Postradioiodine Graves' management: The PRAGMA study.

OBJECTIVE: Thyroid status in the months following radioiodine (RI) treatment for Graves' disease can be unstable. Our objective was to quantify frequency of abnormal thyroid function post-RI and compare effectiveness of common management strategies. DESIGN: Retrospective, multicentre and observational study. PATIENTS: Adult patients with Graves' disease treated with RI with 12 months' follow-up. MEASUREMENTS: Euthyroidism was defined as both serum thyrotropin (thyroid-stimulating hormone [TSH]) and free thyroxine (FT4) within their reference ranges or, when only one was available, it was within its reference range; hypothyroidism as TSH ≥ 10 mU/L, or subnormal FT4 regardless of TSH; hyperthyroidism as TSH below and FT4 above their reference ranges; dysthyroidism as the sum of hypo- and hyperthyroidism; subclinical hypothyroidism as normal FT4 and TSH between the upper limit of normal and <10 mU/L; and subclinical hyperthyroidism as low TSH and normal FT4. RESULTS: Of 812 patients studied post-RI, hypothyroidism occurred in 80.7% and hyperthyroidism in 48.6% of patients. Three principal post-RI management strategies were employed: (a) antithyroid drugs alone, (b) levothyroxine alone, and (c) combination of the two. Differences among these were small. Adherence to national guidelines regarding monitoring thyroid function in the first 6 months was low (21.4%-28.7%). No negative outcomes (new-onset/exacerbation of Graves' orbitopathy, weight gain, and cardiovascular events) were associated with dysthyroidism. There were significant differences in demographics, clinical practice, and thyroid status postradioiodine between centres. CONCLUSIONS: Dysthyroidism in the 12 months post-RI was common. Differences between post-RI strategies were small, suggesting these interventions alone are unlikely to address the high frequency of dysthyroidism.

Burnout among diabetes specialist registrars across the United Kingdom in the post-pandemic era.

Introduction: Burnout syndrome is a condition resulting from chronic work-related stress exposure and can be identified by the presence of one or more of the three classic dimensions of burnout, i.e., emotional exhaustion, depersonalization, and lack of personal accomplishment, which negatively impact physician health and productivity. Objective: This study aimed to identify burnout among Diabetes and Endocrinology Specialty Training Registrars (DStRs) across the United Kingdom. Design/setting: It was a Cross-sectional observational study after ethical approval ERSC_2022_1166, utilizing the gold standard Maslach Burnout Inventory to measure burnout syndrome, and to determine self-reported stressors and compare them with the results of our previous survey in 2018. Participants: Over 430 DStRs across the United Kingdom were invited electronically through their deanery representatives and specialty training bodies. Results: Using Google Forms™ to gather data, we were able to collect 104 completed surveys. Results revealed that 62.5% (n = 65) of participants have burnout (5% increase from the previous survey in 2018), 38.6% (n = 40) have high emotional exhaustion, and 44.2% (n = 46) feel a lack of personal accomplishment. "General Internal Medicine specific workload" was the most common self-reported stressor reported by 87.5% (n = 91) of participants, whereas bullying/harassment and discrimination at work were reported by 35.6% (n = 37) and 30.77% (n = 32) of participants, respectively. Using multivariable logistic regression model, personal stress (OR, 4.00; 95% CI, 1.48-10.86; p = 0.006) had significant, while Bullying/harassment (OR, 3.75; 95% CI, 0.93-15.12; p = 0.063) had marginal impact on the presence of burnout. Conclusion: Diabetes and Endocrinology Specialty Training Registrars frequently experience burnout syndrome, which has increased over the last 4 years. However, organizational changes can help identify, prevent, and treat physician burnout. Trial registration: NCT05481021 available at https://ichgcp.net/clinical-trials-registry/NCT05481021.

Level of adherence to vitamin D supplementation guidelines in an antenatal centre in Birmingham, UK, and its effect on biochemical and obstetrical outcomes: a single-centre cross-sectional study.

OBJECTIVES: A third of pregnant women in the UK are vitamin D deficient, which may confer deleterious consequences, including an increased risk of pre-eclampsia, gestational diabetes mellitus and intrauterine growth restriction. This study aims to determine the proportion of women that met National Institute for Health and Care Excellence (NICE) standards for vitamin D supplementation in pregnancy and compare biochemical and obstetrical outcomes according to supplementation status. DESIGN AND SETTING: This is a single-centre cross-sectional study in an antenatal centre in Birmingham, UK. Participants received a questionnaire regarding their experiences with vitamin D supplementation during their pregnancy with their general practitioner. Serum 25-hydroxyvitamin D and bone profile results were obtained during the same appointment and obstetrical outcomes were collected retrospectively once participants had delivered. RESULTS: 41.8% of participants (n=61) received written and/or verbal advice about supplementation, (NICE standards=100%). 72.6% (n=106) had one or more risk factors for vitamin D deficiency, of which 38.7% (n=41, NICE standards=100%) were asked about supplementation. Among those asked, 85.4% (n=41, NICE standards=100%) received the correct dosage. Compared with the supplementation group, the non-supplementation group had offspring that were 1.40 cm (95% CI 0.01 to 2.80, p=0.04) longer at birth; which was significant after adjusting for confounding factors. No significant differences in any biochemical parameters were observed between supplementation categories (p>0.05). CONCLUSIONS: Adherence to NICE standards was suboptimal. This may be attributed to insufficient training for general practitioners on the importance of supplementation, causing them to underestimate the consequences of gestational vitamin D deficiency. Recommendations include implementing a mandatory screening tool to identify 'at-risk' women and providing more clinician training to ensure that supplementation during pregnancy is standard of care.

Hypertension is the major predictor of poor outcomes among inpatients with COVID-19 infection in the UK: a retrospective cohort study.

OBJECTIVE: To assess the impact of diabetes, hypertension and cardiovascular diseases on inpatient mortality from COVID-19, and its relationship to ethnicity and social deprivation. DESIGN: Retrospective, single-centre observational study SETTING: Birmingham, UK. PARTICIPANTS: 907 hospitalised patients with laboratory-confirmed COVID-19 from a multi-ethnic community, admitted between 1 March 2020 and 31 May 2020. MAIN OUTCOME MEASURES: The primary analysis was an evaluation of cardiovascular conditions and diabetes in relation to ethnicity and social deprivation, with the end-point of inpatient death or death within 30 days of discharge. A multivariable logistic regression model was used to calculate HRs while adjusting for confounders. RESULTS: 361/907 (39.8%) died in hospital or within 30 days of discharge. The presence of diabetes and hypertension together appears to confer the greatest mortality risk (OR 2.75; 95% CI 1.80 to 4.21; p<0.001) compared with either condition alone. Age >65 years (OR 3.32; 95% CI 2.15 to 5.11), male sex (OR 2.04; 95% CI 1.47 to 2.82), hypertension (OR 1.69; 95% CI 1.10 to 2.61) and cerebrovascular disease (OR 1.87; 95% CI 1.31 to 2.68) were independently associated with increased risk of death. The mortality risk did not differ between the quintiles of deprivation. High-sensitivity troponin I was the best predictor of mortality among biomarkers (OR 4.43; 95% CI 3.10 to 7.10). Angiotensin-receptor blockers (OR 0.57; 95% CI 0.33 to 0.96) and ACE inhibitors (OR 0.65; 95% CI 0.43 to 0.97) were not associated with adverse outcome. The Charlson Index of Comorbidity scores were significantly higher in non-survivors. CONCLUSIONS: The combined prevalence of hypertension and diabetes appears to confer the greatest risk, where diabetes may have a modulating effect. Hypertension and cerebrovascular disease had a significant impact on inpatient mortality. Social deprivation and ethnicity did not have any effect once the patient was in hospital.

Young Asian men with diabetes have the highest risk for acute coronary events: retrospective cohort analyses.

OBJECTIVE: To understand the ethnic differences in coronary heart disease risk among inpatients with diabetes following acute coronary syndrome. DESIGN: Single-centre retrospective cohort-analysis of patients with type II diabetes over a six-year period receiving standard care. SETTING: Birmingham, UK. PARTICIPANTS: One thousand and one hundred and five patients with type II diabetes from a multi-ethnic background. MAIN OUTCOME MEASURES: Odds ratios of coronary heart disease events among three ethnic groups. RESULTS: The prevalence of coronary heart disease events was 20.7% in Asian, 13.2% in Caucasian and 7.7% in Afro-Caribbean patients. Asian patients were younger at diagnosis of diabetes (-5.1 years p < 0.001 versus Afro-Caribbeans and -7.1 years p < 0.001 versus Caucasians). The mean number of events was highest amongst Asian (1.2) compared to Caucasian (1.1) and Afro-Caribbean (1.0) patients (p = 0.04). The mean age at first event was 61.3 years for Asians, 62.5 years and 65.8 for Afro-Caribbeans and Caucasians, respectively (analysis of variance F[2,131] = 2.36 p = 0.09). Un-adjusted odds ratios for at least one coronary heart disease event were highest among Asian men (OR 5.04; 95% CI 2.31-11.01; p < 0.0001) with Afro-Caribbean women as baseline (OR 1.0). The odds ratios remain largely unchanged (1.0 Afro-Caribbeans [baseline], 1.27 [p = 0.56] Caucasians and 3.2 [p = 0.001] for Asians) when corrected for age, gender, duration of diabetes, insulin dependency, mean low-density lipoprotein-cholesterol, triglycerides and high-density lipoprotein-cholesterol, mean glycated haemoglobin, mean systolic and diastolic blood pressure (logistic regression; ROC: 79% AUC). Afro-Caribbean patients had the highest mean high-density lipoprotein-cholesterol (1.6 mmol/L) and the lowest risk for coronary heart disease events. CONCLUSIONS: Asian patients were younger at their first event and diagnosed earlier with diabetes. Asian men had the highest risk of coronary heart disease event which correlated with the lowest levels of high-density lipoprotein-cholesterol.

Digital image compression should be limited in diabetic retinopathy screening.

Digital colour retinal photography is a useful modality for diabetic retinopathy screening. Unlike film photography, the size of the image depends on the resolution of the acquired image. With the availability of high-resolution digital cameras, larger images requiring greater storage-memory will inevitably be generated. Image compression may then be necessary so that these images can be viewed conveniently, archived and transmitted across computer networks. Unfortunately with the paucity of clinical studies on retinal image compression, more research is necessary to develop evaluation tools to identify optimum image compression ratios for diabetic retinopathy screening.

A rare case of carbimazole-induced hepatitis in a patient with Graves' disease.

Although carbimazole-induced hepatitis is rare, clinicians should be aware of this potential complication and offer alternative treatment early.

New treatment options for erectile dysfunction in patients with diabetes mellitus.

Erection is a neurovascular event that involves spinal and supra spinal pathways. The final common pathway involves the release of nitric oxide (NO) from both endothelial cells and neurons, which acts as a vasodilator causing penile engorgement and erection. NO is degraded by the enzyme phosphodiesterase (PDE) type 5 in the penis. Erectile dysfunction (ED), defined as the persistent inability to achieve and/or maintain an erection sufficient for satisfactory sexual performance, results when the neurovascular pathway is interrupted by medical conditions or drugs. A 15-item self-administered questionnaire, the International Index of Erectile Function (IIEF), is one of the most useful tools to evaluate erectile function (EF) in clinical trials, although of much less use in routine clinical practice. The MMAS (Massachusetts Male Aging Study) was the first major epidemiological investigation to study the prevalence of ED. The study found that ED was three times more common in patients with diabetes mellitus. The aetiopathogenesis of ED in diabetes is multifactorial, with vascular and neural factors being equally implicated. Hyperglycaemia is believed to give rise to biochemical perturbations that lead to these microvascular changes. In the MMAS, ED in diabetes was strongly correlated with glycaemic control, duration of disease and diabetic complications. The incidence increased with increasing age, duration of diabetes and deteriorating metabolic control, and was higher in individuals with type 2 diabetes than those with type 1.ED in men with diabetes often affects their quality of life and, as patients are often reluctant to come forward with their symptoms, a carefully taken history is one of the most useful approaches in identifying affected individuals. The PDE inhibitors have revolutionised the management of ED and oral drug therapy is currently first-line therapy for the condition. These agents act by potentiating the action of intracavernosal NO, thereby leading to a more sustained erection. Sildenafil was the first PDE5 inhibitor to undergo evaluation and has been studied extensively. More recently two other agents, vardenafil and tadalafil, have been introduced. All the drugs have been shown to be effective across a wide range of aetiologies of ED, including diabetes. The drugs have been shown to improve EF domain scores, penetration and maintenance of erection, resulting in more successful intercourse. Their effects are greater at higher doses. Sildenafil and vardenafil are shorter-acting agents, while tadalafil has a longer half-life allowing the user more flexibility in sexual activity. Common adverse effects include headache, nasal congestion and dyspepsia, all actions related to inhibition of PDE5. The drugs are generally well tolerated and withdrawal from the clinical studies as a result of drug-related adverse effects were rare. The use of PDE5 inhibitors in the presence of oral nitrates is absolutely contraindicated. The clinical studies to date have not evaluated the use of one drug in the case of treatment failure with another agent. Sublingual apomorphine, which stimulates central neurogenic pathways, is a new agent and may be a suitable alternative in those patients in whom PDE5 inhibitors are ineffective or contraindicated. In clinical trials, all IIEF domains except sexual desire were found to have improved after apomorphine. The median times to erection in these studies were 18.9 and 18.8 minutes for the 2 and 3mg doses, respectively. Intraurethral and intracavernosal alprostadil may be a useful alternative when oral drug therapy is ineffective or contraindicated. The management of ED in the diabetic patient may often involve a multidisciplinary approach where psychosexual counselling and specialist urologist advice is required in addition to the skills and expertise of the diabetologist. Finally, the introduction of the new oral agents have completely revolutionised the management of ED and allowed more individuals to come forward for treatment.

Measurement of retinal vessel widths from fundus images based on 2-D modeling.

Changes in retinal vessel diameter are an important sign of diseases such as hypertension, arteriosclerosis and diabetes mellitus. Obtaining precise measurements of vascular widths is a critical and demanding process in automated retinal image analysis as the typical vessel is only a few pixels wide. This paper presents an algorithm to measure the vessel diameter to subpixel accuracy. The diameter measurement is based on a two-dimensional difference of Gaussian model, which is optimized to fit a two-dimensional intensity vessel segment. The performance of the method is evaluated against Brinchmann-Hansen's half height, Gregson's rectangular profile and Zhou's Gaussian model. Results from 100 sample profiles show that the presented algorithm is over 30% more precise than the compared techniques and is accurate to a third of a pixel.

Optic nerve head segmentation.

Reliable and efficient optic disk localization and segmentation are important tasks in automated retinal screening. General-purpose edge detection algorithms often fail to segment the optic disk due to fuzzy boundaries, inconsistent image contrast or missing edge features. This paper presents an algorithm for the localization and segmentation of the optic nerve head boundary in low-resolution images (about 20 microns/pixel). Optic disk localization is achieved using specialized template matching, and segmentation by a deformable contour model. The latter uses a global elliptical model and a local deformable model with variable edge-strength dependent stiffness. The algorithm is evaluated against a randomly selected database of 100 images from a diabetic screening programme. Ten images were classified as unusable; the others were of variable quality. The localization algorithm succeeded on all bar one usable image; the contour estimation algorithm was qualitatively assessed by an ophthalmologist as having Excellent-Fair performance in 83% of cases, and performs well even on blurred images.

Low failure rate of fixed administered activity of 400 MBq 131I with pre-treatment with carbimazole for thyrotoxicosis: the Gateshead Protocol.

BACKGROUND: Thyrotoxicosis is associated with significant morbidity, therefore adequate control of the disease is paramount. The outcome of treatment of thyrotoxicosis using radioiodine shows variable failure rates depending, amongst other things, on the administered activity of radioiodine and the use of anti-thyroid drugs. Thus, management should follow an evidence based protocol, which has a low failure rate. METHOD: We prospectively analysed the outcome of treatment using our Gateshead protocol of a fixed administered activity of radioiodine therapy (400 MBq) given to 201 patients (including 140 with Graves' disease, 48 with toxic multinodular goitre (TMNG) and 13 with toxic nodule) followed up for a median period of 12 months (range, 6-77 months). Carbimazole was discontinued in patients rendered euthyroid 16 days prior to radioiodine. No routine anti-thyroid drugs or thyroxine were given following radioiodine unless hypothyroidism or thyrotoxicosis occurred. RESULTS: Following the Gateshead protocol led to a failure rate of 6.5% (eight females with Graves' disease, four females with TMNG and one female with toxic nodule), 29% euthyroidism and 64% hypothyroidism. The rates of hypothyroidism for women and for men were: in Graves' disease 77% and 79%, in TMNG 29% and 75%, in toxic nodule 42% and 0%, respectively. CONCLUSIONS: Our observations show that withholding an antithyroid drug in excess of just over 2 weeks prior to administering a fixed administered activity of radioiodine in patients with thyrotoxicosis leads to the lowest reported failure rate, irrespective of the underlying cause. One possible mechanism for this could be the avoidance of drug induced radio-resistance.

The syndrome of inappropriate antidiuresis is associated with excess long-term mortality: a retrospective cohort analyses.

INTRODUCTION: The syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of euvolaemic hyponatraemia in patients admitted to hospital. The mortality after discharge from hospital has not been previously studied in patients with SIAD. AIMS: To compare mortality in patients with SIAD and those with kidney injury (KI). To identify underlying diagnoses associated with deaths due to SIAD. METHODS: Single-centre retrospective cohort analyses of 804 patients with severe hyponatraemia over a 3-year period. Five-year survival data in patients with SIAD and those with KI were compared. The underlying diagnoses that contributed to SIAD in this cohort were analysed using ICD-10 codes. RESULTS: 202 patients had SIAD using biochemical cut-off parameters; 248 patients had KI. Patient with KI had a statistically significant (log-rank p<0.0001) shorter median survival time (2.24 months (95% CI 1.3 to 4.3)) compared with those with SIAD (31.0 months (95% CI 21.6 to 54.8)). 53.8% (n=78) of patients with hyponatraemia due to SIAD died within the first year after admission; the corresponding figure for those presenting with KI was 74.1% (n=166). Five years after admission, 80.8% (n=117) of those with SIAD had died; the corresponding figure for those with KI was 88.4% (n=200). In those patients with SIAD that died within the first year, malignancy appeared to be the most common cause (25.4%) followed by infection (23.8%). CONCLUSIONS: Severe hyponatraemia in SIAD carries a high mortality after discharge, and although this seems often to be attributable to the underlying cause, the extent to which treatment with V2-recptor antagonists may help to correct the hyponatraemia associated with SIAD and influence the medium-to-long-term outcome in such patients is worthy of further study.

An automated retinal image quality grading algorithm.

This paper introduces an algorithm for the automated assessment of retinal fundus image quality grade. Retinal image quality grading assesses whether the quality of the image is sufficient to allow diagnostic procedures to be applied. Automated quality analysis is an important preprocessing step in algorithmic diagnosis, as it is necessary to ensure that images are sufficiently clear to allow pathologies to be visible. The algorithm is based on standard recommendations for quality analysis by human screeners, examining the clarity of retinal vessels within the macula region. An evaluation against a reference standard data-set is given; it is shown that the algorithm's performance correlates closely with that of clinicians manually grading image quality.

Automated diagnosis of referable maculopathy in diabetic retinopathy screening.

This paper introduces an algorithm for the automated diagnosis of referable maculopathy in retinal images for diabetic retinopathy screening. Referable maculopathy is a potentially sight-threatening condition requiring immediate referral to an ophthalmologist from the screening service, and therefore accurate referral is extremely important. The algorithm uses a pipeline of detection and filtering of "peak points" with strong local contrast, segmentation of candidate lesions, extraction of features and classification by a multilayer perceptron. The optic nerve head and fovea are detected, so that the macula region can be identified and scanned. The algorithm is assessed against a reference standard database drawn from the Birmingham City Hospital (UK) diabetic retinopathy screening programme, against two possible modes of use: independent screening, and pre-filtering to reduce human screener workload.