Multi-disciplinary diabetic limb salvage programme in octogenarians with diabetic foot ulcers is not futile: An observational study with historical controls.

This study evaluated the effectiveness of a multi-disciplinary diabetic limb salvage programme in improving clinical outcomes and optimising healthcare utilisation in 406 patients aged ≥80 years with diabetic foot ulcers (DFUs), compared to 2392 younger patients enrolled from June 2020 to June 2021 and against 1716 historical controls using one-to-one propensity score matching. Results showed that elderly programme patients had lower odds of amputation-free survival (odds ratio: 0.64, 95% CI: 0.47, 0.88) and shorter cumulative length of stay (LOS) compared to younger programme patients (incidence rate ratio: 0.45, 95% CI: 0.29, 0.69). Compared to the matched controls, participating in the programme was associated with 5% higher probability of minor lower extremity amputation, reduced inpatient admissions and emergency visits, shorter LOS but increased specialist and primary care visits (all p-values <0.05). The findings suggest that the programme yielded favourable impacts on the clinical outcomes of patients aged≥80 years with DFUs. Further research is needed to develop specific interventions tailoring to the needs of the elderly population and to determine their effectiveness on patient outcomes while accounting for potential confounding factors.

Patients, carers and healthcare providers' perspectives on a patient-owned surveillance system for diabetic foot ulcer care: A qualitative study.

Objective: Digital health has recently gained a foothold in monitoring and improving diabetes care. We aim to explore the views of patients, carers and healthcare providers (HCPs) regarding the use of a novel patient-owned wound surveillance application as part of outpatient management of patients with diabetic foot ulcers (DFUs). Methods: Semi-structured online interviews were conducted with patients, carers and HCPs in wound care for DFUs. The participants were recruited from a primary care polyclinic network and two tertiary hospitals in Singapore, within the same healthcare cluster. Purposive maximum variation sampling was used to select participants with differing attributes to ensure heterogeneity. Common themes relating to the wound imaging app were captured. Results: A total of 20 patients, 5 carers and 20 HCPs participated in the qualitative study. None of the participants have used a wound imaging app before. Regarding a patient-owned wound surveillance app, all were open and receptive to the system and workflow for use in DFU care. Four major themes emerged from patients and carers: (1) technology, (2) application features and usability, (3) feasibility of using the wound imaging application and (4) logistics of care. Four major themes were identified from HCPs: (1) attitudes towards wound imaging app, (2) preferences regarding functionality, (3) perceived challenges for patients/carers and (4) perceived barriers for HCPs. Conclusion: Our study highlighted several barriers and facilitators from patients, carers and HCPs regarding the use of a patient-owned wound surveillance app. These findings demonstrate the potential of digital health and areas to improve and tailor a DFU wound app suitable for implementation in the local population.

Diabetic foot in primary and tertiary (DEFINITE) Care: A health services innovation in coordination of diabetic foot ulcer (DFU) Care within a healthcare cluster - 18-month results from an observational population health cohort study.

Diabetic Foot in Primary and Tertiary (DEFINITE) Care is an inter-institutional and multi-disciplinary team (MDT) health systems innovation programme at a healthcare cluster in Singapore. We aim to achieve coordinated MDT care across primary and tertiary care for patients with diabetic foot ulcers (DFU), within our public healthcare cluster - an integrated network of seven primary care polyclinics and two acute care tertiary hospitals (1700-bed and 800-bed) with a total catchment population of 2.2 million residents. Results from prospective DEFINITE Care is referenced against a retrospective 2013-2017 cohort, which was previously published. Cardiovascular profile of the study population is compared against the same population's profile in the preceding 12 months. Between June 2020 and December 2021, there were 3475 unique patients with DFU with mean age at 65.9 years, 61.2% male, mean baseline HbA1c at 8.3% with mean diabetes duration at 13.3 years, mean diabetes complication severity index (DCSI) at 5.6 and mean Charlson Comorbidity Index (CCI) at 6.8. In the 12-months preceding enrolment to DEFINITE Care, 35.5% had surgical foot debridement, 21.2% had minor lower extremity amputation (LEA), 7.5% had major LEA whilst 16.8% had revascularisation procedures. At 18-months after the implementation of DEFINITE Care programme, the absolute minor and major amputation rates were 8.7% (n = 302) and 5.1% (n = 176), respectively, equating to a minor and major LEA per 100000 population at 13.7 and 8.0, respectively. This represents an 80% reduction in minor amputation rates (P < .001) and a 35% reduction in major amputation rates (P = .005) when referenced against a retrospective 2013-2017 cohort, which had minor and major LEA per 100000 population at 68.9 and 12.4, respectively. As compared to the preceding 12 months, there was also a significant improvement in cardiovascular profile (glycemic and lipid control) within the DEFINITE population, with improved mean HbAc1 (7.9% from 8.4%, P < .001), low-density lipoprotein (LDL) levels (2.1 mmol/L from 2.2, P < .001), total cholesterol (3.9 mmol/L from 4.1, P < .001) and triglycerides levels (1.6 mmol/L from 1.8, P = .002). Multivariate analysis revealed a history of minor amputation in the preceding 12 months to be an independent predictor for major and minor amputation within the study period of 18 months (Hazard Ratio 3.4 and 1.8, respectively, P < .001). In conclusion, within DEFINITE care, 18-month data showed a significant reduction of minor and major LEA rates, with improved medical optimisation and cardiovascular profile within the study population.

SARS-CoV-2 mRNA Vaccination and Graves' Disease: A Report of 12 Cases and Review of the Literature.

CONTEXT AND OBJECTIVE: Thyroid autoimmunity has been reported to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the SARS-CoV-2 vaccination recently. We report a series of patients who presented with new onset or relapse of Graves' disease-related hyperthyroidism shortly after receiving the SARS-CoV-2 messenger RNA (mRNA) vaccine at a single tertiary institution in Singapore. METHODS AND RESULTS: We describe 12 patients who developed hyperthyroidism within a relatively short interval (median onset, 17 [range, 5-63] days) after receiving the SARS-CoV-2 mRNA vaccine. The majority were females (11/12) with median age of 35.5 (range, 22-74) years. Six patients had new-onset hyperthyroidism, whereas the other 6 had relapse of previously well-controlled Graves' disease. TSH receptor antibody concentrations ranged from 2.4 to 32 IU/L. The majority of the patients were able to go for the second dose of the vaccine without any further exacerbations. Literature review revealed 21 other similar cases reported from across the world. CONCLUSION: Our case series provides insight into the characteristics of individuals in whom Graves' disease was triggered by the SARS-CoV-2 vaccination. Clinicians need to be vigilant of precipitation or exacerbation of autoimmune thyroid disorders in predisposed individuals after exposure to the SARS-CoV-2 vaccination. Further epidemiological and mechanistic studies are required to elucidate the possible associations between the SARS-CoV-2 vaccines and the development of thyroid autoimmunity.

Clinical and economic outcomes of a multidisciplinary team approach in a lower extremity amputation prevention programme for diabetic foot ulcer care in an Asian population: A case-control study.

Present guidelines recommend a multidisciplinary team (MDT) approach to diabetic foot ulcer (DFU) care, but relevant data from Asia are lacking. We aim to evaluate the clinical and economic outcomes of an MDT approach in a lower extremity amputation prevention programme (LEAPP) for DFU care in an Asian population. We performed a case-control study of 84 patients with DFU between January 2017 and October 2017 (retrospective control) vs 117 patients with DFU between December 2017 and July 2018 (prospective LEAPP cohort). Comparing the clinical outcomes between the retrospective cohort and the LEAPP cohort, there was a significant decrease in mean time from referral to index clinic visit (38.6 vs 9.5 days, P < .001), increase in outpatient podiatry follow-up (33% vs 76%, P < .001), decrease in 1-year minor amputation rate (14% vs 3%, P = .007), and decrease in 1-year major amputation rate (9% vs 3%, P = .05). Simulation of cost avoidance demonstrated an annualised cost avoidance of USD $1.86m (SGD $2.5m) for patients within the LEAPP cohort. In conclusion, similar to the data from Western societies, an MDT approach in an Asian population, via a LEAPP for patients with DFU, demonstrated a significant reduction in minor and major amputation rates, with annualised cost avoidance of USD $1.86m.

Metabolic effects of brown fat in transitioning from hyperthyroidism to euthyroidism.

OBJECTIVE: Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. DESIGN: Participants with newly diagnosed Graves' disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. RESULTS: Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). CONCLUSION: Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.

A Novel HNF4A Mutation Causing Three Phenotypic Forms of Glucose Dysregulation in a Family.

Maturity-onset diabetes of the young (MODY) classically describes dominantly inherited forms of monogenic diabetes diagnosed before 25 years of age due to pancreatic ß-cell dysfunction. In contrast, mutations in certain MODY genes can also present with transient or persistent hyperinsulinemic hypoglycemia in newborn infants, reflecting instead ß-cell dysregulation. Of the MODY genes described to date, only hepatocyte nuclear factor-4-alpha (HNF4A; MODY1) and hepatocyte nuclear factor-1-alpha (HNF1A; MODY3) mutations may result in a biphasic phenotype of hypoglycemia in early life and hyperglycemia in later life. We report a family with a novel HNF4A mutation with diverse phenotypic presentations of glucose dysregulation. The proband was a term, appropriate-for-gestational age male infant with symptomatic hypoglycemia on day 3 of life needing high glucose infusion rate to maintain normoglycemia. He was born to a non-obese and non-diabetic mother. Glucose regulation was optimized using diazoxide upon confirmation of hyperinsulinism. Cascade genetic screening identified the same mutation in his father and elder sister, but mother was negative. Father was diagnosed with Type 1 diabetes at 15 years of age that required insulin therapy. Proband's elder sister, born at term appropriate for gestational age, presented with transient neonatal hypoglycemia needing parenteral glucose infusion for a week followed by spontaneous resolution. The paternal grandparents were negative for this mutation, confirming a paternal de novo mutation and autosomal dominant inheritance in this family. This pedigree suggests that the presence of early-onset paternal diabetes should prompt molecular testing in infants presenting in the newborn period with diazoxide-responsive hyperinsulinemic hypoglycemia, even in the absence of maternal diabetes and macrosomia.

The Development of a Diabetes Application for Patients With Poorly Controlled Type 2 Diabetes Mellitus.

The prevalence of patients with diabetes mellitus has increased in recent years. This has resulted in increased demand for face-to-face diabetes education by diabetes nurse clinicians. The use of mobile-health technologies in diabetes education is an innovative way of learning and has the potential to engage patients and influence positive health behaviors, including meeting desired goals and diabetes-related outcomes. The aim of the study was to develop and test the usability and feasibility of an empirical diabetes application for patients with type 2 diabetes mellitus. The mobile-based, gamified Diabetes Application was developed based on a full systems development life-cycle framework. Eight patients with poorly controlled type 2 diabetes mellitus completed a pilot study that consisted of a postapplication survey to assess the usability and feasibility of the diabetes application. The findings affirmed the usefulness and feasibility of the diabetes application for patients with diabetes mellitus. It increased awareness, enriched knowledge, promoted user engagement, motivated positive behaviors, and affirmed patient belief in diabetes self-management. This article discusses the development and evaluation of the diabetes application, including modifications made based on the results of the pilot study.

ENDOCRINE TRAINEES EXHIBIT SENSITIVE BUT CONSERVATIVE ATTITUDES TOWARDS THE MANAGEMENT OF ENDOCRINE CONDITIONS IN HIV PATIENTS IN SINGAPORE.

OBJECTIVE: With advances in the treatment of human immunodeficiency virus (HIV) infections, the life expectancy of people with HIV (PWH) is fast approaching that of the general population. Endocrine and metabolic disorders occur more frequently in PWH than in the general population. This study assessed the knowledge, practice patterns, and confidence levels among endocrinology trainees in Singapore in managing endocrine disorders in PWH. METHODS: An anonymous, 31-item survey was administered to 23 endocrinology trainees. Four domains were assessed: (1) previous exposure to endocrine disorders in PWH; (2) attitudes towards treating PWH, (3) case studies in endocrinology designed to assess for differences in treatment philosophy between a PWH and a noninfected counterpart, and (4) confidence in managing endocrine disorders in PWH. RESULTS: The participation rate was 73.9%, with the majority of trainees (88.2%) having managed fewer than 5 PWH with endocrine disorders. A total of 94.1% of the trainees had little or no hesitation in treating PWH, but more than half (58.8%) felt inadequate in confidently managing them. A total of 82.4% deemed HIV endocrinology as an emerging field and were open to the idea of pursuing it as a subspecialty in the future. Re-assuringly, most trainees would not compromise medical treatment for a PWH if it were indicated. More than half were ambivalent about prescribing cross-hormonal therapy to transgender individuals. CONCLUSION: Endocrinology trainees feel that while HIV endocrinology is an emerging field, they lack exposure, training, and confidence in the management of these patients. Although they would treat medical conditions well, they lacked knowledge in hormonal treatment of transgender individuals. ABBREVIATIONS: HIV = human immunodeficiency virus PWH = people with HIV.

Hyperparathyroidism due to eutopic PTH secretion from an ectopic intrathymic parathyroid cyst.

Parathyroid cysts rarely cause hyperparathyroidism. In addition, they rarely occur in the thymus. We report a 56-year-old woman with hypertension on telmisartan and hydrochlorothiazide, who developed symptomatic hypercalcemia for a month. Initial serum calcium was 15.6 mg/dL, together with inappropriately elevated intact PTH at 437 pg/mL. Coincidentally, an anterior mediastinal mass on chest imaging was found. Biopsy of the mass revealed parathyroid tissue. She was treated sequentially with saline rehydration and frusemide calciuresis, intravenous pamidronate and calcitonin, which lowered her calcium to 11.1 mg/dL. Normocalcemia was finally achieved following surgical extirpation of the mass. Histology confirmed an intrathymic parathyroid cyst. Definitive treatment by resection of the mass is potentially curative.