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Summary What is known and Objective Direct oral anticoagulants (DOACs) are frequently used for the treatment of pulmonary embolism (PE), but both clinical and laboratory data comparing their efficacy and safety are conflicting. This study investigated and compared the impact of three DOACs (apixaban, rivaroxaban and dabigatran) on coagulation cascade in acute PE patients. Methods After the initial treatment, acute PE patients were randomly allocated to one of three groups, and treatment continued using one of the three DOACs. Following 1 month of treatment, the activity of factors II, VII and VIII, as well as protein C, antithrombin, D‐dimer and fibrinogen, were measured, and the values were compared between the groups. Results and Discussion One hundred consecutive PE patients were included. The mean values for the activity of factors II and VII and protein C were higher in patients on apixaban than in patients on rivaroxaban (1.45 ± 1.12 (IU/mL) vs 1.13 ± 0.92 (IU/mL), P < 0.001; 1.24 ± 1.10 (IU/mL) vs 1.05 ± 0.98 (IU/mL), P = 0.024 and 1.15 ± 0.62 vs 1.02 ± 0.68 (IU/mL), P = 0.019, respectively). The mean of factor II activity and the median of factor VIII activity were also significantly higher in patients on apixaban than in patients on dabigatran (1.45 ± 1.12 vs 1.20 ± 0.96 (IU/mL), P = 0.003 and 2.9 (2.0‐4.0) vs 2.1 (1.5‐2.7) (IU/mL), P = 0.001, respectively). No difference was noticed in D‐dimer concentrations, or in the activity of the other factors measured. Additionally, no difference was noticed between the rivaroxaban and dabigatran groups. What is new and Conclusion Apixaban had a significantly higher thrombin activity, above the laboratory determined normal range, compared to patients on rivaroxaban and dabigatran. This higher thrombin activity in patients on apixaban may contribute to a better haemostatic response during the therapy or increased prothrombotic state after therapy interruption.

Summary Phytopreparations, in addition to the pharmacological activity and positive effects on health, can lead to side effects, toxic effects, allergic reactions, as well as the interaction of conventional and herbal medicines. Despite this, there is a generally positive attitude that herbal medicines and herbal dietary supplements are safe and harmless to health and are most often used on its own initiative, without consultations with a pharmacist or a doctor. The aim of this study was to develop and validate a questionnaire for measuring the general knowledge about phytopreparations. The study was designed as an observational, prospective cross-sectional study, intended for the valiation of the original epidemiological questionnaire to evaluate the knowledge about phytopreparations. The sample consisted of 218 respondents, who were visiting private pharmacies at the territory of Bijeljina, in February and March 2016. The final version of the questionnaire for the evaluation of knowledge about herbal preparations had good internal consistency (α= 0.849) and homogeneity when randomly splitting the questionnaire into two parts (α=0.731; 0.788). Exploratory factor analysis singled out two factors. Based on the results of the study, it can be concluded that the questionnaire was a valid and reliable instrument for the evaluation of general knowledge about safety of use of phytopreparations. This is very important because the evaluation of knowledge could lead to undertaking measures for improving it, which would reduce the potential adverse reactions and interactions of herbal preparations with conventional drugs, and the application would become safe and optimal.

Pregabalin is a gabapentinoid approved for the treatment of general anxiety disorder, neuropathic pain and as adjunctive therapy for focal seizures in patients with epilepsy. In addition, there are a number of conditions for which pregabalin is prescribed off-label. Along with the widespread use there are a significant number of reports describing the misuse of pregabalin over the last decade. Over time, it became clear that pregabalin should become part of routine testing in toxicology laboratories. The aim of this paper was to present validation of a LC-MS/MS method for the quantification of pregabalin in plasma of acutely poisoned patients. Simple sample preparation step and rapid chromatographic separation shortened the overall analysis time, which was the goal of method development. The presence of pregabalin was confirmed with three ion transitions, ensuring high selectivity of the validated method. The statistical data obtained showed good precision and accuracy over a wide concentration range. No endogenous or other interference was detected, and there was no matrix effect influence with this method. The LC-MS/MS method was applied to quantify pregabalin in plasma samples of patients admitted to the emergency department due to a possible acute pregabalin overdose. Different concentrations were found, and we report, to the best of our knowledge, the highest plasma concentration of pregabalin in the plasma of a patient with acute poisoning. In conclusion, we developed a fast and simple LC-MS/MS method for reliable determination of pregabalin and demonstrated the developed method was suitable for routine use in clinical toxicology setting.

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Background: Patients with acute pulmonary embolism (PE) may have various types of atrial fibrillation (AF). The role of AF in hemodynamic states and outcomes may differ between men and women. Methods: In total, 1600 patients (743 males and 857 females) with acute PE were enrolled in this study. The severity of PE was assessed using the European Society of Cardiology (ESC) mortality risk model. Patients were allocated into three groups according to their electrocardiography recordings taken during hospitalization: sinus rhythm, new-onset paroxysmal AF, and persistent/permanent AF. The association between the types of AF and all-cause hospital mortality was tested using regression models and net reclassification index (NRI) and integrated discrimination index (IDI) statistics with respect to sex. Results: There were no differences between the frequencies of the types of AF between men and women: 8.1% vs. 9.1% and 7.5% vs. 7.5% (p = 0.766) for paroxysmal and persistent/permanent AF, respectively. We found that the rates of paroxysmal AF significantly increased across the mortality risk strata in both sexes. Among the types of AF, the presence of paroxysmal AF had a predictive value for all-cause hospital mortality independent of mortality risk and age in women only (adjusted HR, 2.072; 95% CI, 1.274–3.371; p = 0.003). Adding paroxysmal AF to the ESC risk model did not improve the reclassification of patient risk for the prediction of all-cause mortality, but instead enhanced the discriminative power of the existing model in women only (NRI, not significant; IDI, 0.022 (95% CI, 0.004–0.063); p = 0.013). Conclusion: The occurrence of paroxysmal AF in female patients with acute PE has predictive value for all-cause hospital mortality independent of age and mortality risk.

Introduction and aim. The role of antithrombin (AT) activity in the prediction of early mortality in patients with pulmonary embolism (PE), measured at an early stage of the disease, has not yet been investigated. Therefore the aim is to examine the predictive value of AT activity for all-cause 30-day mortality, measured in consecutive PE patients on admission to the hospital. Methodology. This is a single-center, clinical retrospective cross-sectional study, which followed consecutive patients with acute PE in the period from 2014-2021. On admission to the hospital, venous blood was taken from patients for laboratory analyzes, from which, in addition to basic analyzes, the activity of AT was also measured. The basic parameters of the patients were recorded on admission and through univariate analysis, their connection with 30-day mortality was tested. The predictive significance of AT values for 30-day mortality was tested through quartile values by comparing the first quartile with all others together. Cox regression model analysis was used in the multivariate analysis where one parameter marked as significant in the univariate analysis was added to the basic model (AT, age and risk affiliation in two groups). Results. A total of 378 PE patients were included in the study. The total all-cause 30-day mortality was 30 patients (7.8%). Patients with AT activity in the first quartile had significantly higher early mortality compared with the other quartiles combined (log rank p = 0.001). AT retained a significant predictive value for early mortality in the multivariate analysis despite the comorbidity present, which also significantly affected mortality. Conclusion. Low AT activity measured at admission in PE patients is a significant and independent predictor of 30-day mortality.