Real-world effectiveness of antifungal prophylaxis with posaconazole as the primary agent in patients with haematological malignancies.

BACKGROUND AND OBJECTIVES: Patients undergoing induction/reinduction chemotherapy for haematologic malignancies (HM) are at risk for invasive fungal infections (IFIs). In 2015, Duke University Hospital (DUH) implemented a new standardised fungal prophylaxis protocol for adult patients undergoing induction chemotherapy for acute lymphocytic leukaemia, acute myelocytic leukaemia and myelodysplastic syndrome. This study assessed the impact of protocol implementation on (1) use of antifungal prophylaxis, throughout the at-risk period and (2) patient outcomes such as IFI and mortality. METHODS: Retrospective, observational study of adult HM patients admitted to DUH for induction/reinduction chemotherapy pre- (7/1/2013-12/31/2014) and post- (1/1/2015-10/31/2016) implementation of standardised antifungal prophylaxis protocol (which recommended posaconazole as the first-line agent). Patients were followed for up to 100 days after initiation of induction chemotherapy to evaluate use of antifungal prophylaxis and patient outcomes. RESULTS: 218 patients with haematologic malignancies were included (90 pre, 128 post). Use of antifungal prophylaxis increased from 81.1% (pre) to 97.7% (post) (p < .0001). Overall, 71% received posaconazole as initial antifungal prophylaxis (64.4% pre, 75.7% post). Approximately one-fourth of patients (25.6%, pre vs 26.6%, post) developed an IFI (proven/probable or possible using modified EORTC definitions) (p = .868); 100-day mortality remained stable (18.9% pre vs 18.8% post, respectively, p = .979). Lack of antifungal prophylaxis and older age (≥60 years) were associated with higher risk of IFI. CONCLUSION: Implementation of a standardised protocol with posaconazole as the primary agent was associated with increased use of antifungal prophylaxis among patients undergoing induction/reinduction chemotherapy for haematologic malignancies in our hospital. Lack of antifungal prophylaxis was an independent predictor of IFIs, underscoring the importance of prophylaxis in this at-risk population.

Flame etching enhances the sensitivity of carbon-fiber microelectrodes.

Small sensors are useful for in vivo measurements and probing small spaces. In this paper, we compare two methods of fabrication of small, cylindrical carbon-fiber microelectrodes: flame-etching and electrochemical etching. With both methods, microelectrodes can be fabricated with tip diameters of 1 to 3 microm. Electrodes were tested with fast-scan cyclic voltammetry. Flame etching resulted in electrodes that have larger S/N ratios and higher currents per unit area for 1 microM dopamine than normal carbon-fiber microelectrodes or electrochemically etched electrodes. Therefore, the increased sensitivity is not just a property of size. The flame-etched surfaces had nanometer-scale surface features that were not observed on the other electrodes and exhibited increased sensitivity for other electroactive compounds found in the brain, including ascorbic acid, DOPAC, and serotonin. Faster kinetics and a faster response to a step change in dopamine were also observed, when the applied waveform was -0.4 to 1.0 V and back at 400 V/s. The sensitivity of the flame-etched electrodes was enhanced by overoxidizing the surface. The flame-etched electrodes were used to detect dopamine release in anesthetized rats after a single stimulation pulse. The small flame-etched electrodes will facilitate measurements of low concentrations in discrete brain regions or small organisms.