Pharmacogenetics aims to investigate the correlation between patient genetic characteristics and the efficacy of pharmaceutical agents, while concurrently evaluating the risks of adverse reactions. This field of research necessitates the application of complex statistical analysis methodologies, and artificial intelligence (AI) capabilities are increasingly being leveraged for such analyses. AI represents an advanced technology employed to automate the execution of tasks that traditionally demand substantial human intellectual effort. A review of scientific literature on the application of machine learning models in pharmacogenetic research has demonstrated that AI is a highly sophisticated and flexible tool capable of facilitating the widespread implementation of pharmacogenetics in clinical practice. A promising area for the application of AI in pharmacogenetics involves the integration of this technology into tasks related to the analysis, detection, prediction, and support of pharmacogenetic information and decision-making systems. The utilization of deep learning technologies has the potential to expand the understanding of drug pharmacodynamics, indications, and contraindications, which may potentially lead to the updating of educational and methodological literature on pharmacology and substantially advance the quality of patient pharmacotherapy. However, the implementation of AI technologies may be hindered by factors such as a shortage of qualified personnel, ethical disagreements, and complexities in legal regulation of this domain. Nonetheless, the application of AI technologies in pharmacogenetic research demonstrates high effectiveness and expediency, despite the existing challenges.

УДК 615.038АССОЦИАТИВНАЯ СВЯЗЬ МЕЖДУ НОСИТЕЛЬСТВОМ ПОЛИМОРФИЗМА ГЕНОВ БЕЛКОВ, УЧАСТВУЮЩИХ В ФАРМАКОКИНЕТИКЕ И ФАРМАКОДИНАМИКЕ ИНГАЛЯЦИОННЫХ АНЕСТЕТИКОВ, И ФОРМИРОВАНИЕМ ИНДИВИДУАЛЬНОГО ФАРМАКОЛОГИЧЕСКОГО ОТВЕТА Татжикова К.А. 1 , Кантемирова Б

BACKGROUND: There is currently no widespread implementation of pharmacogenetic testing (PGx) methods in the practice of phthisiology service. OBJECTIVE: The aim of this study is to determine how informed and prepared phthisiologists, residents, and postgraduate students of the Russian Medical Academy of Continuing Professional Education (RMACPE, Moscow) use PGx techniques in their work to improve treatment safety, predict the occurrence of adverse reactions (ADRs), and personalize therapy. METHODS: A survey was conducted among phthisiologists (n = 314) living in different regions of the Russian Federation and studying at RMACPE, such as residents and post-graduate students (n = 185). The survey was developed on the Testograf.ru web platform and had 25 questions for physicians and 22 for residents and post-graduate students. RESULTS: More than 50% of respondents are ready to use PGx in clinical practice and thus are aware of the method’s possibilities. At the same time only a small part of participants were aware of the pharmgkb.org resource. The absence of PGx in clinical guidelines and treatment standards, according to 50.95% of phthisiologists and 55.13% of students of RMACPE, the absence of large-scale randomized clinical trials, according to 37.26% of phthisiologists and 43.33% of students, and the lack of physician knowledge on PGx, according to 41.08% of phthisiologists and 57.83% of students, are all factors that prevent the implementation of PGx in Russia. CONCLUSION: According to the survey, the overwhelming majority of participants recognize the importance of PGx and are willing to use the method in practice. However, there is a low level of awareness among all respondents about the possibilities of PGx and the pharmgkb.org resource. The implementation of this service could significantly increase patient compliance, lower ADRs, and enhance anti-tuberculosis (TB) therapy quality.

УДК 616.12-009.72-07АНАЛИЗ КОРРЕЛЯЦИИ МЕЖДУ УРОВНЕМ СЫВОРОТОЧНОГО ТРОМБОЦИТАРНОГО ФАКТОРА РОСТА И ТЯЖЕСТЬЮ ОСТРОГО КОРОНАРНОГО СИНДРОМА Абдуллаев М.А. 1 , Кантемирова Б.И. 1 , Романова А

A priority in the development of modern healthcare is patient-centered medicine, the main tool of which is the ability to predict the individual response to certain interventions, including the use of medications. This is made possible through the use of knowledge-intensive technologies that provide the detection of certain biomarkers, making it possible to obtain individual information about the patient, in order to personalize the choice and dosing regimen of drugs. The most promising for clinical practice are pharmacogenetic/pharmacogenomic, pharmacoepigenomic and pharmacometabolomic biomarkers.

Coronary heart disease (CHD) is one of the most common causes of death worldwide. The pharmacokinetic properties of drugs used to treat coronary heart disease depend on genetic factors, including the genotype of CYP2C19, CYP2C9 and CYP4F2. However, existing studies of the genetic basis of the response to treatment in patients with acute coronary syndrome (ACS) have contradictory results, requiring a more detailed study. Goal. In this study, we studied the distribution of the genotypes of CYP2C19*2, CYP2C9*2 and CYP4F2*3 among 59 patients diagnosed with ACS who received dual antiplatelet therapy. Methods. The polymerase chain reaction (PCR) method was used to determine the genotypes of CYP2C19, CYP2C9 and CYP4F2. A correlation analysis of the results of genotype carriage and clinical and laboratory parameters of patients was carried out. Results. The distribution of CYP2C9*2 genotypes was as follows: wild genotype (CC) was found with a frequency of 78 % (45 patients), heterozygotes (CT) — 22 % (12 patients), homozygotes (TT) were not detected. The CYP4F2*3 genotype was distributed as follows: 56.14 % (32 patients) had a wild genotype (CC), 31.5 % (18 patients) were heterozygotes with reduced enzyme activity (CT), 12.36 % (7 patients) were homozygotes for the T (TT) allele. The distribution of alleles and genotypes of CYP2C9 did not correspond to the Hardy-Weinberg equation (χ2 = 21.55; p = 0.044), while the distribution of alleles and genotypes of CYP4F2 corresponded to it (χ2 = 3.61; p = 0.0574). Conclusion. The study showed a high prevalence of the genotypes CYP2C9*2 (CT) and CYP4F2*3 (CT and TT) among patients with acute coronary syndrome. The carriage of CYP2C19*2 was significantly associated with adverse cardiovascular events in patients. These results suggest that genetic testing can provide valuable information for risk stratification and personalized treatment of patients with acute coronary syndrome

The scientific review of the literature provides information on current clinical observations of the use of proton pump inhibitors in large randomized trials of Russian and foreign scientists, issues of their classification, pharmacokinetics, pharmacodynamics, pharmacogenetics, efficacy and safety of prescribing in pediatric practice, due to the growth of acid-dependent conditions in children and the need for further systematic research with the development of approaches to personalization of prescribing drugs for each age group.

The article contains the results of a comparison pharmacoeconomical cost-utility analysis of several options for dual antiplatelet therapy in patients with acute coronary syndrome after stent implanting. The costs for treatment alternatives with and without prior pharmacogenetic testing for CYP2C19 were calculated. According to the results of the analysis the most cost-effective treatment option for patients with acute coronary syndrome is prior pharmacogenetic testing and the choice of the antiplatelet drug prasugrel in slow and intermediate metabolizers (CUA: 289,111.00 rubles per QALY).

Relevance. The problem of antiplatelet therapy resistance is not fully solved, whereas its manifestations in the form of stent thrombosis cause a negative contribution in treatment and can lead to significant economic damage to the healthcare system. Pharmacogenetic testing as a personalization tool can potentially reduce the cost of treatment, which requires pharmacoeconomic research of pharmacogenetic methods. The aim of this study was a pharmacoeconomic evaluation of the pharmacogenetic testing implementation before the antiplatelet therapy in patients with acute coronary syndrome after percutaneous coronary intervention. Methods. In our study, a decision tree model was built with a time horizon of 1 year and a cost-effectiveness analysis was performed for six compared treatment strategies in patients with acute coronary syndrome after stent implantation with and without genotyping for the drugs clopidogrel, ticagrelor and prasugrel. Results. A treatment strategy with pharmacogenetic testing and the choosing of prasugrel for slow and intermediate metabolizers was the most preferred with CER 35 577.40 rubles per 1 unit of effectiveness. The most expensive strategy was the “blind” use of ticagrelor for all patients. Conclusion. Based on the modeling results, it can be concluded that the implementation of pharmacogenetic testing before prescribing antiplatelet drugs in patients with acute coronary syndrome undergoing stenting can potentially reduce the incidence of adverse events such as stent thrombosis and reduce the overall cost of treatment.

Журнал для непрерывного медицинского образования врачей Полиморфизм генов у больных новой коронавирусной инфекцией COVID-19 АНАЛИТИЧЕСКИЕ ОБЗОРЫ Федеральное государственное бюджетное образовательное учреждение высшего образования «Астраханский государственный медицинский универси-

Background. The role of the VKORC1 (1639GA, rs9923231) gene polymorphism in hypersensitivity to warfarin and hypocoagulation is known. It has been proven that polymorphisms in the VKORC1 gene can lead to the progression of atherosclerosis and hypercoagulability, and, therefore, can be factors contributing to the development of acute coronary syndrome. Aim. To study the effect of polymorphic genotypes carriage of the VKORC1 gene on the clinical and laboratory parameters of patients with acute coronary syndrome. Material and methods. The pilot observational cross-sectional study involved 77 patients who were under observation in the conditions of the Federal Center for Cardiovascular Surgery in Astrakhan and the vascular center of Kirov City Hospital No. 3 (Astrakhan), from October 2020 to May 2021. Genotyping for CYP2C9, VKORC1, CYP4F2 on a PCR analyzer was performed. For statistical processing, the HardyWeinberg and Student criteria; 95% confidence interval were determined using Statistica Trial 13 and IBM SPSS Statistics 26.0. Differences were considered statistically significant at p 0.05. Results. Significant differences related to the frequency of hemodynamically significant stenosis in homozygous carriers of the GG gene for VKORC1 compared with the group of carriers of the GA genotype 3 (8.8%) versus 7 (22.5%); p=0.0058. Carriers of the GA and GG genotypes were most often diagnosed with myocardial infarction (Q- and non-Q-forming). Carriers of the AA genotype were more likely to have new or progressive angina pectoris. The level of hyperglycemia and triglyceridemia was the highest in the group of patients with the AA genotype, VKORC1 gene. Conclusion. Statistically significant differences were established in the clinical and laboratory parameters of patients with acute coronary syndrome, carriers of different genotypes of the VKORC1 gene.

In recent years, the clinical symptomatology of Astrakhan spotted fever and coxiellosis has worsened. The pathogenesis of these two natural focal, endothelium-dependent infections is rather complicated, multifactorial and not properly studied. The current clinical symptomatology is characterized by severe intoxication syndrome, frequently signs of multiple organ failure, development of hemocoagulation and vascular complications [3, 4, 5]. To date, no early markers of endothelial vascular damage have been proposed for use in practical health care, which enable accurately assessing the severity degree and predicting the further course of the rickettsiae and coxiellosis. Platelet-derived growth factor (PDGF), which is widely used in the diagnosis and prognosis of cardiovascular diseases, various injuries and diabetes mellitus, may become such a marker.

Abstract The Aim. Pharmacoeconomic assessment of the oral antiplatelet availability of various drug manufacturers and dosage forms based on the analysis of price characteristics. Materials and methods. The analysis included drugs from the group of platelet aggregation inhibitors (excluding heparin) (ATC code B01AC): clopidogrel, clopidogrel + acetylsalicylic acid (ASA), ASA and dipyridamole in various dosages and number of tablets per package. The cost values were estimated by the resources of large resources "Apteka.ru", "009.rf" with the average value calculations in the eight federal district’s capitals of the country. Results. The cost of drugs in the analyzed group varied depending on the drug manufacturer. The highest amount of the cost variation was in the ASA tablet form (100 mg) – 407.47%, followed by the tablet form of clopidogrel (75 mg) – 311.16%, ASA (50 mg) – 172.20%, dipyridamole (75 mg) – 117.36% and the lowest values for the tablet forms of dipyridamole (25 mg) – 68.19% and the combination of ASA with clopidogrel (100mg + 75mg) – 59.13%. The highest Ca.s values were in ticagrelor (90 mg) – 24.92% and prasugrel (10 mg) – 7.87%, the lowest in ASA (50 mg) – 0.1%. According to the linear index of distribution, the drugs ASA (100 mg) – 89%, clopidogrel (75 mg) – 70%, and less accessible ticagrelor (60 mg) – 18% and prasugrel (10 mg) – 14% had a higher physical availability. Conclusion. Based on the calculated values a high availability of such antiplatelet drugs as ASA (50 mg and 100 mg), clopidogrel (75 mg) was revealed. According to the results of the study, the antiplatelet drugs ticagrelor (60 mg and 90 mg) and prasugrel (10 mg) have the least level of availability.

The aim of the article is the evaluation of the economic damage (ED) because of the absence of pneumococcal vaccination as a leading risk factor for the development of community-acquired pneumonia (CAP) and acute exacerbations of а chronic obstructive pulmonary disease (COPD).Materials and methods. The method of attributive statistics was used for the first time to assess the ED of the vaccination absence as an independent risk factor contributing to the development of CAP and COPD exacerbations in the Astrakhan region for the period of 2015–2019. To do this, at the beginning of the study based on the literature data, a relative risk of COPD complications associated with the absence of pneumococcal vaccination was determined. Using it as a risk factor, prevalence rates (a proportion of non-vaccinated patients with COPD), the population attributable risk (PAR) was calculated. Further, the annual economic damage (ED) from the development of CAP and COPD exacerbations was determined. To assess the cost-effectiveness of the COPD complications prevention, vaccination costs of newly registered patients were calculated and the ratio of these costs to the average annual ED was determined.Results. A decrease in the non-vaccinated patients’ proportion corresponds to the decrease in the total ED from COPD complications: from 13.16 million rubles to 6.06 million rubles during the observation period. The calculations showed that due to the increase in the vaccinated patients’ proportion over a five-year observation period, the ED from the CAP development decreased by 2.1 times, from exacerbations of COPD – by 2.3 times. The vaccination costs of newly diagnosed COPD cases amounted to 0.63 million rubles. Thus, to prevent the annual ED of 3.24 million rubles, the sum for the state to spend, should be 5.2 times as small.Conclusion. A study on the evaluation of the ED due to the risk factor (RF), the pneumococcal vaccination absence, showed that its elimination reduces the risk of acute COPD exacerbations and the development of CAP, as well the ED, as associated with them. Reducing the economic costs of the health care system with significantly lower vaccination costs, makes this preventive measure economically viable.

In recent years, significant advances in the diagnosis and treatment of cardiovascular diseases have been achieved in the healthcare of most countries. However, among the causes of mortality in patients with coronary heart disease, arterial thrombosis takes one of the leading positions. Antiplatelet drugs are prescribed to prevent thrombotic complications, which can be used as mono- or two-component therapy. In case of atherosclerosis in arteries, acetyl-salicylic acid (ASA) or clopidogrel can be used as monotherapy; treatment of acute coronary syndrome (ACS) and percutaneous coronary interventions (PCI) required using of double antiplatelet therapy (DAT), including acetylsalicylic acid drugs together with one antiplatelet agent from the group of thienopyridine derivatives — blockers of P2Y12 platelet receptors (clopidogrel, ticagrelor, prasugrel). In patients with ACS who underwent primary PCI or thrombolysis followed by PCI, the duration of DAT is 12 months, and clopidogrel is the drug of choice [16, 30]. According to various literature sources about 20–40% of patients have low effectiveness of antiplatelet therapy, which can lead to thrombosis, stent thrombosis and thromboembolic complications. This review provides an analysis of modifiable and nonmodifiable factors contribution to the development of clinical and laboratory resistance of antiplatelet agents.

Relevance of the study and the presence of gaps in existing knowledge on topic. The use of inhalation bronchodilators and glucocorticosteroids (GCS) improves the functional parameters of the lungs in patients with chronic obstructive pulmonary disease (COPD), as well as reduces the number of middle and severe exacerbations. There are a large number of inhalation drugs in the modern Russian pharmaceutical market, which are both monocomponent and combinations of two and three drugs. Often, original and generic drugs have different costs and are not always economically or physically available to different population segments. Thus, the aim of this study was to conduct a comparative pharmacoeconomic analysis of inhalation bronchodilators and anti-inflammatory drugs to determine the level of economic availability. Materials and Methods. Drugs from the group of adrenomimetics for inhalational use (ATC code R03A), anticholinolytic and GCS for inhalation used in the COPD treatment (ATC code R03B) were analyzed. Information about the price of drugs is obtained from the state register of maximum selling prices and the Internet resource "Apteka.ru". To evaluate the availability of the analyzed groups of drugs, solvency adequacy coefficients (Ca.s) and price liquidity indicators (Cliq) were calculated. Results . The most available among the GCS was beclomethasone in form of a metered-dose inhalator (MDI) 50 mcg (Cliq = 52%; Ca.s = 0.338%), among short-acting emergency bronchodilators, salbutamol in MDI form 100 mcg (Cliq= 58%; Ca.s = 0.156%) was the most available. Greater availability was found for domestic drug manufacturers (95% CI: 0.690 - 1,000; p = 0.007), however, the opposite data were obtained for several drugs. Conclusions . The obtained results show a heterogeneous structure among the levels of inhalation drugs availability used in COPD treatment. Taking into account the wide range of drug products, in order to inform medical and pharmaceutical workers in a timely way, it is advisable to systematically study these drug groups using pharmacoeconomic analysis methods.

ЦЕЛЬ ИССЛЕДОВАНИЯ : оценить качество жизни пациентов с СХТБ до и после назначения нестероидных противовоспалительных препаратов (НПВП) в зависимости от выраженности болевого синдрома, наличия коморбидной патологии, генотипа CYP2C9, определяющего скорость метаболизма НПВП. МАТЕРИАЛЫ И МЕТОДЫ У больных с СХТБ (средний возраст 49,7±13,43 лет, мужчин - 71, женщин - 81) изучено носительство вариантов мутаций гена CYP2C9. С учетом наличия коморбидной патологии и результатов фармакогенетического тестирования подобрана персонализированная терапия НПВП-препаратами, проведена оценка интенсивности болевого синдрома (шкала ВАШ), исследовано качество жизни (сферы 1,2,3,4, краткий опросник ВОЗ WHOQOL BREF), определено содержание концентрации провоспалительных цитокинов (ИЛ-1β, ИЛ-6) до начала терапии и на 7 сутки терапии НПВП. РЕЗУЛЬТАТЫ При персонализированной терапии (назначение 70 носителям NM-генотипа CYP2C9 целекоксиба в средней дозе 200 мг/сутки однократно, 32 носителям PM-генотипа ацеклофенака 200 мг/сутки в 2 приема) было установлено достоверное снижение интенсивности боли, уровня провоспалительных цитокинов в крови, возрастание показателей качества жизни больных (сферы 1,2,3, t=4,02; p<0,001; t=2,15 p<0,05) во всех группах наблюдения. Минимальное развитие нежелательных побочных реакций (НПР) отмечено у пациентов, получающих персонализированную терапию НПВП-препаратами. ЗАКЛЮЧЕНИЕ Проведенное исследование показало, что назначение персонализированной терапии позволят добиться лучшего результата - уменьшения интенсивности боли, повышения основных показателей качества жизни, при обеспечении безопасности и минимизации НПР, за счет сокращения ЖКТ и ССС осложнений.

Chronic pelvic pain syndrome (CPPS) is equally common in both men and women, causes worsening quality of life, social isolation and disability. The treatment of CPPS requires long-term pharmacotherapy associated with the development of class-specific side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Genetic study of the carriage of polymorphic alleles of the CYP2C9 gene involved in the metabolism of non-steroidal anti-inflammatory drugs (NSAIDs) prescribed to patients with CPPS is an urgent and in-demand task of modern healthcare. This study allows us not only to determine the genotypes of patients with CPPS but also to identify ways of personalized approach to therapy.