Background Oral semaglutide is the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for glycaemic control in patients with type 2 diabetes. Type 2 diabetes is commonly associated with renal impairment, restricting treatment options. We aimed to investigate the efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment. Methods This randomised, double-blind, phase 3a trial was undertaken at 88 sites in eight countries. Patients aged 18 years and older, with type 2 diabetes, an estimated glomerular filtration rate of 30-59 mL/min per 1•73 m², and who had been receiving a stable dose of metformin or sulfonylurea, or both, or basal insulin with or without metformin for the past 90 days were eligible. Participants were randomly assigned (1:1) by use of an interactive web-response system, with stratification by glucose-lowering medication and renal function, to receive oral semaglutide (dose escalated to 14 mg once daily) or matching placebo for 26 weeks, in addition to background medication. Participants and site staff were masked to assignment. Two efficacy-related estimands were defined: treatment policy (regardless of treatment discontinuation or rescue medication) and trial product (on treatment without rescue medication) in all participants randomly assigned. Endpoints were change from baseline to week 26 in HbA1c (primary endpoint) and bodyweight (confirmatory secondary endpoint), assessed in all participants with sufficient data. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered on ClinicalTrials.gov, number NCT02827708, and the European Clinical Trials Registry, number EudraCT 2015-005326-19, and is now complete.

IMPORTANCE: COVID-19 can cause serious illness requiring multimodal treatment and is associated with secondary infections. Studies have suggested an increased risk of fungal infections, including candidemia following severe COVID-19 though understanding of risk factors and clinical outcomes remains unclear. OBJECTIVES: To describe clinical characteristics, outcomes and risk factors of candidemia among patients hospitalized with severe COVID-19. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, case-control study of patients with severe COVID-19 was conducted to evaluate risk factors and clinical outcomes in patients who developed candidemia between August 2020 and August 2021. MAIN OUTCOMES AND MEASURES:Chart review evaluating institutional and patient demographics, clinical and mycological characteristics, concomitant interventions (antibiotics, immunosuppressive agents, parenteral nutrition, degree of oxygen support, mechanical ventilation, surgery), treatment regimens, and outcomes (length of stay and discharge disposition) RESULTS: A total of 275 patients were enrolled in the study, including 91 patients with severe COVID-19 and subsequent candidemia and 184 with severe COVID-19 without candidemia. Most patients received antibiotics prior to candidemia episode (93%), while approximately one-quarter of patients received biologic for COVID-19. In-hospital mortality was significantly higher in the cases compared with the controls (68% vs 40%; p < 0.01). Candida albicans was the most common (53%), followed by C. glabrata (19%). Use of central lines, biologic, and paralytics were independent risk factors for candidemia. CONCLUSIONS AND RELEVANCE:Candidemia following COVID-19 infection is a concern that requires clinical consideration and patient monitoring. Risk factors for the development of candidemia in the setting of COVID-19 infection are largely consistent with traditional risk factors for candidemia in hospitalized patients.

Background In contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity. Methods and results CLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis &gt;50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure. Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest. Conclusion In patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes. ClinicalTrials identifier ISRCTN43070564

Background COVID-19 can cause serious illness requiring multimodal treatment of the viral infection and its associated complications, including the potential for secondary infections. Studies have suggested an increased risk of fungal infections, including candidemia following severe COVID-19 though understanding of risk factors and clinical outcomes remains unclear. Methods A multi-center, case-control study of patients with severe COVID-19 was conducted to evaluate risk factors and clinical outcomes in patients who developed candidemia between August 2020 to August 2021. Risk factors associated with candidemia and mortality were characterized using multivariate analyses. Results A total of 275 patients were enrolled in the study, including 91 patients with severe COVID-19 and subsequent candidemia and 184 patients with severe COVID-19 without candidemia. Most patients received antibiotics prior to candidemia episode (93%), while approximately one-quarter of all patients received biologic for COVID-19. In-hospital mortality was significantly higher in the case group compared to the control group (68% vs 40%, P &lt; 0.01). Multivariable logistic regression revealed that the use of central lines, biologic and paralytic therapy were independent risk factors for candidemia. The presence of candidemia, older age, central line use, and intensive care unit admission were significantly associated with mortality. Demographics and Baseline Characteristics of Study Patients with SARS-CoV-2 Positive With or Without Candidemia Hospitalization Details and Outcomes Conclusion Clinicians should be aware of the possibility of development of candidemia in hospitalized older patients with severe COVID-19 and should closely monitor those patients at risk. Risk factors for developing candidemia in the setting of COVID-19 are largely consistent with classic risk factors previously identified. Disclosures Tanaya Bhowmick, MD, Gilead: Grant/Research Support|Shinogi: Advisor/Consultant Steven Smoke, PharmD, BCPS, BCIDP, Karius: Advisor/Consultant|Shionogi: Advisor/Consultant.

Background Management of bacterial infections typically consist of beta-lactam antibiotics. Individuals with histories of beta-lactam allergy are more likely to receive alternative broad-spectrum antibiotics which may be less efficacious or lead to increased adverse events. Patients can be prescribed full doses of structurally non-related beta-lactam antibiotics due to the low similarity of side chains between these medications and penicillin, and the low incidence of penicillin allergies being true allergies. Nevertheless, there is a lack of data regarding safety outcomes in patients who are treated with a beta lactam with a documented allergy. Methods This was a single-center retrospective observational study of patients with a documented beta-lactam allergy who received at least one dose of any beta-lactam antimicrobial excluding aztreonam from SUNY Downstate Health Sciences University between January 2015 – October 2021. Electronic medical records were reviewed for relevant study data. The primary outcome was the incidence of allergic reaction on full dose beta lactam with a documented allergy in the medical record. Results Baseline characteristics are summarized in Table 1. Two patients experienced a suspected allergic reaction while on beta-lactam therapy. Anaphylaxis was not reported and pharmacologic rescue agents were not required for each case. The antimicrobial agent was changed after the reaction was noted in both cases. Conclusion Patients who were administered beta-lactam antimicrobials with beta-lactam allergy had low rates of allergic reaction. The rate of allergic reactions observed is similar to the incidence of allergy in patients without documented allergies reported in the literature. Administration of beta-lactams with dissimilar side chains such as beta-lactam beta-lactamase inhibitors and third and fourth generation cephalosporins were safely administered to patients with a documented allergy. Disclosures All Authors: No reported disclosures.