Antifungal agents may be associated with significant toxicity or drug interactions leading to sub-therapeutic antifungal drug concentrations and poorer clinical outcomes for patients with haematological malignancy. These risks may be minimised by clinical assessment, laboratory monitoring, avoidance of particular drug combinations and dose modification. Specific measures, such as the optimal timing of oral drug administration in relation to meals, use of pre-hydration and electrolyte supplementation may also be required. Therapeutic drug monitoring (TDM) of antifungal agents is warranted, especially where non-compliance, non-linear pharmacokinetics, inadequate absorption, a narrow therapeutic window, suspected drug interaction or unexpected toxicity are encountered. Recommended indications for voriconazole and posaconazole TDM in the clinical management of haematology patients are provided. With emerging knowledge regarding the impact of pharmacogenomics upon metabolism of azole agents (particularly voriconazole), potential applications of pharmacogenomic evaluation to clinical practice are proposed.
Antifungal agents can have complex dosing and the potential for drug interaction, both of which can lead to subtherapeutic antifungal drug concentrations and poorer clinical outcomes for patients with haematological malignancy and haemopoietic stem cell transplant recipients. Antifungal agents can also be associated with significant toxicities when drug concentrations are too high. Suboptimal dosing can be minimised by clinical assessment, laboratory monitoring, avoidance of interacting drugs, and dose modification. Therapeutic drug monitoring (TDM) plays an increasingly important role in antifungal therapy, particularly for antifungal agents that have an established exposure-response relationship with either a narrow therapeutic window, large dose-exposure variability, cytochrome P450 gene polymorphism affecting drug metabolism, the presence of antifungal drug interactions or unexpected toxicity, and/or concerns for non-compliance or inadequate absorption of oral antifungals. These guidelines provide recommendations on antifungal drug monitoring and TDM-guided dosing adjustment for selected antifungal agents, and include suggested resources for identifying and analysing antifungal drug interactions. Recommended competencies for optimal interpretation of antifungal TDM and dose recommendations are also provided.
Chanting and praying are among the most popular religious activities, which are said to be able to alleviate people’s negative emotions. However, the neural mechanisms underlying this mental exercise and its temporal course have hardly been investigated. Here, we used event-related potentials (ERPs) to explore the effects of chanting the name of a Buddha (Amitābha) on the brain’s response to viewing negative pictures that were fear- and stress-provoking. We recorded and analyzed electroencephalography (EEG) data from 21 Buddhists with chanting experience as they viewed negative and neutral pictures. Participants were instructed to chant the names of Amitābha or Santa Claus silently to themselves or simply remain silent (no-chanting condition) during picture viewing. To measure the physiological changes corresponding to negative emotions, electrocardiogram and galvanic skin response data were also collected. Results showed that viewing negative pictures (vs. neutral pictures) increased the amplitude of the N1 component in all the chanting conditions. The amplitude of late positive potential (LPP) also increased when the negative pictures were viewed under the no-chanting and the Santa Claus condition. However, increased LPP was not observed when chanting Amitābha. The ERP source analysis confirmed this finding and showed that increased LPP mainly originated from the central-parietal regions of the brain. In addition, the participants’ heart rates decreased significantly when viewing negative pictures in the Santa Claus condition. The no-chanting condition had a similar decreasing trend although not significant. However, while chanting Amitābha and viewing negative pictures participants’ heart rate did not differ significantly from that observed during neutral picture viewing. It is possible that the chanting of Amitābha might have helped the participants to develop a religious schema and neutralized the effect of the negative stimuli. These findings echo similar research findings on Christian religious practices and brain responses to negative stimuli. Hence, prayer/religious practices may have cross-cultural universality in emotion regulation. This study shows for the first time that Buddhist chanting, or in a broader sense, repetition of religious prayers will not modulate brain responses to negative stimuli during the early perceptual stage, but only during the late-stage emotional/cognitive processing.
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