Objective: To conduct a cost-effectiveness analysis of first-line treatment regimens based on nurulimab + prolgolimab combination in comparison with ipilimumab + nivolumab combination among adult patients in the Russian Federation with unresectable or metastatic cutaneous melanoma (CM).

Material and methods. An adjusted indirect comparison of the efficacy of nurulimab + prolgolimab combination and ipilimumab + nivolumab combination in both dose regimens was conducted according to data from BCD-217-2/OCTAVA and CheckMate 511 randomized controlled trials, respectively. Only direct medical costs for the first-line immunotherapy of unresectable or metastatic CM were taken into account, i.e. manufacture prices with 10% value-added tax and 5% discount rate. The cost-effectiveness analysis was based on estimation of cost per life years gained (LYG) and patient life preservation for a period from 1 to 5 years. Sensitivity analysis was used to assess the impact of price fluctuations on the study results.

Results. The total direct costs over 5-year horizon for the nurulimab + prolgolimab combination were 19% lower than that for the ipilimumab 3 mg/kg + nivolumab 1 mg/kg combination, and nurulimab + prolgolimab costs were comparable with the ipilimumab 1 mg/kg + nivolumab 3 mg/kg combination. At the same time, the cost per 1 LYG for the nurulimab + prolgolimab combination therapy turned out to be minimal, amounting to 3.07 million rubles versus 3.44–4.21 million rubles for ipilimumab + nivolumab combinations. In addition, cost per patient life preservation for the nurulimab + prolgolimab combination was lower than that for the ipilimumab 3 mg/kg + nivolumab 1 mg/kg therapy in the first year by 0.7 million rubles (10%), with this difference amounting to 9.1 million rubles (49%) by the fifth year. In comparison with the combination of nurulimab + prolgolimab, the costs for the ipilimumab 1 mg/kg + nivolumab 3 mg/kg combination required to reach patient life preservation in the first year was lower by 1.5 million rubles (20%), although increasing by 4.1 million rubles (23%) vs nurulimab + prolgolimab costs by the fifth year of therapy.

Conclusion. Widespread introduction of the nurulimab + prolgolimab combination for unresectable or metastatic CM into current clinical practice will increase patient survival and will contribute to achieving the target indicators of the Russian Ministry of Health in terms of reducing one-year mortality and increasing the proportion of patients with malignant neoplasms registered for 5 or more years. This effect can be achieved in the setting of lower or comparable costs of treatment, which allows improved cost-effectiveness to be achieved when applying the prolgolimab + nurulimab combination.

Backgrоund. Immunoglobulin A nephropathy (IgA-N) is a common form of chronic glomerulonephritis. Its basis is the accumulation of IgA immune complexes in the glomeruli, associated with impaired glycosylation of the IgA molecule. Exogenous antigens, such as gluten, play an important role in the development of the disease. It has been experimentally confirmed that oral immunization with gluten induces mesangial IgA deposits, and a gluten-free diet can improve the course of nephropathy, indicating the significance of the enterorenal axis in the pathogenesis of IgA-N.

Objective: To study structural changes in renal tissue in IgAN patients and to evaluate the clinical and diagnostic significance of IgA antibodies to deamidated gliadin peptides (anti-DGP IgA) in the blood serum.

Material and methods. The study involved 105 patients aged 18 to 64 years diagnosed with IgAN based on a lifetime nephrobiopsy with morphological examination according to the Oxford classification. Patients were divided into two groups: the main group (n=20) included IgAN patients with detected anti-DGP IgA, and the control group (n=85) included IgAN patients seronegative for anti-DGP IgA, IgA antibodies to tissue transglutaminase, and to endomysium.

Results. When comparing fibrous-sclerotic changes, no statistically significant intergroup differences were obtained. However, a clear trend of predominance of irreversible light-optical changes within the area of the nephrobiopsy specimen was noted in patients of the main group compared to the control group: 82.4% and 56.9%, respectively (p=0.059).

Conclusion. The obtained results reflect a high frequency of irreversible fibrous-sclerotic changes in the nephrobiopsy in patients with IgAN and anti-DGP IgA in the blood serum. Timely detection of anti-DGP IgA can improve the ability to predict the outcome of the disease and optimize therapeutic strategies.

Objective: To analyze the applicability of approaches conventionally used to assess the clinical and economic effectiveness of pharmaceuticals to that of digital health products and services (DHPS).

Material and methods. In this study, DHPS was considered to be an umbrella concept that encompasses various health technologies such as mobile health apps and services, including those based on artificial intelligence. Approaches to drug assessment were reviewed based on regulatory documents, methodological guidelines, and monographs on drugs assessment.

Results. The examined approaches to assessing the effectiveness and safety of pharmaceuticals can be applied to DHPS, having no fundamental limitations. Specific characteristics of DHPS that influence the choice of their assessment approaches were identified and described. A draft dossier for DHPS was proposed, with its composition aligned with the goals and objectives of the assessment task.

Conclusion. Future research should address the development of methodological guidelines for assessing DHPS based on the approaches used for drug assessment.

Objective: To conduct a comparative pharmacoeconomic assessment of the use of extended release formulations of lanreotide and octreotide in adult patients (over 18 years of age) with gastrointestinal neuroendocrine tumors (GI NETs) in the Russian healthcare system in 2025.

Material and methods. A comparative analysis of clinical trial data, including randomized controlled trials and retrospective cohort studies, was conducted on the efficacy and safety profiles of lanreotide and octreotide. The focus was on overall survival, progressionfree survival, and the incidence of adverse events. Next the study employed the methods involving the calculation of the costeffectiveness ratio (CER) and the incremental cost-effectiveness ratio (ICER), as well as sensitivity analysis. Economic parameters (costs, CER, ICER) are presented both in absolute values (rubles) and as relative measures (%).

Results. The average costs of drug therapy with lanreotide for 10 years per patient comprised 7,213,219.59 rubles, compared to 4,279,437.69 rubles for a course of extended release octreotide (a difference of 40.67%). At the same time, the costs of treating adverse events were lower for lanreotide compared to octreotide, equaling 24,604.01 and 59,203.81 rubles, respectively (a difference of 58.4%). Direct medical costs for a 10-year course of lanreotide therapy in one patient with GI NETs were 7,237,823.60 rubles, compared to 4,338,641.50 rubles for a course of octreotide, with the difference comprising 2,899,182.10 rubles (40.06%). When calculating CER, the cost of 1 month of extended life with lanreotide therapy was 63,825.60 rubles, compared to 48,046.97 rubles using octreotide (a difference of 32,83%). When recalculated to annual costs, the cost of 1 year of extended life with lanreotide therapy was 765,907.26 rubles, compared to 576,563.65 rubles using octreotide (a difference of 24.73%). ICER for lanreotide was 1,506,068.62 rubles per year, which is within the limits of justified economic costs, being significantly lower than the willingness to pay for the Russian Federation (about 3,350,000 rubles per year). Results of a one-way sensitivity analysis showed that the benefit of lanreotide is achieved with a 25% increase in the price of octreotide or a 33% increase in overall survival with lanreotide.

Conclusion. The use of lanreotide in adult patients with GI NETs is both a clinically justified and economically feasible choice in the context of Russian healthcare.

Background. Nootropics are pharmacological agents that enhance such cognitive functions as memory and attention, as well as the overall mental performance. In recent years, global demand for these pharmaceuticals has significantly increased due to intensified psychological stress, a growing incidence of neurological disorders, and a growing public focus on mental health. In Uzbekistan, the nootropic drug market is experiencing active growth, underscoring the need for a comprehensive analysis of its structure and key trends.

Objective: To analyze trends in the nootropic drug market in Uzbekistan from 2015 to 2024, to identify key trends and factors influencing its development, and to assess the dynamics of supply and demand.

Material and methods. The available data on registered nootropic drugs in Uzbekistan, pharmaceutical company reports, sales statistics, and information on government policy and support measures were used. The dynamics of the number of registered trade names and their distribution by manufacturing country were studied. Leading companies playing a key role in the market were identified. The distribution of nootropics by composition (monodrugs and combination forms) and dosage forms (oral, injectable, etc.) was also examined.

Results. The analysis revealed a steady growth in the nootropic drug market in Uzbekistan throughout the study period. This growth is primarily driven by the increasing demand for cognitive enhancers across various age groups. One evident trend consists in the expanding presence of domestic manufacturers, who are introducing novel drug forms, including combination and injectable formulations. Additionally, innovative compounds, such as citicoline that has shown considerable therapeutic potential across various neurological conditions, are increasingly attracting attention.

Conclusion. The nootropic drug market in Uzbekistan is demonstrating positive growth dynamics, driven by rising consumer demand and reinforced by supportive government initiatives. The market is expected to continue to grow, with improvements in drug variety and accessibility. Both local and international pharmaceutical companies play a pivotal role in enhancing product quality and ensuring broad patient access.

Objective: To evaluate, from a pharmacoeconomic perspective, treatment strategies for adult patients with Hodgkin lymphoma (HL) complicated by human immunodeficiency virus (HIV) infection and HL patients without HIV infection.

Material and methods. The study sampled 67 adult HL patients including 34 HIV-positive (HIV-HL group) and 33 HIV-negative (nonHIV-HL group) subjects. All patients were treated at the Loginov Moscow Clinical Scientific Center between June 2015 and December 2023. The median surface area and body weight of patients were 1.85 m2 and 70.9 kg, respectively. Cost estimation was performed using decision-tree pharmacoeconomic modeling, medical institution price lists (excluding marginal markup). Government-regulated drug prices (for essential medicines), and 2024 public procurement prices (for other drugs, including targeted therapies and autologous stem cell transplantations) were considered. HIV treatment costs were excluded. Clinical endpoints included remission rates, 5-year overall survival, 5-year event-free survival, and 5-year relapse-free survival. Pharmacoeconomic analyses comprised cost-minimization, cost-effectiveness, and incremental cost-effectiveness analyses. Results were validated via probabilistic sensitivity analysis using Monte Carlo simulation (10,000-patient extrapolation).

Results. Treatment in the HIV-HL group was found to be more cost-effective both with the development of complications (1,020,332 vs. 3,935,166.50 rubles) and without complications (440,616 vs. 584,641 rubles), provided that the median cost of treatment is calculated. Weighted average costs favored HIV-HL treatment only with complications (2,416,961.67 vs. 3,578,882.08 rubles); without complications, non-HIV-HL treatment was more cost-effective (575,499.19 vs. 852,010.48 rubles). Monte Carlo simulations revealed model instability, though two of four scenarios (remission in HIV-HL with complications, using median and weighted costs) demonstrated robust outcomes.

Conclusion. The decision-tree model effectively evaluated median and weighted treatment costs for HL by HIV status. A combined pricing approach identified key cost drivers, including median-mean disparities, while cost-effectiveness and Monte Carlo analyses confirmed result stability. Both methods highlighted limitations in extrapolating small-cohort data to broader populations.

Background. At present, the compulsory health insurance (CHI) system in the Russian Federation is lacking a standardized format for tariff agreements. This leads to significant variability in the structure of documents and, consequently, to errors, low transparency of tariff policy, and financial control difficulties.

Objective: To develop a unified form of tariff agreement in the Russian CHI system.

Material and methods. The research methodology was based on an integrated analysis of the regulatory framework and regional tariff agreements, followed by testing of the developed form in pilot Russian regions.

Results. A unified form of tariff agreement has been developed. This standardized form minimizes the administrative burden on participants in the CHI system, ensures transparency in tariff formation, enables comparative analysis of regional indicators, and optimizes the process of document approval by the Federal CHI Fund.

Conclusion. The introduction of the standardized form for tariff agreements and the digitization of their processing will significantly improve the efficiency of tariff policy management in the CHI system of Russia.

Background. Zinc-containing compounds are a promising basis for the development of new non-steroidal anti-inflammatory drugs (NSAIDs), which can raise the effectiveness and safety of pharmaceutical management of inflammation and pain.

Objective: To study the anti-inflammatory, ulcerogenic, etc., effects of zinc-imidazole complexes, such as allyl-2 (bis (N-allyl-2-methylimidazole) zinc diacetate), allim-2 (bis (N-allenyl-2-methylimidazole) zinc diacetate), and propargyl-2 (bis (N-propargyl-2-methylimidazole) zinc diacetate) in comparison with zinc complexes with known NSAIDs, such as diclofenac, nimesulide, and ketorolac.

Material and methods. In silico modeling of candidate molecules allyl-2, allim-2, propargyl-2, zinc-diclofenac, zinc-nimesulide, and zinc-ketorolac was performed using a toolkit of chemoinformatic analysis methods developed by scientific school of Yu.I. Zhuravlev and K.V. Rudakov through topological analysis of chemographs and numerical forecasting of distinguishing features of complex systems. These methods include the theory of chemograph analysis, methods for predicting numerical target variables, the combinatorial theory of solvability/regularity, and topological methods for data analysis. The pharmacological capabilities of molecules within the framework of chemoreactome methodology were evaluated by comparing the chemical structure of the query molecule with the structures of molecules whose molecular-pharmacological properties have been established and available in the PubChem, HMDB, STRING, and PharmGKB databases.

Results. The obtained chemoreactome evaluations revealed the capacity of zinc-imidazole complexes to inhibit of prostaglandin D2 binding to the prostaglandin D2 receptor on platelets (IC50 448–627 nM; zinc-NSAID: 588–997 nM) with comparable effects of zinc-imidazole complexes and zinc-NSAID on cyclooxygenase-2 (COX-2) inhibition in whole blood (IC50 295–428 nM). Zinc-imidazole complexes were characterized by a more pronounced inhibition of the proinflammatory signaling cascade of the NF-κB transcription factor (IC50 173–419 nM; zinc-NSAID 498–508 nM), alpha-1 adrenergic receptor (28 nM; zinc-NSAID: 235–411 nM), and angiotensin receptor-1 (IC50 16–22 nM; zinc-NSAID: 20–74 nM), indicating an antihypertensive effect. The antinociceptive activity of zinc-imidazole complexes (IC50 0.16 mg/kg) upon subcutaneous administration to mice in acetic acid-induced writhing was more pronounced than that of zinc-NSAIDs (0.9–1.0 mg/kg) with the exception of zinc-ketorolac (0.16 mg/kg). Compared to the zinc-NSAIDs, all zinc-imidazole complexes under study were characterized by similar and extremely low values ​​of antimicronutrient action scores (antivitamin score 0.38–0.61, antimicroelement score 0.37–0.88; compared to two- or three-fold higher scores for zinc-NSAIDs), which indicates the absence of adverse effects of zinc-imidazole complexes on micronutrient metabolism.

Conclusion. The studied candidate molecules (zinc-imidazole complexes), in addition to COX inhibition, may exhibit additional pharmacological properties to a greater extent than the studied zinc complexes with known NSAIDs.

Background. Identification of terminological and practical inconsistencies in the field of patent law in regulatory legal acts, including the Civil Code of the Russian Federation (CC RF) is important for lawmakers, regulators, stakeholders in the pharmaceutical market, and patent holders.

Objective: To conduct a comprehensive analysis of Clause 5 of Article 1359 of CC RF, which provides an exception to patent holders’ exclusive rights regarding the compounding of drugs in pharmacies pursuant to physicians’ prescriptions, in terms of its consistency with current pharmaceutical legislation and international legal standards.

Material and methods. The methods of historical-legal, semantic-linguistic, and comparative-legal analysis were applied. The Russian regulation was compared with that in the European Union (EU), the United States of America, Japan, Brazil, etc. Additionally, provisions of international agreements, including the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) and the EU Agreement on a Unified Patent Court, were analyzed.

Results. The current wording of Clause 5 of Article 1359 of CC RF was found to suffer from insufficient terminological clarity regarding the concepts of “individual compounding” and “medicinal product”, thus leading to legal uncertainty and potential conflicts with existing pharmaceutical legislation. The analysis of international practices revealed common regulatory approaches to this exception: the individual (personalized) nature of compounding (for a specific patient), mandatory medical prescription, exclusion of industrial-scale manufacturing, and the professional status of the performer (a pharmaceutical specialist). The Russian norm appears to have been borrowed from regulatory models of EU countries. However, in the absence of clear criteria for its application, risks of a broader interpretation arise, including the preparation of active pharmaceutical ingredients, which contradicts the objectives of patent regulation and the current structure of the pharmaceutical market.

Conclusion. Clause 5 of Article 1359 of CC RF is designed to protect pharmacy organizations and implements the principle of fair use of patented objects, provided that the medicinal products are lawfully obtained. It may serve as a negotiating tool in cases of drug shortages. To uphold constitutional obligations regarding public health protection and to eliminate legal uncertainty, the norm requires legislative clarification and refinement.

Background. Vulvovaginal atrophy (VVA) following antitumor treatment is a common and clinically significant complication. At the same time, the immunoinflammatory mechanisms determining the severity and persistence of atrophic changes are yet to be sufficiently studied. The role of extracellular neutrophil traps (NETs) in the pathogenesis of genital tract mucosal damage remains virtually unexplored.

Objective: To evaluate blood levels of NET markers – citrullinated histone H3 (CitH3), myeloperoxidase (MPO), cathepsin G (CatG) – in various VVA phenotypes after antitumor therapy and to determine their significance as potential biomarkers of atrophy severity.

Material and methods. A cross-sectional comparative study enrolled 215 postmenopausal women divided into five groups as follows: VVA after surgical treatment (n=52), chemoradiotherapy (n=27), antiestrogenic therapy (n=48), VVA without a history of cancer (n=53), and control (n=35). Clinical symptoms, vaginal pH, vaginal health index (VHI), epithelial thickness, and plasma levels of CitH3, MPO, and CatG were evaluated. Statistical analysis was performed using the Mann–Whitney test with Bonferroni correction and calculation of the r effect size.

Results. The NETs profile varied depending on the nature of the treatment received. Maximum levels of CitH3 (0,65 [0,50–0,80] ng/ml), MPO (24 [18–30] ng/ml) и CatG (14 [12–16] ng/ml) were found in women after chemoradiotherapy. Antiestrogenic therapy was accompanied by pronounced immunoinflammatory activation of NETs, while surgical menopause and VVA without a history of gynecological cancer were associated with moderate and minimal levels, respectively. Intergroup differences between the oncological groups and the control group were statistically significant (p<0.005) with a large effect size according to the Mann–Whitney criterion (r≥0.50).

Conclusion. VVA after antitumor therapy is characterized by various immunoinflammatory phenotypes, which are reflected in specific NET profiles. CitH3, MPO, and CatG can be considered pathogenetically significant markers reflecting the degree of immunoinflammatory changes in VVA, thus representing candidates for further research aimed at patient stratification and the development of personalized therapy.

Nitric oxide NO is a signaling molecule involved in numerous physical and pathological processes in biological systems. Highly sensitive sensor materials for measuring NO amounts in vivo in exhaled air and in body fluids (saliva, blood, urine) can be a useful tool in diagnostics and management of patients with bronchopulmonary, cardiovascular, neurological and tumor diseases. Several approaches to measuring NO in biosubstrates (including exhaled air) have been developed: fluorescence/chemiluminescence, electron spin resonance, electrochemical/amperometric (organic and inorganic) and enzymatic/protein sensors. Semiconductors, transition metal nitrides, phthalocyanine complexes, porphyrin and cobalamin derivatives with metals can serve as materials for NO sensors. Creating sensor materials based on vitamin B12 derivatives is an urgent research task in biomedicine. The article systematizes information on using various compounds as materials for NO-sensitive and selective sensors to measure/evaluate NO levels in various biosubstrates.

Objective: To compare modern computer programs (smartphone programs – mobile applications) using artificial intelligence (AI) for diagnosing and dynamic monitoring of skin conditions.

Material and methods. A total of 1,319 publications were identified for AI-powered computer programs using targeted searches in PubMed/MEDLINE and Google Scholar databases, as well as in the eLibrary and CyberLeninka electronic libraries for the period 2016–2025. Queries focused on AI, convolutional neural networks (CNNs), computer programs (mobile apps), and dermatovenereology were used. After a multi-stage screening based on inclusion/exclusion criteria (including the availability of quantitative performance metrics), 9 key articles with specific descriptions of the computer programs (mobile apps) were selected. A search and subsequent analysis identified 9 computer programs (Google DermAssist, SkinIO, Melanoma Check, Derma Onko Check, SkinVision, Tibot, SkinScan, Aysa, and Skinive), which use AI to diagnose and monitor skin conditions.

Results. Effectiveness of the programs varies: Google DermAssist and Derma Onko Check demonstrated high accuracy (96–97%) and sensitivity (97–98%), while Skinive showed improvement in metrics over time from 2020 to 2021 (maximum sensitivity of 97.9% and specificity of 97.1%). Limitations include dependence on photo image quality, low effectiveness for rare conditions and dark skin tones, and the need for a biopsy to confirm a diagnosis. Mobile apps using CNN demonstrate high sensitivity (87–97.9%), though specificity varies significantly (70–98%), which may increase the number of additional consultations with specialist doctors when using these programs in diagnostics.

Conclusion. AI-based software (mobile apps) offers significant potential for increasing the accessibility and accuracy of skin pathology diagnostics, especially in remote areas and regions with a shortage of dermatovenereologists. Promising developments encompass the integration of computer programs with telemedicine, the refinement of algorithms for diagnosing rare pathologies, and the standardization of testing to enhance result reproducibility.

Secondary osteoarthritis (OA) may develop in the setting of various diseases and injuries of the joints, including rheumatoid arthritis (RA), psoriasis (psoriatic arthritis, PsA), and ankylosing spondylitis (AS). This article presents a systematic review of highly purified standardized drugs of chondroitin sulfate (CS) and glucosamine sulfate (GS) used in the treatment of secondary OA in various models of RA, PsA, and AS. The molecular links of targeting the pathogenesis of secondary OA are considered in specific detail. CS and GS are shown to inhibit hyperinflammation through the CD44 and TLR2/4/8 receptors, as well as the NF-κB transcription factor, thus acting as a disease-modifying therapy for RA, PsA, and AS. Experimental and clinical studies of the effects of CS and GS in RA, PsA, and AS have confirmed the prospects of their standardized forms for use in the treatment and prevention of the diseases under consideration.