Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing

During veno-venous extracorporeal membrane oxygenation (vv ECMO) therapy, antimicrobial drugs are frequently used, and appropriate dosing is challenging due to there being limited data to support the dosage. Linezolid is effective against multidrug-resistant Gram-positive pathogens frequently isolated in ECMO patients. In total, 53 steady-state linezolid levels were obtained following 600 mg intravenous (IV) injections every 8 h, and these were used to develop a population pharmacokinetic (PopPK) model in patients with COVID-19-associated acute respiratory distress syndrome (CARDS) on vv ECMO. The data were analyzed using a nonlinear mixed-effects modelling approach. Monte Carlo simulation generated 5000 patients’ individual PK parameters and corresponding concentration–time profiles using the PopPK model, following the administration of 600 mg/8 h (a higher-than-standard dosing) and 600 mg/12 h (standard). The probabilities of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) and the cumulative fraction of responses (CFR) for three pathogens were calculated and compared between the two dosing scenarios. Linezolid 600 mg/8 h was predicted to achieve greater than or equal to 85%Tf>MIC in at least 90% of the patients with CARDS on vv ECMO compared to only approximately two thirds of the patients after dosing every 12 h at a minimal inhibitory concentration (MIC) of 2 mg/L. In addition, for the same MIC, fAUC24/MIC ≥ 80 was achieved in almost three times the number of patients following an 8-h versus a 12-h interval. PopPK simulation predicted that a significantly higher proportion of the patients with CARDS on vv ECMO would achieve the PK/PD targets following the 8-h dosing interval compared to standard linezolid dosing. Nevertheless, the safety concern, in particular, for thrombocytopenia, with higher-than-standard linezolid dosage is reasonable, and consequently, monitoring is essential

COST Action CA19114, Network for Optimized Astatine labelled Radiopharmaceuticals

Cancer is a major health concerns for European citizens. Thus, the main research aim of this Network for Optimized Astatine labeled Radiopharmaceuticals (NOAR) COST Action is to successfully demonstrate that one of the most promising radionuclides for Targeted Alpha Therapy (TAT), namely astatine-211, can become the European standard for treatment of certain cancerous pathologies. To this end, an efficient networking is essential among all European stakeholders interested in promoting astatine-211 for medical applications. NOAR COST Action brings together European and international excellence labs, astatine-211 production centers, hospitals, industry and patient associations from more than 20 countries, thus covering the whole value chain of innovation: production, chemistry, radiochemistry, biology, preclinical and clinical research and delivery of radiopharmaceuticals to patients. A European web portal will be created containing information for patients, practitioners, researchers, Industry and as a contact point for National and European patient associations. The idea is to gather forces at the European level in order to implement actions to leverage hurdles to the development of this powerful radionuclide and to identify pathologies in which it will be particularly relevant. A special emphasis will be given to train a new generation of young researchers and PhD students, promoting interdisciplinary competencies through international and inter-sectoral mobility. The long-term goal of this project is to make Astatine-211 technology available to all European citizen

Skład olejku eterycznego sosny pospolitej (Pinus sylvestris L.) oraz relacje roślina-owad

A review of methods of isolation, chemical composition and biological activity of essential oil of different organs of Scots pine (Pinus sylvestris) was presented. The data on relation between herbivorous insects and plant were also reviewed.Przedstawiono przegląd literatury dotyczącej metod izolowania, składu chemicznego oraz właściwości biologicznych olejku eterycznego z różnych organów sosny pospolitej (Pinus sylvestris). Omówiono interakcje między rośliną a jej szkodnikami - roślinożernymi owadami

Operating cost analysis of anaesthesia: Activity based costing (ABC analysis)

Introduction. Cost of anaesthesiology represent defined measures to determine a precise profile of expenditure estimation of surgical treatment, which is important regarding planning of healthcare activities, prices and budget. Objective. In order to determine the actual value of anaestesiological services, we started with the analysis of activity based costing (ABC) analysis. Methods. Retrospectively, in 2005 and 2006, we estimated the direct costs of anestesiological services (salaries, drugs, supplying materials and other: analyses and equipment.) of the Institute of Anaesthesia and Resuscitation of the Clinical Centre of Serbia. The group included all anesthetized patients of both sexes and all ages. We compared direct costs with direct expenditure, “each cost object (service or unit)” of the Republican Health-care Insurance. The Summary data of the Departments of Anaesthesia documented in the database of the Clinical Centre of Serbia. Numerical data were utilized and the numerical data were estimated and analyzed by computer programs Microsoft Office Excel 2003 and SPSS for Windows. We compared using the linear model of direct costs and unit costs of anaesthesiological services from the Costs List of the Republican Health-care Insurance. Results. Direct costs showed 40% of costs were spent on salaries, (32% on drugs and supplies, and 28% on other costs, such as analyses and equipment. The correlation of the direct costs of anaestesiological services showed a linear correlation with the unit costs of the Republican Healthcare Insurance. Conclusion. During surgery, costs of anaesthesia would increase by 10% the surgical treatment cost of patients. Regarding the actual costs of drugs and supplies, we do not see any possibility of costs reduction. Fixed elements of direct costs provide the possibility of rationalization of resources in anaesthesia

Thrombocytopenia risks in ARDS COVID-19 patients treated with high-dose linezolid during vvECMO therapy: an observational study

Patients treated with ECMO are at great risk of nosocomial infections, and around 10% of isolates are gram-positive pathogens. Linezolid (LZD) is effective in the treatment of these infections but appropriate dosing is challenging. The aim was to evaluate the occurrence of thrombocytopenia during ECMO when treated with LZD. An LZD trough concentration of 8 mg/L was set as the cutoff value for thrombocytopenia occurrence among critically ill patients who received parenteral LZD therapy at a dose of 600 mg every 8 h during ECMO. Eleven patients were included in this prospective observational study. Median LZD trough concentrations were 7.85 (interquartile range (IQR), 1.95-11) mg/L. Thrombocytopenia was found in 81.8% of patients. Based on the median LZD trough concentrations cutoff value, patients were divided into two groups, 1.95 (IQR, 0.91–3.6) and 10.3 (IQR, 9.7–11.7) mg/L, respectively. Median platelet values differed significantly between groups on admission, ECMO day 0, ECMO day 1, and LZD sampling day [194 and 152.5, (p < 0.05)], [113 and 214, (p < 0.05)], [76 and 147.5, (p < 0.01)], and [26 and 96.5, (p < 0.01)], respectively. Duration of LZD therapy was similar between the groups. Significant platelet reduction was observed in both groups, emphasizing the need for closer monitoring to prevent LZD-associated thrombocytopenia