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Therapeutically, new oral anticoagulants (NOACs) are considered to be non-inferior or superior to vitamin K antagonists (warfarin). NOACs are included in current guidelines for the treatment of various cardiovascular diseases. Rivaroxaban medicinal products have been shown to effectively fight thrombotic complications of the new coronavirus infection, COVID-19. The wide clinical use of rivaroxaban products motivates the development of generics. The aim of the study was to compare the pharmacokinetics and safety of rivaroxaban medicinal products in a single-dose bioequivalence study in healthy volunteers under fasting conditions. Material(s) and Method(s): the bioequivalence study compared single-dose oral administration of Rivaroxaban, 10 mg film-coated tablets (NovaMedica Innotech LLC, Russia), and the reference product Xarelto, 10 mg film-coated tablets (Bayer AG, Germany), in healthy volunteers under fasting conditions. The open, randomised, crossover trial included 46 healthy volunteers. Each of the medicinal products (the test product and the reference product) was administered once;blood samples were collected during the 48 h after the administration. The washout between the study periods lasted 7 days. Rivaroxaban was quantified in plasma samples of the volunteers by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Result(s): no adverse events or serious adverse events were reported for the test and reference products during the study. The following pharmacokinetic parameters were obtained for Rivaroxaban and Xarelto, respectively: Cmax of 134.6 +/- 58.0 ng/mL and 139.9 +/- 49.3 ng/mL, AUC0-48 of 949.7 +/- 354.5 ngxh/mL and 967.6 +/- 319.9 ngxh/mL, AUC0- of 986.9 +/- 379.7 ngxh/mL and 1003.6 +/- 320.4 ngxh/mL, T1/2 of 8.2 +/- 3.2 h and 7.8 +/- 3.3 h. The 90% confidence intervals for the ratios of Cmax, AUC0-48, and AUC0- geometric means were 88.04-108.67%, 89.42-104.92% and 89.44-104.81%, respectively. Conclusion(s): the test product Rivaroxaban and the reference product Xarelto were found to have similar rivaroxaban pharmacokinetics and safety profiles. The study demonstrated bioequivalence of the medicinal products. Copyright © 2022 Obstetrics, Gynecology and Reproduction. All rights reserved.
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In this overview, we discuss the impact of antibiotic therapy on the COVID infection, the complications after vaccination, possible causes of adverse events, and ways to protect against pandemic infection, as well as try to dispel myths about COVID. Antibiotics are necessary only in case of secondary infection, but overlapping with bacterial infection mainly occurs after hospitalization, and the vast majority of infections were caused by the Acinetobacter baumannii strain. Commonly used antimicrobial disinfectants are chlorhexidine derivatives;due to their frequent use, microorganisms have become resistant to them, and in addition, chloroquine has no clinical benefit in the treatment of COVID-19. Virus escapes from the immune response due to multiple mutations in the receptor-binding domain, or the N-terminal end, which are the sites responsible for antibody binding and virus neutralization. The COVID infection itself is characterized by a rather powerful suppression of immunity. For this reason, the use of antibiotics in the absence of a secondary infection layer leads to greater suppression of the immune system and an aggravation of the process, which often ends up fatally. Immune dysregulation predisposes to the development of severe COVID-19. A decrease in the number of leukocytes gives an unfavorable prognosis for the severity of the COVID infection course. The main reason for the death cases after vaccination seems to be an increase in blood clotting, which is observed not only among the population over 60 years old, but also amid young people.
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INTRODUCTION: Bivalirudin remains a viable strategy during extracorporeal membrane oxygenation (ECMO). The accuracy of activated partial thromboplastin time (aPTT) for bivalirudin intensity in ECMO may be imperfect resulting in suboptimal dosing, which may increase the risk of bleeding or thrombotic complications. The purpose of this study was to evaluate the correlation between PTT and thromboelastography (TEG) reaction (R) time in adult ECMO patients anticoagulated with bivalirudin. METHOD(S): This was a multicenter, retrospective study conducted over a 22-month period (January 2020 to October 2021. Adult ICU patients requiring ECMO and bivalirudin therapy with >=1 corresponding TEG and aPTT samples drawn <=4 hours of each other were included. The primary endpoint was to determine the correlation coefficient between the TEG R time and bivalirudin aPTT serum concentrations. Pearson's correlation coefficient was used to evaluate the correlation using a kappa measure of agreement between TEG results and bivalirudin aPTT serum concentrations. RESULT(S): A total of 104 patients consisting of 848 concurrent laboratory assessments of R time and aPTT were included. COVID-19 positive tests were confirmed in 48.1% (n=50) of included patients. A moderate correlation between TEG R time and aPTT was demonstrated in the study population (r=0.41;p< 0.001). A similar relationship between TEG R time and aPTT was observed in both COVID-19 positive (r=0.44;p< 0.0001) and negative (r=0.45;p< 0.0001). Overall, 59.2% of all concurrent TEG R time and aPTT values showed agreement on the study institution's therapeutic category (sub-, supra-, and therapeutic) of bivalirudin. 78.3% (n=277) of aPTT values were categorized as therapeutic among all discordant assessment (n=346) between TEG R time and aPTT. The discordant TEG R times with a therapeutic PTT were almost equally distributed between subtherapeutic and supratherapeutic categories. CONCLUSION(S): Moderate correlation was found between TEG R time and aPTT associated with bivalirudin during ECMO in critically ill adults. Further research is warranted to address the optimal test to guide clinical decision-making for anticoagulation dosing in ECMO patients with discordant results.
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These proceedings contain articles that discuss setting the stage: the current state of the TB epidemic and COVID-19 effects, recap of events after the UN high-level conference in 2018, and direction for the UN high-level meeting in 2023. The ITFDE last discussed tuberculosis (TB) in 2010 and identified the following objectives: accelerated improvement and expansion of laboratory services for diagnosis and treatment, including assessment of drug resistance;increased support for better control and research;improved access to care and coverage of the most vulnerable populations;and political advocacy for TB control by potential allies inside and outside the health sector.
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Background: In 2020 the COVID-19 pandemic spread due to the coronavirus SARS-CoV-2. Vaccination is crucial to fight the COVID-19 pandemic. Initial reports of anaphylaxis after vaccination caused concern and fear of the population and consequently a high demand for allergy testing. Method(s): The need and reasons for allergy testing were recorded via questionnaires and the patients' medical history. To study the possibility of higher-throughput allergy evaluation, additional new skin test appointment slots were created for patients concentrated during the Christmas week 2021 and the amount of material, time required, as well as the organization and the tolerability of subsequent vaccination were analyzed. Result(s): The demand for testing greatly exceeded the number of available standard appointment slots. Test indications were mostly the patients' fear of an allergic reaction to the vaccine when a polyethylene glycol (PEG) allergy could not be unequivocally excluded in the patients' history. Forty-one patients (38 females, 3 men, age 51 +/- 17.7) were tested on 3 days. The average contact time needed per patients for the nurse was 30 minutes and for the physician 25 minutes. One patient could not be tested due to antihistamine use. After testing, in 36 cases routine vaccination was recommended;of those 35 patients got vaccinated. In four patients, an indication for inpatient PEG provocation or inpatient vaccination was given. Two thirds (27/41 patients, 65.9%) of all who were initially refusing vaccination got vaccinated shortly after allergy tests and tolerated this vaccination without major complications, an additional 9.8% intended future vaccination. Only four patients (9.8%) persistently refused vaccination after testing. Conclusion(s): In this pilot study, we show a useful and effective option to triage patients requesting COVID-19 vaccine allergy testing and generally how to process allergy appointments in a more time effective manner. Optimizing intraclinical processes leads to a substantially higher number of patients that can be allergy tested and vaccinated. Copyright © 2022 Dustri-Verlag Dr. K. Feistle.