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Objectives: The Fluconazole pharmacokinetic-pharmacodynamic relationship was investigated in a few clinical settings and only limited studies regarding burned patients are available. Thus, the authors aimed to investigate fluconazole pharmacokinetics changes and its impact on antifungal therapy coverage against dose-dependent Candida spp. applying the PK/PD approach in critically ill severely burned patients., Methods: Fluconazole was administered as a one-hour intravenous infusion of 200 mg q12h. Doses were increased according to the coverage based on the PK/PD approach. Blood samples were collected at the end of the infusion (1 st hour), two hours after (3 rd hour), and before the next dose (12 th or 24 th hour). Serum concentrations were obtained by HPLC-UV. Pharmacokinetic parameters were estimated by noncompartmental analysis and compared with data described in healthy subjects. The effectiveness predictive index was based on the AUC ss 0-24h /MIC ratio, with a target above 25., Results: Every pharmacokinetic parameter was reduced throughout all three sets of the study. Compared to healthy subjects, the volume of distribution was decreased about 3‒7 times, biological half-life was 2‒3 times shorter and total body clearance was slightly altered but statistically significant. Both half-life and total body clearance were correlated to the volume of distribution. Consequently, an increase in fluconazole daily dose was necessary to improve empiric coverage., Conclusions: Fluconazole pharmacokinetics is altered in critically ill severely burned patients, mainly related to the volume of distribution. Doses higher than usual may be necessary to reach the PK/PD target and guarantee antifungal coverage against dose-dependent Candida spp. up to MIC 32 mg/L., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: Despite significant advancements in understanding risk factors and treatment strategies, ischemic heart disease (IHD) remains the leading cause of mortality worldwide, particularly within specific regions in Brazil, where the disease is a burden. Therefore, the aim of this study was to estimate the risk of hospitalization and mortality from IHD in the state of Paraná (Brazil), using spatial analysis to identify areas with higher risk based on socioeconomic, demographic and health variables., Methods: This is an ecological study based on secondary and retrospective IHD hospitalization and mortality data obtained from the Brazilian Hospitalization and Mortality Information Systems during the 2010-2021 period. Data were analyzed for 399 municipalities and 22 health regions in the state of Paraná. To assess the spatial patterns of the disease and identify relative risk (RR) areas, we constructed a risk model by Bayesian inference using the R-INLA and SpatialEpi packages in R software., Results: A total of 333,229 hospitalizations and 73,221 deaths occurred in the analyzed period, and elevated RR of hospitalization (RR = 27.412, CI 21.801; 34.466) and mortality (RR = 15.673, CI 2.148; 114.319) from IHD occurred in small-sized municipalities. In addition, medium-sized municipalities also presented elevated RR of hospitalization (RR = 6.533, CI 1.748; 2.006) and mortality (RR = 6.092, CI 1.451; 2.163) from IHD. Hospitalization and mortality rates were higher in white men aged 40-59 years. A negative association was found between Municipal Performance Index (IPDM) and IHD hospitalization and mortality., Conclusion: Areas with increased risk of hospitalization and mortality from IHD were found in small and medium-sized municipalities in the state of Paraná, Brazil. These results suggest a deficit in health care attention for IHD cases in these areas, potentially due to a low distribution of health care resources., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)