Actuality. Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality and is a medical and social problem accompanied by major economic damage. A direct relationship between COPD severity and treatment costs. The costs of hospitalization, outpatient visits, and oxygen supply increase dramatically with increasing COPD severity. Reducing the frequency of exacerbations and hospitalizations and slowing disease progression are ways to reduce the costs of COPD. Certain hopes are associated with the introduction of healthcare technology using targeted therapy with genetically engineered biological drugs, particularly with the addition of dupilumab to triple therapy (standard: inhaled glucocorticosteroid, long-acting anticholinergic drug and β2-agonist).

Objective. The clinical and economic effectiveness of this technology in COPD with T2-inflammation in adult patients in the Russian Federation (RF) should be assessed.

Materials and methods. An analytical Markov decision-making model in MS Excel with a 5-year horizon has been created. The calculation of the potential population of patients with COPD is based on the population of the RF, the prevalence of COPD, the percentage of patients with frequent exacerbations, having T2-inflammation, and receiving triple therapy. To quantify the dynamics of COPD exacerbations, data from digitized curves of the cumulative average number of exacerbations, survival analysis of patients with COPD, and the development of serious undesirable cardiovascular events (MACE) were used to calculate the number of life year gains and the number of prevented hospitalizations with dupilumab. The costs of medications, medical care (hospitalization due to COPD exacerbations, MACE, and deaths), DRG payments, and rehabilitation after a heart attack and stroke are considered. Indirect costs are calculated for patients up to the age of 72 years, adjusted for the level of employment by age, including payments for temporary disability, the reference ICER (triple therapy), and ICER for dupilumab.

Results. The annual incidence of moderate or severe exacerbations was significantly lower for dupilumab than for standard therapy: 0.79 (95% CI 0.69-0.92) and 1.16 (95% CI 1.01-1.33), respectively. Dupilumab therapy was associated with a significant decrease in overall mortality (Odds Ratio [OR], 0.53; 95% CI 0.43-0.65), a decrease in the need for emergency care (OR, 0.78; 95% CI 0.69-0.89), and actual exacerbations of COPD (OR, 0.59; 95% CI 0.53-0.65). The amount of additional funding that needs to be provided to expand the use of dupilumab when added to standard triple therapy amounts to 788,998 billion rubles over 5 years for all those in need of treatment. Simultaneously, budget savings (considering cost savings on hospitalization, mass, and deaths with a lower probability of disease progression) will amount to 590.301 billion RUB over 5 years on the analysis horizon. The ICER of dupilumab to prevent one exacerbation is 1.84 million rubles (below the threshold of willingness to pay 4.12 million RUB), one MACE is 4.61 million RUB, and fatal outcome is 12.6 million RUB. Sensitivity analysis confirmed the stability of the results obtained to changes in dupilumab prices while improving the clinical and economic indicators of drug use in patients with frequent severe exacerbations.

Conclusion. Dupilumab is a clinically and economically feasible healthcare technology for treating COPD with T2-inflammation in addition to standard triple therapy.

Relevance. The relevance of primary and secondary prevention of cardiovascular disasters associated with atherothrombotic complications has increased in recent decades and is due to the steady increase in diseases of the circulatory system. In this regard, both long-known medicinal products with antiplatelet properties and innovative products are of particular interest.

Objective. Conduct an information search and fill the “Clinical Research Database” service for antiplatelet agents with high levels of proven efficacy and manageable safety.

Materials and methods. Search and analysis of the results of randomized clinical trials and meta-analysis were conducted in the international databases of medical publications with subsequent submission of the results to the “Clinical Research Database” for antiplatelet agents.

Results. Antiplatelet agents have a positive effect on “hard” endpoints of randomized clinical trials in the form of a statistically significant decrease in the number of cardiovascular complications and mortality.

Conclusions. The information service “Clinical Research Database” and evidence-based information about antiplatelet agents can be used by healthcare professionals for the rational prescription of medicines in clinical practice.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice and is associated with a high risk of death from stroke and thromboembolic complications, the prevention of which is achieved through anticoagulant therapy. The risk of AF increases with age. Managing elderly patients with AF always presents challenges for clinicians due to the need to constantly balance the risks of thromboembolic complications with the potential for bleeding associated with their prevention. However, most studies have shown that bleeding occurs not because the patient is taking an anticoagulant at the selected therapeutic dose, but because the patient has a bleeding substrate. Furthermore, it is necessary to consider possible age-related changes in the pharmacokinetics and pharmacodynamics of drugs, as well as their dangerous combinations and interactions. Another question that arises for clinicians is the strategy for discontinuing anticoagulant therapy in elderly patients due to upcoming invasive examinations or surgery. The article presents algorithms that provide answers to all the questions posed to clinicians.

Drug-induced disorders of the musculoskeletal system represent a significant category of adverse drug reactions (ADRs). This review systematizes the main types of iatrogenic damage to bones, muscles, and joints, classified as osteopathies, myopathies, and arthropathies. Risk groups include children, the elderly, and postmenopausal women, with polypharmacy being a significant contributing factor. The article examines antenatal drug-induced embryopathies (e. g., associated with thalidomide, vitamin A, anticonvulsants, warfarin) and postnatal lesions. Key postnatal disorders discussed are statin-induced myopathy, glucocorticoid-induced myopathy and osteoporosis, musculoskeletal complications of immune checkpoint inhibitors, colchicine and propofol toxicity. Drug-induced osteopathies, particularly secondary osteoporosis from glucocorticoids, anticonvulsants, and other long-term medications, are analyzed. The review also covers drug-induced arthropathies, such as drug-induced lupus and fluoroquinolone-associated tendinopathy and arthropathy. The mechanisms underlying these ADRs, including dose-dependency, metabolic pathways, and immune-mediated processes, are considered. The conclusion emphasizes the importance of clinician awareness of the potential for musculoskeletal toxicity when prescribing these medications to enable timely diagnosis, management, and prevention.

Background. Fluoroquinolones (FQs) are a group of antibacterial drugs (AB), and their consumption is increasing in both the general and pediatric populations. The main FQ prescribed in pediatrics is ciprofloxacin, which is used in patients with cystic fibrosis, oncology, and severe multidrug-resistant infections. The potential toxic effects of ciprofloxacin on various organs and systems (e.g., musculoskeletal, nervous, and cardiovascular systems) highlight the importance of monitoring the real-world safety of this FQ in children.

Objective. The safety profile of ciprofloxacin in children was assessed using the National Spontaneous Reporting Database.

Methods. Retrospective pharmacoepidemiologic study of spontaneous reports (SRs) received in the Pharmacovigilance 2.0 subsystem of the Automated Information System (AIS) of Roszdravnadzor from 01.04.2019 to 01.03.2023.

Results. Most adverse reactions (ADRs) developed within the first 24 h (43.3%) after the AB prescription. Most ADRs were registered in male patients (73,2%). The most involved age groups were 0–1 year (31,7%) and 10–15 years (36,6%). Immune system disorders (31.3%) were the leading cause of ADRs.

Conclusion. The identified ADR profile of ciprofloxacin indicates the need for rational restriction of the use of this AB in the pediatric population; if it is impossible to replace it with another AB with a similar spectrum of activity, constant monitoring of symptoms of adverse reactions is recommended, which is especially important in the population of children under one year of age.

The article analyzes the practice of state procurement of combined inhaled medicinal products (CIMPs) in the Russian Federation for the period 2024-2025.

Objective. The aim of the study was to verify the application in procurement activities of the provision of subparagraph "b" of paragraph 3 of the Specifics for the Description of Medicinal Products (Government Decree No. 1380), which allows for the possibility of replacing a multicomponent drug with a set of single-component ones.

Materials and methods. Based on the analysis of 202 procurement notices and 167 contracts concluded in the Unified Information System, a complete absence of cases of using this norm in relation to the studied CIMPs was established.

Results. The results demonstrate that none of the analyzed combined drugs is recognized as interchangeable with a set of single-component drugs either in the State Register of Medicinal Products or in the Unified Structured Directory-Catalogue of Medicinal Products.

Conclusions. It is concluded that the non-application of this opportunity in practice is due both to the lack of officially established interchangeability and the existence of a special position of the Russian Ministry of Health, set out in an explanatory letter, regarding the impossibility of achieving a similar therapeutic effect when replacing CIMPs with separate single-component drugs.

This article analyzes the historical role of the Nuremberg Trials of Nazi doctors (1945-1947) in shaping modern biomedical ethics and the system of ethical review. It examines the key principles of the Nuremberg Code, such as voluntary informed consent, risk minimization, and scientific validity, which became the cornerstone for subsequent international ethical and legal documents. It is shown that the lessons of Nuremberg were reflected in the development of international instruments aimed at regulating medical and research activities (the Helsinki Declaration, the Council of Europe Convention on Human Rights and Biomedicine, the UNESCO Universal Declaration on Bioethics and Human Rights, the World Health Organization Code of Ethics, the World Medical Association's Geneva Declaration) and directly led to the establishment of the institution of ethics committees, which protect the rights and dignity of research participants. The conclusion is made about the enduring relevance of the Code's principles in the face of new challenges of the 21st century.

Background. Left ventricular (LV) remodeling after acute myocardial infarction (AMI) is a key process that determines the risk of heart failure (HF) progression and adverse clinical outcomes in patients following revascularization. The heterogeneity of the remodeling trajectories and the limitations of conventional risk stratification approaches necessitate the implementation of advanced methods of phenotyping and assessment of HF treatment adherence.

The objective of this study was to determine the extent to which baseline left ventricular remodeling phenotypes, derived via cluster analysis, drive favorable changes in structural and functional echocardiographic parameters over 12 months after acute myocardial infarction and to assess the role of adherence to pharmacotherapy in this process.

Methods. This retrospective cohort study enrolled 105 patients after acute myocardial infarction who underwent revascularization and were followed for 12 months. Cluster analysis based on five echocardiographic parameters — left ventricular ejection fraction, end-diastolic volume, end-systolic volume, left ventricular myocardial mass index, and left atrial size — was used to define the left ventricular remodeling phenotypes at baseline and at 12 months. Medication adherence was assessed using the proportion of days covered, with adherence defined as PDC ≥80% across all prescribed drug classes.

Results. At both time points (baseline and 12 months), three left ventricular remodeling phenotypes were identified: favorable (normal ejection fraction with minimal chamber dilatation — end-diastolic and end-systolic volumes — limited hypertrophy by left ventricular mass index, and borderline left atrial size), intermediate, and unfavorable (reduced ejection fraction with marked dilatation and hypertrophy and enlarged left atrium). At 12 months, 72% of patients with a baseline favorable phenotype retained it, whereas nearly half of those with intermediate or unfavorable phenotypes transitioned toward more favorable categories. High composite adherence to heart failure pharmacotherapy (PDC comp ≥80%) was significantly more prevalent in favorable phenotypes at 12 months (p <0.001). Composite adherence emerged as a significant effect modifier associated with reverse left ventricular remodeling irrespective of the baseline phenotype.

Conclusions. Cluster analysis delineated clinically meaningful left ventricular remodeling phenotypes and enabled the tracking of their trajectories over the first year postmyocardial infarction. High adherence to guideline-directed HF pharmacotherapy substantially increased the likelihood of favorable remodeling and mitigated an initially unfavorable course. These findings support personalized monitoring and adherence support strategies for patients with heart failure after myocardial infarction.

Gout is a chronic metabolic disease that occupies a significant place among chronic diseases worldwide. In 2020, 55.8 million people worldwide suffered from gout, corresponding to 0.7% of all mankind, and the prevalence continues to increase annually. Given the increasing incidence of gout, more personalized approaches to the treatment of patients with gout need to be developed. This study aimed to identify various subgroups (phenotypes) of gout patients and describe their characteristics based on a comprehensive analysis of plasma immunological and metabolic biomarkers.

Three phenotypes were identified using cluster analysis:

• The "permeable intestine" phenotype is characterized by the highest levels of lipopolysaccharide-binding protein (LBP) — 26.1 [22.6; 30.7] ng/ml and zonulin — 74.7 [58.9; 120.1] ng/ml, as well as a high BMI — 31.38 [30.64; 35.06] kg/m2 and elevated levels of TGF-B — 6.32 [3.33; 30.5] ng/ml.
• The phenotype is "metabolic", which is characterized by the highest BMI — 39.79 [35.99; 40.89] kg/m2, as well as the highest levels of nitric oxide synthase 3 (NOS-3) — 6,6 [3,1; 8,5] ng/ml and BPI — 298 [249; 367.2] pg/ml.
• The phenotype with "hyporesponders on LPS", demonstrating the low levels of most inflammatory and metabolic markers: LBP — 11.65 [10.27; 14.72] ng/ml, zonulin — 34.1 [23.8; 43.4] ng/ml, NOS-3–0 [0; 2.35] ng/ml, BPI — 64.6 [43.4; 87.7] pg/ml and the low BMI was 29.15 [27.9; 29.4] kg/m2.

The data obtained suggest new targets for therapeutic effects, for example, by influencing the manifestations of endotoxinemia in gout, LPS-binding systems, and LPS itself.