Objective: the development and approbation of the method for comparative analysis of the lists of medicines in different countries and systems of healthcare.

Material and methods. Based on the open-access data on the lists of medicines published on official websites of the authorized regulators, the authors selected the national lists of medicines of Russia, England, and Italy for the development and approbation of the method. It was proposed to use three parameters: the absolute number of medicines by international nonproprietary name (INN); the structure of the lists based on anatomical therapeutic chemical (ATC) classification; and the coverage of the indications based on the International Classification of Diseases, 10th edition (ICD-10). The results of the analysis provided grounds for the review of the approaches to the formation of the lists of medicines required for medical help in Russia, England, and Italy and reimbursed from the state budget.

Results. The number of medicines by INN in the national lists of England and Italy exceeds the total number of drugs included in the list of vital essential and desirable (VED) in Russia. All the analyzed lists were characterized by an uneven distribution of medicines within the lists by the ATC groups. The lists of medicines in England and Italy significantly exceed the list of VED by the number of the included medicines by all ATC groups excluding groups J and H in comparison with Italy, and groups J and V in comparison with England. At the same time, the list of VED significantly exceeds the list in England by the number of covered indications from the ATC L group. During the approbation, the method showed to be effective and can be used for further comparative studies of the national lists of medicines.

Conclusion. Non-uniform lists of medicines by ATC-codes show that each country has priority areas in their healthcare systems. The list of VED can be shorter by the absolute number of the included medicines in England and Italy but it can exceed them by the coverage of indications due to peculiarities of the procedure of the list formation (reimbursement of medicines by all the registered indications). The results of the study with the proposed method can serve for the optimization of the VED list and the analysis of therapeutic areas that are undercovered.

Background. Severe forms of COVID-19 are associated with the development of a cytokine storm that is characterized by an increased secretion of anti-inflammatory cytokines. Thus, one of the leading strategies of treatment for patients with severe forms of COVID-19 is a decrease in the concentration of anti-inflammatory cytokines and inhibition of their effect on the organism.

Objective: to perform a comparative analysis of clinical and economic constituents of the application of an IL-6 inhibitor tocilizumab and systemic glucocorticosteroid dexamethasone for the therapy of severe conditions in patients with COVID-19 based on the published data review.

Material and methods. The authors analyzed the data obtained from PubMed/MEDLINE databases on the study dedicated to the application of tocilizumab and dexamethasone for the therapy of severe conditions in patients with COVID-19. A statistical evaluation of the influence of these drugs on the 28-day survival rate of patients with a severe form of COVID-19 was performed. The statistical tools included methods of the attribute-based statistic (attribute-based efficiency, relative efficiency (RE), populational attributive efficiency (PAE)). For the visualization of the clinical efficiency of the compared drugs, the authors applied beta-distribution. Markov’s model was used for modeling of the mortality rate. The modeling included the study of a hypothetical cohort of patients (1,000 patients with COVID-19). Besides, the authors evaluated the economic constitutive of the therapy with tocilizumab and dexamethasone. The cost-effectiveness analysis was performed.

Results. The indication of dexamethasone statistically significantly increases the survival rate by 3.1% and tocilizumab – by 22.5%. RE was 1.04 (95% CI 0.040–2.042) for dexamethasone and 1.66 (95% CI 0.400–2.917) for tocilizumab. The lower border of 95% CI for both drugs was within the range of values <1, which was statistically significant. PAE for dexamethasone was 1.0% (95% CI –0.6–2.6), for tocilizumab – 16.5% (95% CI –0.7–33.7). Lower borders of 95% CI for both drugs ranged within negative values, which was not statistically significant. NNT (dexamethasone) was 32; NNT (tocilizumab) was 4. Markov’s modeling showed that the mortality rate among patients who received these drugs was 36 out of 1000 patients with COVID-19 for dexamethasone (initially distributed by the degree of severity according to the official statistical data) and 30 out of 1000 patients for tocilizumab, respectively. The cost of the treatment course with dexamethasone was 107.45 rub., tocilizumab – 78,827.20 rub. Clinical efficiency by the rate of cured patients obtained as a result of Markov’s modeling among patients with severe forms of COVID-19 for both drugs was comparable (0.964 for dexamethasone and 0.970 for tocilizumab) with slightly higher values for tocilizumab.

Conclusion. Despite relatively comparable clinical efficiency of dexamethasone and tocilizumab and a significantly higher cost the later, it is not impossible to replace tocilizumab with dexamethasone because of a great number of side effects and potential inter-drug interactions during the treatment of severe forms of COVID-19. In particular, dexamethasone therapy should be performed with caution in patients with diabetes mellitus. Procurement planning should be made taking account the reserves of tocilizumab for the stabilization of patients with cytokine storm when dexamethasone application is not safe.

Objective: analysis of the osteoarthritis (OA) comorbidity taking into account the microelement status and genetic polymorphisms of the examined patients, determination of the prospects for the OA prevention and therapy.

Material and methods. A cross-sectional study of a multiethnic cohort (n=655, mean age 43±14 years, 95% CI 29–70) formed on the basis of the Institute of Microelements database, was carried out. For all participants, the content of the 62 elements of the Element Periodic Table profile in hair was identified and variants of 120 nucleotide polymorphisms associated with various pathologies were defined

Results. The study found that 18 of the 27 ICD-10 diagnoses examined were comorbid with OA. Osteoarthritis was comorbid with pathologies with a pronounced component of inflammation (ulcerative colitis, atherosclerosis, unspecified encephalopathy, obesity, diabetes mellitus, essential (primary) hypertension, urine calculus, acute myocardial infarction, cholelithiasis, etc.). The core of OA comorbidity was established, which included following pathologies: chronic cerebral ischemia, diabetes mellitus, thrombophlebitis, atherosclerosis, cholelithiasis. Seven profiles of the most frequent combinations of these diagnoses were identified. The presence of 2 out of 5 of these pathologies was recorded in 92% of patients with OA (n=50) and only in 2% of control patients (n=600), which corresponded to an extreme increase in the risk of OA (OR 56.3, 95% CI 17.4–181.6, p<10–20). Analysis of the 62 elements profile of the Element Periodic Table content in hair showed that reduced levels of silicon, molybdenum, vanadium and calcium are significantly associated with OA. As a result of studying data on 120 nucleotide polymorphisms, OA was significantly associated with the LPL Ser447Stop CC, LPL N291S AA, NOS3 E298D GG, and MTHFR 677 CC genotypes, which regulate lipid metabolism and inflammation.

Conclusion. Based on the obtained results the prospects for the use of chondroitin sulfate and glucosamine sulfate in patients with an increased risk of OA development are shown.

Objective: analyzing the acquisition and monthly costs for patients on modern fixed-dose antihypertensive combinations in three regions of the Far Eastern Federal District.

Material and methods. Intra-group analysis of retail of antihypertensive drugs for 2019 in drugstores of the Khabarovsk Region, Sakhalin Region, Amur Region (n=100) was carried out. The calculation of the monthly cost of therapy was performed and total sales indicators were identified. Statistical analysis: dispersion analysis, Spearman's rank correlation coefficient, Kruskal–Wallis test.

Results. The maximum demand in patients among combinations of -blockers in the price range of 100-500 rubles: atenolol+chlortalidone; bisoprolol+amlodipine. In the grope of combinations of angiotensin-converting enzyme inhibitors with diuretics/calcium channel blockers, the most often acquired were: perindopril/ramipril+indapamide/amlodipine, enalapril+hydrochlorothiazide – in the price segment of 500–1000 rubles. Preferences for the use of combinations of angiotensin II receptor blockers+diuretic/calcium channel blockers: valsartan+amlodipine with a monthly cost of therapy of 300–500 rubles; losartan+hydrochlorothiazide – 100–500 rubles and azilsartan+chlortalidonee – 500–1000 rubles. The most popular three-component drugs were valsartan+amlodipine+hydrochlorothiazide, perindopril+amlodipine+indapamide with a monthly cost over 500 rubles. Differences in the acquisition structure of fixed-dose antihypertensive combinations between regions were statistically significant.

Conclusion. The share of sales of combined antihypertensive drugs remains insignificant. The main selection criteria within an international nonproprietary name are affordability or trust in a brand. The presence of a reliable correlation of the acquisition structure with the region proves the influence of regional preferences of specialists in drug prescribing.

Objective: a comparative analysis of 6 different chondroprotectors for injection, containing chondroitin sulfate (CS) based on natural extracts.

Material and methods. Five samples were studied for each CS extract. The preparations were compared on the basis of profiles of trace element composition, sulfur content, chromatographic analysis and test for total protein. In each sample, the concentration of 72 elements was determined, then averaging was performed and the variances of the content of each element were calculated. To assess the content of the protein fraction, a modified Lowry method with bicincholic acid was used. Chromatographic profiles of the studied CS extracts were measured to estimate the molecular weight distribution.

Results. The studied samples differ significantly from each other in the total and individual content of sulfur, toxic and conditionally toxic microelements. According to the analysis of sulfur and trace elements, a cluster of more standardized CS extracts was identified. It was shown that the assessments of the pharmaceutical quality of the studied extracts made by the elemental profile, correspond to the assessments of the quality by the degree of proteins elimination and by the molecular weight characteristics of CS extracts. In particular, the highest total content of toxic elements was found for CS-6 (14.87±1.81 μg/l) and CS-2 (9.20±1.12 μg/l), and the lowest – for CS-4 (1.46±0.23 μg/l), CS-3 (1.92±0.33 μg/l) and CS-1 (2.98±0.25 μg/l). The highest content of protein impurities was also found in CS-6 (9.62 mg/ml) and CS-2 (6.64 mg/ml), and the lowest – in CS-1 (2.87 mg/ml). At the same time, the highest amount of sulfur was found CS-1 (6400 mg/kg) and much less – for CS-2 (370 mg/kg) and CS-6 (100 mg/kg). Significant amounts of the high-molecular fraction of CS (1–40 kDa) were found only in CS-1, and only trace amounts of high-molecular CS forms were present in CS-2 and CS-6.

Conclusion. The highest content of cholesterol and sulfur and, at the same time, the lowest content of toxic microelements and proteins were distinguished by the extract obtained from the trachea of a bovine.

A review of studies, presentations and reports of the Regional Office for Europe of the World Health Organization (WHO) devoted to the experience of European countries in the formation of cross-border eHealth and the use of quality management tools for medical activities to reduce risks when introducing innovative solutions in health systems was carried out. In order to comprehensively assess the information received, a SWOT analysis was fulfilled – an analysis of strengths (S), weaknesses (W), opportunities (O) and threats (T), internal and external factors that influenced the development of cross-border eHealth in the European Union. It is shown that in European countries with a developed health care system, the leading direction in building cross-border e-Health are innovative technologies and advanced solutions aimed at improving the interaction of medical systems: Electronic Health Record (EHR), Health Information Exchange (HIE), Telemedicine Technologies (Telehealth), and Personal Health Records (PHR). The analysis of the strengths and weaknesses of this technologies, as well as the main problems that have affected the transition to eHealth and the implementation of information and communication technologies in medical organizations of European countries has revealed common factors and patterns that can be taken into account for the digital transformation of the health system in the Russian Federation.

The three-report review was aimed at describing the historical development of clinical trials, controlled trials (CT) and randomized controlled trials (RCT), and the inclusion of these experimental approaches in disciplines related to both the health of individuals and populations (medicine and epidemiology). In Report 1, the authors consider the terminology issues applied to CT and RCT, the sources of the involved concepts, and relevant disciplines. It was shown that the terms ‘control’ and ‘trial’ appeared in experimental literature only at the end of the 19^th century, ‘CT’ appeared in the first third or quarter of the 20^th century, and the term ‘RCT’ appeared only in 2000s. It was found that approaches with CT and RCT were often included even in classical epidemiology, and this fact eliminates the specificity of differences between observational and experimental disciplines and blurred the difference between inductive and deductive methodologies. Scientific, philosophical, conceptual, and historical aspects were also considered for three areas that included CT and RCT: epidemiology, clinical epidemiology and evidence-based medicine (EBM). It was concluded that classical epidemiology, using predominantly inductive approaches, was not the scope of real medical experiments, in the first place, and, secondly, its prognosis was not aimed at the individual. At the same time, both clinical epidemiology and EBM, which mainly use deductive approaches, involve experiments, making it possible to make prognosis for a particular patient. The proposed summarizing scheme of the historical origins and philosophical foundations of disciplines aimed at finding and proving health effects using observational and experimental approaches reflects the problems considered and covers individual time milestones, which, as a rule, are not named in modern epidemiology textbooks and textbooks of other disciplines.