Jennifer A; Chen, Shiuan; Africander, Donita; Arlt, Wiebke; Foster, Paul A; Storbeck, Karl-HeinzAndrogens are the obligatory precursors of estrogens. In humans, classic androgen biosynthesis yields testosterone, thought to represent the predominant circulating active androgen both in men and women. However, recent work has shown that 11-ketotestosterone, derived from the newly described 11-oxygenated androgen biosynthesis pathway, makes a substantial contribution to the active androgen pool in women. Considering that classic androgens are the obligatory substrates for estrogen biosynthesis catalyzed by cytochrome P450 aromatase, we hypothesized that 11-oxygenated androgens are aromatizable. Here we use steroid analysis by tandem mass spectrometry to demonstrate that human aromatase generates 11-oxygenated estrogens from 11-oxygenated androgens in 3 different cell-based aromatase expression systems and in human ex vivo placenta explant cultures. We also show that 11-oxygenated estrogens are generated as a byproduct of the aromatization of classic androgens. We show that 11β-hydroxy-17β-estradiol binds and activates estrogen receptors α and β and that 11β-hydroxy-17β-estradiol and the classic androgen pathway-derived active estrogen, 17β-estradiol, are equipotent in stimulating breast cancer cell line proliferation and expression of estrogen-responsive genes. 11-oxygenated estrogens were, however, not detectable in serum from individuals with high aromatase levels (pregnant women) and elevated 11-oxygenated androgen levels (patients with congenital adrenal hyperplasia or adrenocortical carcinoma). Our data show that while 11-oxygenated androgens are aromatizable in vitro and ex vivo, the resulting 11-oxygenated estrogens are not detectable in circulation, suggesting that 11-oxygenated androgens function primarily as androgens in vivo.Publication Adrenal Insufficiency(Nature Publishing Group, 2021-03-11) Hahner, Stefanie; Ross, Richard J; Arlt, Wiebke; Bancos, Irina; Burger-Stritt, Stephanie; Torpy, David J; Husebye, Eystein S; Quinkler, MarcusAdrenal insufficiency (AI) is a condition characterized by an absolute or relative deficiency of adrenal cortisol production. Primary AI (PAI) is rare and is caused by direct adrenal failure. Secondary AI (SAI) is more frequent and is caused by diseases affecting the pituitary, whereas in tertiary AI (TAI), the hypothalamus is affected. The most prevalent form is TAI owing to exogenous glucocorticoid use. Symptoms of AI are non-specific, often overlooked or misdiagnosed, and are related to the lack of cortisol, adrenal androgen precursors and aldosterone (especially in PAI). Diagnosis is based on measurement of the adrenal corticosteroid hormones, their regulatory peptide hormones and stimulation tests. The goal of therapy is to establish a hormone replacement regimen that closely mimics the physiological diurnal cortisol secretion pattern, tailored to the patient's daily needs. This Primer provides insights into the epidemiology, mechanisms and management of AI during pregnancy as well as challenges of long-term management. In addition, the importance of identifying life-threatening adrenal emergencies (acute AI and adrenal crisis) is highlighted and strategies for prevention, which include patient education, glucocorticoid emergency cards and injection kits, are described.Publication DEKODE - a cloud-based performance feedback model improved DKA care across multiple hospitals in the UK(Wiley, 2025-06) Rengarajan, Lakshmi N; Cooper, Catherine; Malhotra, Kashish; Sharma, Angelica; Philip, Nevil; Abraham, Anu Ann; Dhatariya, Ketan; Narendran, Parth; Kempegowda, Punith; University of Birmingham; University Hospitals Birmingham NHS Foundation Trust, Walsall Healthcare NHS Trust; Rama Medical College Hospital and Research Centre; University of Adelaide; Norfolk and Norwich University Hospitals NHS Foundation Trust; Endocrinology and Diabetes; Doctors; Medicine; Medical and Dental; Cooper, Catherine; Philip, Nevil; Abraham, Anu; Narendran, Parth; Kempegowda, PunithAim: A current gap in Diabetes-related ketoacidosis (DKA) research is understanding the factors contributing to variations in care and outcomes between people admitted with DKA. We aimed to create a system to facilitate gathering data on DKA management across multiple centres and identify trends in complications and outcomes associated with DKA. Research design and methods: Between January 2020 and December 2022, we set up a cloud-based Quality improvement project (QIP) that provided regular feedback to 11 hospitals in the United Kingdom (UK). Results: Of the 1977 episodes, we observed an increase in adherence in fluid prescription in hospitals C, D, E, F and G (C- 23% vs. 75% p = <0.001; D- 27% vs. 60%, p = <0.001; E- 17 vs. 79% p = <0.001; F- 16% vs. 57%, p = <0.001; G- 36% vs. 75% p = <0.001). Notable improvements in adherence to glucose monitoring were observed in hospitals B, D, and G (B- 11 vs. 38% p = <0.001; D- 36% vs. 56%, p = 0.05; G- 22% vs. 67% p = <0.001). Although we didn't observe significant changes in complications and outcomes among participating hospitals from the start to the end of the reported period, notable fluctuations were evident across quarters. These variations were relayed to the respective hospitals, underscoring how feedback and interventions could influence the care provided. This initiative also marks the initial move towards establishing and improving data collection practices in acute diabetes. Conclusions: We demonstrate a sustainable QIP that improves adherence to national guidelines in some indicators for DKA care and serves as an early warning system to identify adverse trends.Publication All-cause mortality in patients with diabetes under glucagon-like peptide-1 agonists : a population-based, open cohort study(Elsevier Masson, 2017-03-18) Toulis, K. A.; Hanif, W.; Saravanan, P.; Willis, B. H.; Marshall, T.; Kumarendran, B.; Gokhale, K.; Ghosh, S.; Cheng, K. K.; Narendran, P.; Thomas, G. N.; Nirantharakumar, K.; University of Birmingham; University Hospitals Birmingham NHS Foundation Trust; University of Warwick; George Eliot Hospital, Nuneaton; Diabetes and Endocrinology; General Surgery; Medical and Dental; Saravanan, P.; Hanif, Wasim; Narendran, ParthAim: The glucagon-like peptide-1 receptor agonist (GLP1a) liraglutide has been described to benefit patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk. However, there are still uncertainties relating to these cardiovascular benefits: whether they also apply to an unselected diabetic population that includes low-risk patients, represent a class-effect, and could be observed in a real-world setting. Methods: We conducted a population-based, retrospective open cohort study using data derived from The Health Improvement Network database between Jan 2008 to Sept 2015. Patients with T2DM exposed to GLP1a (n=8345) were compared to age, gender, body mass index, duration of T2DM and smoking status-matched patients with T2DM unexposed to GLP1a (n=16,541). Results: Patients with diabetes receiving GLP1a were significantly less likely to die from any cause compared to matched control patients with diabetes (adjusted incidence rate ratio [aIRR]: 0.64, 95% CI: 0.56-0.74, P-value<0.0001). Similar findings were observed in low-risk patients (aIRR: 0.64, 95% CI: 0.53-0.76, P -value=0.0001). No significant difference in the risk of incident CVD was detected in the low-risk patients (aIRR: 0.93, 95% CI: 0.83-1.12). Subgroup analyses suggested that effect is persistent in the elderly or across glycated haemoglobin categories. Conclusions: GLP1a treatment in a real-world setting may confer additional mortality benefit in patients with T2DM irrespective of their baseline CVD risk, age or baseline glycated haemoglobin and was sustained over the observation period.Publication Glucagon-like peptide 1 agonists and death from any cause in primary care setting(Wiley, 2017-03-08) Nirantharakumar, K.; Willis, B. H.; Marshall, T.; Kumarendran, B.; Ghosh, S.; Narendran, P.; Thomas, G. N.; Ponnusamy, S.; Hanif, W.; Toulis, K. A.; Cheng, K.; Gokhale, K.; University of Birmingham; University Hospitals Birmingham NHS Foundation Trust; George Eliot Hospital, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Diabetes; Ponnusamy, S.; Narendran, Parth; Hanif, WasimPoster abstract P417 from the section Clinical care and other categories posters: new technology, therapies and treatment, Diabetes UK Professional Conference 2017, Manchester Central, Manchester, 8–10 March 2017.Publication Diagnostic performance of ultrasound vs. ultrasound-guided FNAc in thyroid nodules: data from the ElaTION trial.(Oxford University Press, 2024-10-03) Mehanna, Hisham; Nankivell, Paul; Boelaert, Kristien; Woolley, Rebecca; Sharma, Neil; Sidhu, Paul S; Madani, Gitta; Da Forno, Philip; Moreman, Catherine; Palmer, Andrew; Fulton-Lieuw, Tessa; Taylor, Judith; Rajaguru, Kanchana; Bekker, Jasper; Vaidhyanath, Ram; Rehman, Thaj; Deeks, Jon; ENT; Medical and Dental; Sharma, NeilIntroduction: ElaTION is a large multi-centre pragmatic randomised controlled trial, performed in 18 secondary/tertiary hospitals across England, comparing elastography ultrasound-guided fine needle aspiration cytology (EUS-FNAC) with ultrasound-guided FNAC (US-FNAC) alone in the diagnostic assessment of thyroid nodules. Secondary trial outcomes, reported here, assessed the accuracy of ultrasound-alone (US) compared with US-guided FNAC to inform and update current practice guidelines. Methods: Adults with single or multiple thyroid nodules who had not undergone previous FNAC were eligible. Radiologists assessed all thyroid nodules using US alone, thereby enabling assessment of its accuracy (sensitivity and specificity) versus US-FNAC. Results: Of the 982 participants, a final definitive diagnosis was obtained in 688, who were included in the final analyses. The sensitivity of US-alone was the same as US-FNAC (0.91, [95% CI 0.85, 0.97] vs 0.87 [95%CI 0.80-0.95], p=0.37). US alone had statistically significant lower specificity than US-FNAC alone (0.48 vs 0.67 respectively, p<0.0001). The malignancy rate on histology in a nodule classified as benign on ultrasound (U2) was 9/263 (3.42%) and on cytology (Thy2) was 15/353 (4.25%), whereas the malignancy rate in a nodule that was benign on both (U2, Thy2) was 3/210 (1.43%). Malignancy risk for U3, U4, and U5 nodules was 68/304 (22.4%), 43/83 (51.8%), and 29/38 (76.3%) respectively (p<0.0001). Yet 80/982 (8%) patients were discharged despite having U3-U5 scans with Thy1 (non-diagnostic) FNAC and no definitive diagnosis.Malignancy risk was higher in smaller nodules: <10mm 23/60 (38.3%), 10-20mm 46/162 (28.4 %), and >20mm 80/466 (17.2%) (p<0.0001). Nodules with indeterminate cytology with atypical features (Thy3a) carried a similar malignancy risk to those with indeterminate cytology (Thy3/3f): 27/95 (28.4%) versus 42/113 (37.2%) respectively (p=0.18). Conclusion: Ultrasound alone appears to be an effective diagnostic modality in thyroid nodules, confirming the recommendations of recent guidelines and the BTA classification. However, findings also suggest caution regarding existing recommendations for conservative management of non-diagnostic (Thy1/Bethesda I) and atypical (Thy3a/Bethesda III) nodules. In those cases, ultrasound (U3-5) features may help identify high-risk subgroups for more proactive management.Publication Protocol for a feasibility and acceptability study for UK general population paediatric type 1 diabetes screening-the EarLy Surveillance for Autoimmune diabetes (ELSA) study(Wiley, 2024-12-02) Quinn, Lauren M; Dias, Renuka P; Greenfield, Sheila M; Richter, Alex G; Garstang, Joanna; Shukla, David; Acharjee, Animesh; Gkoutos, Georgios; Oram, Richard; Faustini, Sian; Boiko, Olga; Litchfield, Ian; Boardman, Felicity; Zakia, Fatima; Burt, Christine; Connop, Clair; Lepley, Amanda; Gardner, Christine; Dayan, Colin; Barrett, Tim; Narendran, Parth; Diabetes; Medical and Dental; Narendran, ParthAim: The EarLy Surveillance for Autoimmune (ELSA) study aims to explore the feasibility and acceptability of UK paediatric general population screening for type 1 diabetes. Methods: We aim to screen 20,000 children aged 3-13 years for islet-specific autoantibodies through dried blood spot sample collection at home, hospital or community settings. Children with two or more autoantibodies are offered metabolic staging via oral glucose challenge testing. Feasibility assessments will compare recruitment modalities and uptake according to demographic factors (age, gender, ethnicity, level of deprivation and family history of diabetes) to determine optimal approaches for general population screening. The study is powered to identify 60 children (0.3%) with type 1 diabetes (stage 1-3). Parents are invited to qualitative interviews following ELSA completion (child screened negative or positive, single autoantibody or multiple, stage 1-3) to share their screening experience, strengths of the programme and any areas for improvement (acceptability assessments). Parents who decline screening or withdraw from participation are invited to interview to explore any concerns. Finally, we will interview professional stakeholders delivering the ELSA study to explore barriers and facilitators to implementation. Conclusion: Early detection of type 1 diabetes allows insulin treatment to be started sooner, avoids diagnosis as an emergency, gives families time to prepare and the opportunity to benefit from future prevention trials and treatments. ELSA will provide essential feasibility and acceptability assessments for UK general population screening to inform a future national screening programme for paediatric type 1 diabetes.Publication To establish the utility of neck circumference as a novel and simple risk marker for detection of metabolic syndrome and cardiometabolic risk factors in Indians(Association of Physicians of India, 2024-12) Sahay, Nikita; Acharya, Raviraj V; Sahay, Kritika; Sahay, Manisha; University Hospitals Birmingham NHS Foundation Trust; Kasturba Hospital; Sahay Diabetic Clinic and Research Center; Osmania General Hospital; Internal Medicine; Medical and Dental; Sahay, NikitaIntroduction: Waist circumference (WC) is used as a measure of metabolic syndrome (MeS); neck circumference (NC) can predict MeS. It is simpler to measure and may provide an indication of obstructive sleep apnea (OSA). Materials and methods: NC was measured. The mean NC was correlated with the markers of MeS and sleep apnea. Results: A total of 183 participants were recruited in the study. The average age was 48.13 ± 13.3 years in men and 48.09 ± 11.1 years in women. The mean body mass index (BMI) was 26.42 ± 4.69 kg/m2 in men and 28.25 ± 4.92 kg/m2 in women. The mean WC in men and women were 91.1 ± 12.92 cm and 90.86 ± 12.7 cm, respectively, while the NC was 38.4 ± 6.60 cm in men and 33.9 ± 2.40 cm in women. MeS was diagnosed in 17.6% of men and 12.7% of women. Sleep apnea was noted in 33.1% of males and 29.2% of females. There was a positive correlation between the NC and systolic blood pressure (SBP) (r = 0.316 in males), fasting blood glucose (FBG) (r = 0.522 in males and 0.263 in females), triglyceride (TG) (r = 0.172 in males; 0.320 in females), while high-density lipoprotein cholesterol (HDL-C) showed a negative correlation in males and females. There was a positive correlation of NC with sleep duration in both males and females (r = 0.346 in males and 0.344 in females). Those with a NC of <35 cm had a sleep score of 7, while those with a NC of >35 cm had a score of 15, showing poor sleep quality. Conclusion: NC was comparable to WC and waist-hip ratio (WHR) for cardiometabolic risk factors and also showed a good association with sleep apnea.Publication Medications for obesity as preventatives: a public and patient safety issue(The Lancet, Diabetes & Endocrinology, 2024-11-26) Flint, Stuart W; Brown, Adrian; Vázquez-Velázquez, Verónica; Hazlehurst, Jonathan M; University of Leeds; University College London; University College London Hospital NHS Trust; National Institute of Health Research; Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; University of Birmingham; University Hospitals Birmingham NHS Foundation Trust; Endocrinology; Medical and Dental; Hazlehurst, JonathanNo abstract availablePublication The impact of closed-loop automated insulin delivery systems on hypoglycaemia awareness in people living with type 1 diabetes: a systematic review and meta-analysis(Springer International, 2024-09-05) Efthymiadis, Agathoklis; Bastounis, Anastasios; Liu, Linda; Bourlaki, Marianthi; Spinos, Dimitrios; Tsikopoulos, Konstantinos; London North West University Healthcare NHS Trust; University of Sheffield; University Hospitals Birmingham NHS Foundation Trust; South Warwickshire University Hospitals NHS Trust; Oxford University Hospitals NHS Trust; Ophthalmology; Medical and Dental; Bourlaki, MarianthiObjectives: Impaired awareness of hyperglycaemia (IAH) affects approximately 20-40% of people living with type 1 diabetes (T1D), predisposing them to severe hypoglycaemia. This systematic review evaluated the efficacy of closed-loop automated insulin delivery systems (CL-AID) in restoring IAH compared with standard diabetes care, including other diabetes technologies. Methods: Six electronic databases were searched for published and unpublished observational and randomised-control studies (RCTs) from inception to 29th of May 2024. The results of observational studies and RCTs were meta-analysed separately to calculate the effect of CL-AID on IAH in people living with T1D. Quality assessment of studies was performed using the Joanna-Briggs appraisal tool for cohort studies and the Risk of Bias (Rob-2) tool for RCTs. Results: Meta-analysis of four prospective observations studies (n = 583) demonstrated a statistically significant improvement in hypoglycaemia awareness upon transition to a hybrid closed-loop (HCL) system compared with standard diabetes care in people with T1D, Clarke score mean difference (MD) of -0.45 (-0.69 to -0.22, p = 0.0001). However, this was less than 1 point, which is the minimum clinically important difference (MCID) of Clarke score. Meta-analysis of three RCTs (n = 55) comparing standard diabetes care did not demonstrate any statistically significant effect on hypoglycaemia awareness, Clarke score MD of -0.69 (-1.89 to 0.50, p = 0.26). Conclusions: This systematic review demonstrated that transition from standard diabetes care to HCL has the potential to improve hypoglycaemia awareness in people with T1D and IAH, but this might not be of major clinical significance. Hence, psychoeducational interventions continue to be the cornerstone of IAH management. Novel therapeutic modalities, such as bi-hormonal automated delivery systems, need to be further explored to help restore hypoglycaemia awareness.Publication Efficacy of continuous glucose monitoring in people living with diabetes and end stage kidney disease on dialysis: a systematic review(BioMed Central, 2024-10-25) Zhang, Yimeng; Singh, Pushpa; Ganapathy, Kavitha; Suresh, Vijayan; Karamat, Muhammad Ali; Baharani, Jyoti; Bellary, Srikanth; General Medicine; Renal Medicine; Endocrinology and Diabetes; Medical and Dental; Zhang, Yimeng; Singh, Pushpa; Suresh, Vijayan; Karamat, Muhammad Ali; Baharani, Jyoti; Bellary, SrikanthBackground: Patients with diabetes on dialysis experience wide variations in glucose levels and an increased risk of hypoglycaemia. Due to the inaccuracies of HbA1c in dialysis patients, JBDS-IP and KDIGO recommend the use of continuous glucose monitoring (CGM). We conducted a systematic review to examine the current evidence for CGM use and its impact on clinical outcomes in patients with diabetes on dialysis. Methods: A search of MEDLINE(R) ALL, Ovid Emcare, Journals@Ovid Full Text and Embase databases were conducted. Clinical or observational trials in adults with Type 1(T1D) or Type 2 (T2D) diabetes on dialysis and CGM intervention reporting on glycaemic outcomes were included. Results: Of the 936 citations identified, 49 duplicates were removed. 887 citations were screened by title and abstract. 9 full texts were reviewed and a further 7 excluded due to duplications or failure to meet to selection criteria. Data was extracted for 2 studies, both prospective before-and-after interventional studies with no control group. Joubert et al. (2015) showed results for 15 participants with T1D. Mean CGM glucose level decreased from 8.37mmol/L at baseline to 7.7mmol/L at the end of the CGM period (p < 0.05) while HbA1c decreased from 6.9 to 6.5% (p < 0.05) during the same period. Mean CGM was lower on dialysis days (7.68mmol/L vs. 7.8mmol/L, p < 0.05). Képénékian et al. (2014) reported on data from 29 T2D patients. Following a 3 month CGM-adapted insulin regimen, HbA1c decreased from 8.4% at baseline to 7.6% (p < 0.01) by the end of study. Mean CGM values decreased from 9.9mmol/L to 8.9mmol/L (p = 0.05) and the frequency of glucose values > 10mmol/L decreased from 41 to 30% (p < 0.05), without a significant increase in hypoglycaemia frequency. Both studies were deemed to be of 'good' quality. Conclusion: Evidence demonstrating the benefits of CGM in patients with diabetes receiving dialysis is lacking. There is a need for well-designed randomised controlled trials to ascertain the benefits of this technology in this patient group. Trail registration: PROSPERO registration number: CRD42023371635, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=371635 .Publication Response to commentary "Vasopressin deficiency following operated craniopharyngiomas: fear or fatality?".(Oxford University Press, 2024-10-29) Fountas, Athanasios; Karavitaki, Niki; Endocrinology; Medical and Dental; Karavitaki, NikiNo abstract available