Background. Respiratory syncytial virus (RSV) is a common virus causing lower respiratory tract infections (LRTI), including acute bronchiolitis and pneumonia, in children in the first 5 years of life.
Objective: to estimate the annual socio-economic burden for the Russian Federation (RF) due to RSV-LRTI in children aged under 5 years.
Material and methods. Based on published results of meta-analysis of epidemiological data for RSV-induced infections, the annual number of RSV-LRTI cases, the number of hospitalizations, and associated lethal outcomes were calculated in the model for groups of children aged 0 – <12 months, 12 – <24 months, and 24 – 60 months. The costs of medical care were determined according to the current tariffs of the Compulsory Health Insurance system and published Russian data on the distribution of the number of RSV-LRTI cases by severity. The damage to gross domestic product (GDP) associated with fatalities was estimated taking into account life expectancy and employment.
Results. According to the estimates, 397.2 thousand children aged under 5 years in the RF fall ill with RSV-LRTI during a year, including 44.6 thousand cases requiring hospitalization, and in 268 cases, the infection becomes lethal. Medical costs for treatment exceed 2.2 billion rubles, and the damage to GDP as a result of lethal outcomes reaches almost 10 billion rubles. The main damage is related to RSV-LRTI cases in children aged under 1 year, the share of which is over 50% among those hospitalized and over 70% among those who died.
Conclusion. RSV significantly affects morbidity and mortality among children aged under 5 years. According to modeling data, it causes up to 3.5% of deaths in this age group, and the associated economic losses exceed 12.2 billion rubles, which justifies the need for RSV-LRTI immunoprophylaxis.

Objective: to evaluate the clinical and economic effectiveness of benralizumab in comparison with standard therapy in patients with severe bronchial asthma (SBA) with an eosinophilic phenotype in the Russian Federation.
Material and methods. A clinical and economic analysis of using benralizumab in addition to standard therapy was carried out in comparison with standard therapy for SBA with an eosinophilic phenotype by means of a modeling method. Cost calculations were performed in a mathematical model adapted to the Russian healthcare conditions with the help of cost indicators and patient population characteristics.
Results. The use of benralizumab as a mandatory component of standard therapy compared with standard therapy alone for SBA with an eosinophilic phenotype will allow for an additional 0.65 life years gained (LYGs) and 1.12 quality-adjusted life years (QALYs) per 1 patient during lifelong therapy. It will provide avoiding 4.95 exacerbations, simultaneously with a reduction in total costs by 584,144 rubles by reducing gross domestic product (GDP) losses due to mortality and temporary disability over an assessment horizon equal to life expectancy. The costs of 1 LYG and 1 QALY in the case of benralizumab were 869,455 and 1,252,056 rubles, in the case of standard therapy they were 911,615 and 1,303,811 rubles, respectively.
Conclusion. Intensification of SBA therapy with an eosinophilic phenotype with benralizumab is clinically justified (leads to an increase in life expectancy, a decrease in the rate of exacerbations and an increase in patients’ working life), and is also economically feasible, as it allows to reduce direct costs and GDP losses of the state.

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.

Objective: evaluation of the comparative pharmacoeconomic effectiveness of treatment sequences with prolgolimab as the first line and combination therapy with BRAF/MEK inhibitors as the second line versus a regimen with BRAF/MEK inhibitors as the first line and prolgolimab as the second line in adult patients with metastatic or unresectable cutaneous melanoma.
Material and methods. A detailed Markov and decision tree model was developed to allocate patients with metastatic cutaneous melanoma (mCM) with BRAF gene mutation (BRAF+) to treatment with prolgolimab or to targeted therapy with BRAF/MEK inhibitors (“dabrafenib + trametinib”, or “vemurafenib + cobimetinib” combinations). The costs of BRAF+ mCM therapy and the number of life years gained (LYGs) depending on the treatment regimen were calculated using approximated overall survival (OS) and progression-free survival (PFS) curves taken from relevant publications.
Results. The treatment sequence for BRAF+ mCM had a significant impact on patient treatment outcomes: the median OS for the “prolgolimab → BRAF/MEK inhibitors” regimen was 41 months, while for the “BRAF/MEK inhibitors → prolgolimab” regimen it was 26 months; the median PFS was 11.5 months for the sequence starting with prolgolimab and 12.2 months for the strategy starting with “dabrafenib + trametinib” combination. The number of LYGs for a therapy regimen starting with prolgolimab and a regimen starting with “dabrafenib + trametinib” combination when modeling in the 1st year of therapy was 0.92 and 0.94 years, and at a 5-year horizon it was 3.19 and 2.75 years, respectively. At the same time, the cost of 1 LYG with a strategy starting with prolgolimab was 156 thousand rubles (5%) lower than the strategy starting with “dabrafenib + trametinib” combination.
Conclusion. The developed pharmacoeconomic research model facilitated a clinical and economic analysis of using prolgolimab compared to targeted therapy with BRAF/MEK inhibitors across four lines of therapy, closely reflecting real clinical practice in the treatment of BRAF+ mCM patients.

Background. Renal-hepatic dysfunction, which often occurs in liver dysfunction, requires the use of effective and safe nephroprotective agents. Human placenta hydrolysates (HPH) are hepatoprotectors, but little is known about HPH nephroprotective properties and the molecular mechanisms of their implementation.
Objective: identification of potential molecular mechanisms of Laennec® HPH neuroprotective action based on bioinformatic analysis of collected mass spectrometric data.
Material and methods. Methods of proteomic analysis of peptide preparations were used. The analysis of Laennec® HPH peptide composition included four stages: drug purification, chromatographic separation of peptides, determination of the multidimensional mass spectrum of peptide fraction and de novo sequencing of the isolated peptides.
Results. The study of Laennec® HPH peptide composition allowed to identify 48 peptides that can exhibit nephroprotective effects. It was shown that HPH contains biologically active fragments of nephroprotective adrenomedullins, inhibitor peptides of a number of kinases (FYN, SHH, WNK1/4, SGK1, IRAK4, ROCK1/2) and fibrogenic receptors (PDGFR, TGFB1I1).
Conclusion. By inhibiting the listed target proteins, HPH peptides provide nephroprotection through reducing inflammation, anti-stress effects and preventing fibrotic changes in kidney tissue

Background. There are numerous diagnostic methods and therapy regimens for chronic tonsillitis (CT). Different methods of treatment in certain conditions do not always show high efficiency, so the search for new ways of conservative management of CT is needed, the main task of which is palatine tonsils preservation.
Objective: to evaluate the efficacy and tolerability of a multicomponent preparation with low dosage of active substances Lymphomyosot® in adult patients with CT and cervical lymphadenopathy in real clinical practice.
Material and methods. A total of 170 male and female patients aged 18–65 years with CT (simple form and 1st degree toxic-allergic form) and cervical lymphadenopathy were included in an observational, open, prospective study. In the main group (n=85), a combined therapy consisting of standard CT therapy (a course of palatine tonsils lavage with 0.9% NaCl solution) with the addition of Lymphomyosot® was administered. In the control group (n=85), topical non-steroidal anti-inflammatory drugs or phytotherapy were used instead of the studied drug. Ultrasound examination of regional cervical lymph nodes with measuring of their diameter (longitudinal, transverse) was chosen as a parameter of objective assessment of patients' condition dynamics. The results of therapy at Visit 1 and Visit 2 (12±2 days after Visit 1) were compared. The effectiveness of treatment regimens was analyzed according to the following parameters: complaints related to CT; oropharyngoscopic data; evaluation of CT indicators by the doctor and the patients; dynamics of cervical regional lymph nodes size; satisfaction of the doctor and the patients with the clinical effect and tolerability of therapy.
Results. The dynamic observation showed a significant decrease in the number of complaints and symptoms according to objective examination, oropharyngoscopy, as well as evaluation of symptoms by the doctor and the patients at Visit 2 in both groups (p<0.001). However, in the main group, where Lymphomyosot® was administered in the complex treatment, there was a more significant decrease in cervical lymph nodes size compared to the control group (p<0.01).
Conclusion. The study demonstrated that Lymphomyosot® increased the efficacy of complex therapy, reducing cervical lymphoadenopathy and other manifestations of the disease in patients with CT (simple and 1st degree toxic-allergic forms).

Background. Sentinel lymph node (SLN) biopsy is a reliable diagnostic method used to assess the spread of the malignant process in regional lymph nodes. Currently, this method is of great importance in treatment planning for early breast cancer and allows to avoid immediate and long-term complications of lymph node dissection. SLN detection can be performed using the radionuclide method, the disadvantages of which are associated with the peculiarities of working with radiopharmaceuticals and additional costs when using them. An alternative method is fluorescence lymphography (FL) with indocyanine green.
Objective: performing a pharmacoeconomical study (cost-effectiveness analysis) comparing the cost-effectiveness of methods for detecting SLN in breast cancer: radionuclide diagnosis (RD) using a radiopharmaceutical based on sodium pertechnetate [^99mТс] and FL using indocyanine green (Life Sciences OCPK LLC, Russia) and "IC GOR System" device (Central Design Bureau of Information and Control Systems JSC, Russia).
Material and methods. The values of the cost-effectiveness ratio (CER) were calculated and compared for the two indicated methods of detecting SLN in breast cancer. Information on the RD method clinical efficacy was taken from the published data. SLN detection by the FL method with the use of indocyanine green and domestic apparatus was performed on the basis of the Regional Clinical Oncology Dispensary (Ryazan) in 53 patients with breast cancer. To assess the reliability of the obtained results a deterministic multivariate sensitivity analysis was performed.
Results. The obtained CER_FL values were significantly lower than the median CER_RD values by average of 43.29% (p<0.001): from 40.36% (p<0.001) to 44.96% (p<0.001). The geometric mean CER_FL was lower than CER_RD by 39,40% (from 37.99% to 42.80%), and their 95% confidence intervals (CI) did not intersect. Deterministic multivariate sensitivity analysis demonstrated robustness of the obtained data to the transformation of RD cost parameters. Nevertheless the geometric mean and its 95% CI of CER_RD and CER_FL did not intersect under any circumstances.
Conclusion. According to the results of a pharmacoeconomic study, it is more economically profitable to detect SLN in breast cancer using indocyanine green and a domestic device for FL, as its costs per unit of efficiency were 38–45% lower than for RD using a radiopharmaceutical based on sodium pertechnetate [^99mТс].

Objective: to analyse the consumption pattern of antiviral therapy (AVT) for chronic hepatitis C on the example of an infectious hospital.
Material and methods. The study was based on data from 380 discharge summaries of an infectious diseases hospital for 2011–2019. The criterion of sampling was the established diagnosis of chronic hepatitis C. The first line therapy regimens were analyzed and compared; the calculations were based on direct treatment costs of the study sample. The pharmacoeconomic effectiveness of therapy was assessed by calculating the cost-effectiveness ratio (CER).
Results. A retrospective analysis of patients’ sampling allowed to establish a general profile: a 40-year-old man with hepatitis C virus genotype 1 and a mild degree of liver fibrosis. A total of 18 international nonproprietary names (17 trade names) were used for AVT. The pattern of drugs prescribed correlated with the clinical guidelines for the studied period and allowed to distinguish the beginning of the transition from interferonbased regimens to direct-acting antivirals (DAAs). The change in the treatment paradigm was associated not only with increased efficacy in achieving a sustained virologic response, but also with minimization of side effects. The high frequency of prescribing interferon regimens as AVT was accompanied by low rates of achieving virus elimination (63.69%), high frequency of relapses (12.88%), as well as the lack of response to pharmacological correction (21.32%) and premature discontinuation of therapy due to adverse events (2.11%). A total of 142,450,414.91 rubles was spent on the first line pharmacotherapy in the study cohort during the study period. Costs per 1 patient with the diagnosis “chronic hepatitis C” and F0–F3 fibroses according to METAVIR were 372,847.07 rubles with achieving sustained virologic response without relapse in 66% of cases, costs per patient with F4 liver lesion were 398,464.73 rubles (45,16%, respectively).
Conclusion. The findings allow us to note the transition from interferon-, nucleoside- and nucleotide-based drugs to DAAs, which can be associated with an increase in therapy effectiveness and proportion of cases with sustained virologic response achieved along with a decrease in the number of adverse events. The results of the study have practical implications for building a strategy for hepatitis C virus elimination in terms of choosing effective pharmacotherapy while reducing the economic burden.

Objective: to study the features of the population consumption of antitumor drugs (ATDs) of groups L01 and L02 according to the anatomical, therapeutic and chemical classification (ATC), purchased at the expense of personal funds of citizens in the retail sector of the pharmaceutical market of the Russian Federation (RF).

Material and methods. We analyzed data on the range of ATDs sold in retail pharmacies in all federal districts of the RF in 2020–2023. The methods of comparative, retrospective, logical, graphical and content analysis, the method of grouping data by ATC groups and methods of descriptive statistics were used.

Results. At the end of 2022, in the RF, about 6 million packages of ATDs worth 6.5 billion rubles were purchased at the expense of citizens’ personal funds, i.e. approximately 1/6 of the total sales of oncology medications in monetary terms and 3.0% of the total sales in physical terms. The maximum sales in monetary terms per 100 thousand population were noted in the Central, Northwestern and Southern Federal Districts. The Central Federal District accounts for about 50% of total sales of ATDs in monetary terms and 35% of sales in physical terms. The maximum costs were for medications in ATC groups L01B Antimetabolites, L02A Hormones and related compounds and L02B Hormone antagonists and related compounds. The average shares of ATDs in the ATC group L01B were 32.8% in total sales in monetary terms and 50.8% in physical terms, in the ATC group L02B – 27.3% and 31.9%, L02A – 21.8% and 5.7%, L01X – 8.9% and 7.9%, respectively. In the RF as a whole, the top-3 international nonproprietary names of greatest demand in the pharmaceutical market retail segment included methotrexate, buserelin and anastrozole, which account for more than 40% of sales volume in monetary terms.

Conclusion. The obtained results can be used by healthcare organizers to clarify the real need for ATDs, as well as to improve drug care for cancer patients.

Objective: to assess the relevance and commercial prospects of bringing to market a drug for the local treatment of infectious and inflammatory diseases of oral cavity and oropharynx.
Material and methods. The objects of the study were the drug nomenclatures in the State Register of Medicines, the Register of Medicines of Russia, as well as data from the Federal Service for Surveillance in Healthcare. The analysis of scientific publications in the field of marketing research of drugs, found in eLibrary.ru and PubMed/MEDLINE databases was carried out. For analyzing the structure and marketing research of drugs in the study group, specific methods of information retrieval, content analysis, description, data aggregation, ranking, data grouping method, system approach, as well as such methods of marketing analysis as determining the breadth and depth of the assortment, the renewal index, the vital importance index, SWOT analysis (strengths, weaknesses, opportunities, threats) were used.
Results. The assortment of drugs for the local treatment of oral cavity and oropharyngeal infectious and inflammatory diseases was structured by the nature of the active substance, type of dosage form, and country of origin. The main trends in the development of the market of drugs of this group were identified. An analysis of the range of drugs using marketing research methods made it possible to establish the breadth and completeness of the range. The calculated renewal and vitality indices confirmed the relevance of developing new drugs with the considered pharmacotherapeutic action.
Conclusion. The study revealed the main trends in the development of the market of drugs of the action in question. The SWOT analysis showed a possible strategy for developing and launching a new drug on the market.

Objective: comprehensive analysis of the spectrum of antibacterial action of bactеriocins.
Material and methods. Chemomicrobiome analysis of bacteriocins A/B, C, S, 28b, RS-2020 was performed to assess the minimum inhibitory concentration (MIC) values for 152 strains of pathogenic bacteria and the area under the growth curve (AUC) values for a representative sample of normobiota (38 human commensal bacteria).
Results. Compared to other molecules, bacteriocin C was characterized by lower MIC constants for a wide range of pathogenic bacterial strains. Thus, it more effectively inhibited strains of pathogens of bacterial pneumonia (H. influenzae, S. mutans, S. pneumoniae, S. pyogenes), nosocomial infections (K. pneumoniae, P. aeruginosa, S. aureus, S. epidermidis, S. pneumoniae), skin diseases (M. audouinii, T. mentagrophytes, etc.), urinary tract infections (E. cloacae, P. mirabilis and P. vulgaris), Fusobacterium necrophorum and Candida fungi. At the same time, bacteriocin C to a lesser extent than the reference molecules inhibited the growth of the normophysiological microbiota of the Bacteroides, Enterococcus genera, non-pathogenic Escherichia, yeast S. cerevisiae and others. By stimulating butyrate (butyric anion) producing microorganisms, bacteriocin C can exhibit prebiotic properties.
Conclusion. The main structural features of the bacteriocin C molecule associated with the antibacterial effect on pathogenic microbiota were identified and described.

In recent decades, technological progress has contributed to a consistent change in approaches to organizing the provision of medical care in various regions of the world. Electronic data-gathering systems make it possible to create extensive information databases about the health status of the population of certain territories or entire states. The introduction of technological solutions based on the use of artificial intelligence (AI) technologies makes it possible to provide a systematic analysis of large volumes of information, as well as to develop new treatment methods of life-threatening diseases. The use of AI technologies not only has significant potential for improving the organization of medical care, but also brings essential risks of human rights restriction, it may also form discriminatory practices or even cause harm to health. The authors demonstrate the importance of AI technologies in improving separate stages of medical care and the circulation of healthcare technologies, and also present various approaches to defining the notion of “artificial intelligence”, that is a crucial element in specifying the object of legal regulation. The article systematizes the list of threats and challenges to human security associated with the use of AI technologies. The development of legal regulation of this sphere at the national (United States of America) and supranational (European Union) levels is analyzed, and also the main directions of development of this field in the Russian Federation are presented.

The article is devoted to the study of regulatory approaches to the sphere of real-world data (RWD) and real world evidence (RWE) in the countries of the Asia-Pacific Region (China, South Korea, Japan, Taiwan, etc.) and examples of their practical application for health technology assessment. The peculiarities of collecting and gaining access to RWD/RWE in Asian countries, prerequisites for the development of this direction, adopted regulations, developed methodological guidelines, promising areas of application, and clinical and economic research based on country-specific data are considered. The existing practices in Asian countries represent valuable experience, some of which could be considered for implementation in the national practice.

Objective: to systematize fundamental, clinical, and epidemiological data on the oncoprotective effects of chondroprotectors: chondroitin sulfate (CS), glucosamine (including glucosamine sulfate, GS), and undenatured type II collagen (UC-II).
Material and methods. A systematic computer analysis of 6176 publications on the relationship between CS/GS/UC-II and tumor diseases found by the query “(glucosamine OR chondroitin OR ((“Collagen Type II” OR “type II collagen”) AND pharmacology)) AND (Cancer OR cancers OR tumor OR tumors OR tumors OR tumour*) NOT tumor necrosis)” in PubMed and Embase databases was performed. All articles of any format from 1900 to the present day with full available abstracts were taken. A topological approach to data analysis was used.
Results. Large-scale clinical and epidemiological studies and meta-analyses showed that regular consumption of CS/GS reduced the risk of colorectal cancer and lung cancer, as well as mortality from tumor diseases. The mechanisms of oncoprotective action of CS/GS are through inhibition of the pro-inflammatory cascade of tumor necrosis factor alpha, CD44 receptor and nuclear factor kappa B, and initiation of tumor cell apoptosis. By modulating the CD44 receptor and specific O-glycosylation of intracellular proteins, GS inhibits the pro-inflammatory effects of arachidonic acid cascade, interleukins IL-6, IL-8, the PI3K/Akt proliferative pathway, and cyclin-dependent kinases. The first postgenomic studies of CS/GS oncoprotective effects, including microbiome studies, was performed. Additionally, CS contributes to the inhibition of the effects of vascular endothelial growth factor and matrix metalloproteinases involved in tumor metastasis and invasion. Potentially, CS/GS oncoprotective effects may be enhanced by the anti-inflammatory effect of UC-II: the addition of NC-II substance to CS/GS complex makes it possible to reduce the autoimmune branch of pathogenesis not only in primary, but also in secondary OA and rheumatoid arthritis.
Conclusion. The CS and glucosamine (including GS) chondroprotectors exhibit oncoprotective effects. The use of CS and GS together with UС-II standardized pharmaceutical forms can enhance their anti-inflammatory and immunomodulatory effects.

The data on the classification of drugs, which are prescribed for the treatment of patients with joint and spine diseases, such as osteoarthritis (OA) and rheumatoid arthritis (RA), are presented. The groups of drugs widely used in clinical practice are disease-modifying osteoarthritis drugs (DMOADs) and disease-modifying antirheumatic drugs (DMARDs). To help the practitioner, consolidated information is provided on the main differences between these groups according to the mechanism of action (immunomodulatory vs. immunosuppressive) and the main indications for use (autoinflammatory joint diseases (OA) vs. autoimmune joint diseases (RA, psoriatic arthritis, ankylosing spondyloarthritis)). The material of the article is focused on the clinicians to help them make a right choice of OA therapy, and to identify the problem of drug choice in RA. Information about the possibility of using nutritional support in patients with OA is presented.