Injectable semaglutide and reductions in HbA1c and weight in the real world in people switched from alternative glucagon-like peptide-1 receptor agonists.

The ABCD semaglutide audit was designed to capture the routine clinical outcomes of people commenced on semaglutide in the UK. Previous work showed differential reductions in HbA1c and weight dependent on previous glucagon-like peptide-1 receptor agonist (GLP-1RA) exposure. The analysis, in this research letter, shows that decreases in HbA1c and weight associated with semaglutide occur irrespective of previous GLP-1RA use. However, HbA1c reductions were less if switched from dulaglutide or liraglutide and weight changes were attenuated if switched from dulaglutide or exenatide, potentially suggesting differing potencies between GLP-1RAs. Dedicated studies with head-to-head comparisons are needed to confirm these findings.

Using differential item functioning to evaluate potential bias in a high stakes postgraduate knowledge based assessment.

BACKGROUND: Fairness is a critical component of defensible assessment. Candidates should perform according to ability without influence from background characteristics such as ethnicity or sex. However, performance differs by candidate background in many assessment environments. Many potential causes of such differences exist, and examinations must be routinely analysed to ensure they do not present inappropriate progression barriers for any candidate group. By analysing the individual questions of an examination through techniques such as Differential Item Functioning (DIF), we can test whether a subset of unfair questions explains group-level differences. Such items can then be revised or removed. METHODS: We used DIF to investigate fairness for 13,694 candidates sitting a major international summative postgraduate examination in internal medicine. We compared (a) ethnically white UK graduates against ethnically non-white UK graduates and (b) male UK graduates against female UK graduates. DIF was used to test 2773 questions across 14 sittings. RESULTS: Across 2773 questions eight (0.29%) showed notable DIF after correcting for multiple comparisons: seven medium effects and one large effect. Blinded analysis of these questions by a panel of clinician assessors identified no plausible explanations for the differences. These questions were removed from the question bank and we present them here to share knowledge of questions with DIF. These questions did not significantly impact the overall performance of the cohort. Group-level differences in performance between the groups we studied in this examination cannot be explained by a subset of unfair questions. CONCLUSIONS: DIF helps explore fairness in assessment at the question level. This is especially important in high-stakes assessment where a small number of unfair questions may adversely impact the passing rates of some groups. However, very few questions exhibited notable DIF so differences in passing rates for the groups we studied cannot be explained by unfairness at the question level.

Hormone replacement therapy for women with type 1 diabetes mellitus.

BACKGROUND: There is conflicting information about the impact of the menopause on glycaemic control amongst women with type 1 diabetes. Some menopausal women with type 1 diabetes are treated with hormone replacement therapy (HRT) but the effects of this treatment have, to date, not been established. OBJECTIVES: To assess the effects of HRT for women with type 1 diabetes mellitus. SEARCH METHODS: We searched The Cochrane Library, MEDLINE, EMBASE, CINAHL and PsycINFO from their inception to June 2012. The last search was run for all databases on 18 June 2012. SELECTION CRITERIA: We selected randomised controlled trials or controlled clinical trials that involved peri- or postmenopausal women with type 1 diabetes undergoing HRT as an intervention. DATA COLLECTION AND ANALYSIS: Two researchers independently applied the inclusion criteria to the identified studies and assessed risk of bias. Disagreements were resolved by discussion or by intervention by a third party. Descriptive analysis was conducted for the review. MAIN RESULTS: Ninety-two publications were screened. No studies met the inclusion criteria exclusively but one study that included both type 1 and type 2 diabetes participants was considered. This randomised clinical trial (RCT) compared HRT (N = 27) with placebo (N = 29) over 12 months. The outcome measures were cardiovascular risk factors, including lipid profile, glycaemic control, blood pressure and body weight. No significant differences between placebo and HTR were detected. Patient-important outcomes like all-cause mortality, cardiovascular disease, diabetic complications or health-related quality of life were not investigated. AUTHORS' CONCLUSIONS: There is a lack of evidence around the use of HRT in women with type 1 diabetes. The one study that has been undertaken in this area is underpowered. More RCTs are required in the area to examine the impact of HRT on glycaemic control and cardiovascular outcomes.

Lifestyle Medicine Core Competencies: 2022 Update.

The lifestyle medicine core competencies were developed by a committee of physicians from several medical specialties to provide guidance on the knowledge and skills needed for physicians to provide high quality lifestyle interventions that optimize chronic disease outcomes. These competencies were published in the Journal of the American Medical Association (JAMA) in 2010 and used as the foundation for the first lifestyle medicine course and for the lifestyle medicine board certification examination. In the ensuing years, interest in the field and application has expanded to a variety of health professionals. With evolution of the lifestyle medicine evidence-base, the competencies have been updated. This article sums up the changes in their organization and content. Regular updates are anticipated to align with the ongoing scientific studies and evolution of the field.

Impact of a new daily rapid access medical clinic in a Scottish district general hospital.

BACKGROUND: Medical admissions to hospital in the UK are rising by approximately 10% per year. A Medical Assessment Unit (MAU) was opened to help deal with the rising influx of patients. The objectives of this study were to determine if a daily rapid access medical clinic could provide a safe alternative to hospital admission and aid safe discharge for medical patients. METHODS: The rapid access clinic was embedded within the MAU, utilising existing resources. Patients were allocated and reviewed by a senior acute medicine specialist registrar (SpR). Data were collected from January to September 2008. RESULTS: 74 patients seen in the clinic were analysed. 93% of these were managed in an ambulatory fashion, avoiding admission and saving a potential 280 bed days. The same day discharge rate of all patients seen and assessed in the MAU was increased from 17% to 26% (p<0.001), following institution of the clinic. The readmission rate fell from 8% to 4% (p=0.12). CONCLUSIONS: A daily rapid access medical clinic embedded within a MAU was piloted and allowed the safe management of a variety of medical complaints in an ambulatory fashion. It enabled an increase in the discharge rate of patients referred for admission by general practitioners. This seemed to be more robust than as evidenced previously by a trend towards lower readmission rates. These results were dependent on the presence of a senior clinical decision maker to facilitate safe discharges.

Decision Support for Diabetes in Scotland: Implementation and Evaluation of a Clinical Decision Support System.

BACKGROUND: Automated clinical decision support systems (CDSS) are associated with improvements in health care delivery to those with long-term conditions, including diabetes. A CDSS was introduced to two Scottish regions (combined diabetes population ~30 000) via a national diabetes electronic health record. This study aims to describe users' reactions to the CDSS and to quantify impact on clinical processes and outcomes over two improvement cycles: December 2013 to February 2014 and August 2014 to November 2014. METHODS: Feedback was sought via patient questionnaires, health care professional (HCP) focus groups, and questionnaires. Multivariable regression was used to analyze HCP SCI-Diabetes usage (with respect to CDSS message presence/absence) and case-control comparison of clinical processes/outcomes. Cases were patients whose HCP received a CDSS messages during the study period. Closely matched controls were selected from regions outside the study, following similar clinical practice (without CDSS). Clinical process measures were screening rates for diabetes-related complications. Clinical outcomes included HbA1c at 1 year. RESULTS: The CDSS had no adverse impact on consultations. HCPs were generally positive toward CDSS and used it within normal clinical workflow. CDSS messages were generated for 5692 cases, matched to 10 667 controls. Following clinic, the probability of patients being appropriately screened for complications more than doubled for most measures. Mean HbA1c improved in cases and controls but more so in cases (-2.3 mmol/mol [-0.2%] versus -1.1 [-0.1%], P = .003). DISCUSSION AND CONCLUSIONS: The CDSS was well received; associated with improved efficiencies in working practices; and large improvements in guideline adherence. These evidence-based, early interventions can significantly reduce costly and devastating complications.

Clinical risk factors predicting genital fungal infections with sodium-glucose cotransporter 2 inhibitor treatment: The ABCD nationwide dapagliflozin audit.

INTRODUCTION: Treatment of type 2 diabetes with sodium-glucose cotransporter 2 (SGLT2) inhibitors may result in genital fungal infections. We investigated possible risk factors for developing such infections among patients treated with the SGLT2 inhibitor dapagliflozin. METHODS: The Association of British Clinical Diabetologists (ABCD) collected data on patients treated with dapagliflozin in routine clinical practice from 59 diabetes centres. We assessed possible associations of patient's age, diabetes duration, body mass index, glycated haemoglobin, renal function, patient sex, ethnicity and prior genital fungal infection, urinary tract infection, urinary incontinence or nocturia, with the occurrence of ≥1 genital fungal infection within 26 weeks of treatment. RESULTS: 1049 out of 1116 patients (476 women, 573 men) were analysed. Baseline characteristics were, mean±SD, age 56.7±10.2years, BMI 35.5±6.9kg/m2 and HbA1c 9.4±1.5%. Only patient sex (13.2% women vs 3.3% men) and prior history of genital fungal infection (21.6% vs 7.3%) were found to be associated with occurrence of genital fungal infections after dapagliflozin treatment, adjusted OR 4.22 [95%CI 2.48,7.19], P<0.001 and adjusted OR 2.41 [95% CI 1.04,5.57], P=0.039, respectively. CONCLUSION: Women and patients with previous genital fungal infections had higher risks of developing genital fungal infections with dapagliflozin treatment.

Rapid onset childhood cataracts leading to the diagnosis of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

PURPOSE: To report a case of bilateral cataracts in a child that led to diagnosis of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. DESIGN: Observational case report. METHODS: A 12-year-old boy was being investigated for weakness, lethargy, short stature, and blurred vision. He developed bilateral, dense cataracts over a 2-week period. He was found to be hypocalcemic and diagnosed with hypoparathyroidism and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. RESULTS: Because of hypoparathyroidism, adrenocortical failure, and insulin-dependent diabetes, it was 9 months before the patient's metabolic imbalance was brought under sufficient control to allow cataract surgery. CONCLUSIONS: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy should be considered with diagnoses of hypocalcemic cataract.

Notch1 co-localizes with CD4 on activated T cells and Notch signaling is required for IL-10 production.

The effector function of activated CD4(+) T cells and secretion of cytokines are important in the establishment of productive immune responses and tolerance. We identified expression by CD4(+) T cells of Notch receptors and ligands and enhanced Notch signaling upon activation. Notch1 expression was up regulated and co-localized with CD4 upon T cell stimulation. Disruption of Notch signaling did not affect proliferation, but attenuated cytokine secretion following CD3 ligation in the absence of anti-CD28 antibody. Notch signaling was absolutely necessary for transcription of IL-10 by stimulated CD4(+) T cells. CD4(+) T cells transfected with constitutively active Notch1 failed to proliferate, but exhibited enhanced cytokine secretion upon stimulation. Our data indicates that Notch receptor signaling can influence both proliferative and cytokine responses of CD4(+) T cells. In addition, the finding that Notch signaling is required for production of IL-10 may allude to a role in immune regulation.