Effect of CYP3A4, CYP3A5, ABCB1 Gene Polymorphisms on Rivaroxaban Pharmacokinetics in Patients Undergoing Total Hip and Knee Replacement Surgery
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01.10.2019 |
Sychev D.
Minnigulov R.
Bochkov P.
Ryzhikova K.
Yudina I.
Lychagin A.
Morozova T.
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High Blood Pressure and Cardiovascular Prevention |
10.1007/s40292-019-00342-4 |
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© 2019, Italian Society of Hypertension. Introduction: Population ageing in developed countries will inevitably increase the need for knee and hip replacement surgery. Over the years, direct oral anticoagulants, such as rivaroxaban, have been widely used for thromboprophylaxis in patients undergoing knee and hip replacement surgery. The study of pharmacogenetic characteristics of rivaroxaban is important for enhancing the effectiveness and safety of rivaroxaban thromboprophylaxis. Aim: Evaluation of CYP3A4, CYP3A5 and ABCB1 gene polymorphisms influence on rivaroxaban pharmacokinetics and prothrombin time dynamics in patients undergoing total hip and knee replacement surgery. Methods: The study included 78 patients undergoing total hip and knee replacement surgery. The patients received 10 mg of rivaroxaban once a day. Genotyping of polymorphisms ABCB1 rs1045642, ABCB1 rs4148738, CYP3A4 rs35599367 and CYP3A5 rs776746 was performed. Peak steady-state and trough steady-state rivaroxaban concentrations were determined. Prothrombin time was also evaluated. Results: The study revealed the following haplotypes: (1) ABCB1 rs1045642—CYP3A4 rs35599367 and (2) ABCB1 rs4148738—CYP3A4 rs35599367. The analysis of the peak steady-state rivaroxaban concentration between mutant haplotypes and wild haplotypes revealed no significant differences. However, there was a statistically significant average correlation between peak steady-state rivaroxaban concentration and prothrombin time (r = 0.421; r2 = 0.178; p < 0.001). Conclusion: No significant difference was identified in peak steady-state rivaroxaban concentration between mutant haplotypes and wild haplotypes. The revealed statistically significant average correlation between the prothrombin time and peak steady-state rivaroxaban concentration is important in clinical practice for assessing the anticoagulant activity of rivaroxaban.
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Diagnosis and Treatment of Migraine: Recommendations of Russian Experts
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01.06.2018 |
Osipova V.
Filatova E.
Artemenko A.
Lebedeva E.
Azimova Y.
Latysheva N.
Sergeev A.
Amelin A.
Koreshkina M.
Skorobogatykh K.
Ekusheva E.
Naprienko M.
Isagulyan E.
Rachin A.
Danilov A.
Kurushina O.
Parfenov V.
Tabeeva G.
Gekht A.
Yakhno N.
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Neuroscience and Behavioral Physiology |
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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Recommendations for the diagnosis and treatment of migraine based on the principles of evidence-based medicine are presented. The latest edition of the International Classification of Migraine is provided. Diagnostic methods and criteria are oriented to discriminating different types of migraine. Recommendations are given on the basis of data on the epidemiology and pathophysiological mechanisms of migraine. The most effective medication-based and non-medication-based approaches to the management of migraine patients are discussed.
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Clinical efficacy of vaccination against hemophilic type B and pneumococcal infections in children with chronic respiratory diseases
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01.03.2018 |
Magarshak O.
Kostinov M.
Krakovskaya A.
Kozlov V.
Blagovidov D.
Polishchuk V.
Ryzhov A.
Kostinov A.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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© 2018, Pediatria Ltd. All rights reserved. Materials and methods: the study assessed safety and clinical efficacy of combined use of vaccine preparations against S. pneumoniae and H. influenzae type b, leading pathogens in bronchopulmonary diseases exacerbations development, in previously unvaccinated 38 children aged 2–17 years with chronic bronchopulmonary diseases: 19 with malformations of the bronchi and lungs (MBL); 10 with malformations of bronchi and lungs in combination with bronchial asthma (MBL+BA); 9 with bronchial asthma (BA). The control group consisted of 19 unvaccinated children of the same age with a similar pathology. Combined vaccination against these infections, as well as their separate administration, did not cause adverse effects. Results: a year after the introduction of Pneumo-23 vaccine, the incidence of acute respiratory infections (ARI) and exacerbations of the main disease decreased by 2,3 times; Act-HIB by 2,3 and 2,1 times respectively; by 1,7 and 1,5 times respectively with simultaneous administration of these preparations. In children with BA the duration of one exacerbation decreased by 3,4 times, the average duration of temperature reaction by 1,9 times and the systemic antibiotic therapy of one exacerbation episode by 2,4 times. In the group of children with MBL+BA these indicators decreased by 2,1, 1,8 and 1,6 times, respectively, and in patients with MBL by 1,6, 1,5 and 1,4 times, respectively. Conclusion: vaccination against pneumococcal and hemophilic type b infections using one or both vaccines in patients with MBL and with MBL+BA is safe and positively affects the clinical course of the main disease.
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Assessment of perioperative prophylaxis of infectious complications in post-op patients
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01.01.2018 |
Morozova T.
Lukina M.
Andrushishina T.
Chukina M.
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Bulletin of Russian State Medical University |
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© 2018 Pirogov Russian National Research Medical University. All rights reserved. Perioperative antimicrobial prophylaxis (PAP) involves administration of antimicrobial agents (AMA) to patients undergoing a surgical intervention and aims to reduce the risk of postoperative infectious complications, especially at surgical sites. In the present work we assess efficiency and safety of AMA used for prevention of postoperative infectious complications. In the course of our study we pre-analyzed 576 medical histories of post-op patients aged 18 to 87 years (mean age M ± SD was 57.4 ± 14.5 years), of which 347 (60.2%) were male and 229 (39.8%) female. Only 481 histories were selected for final analysis. We assessed the choice of antibacterial therapy, the frequency of adverse reactions (AR) and infectious complications and the type of the latter. PAP regimens were consistent with the official guidelines in 207 (43.04%) cases. PAP recommendations were ignored in 274 cases (56.96%), and the timing was wrong in 364 cases (75.7%). Incorrect dosages were administered in 225 cases (46.8%). We also discovered an association between irrational PAP regimens and 1) the length of patient's stay in the intensive care unit (p = 0.003 and p < 0.005), 2) the frequency of reoperations associated with infection (p = 0.001), 3) mortality rates (p = 0.002), and 4) isolation of strains with multidrug resistance (p = 0.016). We conclude that PAP regimens for the inpatients of surgical wards are often compromised by failure to comply with the official guidelines, wrong timing and incorrect dosage, which negatively affects hospital statistics.
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Evaluation of the rivaroxaban-influenced effect of ABCB1 and CYP3A5 gene polymorphisms on prothrombin time in patients after total hip or knee replacement surgery
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01.01.2018 |
Sychev D.
Minnigulov R.
Ryzhikova K.
Yudina I.
Lychagin A.
Morozova T.
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Bulletin of Russian State Medical University |
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0 |
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© 2018 Pirogov Russian National Research Medical University. All Rights Reserved. Rivaroxaban is a safer and more effective alternative to warfarin. However, there are reports of some cases of major hemorrhagic complications associated with rivaroxaban that significantly impair the patients' quality of life and can lead to a fatality. Personalized therapy, including pharmacogenetic testing, may help prevent such adverse events. This study aimed to investigate how ABCB1 3435C>T (rs1045642) and CYP3A5 6986A>G (rs776746) gene polymorphisms, when carried by a patient taking rivaroxaban to prevent thrombosis after total hip or knee replacement surgery, affect prothrombin time (PT). Sixty-five patients participated in the study. Their genotypes were identified by PCR in real time. To learn PT peculiar to each patient, we collected venous blood on the 5 th day of their anticoagulation therapy, 1 hour before they took rivaroxaban and 3 hours after. Having calculated %∆PT, we divided the patients into 2 groups: 1) %∆PT ≤ 0 (n = 7; 10.8%); 2) %∆PT > 0 (n = 58; 89.2%). Regarding the distribution of rs1045642 polymorphism, we determined the difference between the groups to be statistically significant (χ 2 = 6.64; p = 0.027). As for rs776746 polymorphism, the difference was insignificant (χ 2 = 0.101; p = 1.0). We discovered that rs1045642 polymorphism has a significant effect on PT variance in patients taking rivaroxaban to prevent thrombosis after total hip or knee replacement surgery.
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Comparative effectiveness of vitamin-mineral complexes with iron in correcting iron deficiency in women in the outpatient setting
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01.01.2018 |
Svistunov A.
Osadchuk M.
Kireeva N.
Lazareva A.
Shorina D.
Vasil'eva I.
Savina T.
Tuaeva E.
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Terapevticheskii Arkhiv |
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© 2018 Media Sphera Publishing Group. All rights reserved. Àim. To compare the efficacy of prophylactic administration of mineral-vitamin complexes "Feroglobin-B12" and "Complivit iron" with different degrees of Fe valence. Materials and methods. 120 female subjects were examined. To determine the quality of life, the SF-36 questionnaire was used. The presence of anxiety was determined on the Spielberger-Khanin Alarm Scale. 30 women with a deficit of Fe were divided into 2 groups of 15 people each. The first group received "Ferroglobin-B12", the second – "Complivit iron" for a month. Results. In a month after the initiation of preventive therapy in women of the 1 group the content of Fe serum was normalized. In the second group, its concentration approached the control values. The difference in Fe content in the 1 and 2 groups was of a reliable nature. Conclusion. The intake of "Ferroglobin-B12" was not accompanied by side effects, and performance indicators, social activity and mental health reached control values, unlike the group of patients taking Complivit iron.
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Some methodological problems of the optimization of microecological risk factors to health
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01.01.2018 |
Shandala M.
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Gigiena i Sanitariya |
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© 2018 Techno-Press, Ltd. In order to prevent the phenomena of "microbiological genocide", unjustified and unfavorable violations in microecological systems, and, first of all, human microbiota during the implementation of the disinfection prevention of diseases, the necessity for the scientific justification and practical provision of sufficient antimicrobial selectivity of disinfecting effects, is substantiated in the article. It is necessary to decode and take into account the susceptibility of different microbe pathogens to various disinfectants in comparison with saprophyte, and even more so, useful microflora.
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Problems of clinical diagnosis and treatment of P. Falciparum malaria in Russian Federation
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01.01.2018 |
Sergiev V.
Baranova A.
Kozhevnikova G.
Tokmalayev A.
Chernyshov D.
Chentsov V.
Kouassi D.
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Terapevticheskii Arkhiv |
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© 2018 Media Sphera Publishing Group.All Rights Reserved. Aim. To study the causes of falciparum malaria deaths in Russian Federation and to optimize therapy for severe forms of the disease. Materials and methods. The analysis of falciparum malaria cases with deaths recorded in Russian Federation from 2013 to 2017 was conducted. The results of optimization of pathogenetic therapy of severe forms of falciparum malaria for the prevention of adverse outcomes in the intensive care unit of the Infectious Clinical Hospital №2 of Moscow in 44 patients with severe course are presented. Treatment, clinical laboratory and instrumental investigations were carried out in accordance with our intensive care protocol, which took into account the current WHO recommendations. Results. From 2013 to 2017 there were nine deaths from falciparum malaria reported in patients from African countries (6) and India (3). In Russia, due to the lack of effective drugs of artemisinin group, quinine with tetracycline or doxycycline is used for etiotropic therapy of patients with complicated form of falciparum malaria. In the management of such patients, the basis for treatment was the prevention of is-chemic, reperfusion injuries of organs and hemorrhagic complications. In the infectious clinical hospital №2 of Moscow, since 2007, the intensive care unit has developed and tested a protocol for intensive therapy in patients with severe and complicated forms of falciparum malaria, including preventive methods of extracorporeal hemocorrection with prolonged veno-venous hemodiafiltration therapy and plasmapheresis, as a result of which the mortality rate decreased from 84 to 6.8% Conclusion. The country's lack of anti-malarial drugs, the insufficient awareness of the population about the risk of infection and measures to prevent malaria, late referral of cases for medical care and errors of clinical diagnosis and treatment annually lead to fatal outcomes. In such situation, the experience of optimizing the treatment of severe falciparum malaria is particularly useful, allowing decreasing the mortality.
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