Assessing the safety profile of voriconazole use in suspected COVID-19-associated pulmonary aspergillosis-a two-centre observational study.

The decision to use voriconazole for suspected COVID-19-associated pulmonary aspergillosis (CAPA) is based on clinical judgement weighed against concerns about its potential toxicity. We assessed the safety profile of voriconazole for patients with suspected CAPA by conducting a retrospective study of patients across two intensive care units. We compared changes in any liver enzymes or bilirubin and any new or increasing corrected QT interval (QTc) prolongation following voriconazole use to patient baseline to indicate possible drug effect. In total, 48 patients with presumed CAPA treated with voriconazole were identified. Voriconazole therapy was administered for a median of 8 days (interquartile range [IQR] 5-22) and the median level was 1.86 mg/L (IQR 1.22-2.94). At baseline, 2% of patients had a hepatocellular injury profile, 54% had a cholestatic injury profile, and 21% had a mixed injury profile. There were no statistically significant changes in liver function tests over the first 7 days after voriconazole initiation. At day 28, there was a significant increase in alkaline phospahte only (81-122 U/L, P = 0.006), driven by changes in patients with baseline cholestatic injury. In contrast, patients with baseline hepatocellular or mixed injury had a significant decrease in alanine transaminase and aspartate transaminase. Baseline QTc was 437 ms and remained unchanged after 7 days of voriconazole therapy even after sensitivity analysis for concomitantly administered QT prolonging agents. Therefore, at the doses used in this study, we did not detect evidence of significant liver or cardiac toxicity related to voriconazole use. Such information can be used to assist clinicians in the decision to initiate such treatment.

Our study did not show significant voriconazole-related liver or cardiac side effects in a critically ill cohort of patients with suspected COVID-19-associated pulmonary aspergillosis. These findings may allay specific clinician concerns when commencing therapy for such patients.

'A Missed Therapeutic Opportunity? SGLT-2 Inhibitor Use in General Medicine Patients With Heart Failure: A Retrospective Audit of Admissions to a Tertiary Health Service'.

Objective: Sodium-glucose co-transporter-2 inhibitors (SGLT2-I's) are novel oral hypoglycaemic agents, with proven decreased MACE and re-hospitalisation risk in type 2 diabetic patients with concomitant heart failure. This study aimed to assess the current practice in the use of SGLT2-I's in general medical units at a large metropolitan health service. Methods/Results: A retrospective audit was conducted of patients admitted to general medicine over a 12 month period (between April 2018 and 2019). Inclusion criteria included decompensated heart failure of any aetiology and ejection fraction, and type 2 diabetes mellitus with an HbA1c ⩾ 7 within 6 months of the admission period. A total of 150 admissions fulfilled criteria. Baseline demographics and comorbidities identified an older, more comorbid population than reference trials. These included age (75% over 75 years), smoking history (46%), hypertension (83%), chronic kidney disease grade IV or V (26%), previous myocardial infarction (57%), stroke (18%), atrial fibrillation (55%) and known left ventricular ejection fraction < 50% (38%). Co-prescribed medications included ACE-I/ARB (53%), beta-blocker (67%), loop diuretic (87%), thiazide (7%), MRA (31%), insulin (57%), metformin (47%), sulphonylurea (31%), DPP-4 Inhibitor (21%), GLP-1 analogue (6%) and 15% of patients had an HbA1c > 10. There was a significant difference between patients in our study eligible for and prescribed metformin (66/111) compared to SGLT-2 inhibitors (4/25) (P = .013). A total of 26 patients had readmissions within 28 days, of which one had been discharged on an SGLT2-I. Conclusion: The results of this study identified significant under prescribing of SGLT2-I's in eligible type 2 diabetic patients with heart failure admitted under general medicine.

In-hospital 'CODE STEMI' improves door-to-balloon time in patients undergoing primary percutaneous coronary intervention.

OBJECTIVE: Reducing time to reperfusion for ST-segment elevation myocardial infarction (STEMI) is essential in improving outcomes. Consequently, numerous strategies have been employed to reduce median door-to-balloon time (DTBT). METHODS: CODE STEMI is an ED physician-activated STEMI notification system. On activation, an announcement is made over the hospital's public announcement (PA) system. We prospectively analysed all in-hours STEMI patients who had primary percutaneous coronary intervention (PPCI) Pre-CODE STEMI (2014) and after CODE STEMI was implemented (2015). The primary end-points were median DTBT and the proportion of STEMI patients achieving a DTBT ≤90 min. The secondary end-points were in-hospital outcomes, and a composite of major adverse cardiac events (MACE) and hospital readmission rates at 30 days and 12 months. RESULTS: There were 41 and 42 patients in Pre-CODE STEMI and CODE STEMI groups respectively. Baseline characteristics were similar. DTBT was significantly reduced by 22.1 min from 67.1 ± 34.9 min Pre-CODE STEMI to 45.0 ± 22.7 min (P = 0.001) in the CODE STEMI group. Door-to-door time (DTDT) was also reduced from 46.3 ± 30.9 min to 29.4 ± 23.3 min (P = 0.006). A greater proportion of CODE STEMI patients achieved the target DTBT ≤90 min (95.2% vs 73.2%, P = 0.007). CODE STEMI patients had less systolic dysfunction measured by a left ventricle ejection fraction of ≤40% (10.0% vs 27.8%, P = 0.07). There were trends to lower in-hospital mortality rates (4.8% vs 9.8%, P = 0.43), MACE at 30 days and 12 months (4.8% vs 9.8%, P = 0.43; 11.9% vs 22.0%, P = 0.25). CONCLUSION: The novel in-hospital in-hours CODE STEMI notification system significantly reduced DTBT in patients undergoing PPCI.