Introduction: Losartan, a selective angiotensin II receptor type 1 antagonist, is transported across cell membrane mediated by P-glycoprotein, the product of the ABCB1 (also known as MDR1) gene. The level of expression of this transporter protein is characterized by significant individual variability, caused by genetic factors. Well-known polymorphisms C3435T and C1236T in the ABCB1 gene potentially could affect a functional activity of the P-glycoprotein, thus modulating the pharmacokinetic parameters and clinical efficacy of the substrates of this transporter, including losartan. Therefore, the aim of this research is to indicate the correlation between common SNPs C3435T and C1236T of the MDR1 gene and the efficacy of 6-week losartan monotherapy course in patients with a newly diagnosed arterial hypertension (AH). Materials and Methods: The study included 34 patients (70.6% women, mean age 48.3 ± 7.4 years). All participants were given losartan 100 mg/day for 6 weeks. Genotyping for C3435T and C1236T polymorphisms was made by using allele-specific PCR with electrophoretic detection. The efficacy of the therapy was evaluated by the reduction of systolic (SBP) and diastolic (DBP) blood pressure from the reference level. Results: Patients with CT or TT genotypes for the C3435T polymorphism showed a statistically meaningful, greater reduction in SBP (11.8% ± 9.7) compared to homozygous CC genotype (”wild” type; 6.7% ± 9.6; p=0.03). No significant differences were found in SBP reduction for the C1236T polymorphism (p=0.07). Changes in DBP did not correlate with either of the studied polymorphisms. Conclusions: The C3435T genetic polymorphism of the MDR1 gene is a potential predictor of the efficacy of losartan antihypertensive therapy. The carriers of the T allele (CT/TT genotypes) demonstrate more expressed hypotensive response, which may be caused by modulation of tissue distribution of the drug or its interaction with endogenous systems (ouabain) regulating blood pressure. The obtained data highlights the importance of a pharmacogenetic approach for personalizing AH treatment.

Introduction: Arterial hypertension (AH) is a significant risk factor for cardiovascular diseases and premature mortality. The aim of the study: To assess the level of knowledge and cognizance of physicians and medical students in a field of pharmacotherapy of AH. Materials and Methods: This article analyzes the second phase (2019-2023) of the PHYSTARH project, a multicenter anonymous survey involving 494 therapeutic physicians from 10 Russian cities/regions and 426 students from 10 Russian and Kyrgyz universities. Comparisons were made with the previous phase (2017-2019) of student and physician research. Statistical methods included descriptive statistics, Kolmogorov-Smirnov, U-Mann-Whitney, Kruskal-Wallis, Pearson correlation, median test, ANOVA, and regression analysis (p<0.05). Results: The study revealed that the knowledge levels among both students and physicians is not sufficiently high. Moreover, some questions showed a fatally low level of knowledge. The average level of correct answers in the second part of the survey (LCA) was 44.9% for students and 53.5% for physicians. The LCA for students in the previous phase was 57.7%, while the LCA for physicians (2017-2019) in the second part of the survey was 60%. Conclusion: The common level of knowledge base among students and physicians regarding key aspects of AH is insufficient. It is essential to implement additional educational programs to fill the recognized knowledge gaps. The results of studies highlight the necessity of improving educational programs for medical specialists in the field of arterial hypertension. The lowest correct answers rates were found in questions regarding the use of acetylsalicylic acid in patients with AH. The highest correct response rate was recorded for a question about selecting the optimal drug for managing uncomplicated hypertensive crises.

Background: the Global Burden of Disease (GBD) study has shown a significant increase in the prevalence of cutaneous and subcutaneous tissue diseases. Despite the high prevalence of non-healing wounds, there are very few economic estimates of specific treatment methods, which makes this issue very relevant. Aim: to conduct a clinical and economic analysis concerning the Zetuvit Plus Silicone / Zetuvit Plus Silicone Border superabsorbent dressing for the treatment of moderately and severely chronic non-healing wounds and ulcers of the lower extremities versus standard therapy with other dressings. The target group consisted of patients with moderately and severely chronic non-healing wounds and ulcers of the lower extremities. Patients and Methods: the Markov model was applied during the clinical and economic analysis, conducted with regard to the Russian healthcare system. The horizon analysis corresponded to the mean treatment duration of 24 weeks (about 6 months). Results: simulation showed that the dressing cost for one patient in the group who used superabsorbent dressing (100.6 thousand rubles) was 192.2 thousand rubles less than with standard therapy (292.7 thousand rubles). At the same time, the total cost per patient when using superabsorbent dressing (319 thousand rubles) was 195.8 thousand rubles less than with standard therapy (514.8 thousand rubles). In terms of the projected number of patients (307.4 thousand people), the use of superabsorbent dressing instead of standard therapy will lead to a cost reduction of 60.2 billion rubles. Conclusion: based on the data obtained during the study, the use of Zetuvit Plus Silicone / Zetuvit Plus Silicone Border superabsorbent dressing in the treatment of moderately and severely chronic non-healing wounds and ulcers of the lower extremities is associated with lower costs for both dressing and medical care, which leads to budget savings. KEYWORDS: chronic non-healing wounds, venous trophic ulcers, Zetuvit Plus Silicone Border, Zetuvit Plus Silicone superabsorbent dressing, cost analysis, budget impact analysis, Markov model. FOR CITATION: Zhuravleva M.V., Kokushkin K.A., Luchinina E.V., Krysanova V.S., Luchinin E.A., Petrikov A.S., Lesovik V.S. Treatment optimization of chronic non-healing wounds and ulcers of the lower extremities: economic and clinical justification of new techniques. Russian Medical Inquiry. 2024;8(4):195–200 (in Russ.). DOI: 10.32364/2587-6821-2024-8-4-2.

Among hematological diseases, Multiple myeloma (MM) is the second most common malignancy in adults worldwide. In the vast majority of cases, MM remains incurable, despite improvements in progression-free survival and overall survival due to advances in pharmacotherapy, as well as the emergence of innovative drugs in recent years. Unfortunately, this does not prevent patients from relapse and, ultimately, multidrug resistance and poor prognosis. In conditions of limited funding, one of the determining factors for the success of therapy is the cost of treatment. There is a need to conduct a clinical and economic analysis of the use of targeted drugs to determine the most economically feasible treatment option. The purpose of the review is to provide an overview of current and experimental treatments for relapsed/refractory MM (RRMM), with an emphasis on their pharmacoeconomic availability to assist clinicians in their decision-making process. Let's look at the latest data that will help improve approaches to the treatment of this still incurable disease and analyze pharmacoeconomic studies of modern expensive treatment regimens for RRMM in various countries.

The purpose of this review is to provide clinicians with information and a concise interpretation of the results of pharmacogenetic testing for the cytochrome P450 2C19 (CYP2C19) genotype when choosing a proton pump inhibitor (PPI) dosage. PPIs are widely used for the treatment and prevention of common gastrointestinal diseases, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, and other hypersecretory conditions. Most PPIs are metabolized predominantly by cytochrome P450 2C19 (CYP2C19) to form inactive metabolites, and the CYP2C19 genotype determines the action of PPIs, their efficacy and possible side effects. In clinical practice, a gastroenterologist or therapist is faced with problems of insufficient effectiveness or the development of adverse reactions when prescribing PPIs. Thus, consideration of CYP2C19 genotype appears to be necessary to determine the optimal PPI dosing regimen. The above served as a reason for generalizing in the presented review of literature data on the prescription of PPIs depending on the CYP2C19 genotype.

Objective. To determine the level of basic knowledge of 5–6-year medical students in the issues of appropriate antimicrobial therapy. Materials and Methods. A multicenter questionnaire survey with analysis of results – stage of KANT project (full name of the project – «Physicians’ (Students’) knowledge in antimicrobials usage») conducted in 2020-2023. Results. A total of 277 students in 6 regions of Russia were surveyed. The average level of correct answers for the whole questionnaire amounted to 42.2%, taking into account the extended analysis of sub-items questions #8,9 – 42.6%. The respondents were best able to answer the questionnaire questions about the choice of time interval during which the effectiveness of antimicrobial therapy is assessed (average level of completeness of the answer – 90.6%); the choice of the most rational action when diagnosing acute tonsillitis or pharyngitis at the appointment (average level of completeness of the answer – 57.8%); indication of the regimen of different AMD (average level of completeness of the answer – 55.2%). The worst results were recorded when answering the following questions: justification of the situation of prolongation of antimicrobial therapy (AMT) for more than 5-7 days in a patient with positive clinical dynamics in the treatment of outpatient pneumonia (average level of completeness of the answer – 19.5%), indication of AMD of choice in the therapy of various infections (average level of completeness of the answer – 22.9%), prescription of auxiliary drugs to the justified prescription of AMD in the treatment of respiratory tract infections (average level of completeness of the answer – 21.3%). Conclusions. Having researched the results of this study, we can conclude that the level of knowledge of senior medical students in rational antibiotic therapy is quite low. In this regard, according to the authors, it is necessary to allocate an additional number of academic hours in the disciplines of "Pharmacology", "Clinical Pharmacology", specialized therapeutic disciplines, to optimize the educational program, as well as to provide students with modern sources of information that relate to the topic of rational antimicrobial therapy.

Multiple myeloma (MM) accounts for 1 % of all cancers and about 10 % of all hemoblastoses. The use of innovative technologies with the inclusion of targeted drugs leads to a significant improvement in the quality of pharmacotherapy and the achievement of overall survival (OS).The aim of the work is to conduct a pharmacoeconomic analysis of the most used MM therapy regimens with the use of targeted drugs and to determine the dominant treatment regimens using a costeffectiveness analysis.Materials and methods. To determine the cost of a course of treatment, we summed up the costs of drugs included in the pharmacotherapy regimen, taking into account taxes, marginal trade markup and duration of the course. Dosing of the targeted drug included in the regimen was determined according to the official instructions for the drug. Progression-free survival (PFS) was adopted as the main criterion for the effectiveness of treatment. Information on PFS of targeted drugs was obtained from data from international phase III RCTs — ASPIRE, TOURMALINEMM1, POLLUX and ELOQUENT2.Results. Based on the results of the pharmacoeconomic analysis, the dominant treatment regimen for MM was determined — daratumumab / lenalidomide / dexamethasone, which has the best cost-effectiveness ratio. The combination of elotuzumab / lenalidomide / dexamethasone was recognized as the least effective technology.

Objective: to assess budget impact of using empegfilgrastim for the prevention of febrile neutropenia in patients with early and locally advanced human epidermal growth factor receptor 2 positive (HER2+) breast cancer who receive neoadjuvant “docetaxel / carboplatin / trastuzumab + pertuzumab” regimen, considering possible subsequent adjuvant therapy with trastuzumab emtansine or trastuzumab within the Russian healthcare system.Material and methods. We searched and analyzed published clinical, epidemiological and pharmacoeconomic studies as well as regulatory and legal documents. A decision tree model was constructed to reflect the probabilities of switching to different adjuvant therapy regimens depending on the achievement of pathomorphological complete response in patients with early and locally advanced HER2+ breast cancer. The budget impact analysis was carried out comparing two primary prophylactic options, empegfilgrastim and filgrastim.Results. Despite the higher costs of prevention with empegfilgrastim compared to filgrastim (249 vs. 134 thousand rubles), due to the higher rate of achieving a pathomorphological complete response and, accordingly, fewer cases requiring adjuvant therapy with the more expensive trastuzumab emtanzine, savings of 916 thousand rubles per 1 patient per 1 year of therapy are possible. In general, prophylaxis in the target population diagnosed with early and locally advanced HER2+ breast cancer using empegfilgrastim will result in a cost reduction of 9.4 billion rubles per 1 year compared to filgrastim.Conclusion. Empegfilgrastim prophylaxis, despite its higher annual cost, is an efficient option within the Russian healthcare system. In addition to reducing the incidence of febrile neutropenia, the frequency and dose of chemotherapy are preserved, resulting in increased efficacy of the primary therapy.

When analyzing pharmacoeconomic studies of the skin melanoma treatment conducted in various countries, the combinations of vemurafenib + cobimetinib and encorafenib + binimetinib are the most acceptable therapy options in terms of increasing life expectancy with adjustments for quality, but, according to the clinical guidelines of the National Joint Oncology Network (NCCN), USA, version 2.2023 – “Melanoma: Cutaneous”, not for adjuvant therapy. At the same time, social networks can be a valuable asset of information about patient’s quality of the life. For the patients with advanced melanoma with a BRAF mutation, the combination of atezolizumab + vemurafenib + cobimetinib indicated the highest clinical effectiveness and can be recommended for pharmacotherapy under condition of drug price reduction.Comparison various drugs combinations with monotherapy for patients with unresectable or metastatic melanoma with a positive BRAF V600 mutation indicated that nivolumab + ipilimumab therapy is not cost-effective in comparison with nivolumab monotherapy, but combination of dabrafenib + trametinib, on the contrary, increases the patient's life expectancy compared to vemurafenib and it’s more cost-effective. It was shown that Pembrolizumab to increase life expectancy but it’s associated with increased costs compared to ipilimumab when comparing different monotherapy options. The assumed additional cost-effectiveness factor is acceptable for most European countries, because it does not exceed the “willingness to pay” threshold. It is necessary to conduct large-scale pharma-economic studies in order to identify the most cost-effective treatment for Russia for various variants of the course of melanoma, both of various combined regimens with each other, and their comparison with monotherapy. It is important to take into account also the costs of correcting undesirable adverse drug reactions, since they have a significant impact to the structure of direct costs. The development of innovative drugs for the treatment of melanoma is proceeding rapidly, however, access to these drugs is limited due to their high cost. Patient-centred drug development and reimbursement options need to be found.

The relevance of the study of chronic obstructive pulmonary disease (COPD) can be explained by the persistence of unfavorable dynamics of the disease, even despite the achieved success in the pharmacotherapy of this pathology. In 2016, World Health Organization (WHO) ranked COPD as the third leading cause of death worldwide, far exceeding the experts' predictions, who believed that such an increase in the death rate would occur by 2030. This study aimed to determine the level of senior medical students' knowledge in the management of patients with COPD, based on the method of anonymous questioning. This research work describes the results of the second stage of the ASCO project (Assessment of Senior Medical Students in the Field of COPD) conducted in 2017-2019 among 338 senior medical students from six large cities of Russia and Ukraine. The survey revealed the average level of knowledge among senior medical students, based on the average level of correct answers (56.6%) obtained in the study. The best results were obtained for the questions about COPD risk factors, influenza vaccine prevention, and pneumococcal vaccine prevention in COPD patients. The worst results were recorded on the questions about the severity of COPD clinical symptoms, the choice of initial therapy for COPD with advanced symptoms, a high risk of exacerbations, and the moderate exacerbation of COPD. The obtained results indicated an insufficient level of students' basic knowledge in questions regarding etiopathogenesis, diagnosis, treatment, and prevention of COPD.

Relevance . Ademetionine is a hepatoprotective drug, is included in the draft Russian clinical guidelines for the diagnosis and treatment of non-alcoholic fatty liver disease (NAFLD) and in the clinical guidelines for treating intrahepatic cholestasis (ITH), the cost analysis of treating patients with ITH and NAFLD is topical. Aim . The cost analysis of treatment with ademetionine for ITH and NAFLD in the Russian Federation. Methods . This clinical and economic analysis was conducted in accordance with the requirements of GOST R 57525–2017 and the methodological recommendations of the Center for Expertise and Quality Control of Medical Care. At the first stage, to determine the structure and number of costs, a review of legal acts and publications on the pharmacoeconomic analysis of clinical situations and drugs of interest in the e-Library and ConsultantPlus databases was carried out. The source of prices for medical services was the tariffs of the compulsory medical insurance system and data from the tariff agreement in Moscow within the framework of the compulsory medical insurance system, and in the absence of tariffs, the prices for paid medical services. Prices for drugs were obtained from an open source — the Russian Pharmaceutical Portal (Pharmindex.rf). In the absence of data on the cost structure, a survey of physicians conducted through a questionnaire. Results . Because of the literature review, 34 publications were found in the e-Library database on the use of ademetionine in NAFLD and ITH. Additionally, outside the scope of the literature review, a study was found in 2011, which provides a comparative clinical and economic analysis of the use of ademetionine (Heptral®) and essential phospholipids (Essentiale) in alcoholic liver damage and in infectious hepatitis. A review of legal acts in the ConsultantPlus database initially identified 93 documents, of which 25 turned out to be irrelevant to the current purpose of the study, that is, they didn’t allow analyzing the costs of ademetionine therapy. Of the 20 identified standards of medical care, only 2 are devoted to diseases of the liver and biliary tract. Because of the analysis, it was revealed that the cost per case of NAFLD treatment in a round-the-clock hospital amounted to 24.6 thousand rubles; in a day hospital, the cost per case of both NAFLD and ITH in adults amounted to 19.8 thousand rubles each. The average total cost of treating one patient during the year on an outpatient basis for NAFLD amounted to 65.3 thousand rubles, of which only 14.3 thousand rubles. covered by the compulsory medical insurance system, 16.9 thousand rubles outside the compulsory medical insurance system and 34.1 thousand rubles — drug costs. The average total costs for treating one patient during the year on an outpatient basis from ITH amounted to 65.4 thousand rubles, of which 23.9 thousand rubles. covered by the compulsory medical insurance system, 17.6 thousand rubles outside the compulsory medical insurance system and 23.9 thousand rubles — drug costs. Conclusion . Because of the study, the average costs for treating patients with NAFLD and ITH were calculated, which can later be used to conduct other types of pharmacoeconomic analysis.

The aim of the study was to assess the tolerability and impact on the quality of life of pharmacotherapy for gastric ulcer, erosive gastritis using regimens including rebamipide. The quality of life of patients was assessed using the SF-36 questionnaire. Pharmacotherapy of gastric ulcer with the inclusion of rebamipide as part of the conventional treatment regimen provides data comparable to the healthy group on the scales of physical functioning, role functioning due to physical condition, pain intensity, general health, and vital activity. The results of our own research and data from literary sources indicate that rebamipide is a drug with a confident evidence base, good tolerance and safety of use.

This review aims at describing clinical benefits and characteristics of the main highly effective disease modifying drugs (DMD) for multiple sclerosis (MS): alemtuzumab, cladribine tablets, ocrelizumab, natalizumab, fingolimod based on the efficacy and safety. The authors highlight that all MS DMDs have certain benefits and features that shall be considered in prescribing pharmacotherapy. Cladribine in tablets are comparable by the efficacy to other modern highly effective second-line drugs, have a high level of evidence and a favorable safety profile, as well as the most preferred benefit/risk ratio among other MS DMDs indicated for the treatment of highly active MS, which offers an advantage to the drug. The use of cladribine in tablets will contribute to further study of the efficacy and safety of this highly efficient drug for MS treatment.

Arterial hypertension and dyslipidemia is a very frequent comorbid condition. Arterial hypertension and dyslipidemia are combined in 40-70% of patients. The statins is the basic drug in primary and secondary prevention of cardiovascular disease and in the reduction of cardiovascular complications. We`ve attempted to summarize some data about the statins and interaction of antihypertensive drugs. Rosuvastatin is a medicine that provides an intensive reduction of low-density lipoproteins, does not require dose adjustment when applied in conjunction with antihypertensive drugs. The absence of inhibition and activation of rosuvastatin cytochrome P450 provides a low risk of negative interactions in the clinical situations of induced polypharmacy. Every clinician is to remember that it`s crucial to take into account some adverse reactions combining the statins with drugs of other pharmacological groups.