OBJECTIVES To characterize the voriconazole and posaconazole serum trough ordering practices in patients receiving prophylactic and treatment antifungal therapy. METHODS A retrospective chart review over a 6-year period of pediatric patients who received voriconazole and/or posaconazole for >24 hours. RESULTS A total of 113 patients were included in this study and of these patients, 105 received voriconazole and 16 received posaconazole during the study period. Additionally, 167 trough levels were assessed in this study. Only 50% and 54% of levels were considered within goal recommendations for voriconazole and posaconazole, respectively. The median dose required to achieve goal trough concentration was dependent on drug, indication, and dosage form. Lastly, the most common adverse drug reactions (ADRs) were hepatoxicity, QTc prolongation, and CNS changes, which were in concordance with ADRs documented in the clinical trials for voriconazole and posaconazole. Approximately 20% of patients receiving either voriconazole or posaconazole died during the study period and the median trough in both groups was subtherapeutic. CONCLUSIONS Increased monitoring of trough concentrations may be warranted to prevent death or breakthrough invasive fungal infections. Further studies are warranted for assessing the relationship between trough concentrations and treatment outcomes as well as relationship between dosing and achieving goal trough concentrations.
The cognitive rehabilitation (CR) for patients with alcohol use disorder (AUD) is proposed during prolonged institutional stays.However, the results of such a program remain poorly known.The aim of this study was to describe the primary results of a 6-week CR performed in an AUD treatment center.Patients and Methods: We retrospectively selected from our files AUD patients with following criteria: cognitive deficit assessed by the Montréal Cognitive Assessment (MoCA) at admission (i.e.MoCA < 26); evaluation at discharge; absence of neurological disease or a severe psychiatric trouble.The 6-week CR program is specifically adapted to the diagnosed abnormalities, and is performed by several
Background: Busulfan has a narrow therapeutic index with dose-limiting toxicity of veno-occlusive disease, and increased risk of graft failure with low drug exposure. Therapeutic drug monitoring (TDM) is recommended in children due to large interpatient variability in busulfan dose-concentration relationships. TDM and dose adjustments following initial busulfan dose to achieve targeted exposure is in routine practice. Materials and Methods: Patients who received busulfan for HCT conditioning and had more than one set of busulfan pharmacokinetic (PK) analysis were included. All PK samples were drawn with the 1st dose (PK1) and then a subsequent dose midway through the regimen (PK2). For 24-hour dosing (q24), each infusion was over 3-hr and blood samples were drawn at the end of infusion (EOI), 15 min. after the EOI, 4, 5, 6, and 8 hr from the start of the infusion. For 6-hr (q6) dosing, each infusion was over 2-hr, samples were drawn at the EOI, 15 and 30 minutes after EOI, 3, 4, 5 and 6 hr from the start of the infusion. For 2nd PK analysis, similar samples were drawn with the addition of a pre-infusion sample. Plasma concentrations of busulfan were measured using a validated HPLC/mass spectrometry method. Results: Busulfan PK profiles were evaluated in 26 patients. The median age at transplant was 7.6 years (.2; 19.1) and median dose weight 25.4 kg (4.5; 76). Twenty patients (77%) received HCT for a malignancy, and myeloablative conditioning used in 20 (77%) cases. Eighteen patients (69.2%) received busulfan dosed q24, and 8 (30.8%) on q6 schedule. Median initial dose of busulfan was 3.7 mg/kg (3.2; 4.8), and .8 mg/kg (.8; 1) for q24 and q6, respectively. Overall, the median busulfan clearance with PK1 was 3.31 mL/min/kg (2; 5.1) and the clearance with PK2 was 2.87 mL/min/kg (1.7; 3.96). The median change in clearance from PK1 to PK2 was -13.6% (-36%; 5.2%) (Figure 1). The observed change in clearance was -14.4 (-36%; 5.2%) and -11.2% (-27.3%; .3%) for q24 and q6 dosing, respectively. Busulfan exposure targets ranged from 4000-5200 µMolar × min for q24 and 700-900 ng/ml for q6 dosing. PK1 results led to dose adjustment in 23 (88.4%) patients. PK2 analysis led to further dose adjustments in 18 patients (69.2%). Eleven patients (61%) who received q24 and 4 patients (50%) who received q6 required a decrease in dose of ≥ 10%. We extrapolated what the cumulative weight based busulfan dose would have been based on PK1 alone and compared it to the cumulative dose the patients received. Overall, the percentage difference was 4.2% (-25; 0). Conclusion: Our study found that busulfan clearance declines with subsequent dosing. This was observed with q24 and q6 dosing schedules. Results from PK2 led to further dose adjustments in ~69% of patients. Further studies are warranted to validate these findings. Refinements to current practice of TDM around first dose may be necessary in order to achieve targeted busulfan exposure.
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