Objective: to conduct a clinical and economic study of acalabrutinib for the treatment of adult patients with relapsed/refractory form of mantle cell lymphoma who previously received at least one line of therapy in the Russian Federation.

Material and methods. Acalabrutinib and ibrutinib were considered as compared treatment options. Based on the adjusted indirect comparison, they were found to be comparable in terms of overall survival and progression-free survival. Therefore, a cost minimization analysis method was selected for the study. Based on results of ACE-LY-004 clinical trial a distributed survival model was developed. The model was used to calculate drug costs over a 3-year horizon. To explore uncertainty in the results of economic evaluations we conducted a sensitivity analysis. A number of patients in the hypothetical cohort who could be further treated with a less expensive drug was determined during a missed opportunity analysis. Both mean life years gained and mean progression-free life years were calculated too.

Results. Based on simulations over a 3-year horizon, the mean life years gained were 2.45, and the mean progression-free life years were 1.75. The average costs of acalabrutinib therapy both over 1 year and in total over 3 years were 36.6% lower compared to ibrutinib. So, in the 1st year, the costs for acalabrutinib were 3,546,237,60 rubles, for ibrutinib – 5,591,391,00 rubles (a difference of 2,045,153,40 rubles). Using acalabrutinib for 3 years was associated with costs of 7,252,980,60 rubles compared to 11,435,852,60 rubles for ibrutinib (a decrease of 4,182,872,00 rubles). Univariate multi-way sensitivity analysis showed the robustness of modeling results to price fluctuations in the range ±10%. For a hypothetical cohort of 100 patients, using acalabrutinib instead of the more expensive ibrutinib within the same budget will provide therapy to additional 57 patients per year.

Conclusion. The results of the study demonstrated that acalabrutinib compared to ibrutinib for the treatment of adult patients with relapsed/ refractory form of mantle cell lymphoma can reduce costs for the 1st year of therapy by 2,045,153,40 rubles (36.6%), and by 4,182,872,00 rubles (36.6%) for 3 years. Thus, acalabrutinib is the cost-saving option for previously treated adult patients with relapsed/refractory mantle cell lymphoma in the Russian Federation.

Background. A wide range of endosurgical treatment methods in various medical care profiles and the need for uniformity of calculations required developing a unified approach to the formation of diagnosis-related groups (DRGs) for cases of surgical medical care provided by laparoscopic access.

Objective: to develop a methodology for the formation of a DRG model for cases of medical care using surgery performed by laparoscopic access in the context of the following medical care profiles: “coloproctology”, “urology”, “surgery (abdominal)”, “obstetrics and gynecology”, “pediatric urology-andrology”, “pediatric surgery”.

Material and methods. The methodology for the formation of DRGs to pay for cases of medical care using surgery with laparoscopic access included the implementation of several stages: analysis of scientific and methodological documents, analysis of regulatory legal documents on the research topic, standardized expert survey of federal and regional medical centers (carried out in August 2023), formation of DRGs in the context of each profile, and calculation of cost-intensity coefficients.

Results. Due to significant increase in the cost-intensity coefficient in nine newly formed DRGs to pay for cases of medical care provided by surgery with laparoscopic access, financial support of this type of surgical medical care almost doubled. The formed DRGs with appropriate cost-intensity coefficients were included in the Program on State Guarantees to Deliver Free Medical Care to the Citizens for 2024 and for the planning period of 2025 and 2026.

Conclusion. The methodology of forming DRGs to pay for cases of medical care using surgery performed by laparoscopic access with a unified methodology for calculating costs for medical care provided an integrated approach to the process of forming DRGs for cases of surgical medical care, and unification of calculations for different medical care profiles.

Background. The analysis of the exports of medicines of the Russian Federation (RF) by group 30 (pharmaceutical products) of the commodity nomenclature of foreign economic activity of the Eurasian Economic Union (equal to Harmonized System Code 30, HS 30) is an important task for determining the economic potential of the country in the pharmaceutical industry.

Objective: building an export regression model. Development of an alternative mathematical model of pharmaceutical products’ export, suitable for making the forecast.

Material and methods. Statistical data on HS 30 exports from 2010 to 2021 were taken from an open source: The International Trade Center (Trade Map). Data for 2022 and later for the Russian Federation are not available in open sources. Registration on the website is not required to collect statistics on export and import volumes based on annual data. The well-known statistical methods and methods of mathematical modeling were used. An alternative approach to regression analysis was developed. Technical data analysis was performed using MAPLE (Watcom Products Inc., Canada) and R (Bell Laboratories, USA) software.

Results. Two models were constructed: Model I – a differential model based on cumulative data by year, and Model II – a model of standard regression analysis, the input parameters of which were quarterly export data, and the influencing parameters were a certain group of factors. Model I allowed considering the dynamics of changes in pharmaceutical exports over time (dynamic factors and nonlinear interactions). Model II, in turn, made it possible to determine the dependence of the volume of pharmaceutical exports on various economic indicators, such as gross domestic product, the volume of government procurement, and measures of protectionism. The relative error of Model I does not exceed 10%, which makes it suitable for forecasting.

Conclusion. The construction and analysis of specified models help to provide main information about the trends in pharmaceutical product exports in the RF and assess its potential in the global market. The obtained results can be useful for developing strategies of the pharmaceutical industry development, making management decisions and forecasting future exports.

Objective: pharmacoeconomic analysis of the feasibility of using topical bacterial lysate Imudon® for the treatment and prevention of acute upper respiratory tract infections in the pediatric population in comparison with other medicines belonging to the class of topical antiseptics.

Material and methods. For the population calculated on the basis of Rosstat data, taking into account the Russian clinical recommendations "Acute respiratory viral infection (ARVI)" and "Acute tonsillitis and pharyngitis (acute tonsillopharyngitis)", the direct medical costs of medical care were determined. The cost of basic therapy of 1 case of acute respiratory infection (ARI) with symptoms of pharyngitis was calculated for two variants of clinical course: favorable (when ARI proceeds without complications and the patient does not need to be prescribed antibacterial drugs), and unfavorable (when confirmed bacterial infection joins and antibiotics are required). The indirect costs of child care are associated with lost gross domestic product (GDP). In estimating the GDP shortfall, it was assumed that the parent does not contribute to the country’s GDP during the entire childcare period.

Results. GDP per capita for 2022 amounted to 2853.13 rubles per day. Thus, with a favorable course of the disease, indirect costs will be 19,972 rubles, and with an unfavorable course – 39,944 rubles. The total costs of the healthcare system and the state for 1 ARI patient are 32,192 rubles in case of favorable course and 71,644 rubles in case of unfavorable course. Imudon® administration allows reducing direct costs of parents for purchase of medicines for treatment of 1 ARI case by 23.6% compared to the therapeutic strategy associated with the use of local antiseptics.

Conclusion. For the first time in Russian economic conditions, the use of Imudon® for the treatment and prevention of acute upper respiratory tract infections in children was evaluated. Its use from the first ARI symptoms allows refusing the use of local antiseptics, shortens the duration of the disease symptoms, and reduces the need for antibiotics, i.e. is feasibleable compared to local antiseptics.

Objective: to conduct chemoreactomic, pharmacoinformatic and chemoneurocytological analyzes of the properties of racetams (piracetam, aniracetam, pramiracetam, levetiracetam, fonturacetam).

Material and methods. Chemoreactomic, pharmacoinformatic and chemoneurocytological methods of molecule properties analyzis are based on chemoreactomic methodology – the latest direction in the application of machine learning systems in the field of postgenomic pharmacology. Analysis of pharmacological capabilities of molecules within the framework of chemoreactomic methodology is carried out by comparing the chemical structure of racetam molecules with the structures of molecules for which pharmacological properties were studied using training artificial intelligence algorithms based on big data information presented in PubChem, HMDB, STRING, PharmGKB databases. Based on the entire complex of differences between molecules in interactions with receptor proteins, an “anti-obesity” score was calculated for each one as a serial number of this molecule in descending order by corresponding IC50, EC50 chemoreactomic constants values.

Results. The lipolytic effect is predicted specifically for fonturacetam as a result of activation by this molecule of β3-adrenoceptors, adenosine receptors, glucagon-like peptide, sphingosine phosphate and peroxisome proliferators, as well as specific inhibition of cannabinoid, opioid, histamine, glutamate, nociceptin, orexin and neuropeptide Y receptors. Due to these mechanisms fonturacetam will contribute to normalizing appetite and improving adipose tissue metabolism. The total lipolytic effect score was calculated for all established interactions with receptors and amounted to 4.3±0.9 for fonturacetam, 3.0±1.4 for pramiracetam, and 2.5±1.5 for all other molecules.

Conclusion. The results of the analysis suggest that the lipolytic effects of fonturacetam (Actitropil – Pharmstandard, Russia) will be much stronger than for other racetams (piracetam, aniracetam, pramiracetam, levetiracetam). Chemoreactomic analysis of fonturacetam indicated new mechanisms of pharmacological action of the molecule, providing a decrease in excess appetite and body weight normalization. Fonturacetam is the only nootropic drug indicated for the treatment of obesity.

Objective: to perform pharmacoeconomic analysis of the feasibility of using topical bacterial lysate in the form of nasal spray (IRS®19) for the treatment and prevention of upper respiratory tract infections in pediatric population in comparison with other drugs registered in Russia, belonging to the class of topical interferons.

Material and methods. Based on the Rosstat data and information from open sources, the population of patients with acute respiratory infections (ARI) was calculated. Considering the Russian clinical recommendations “Acute respiratory viral infection (ARVI)” and “Acute tonsillitis and pharyngitis (acute tonsillopharyngitis)”, the direct medical costs of providing medical care to specialized patients were determined. Direct costs on the part of parents included all costs for purchasing medicines for basic or concomitant therapy. Direct costs on the part of the healthcare system and the state included the costs of providing medical care at the outpatient stage. Direct non-medical costs included payments for disability leaves, indirect costs – lost gross domestic product (GDP) due to absence from work.

Results. The total costs of the healthcare system and the state for 1 AVI patient are 42,472 rubles in case of uncomplicated course and 70,649 rubles in case of complicated course. In case of IRS®19 application from the first day of the disease, it is possible to reduce its duration by more than two-fold. Thus, the costs of medical care amount to 2,078 rubles. Payments for disability leaves by the Social Fund of Russia will amount to 2,287 rubles, and the lost GDP – 9,148 rubles (total costs 13,513 rubles).

Conclusion. For the first time in Russian economic conditions, the use of IRS®19 for ARI treatment and prevention in children was evaluated. IRS®19 application from the first symptoms of the disease allows refusing the use of topical interferons, reduces the duration of symptoms and the need for prescription of antitussives, vasoconstrictors, and antibiotics.

Objective: to determine the molecular mechanisms of action of 7-hydroxymatairesinol (7(OH)MR), the main lignan of spruce extracts, characterized by oncoprotective and anti-inflammatory properties.

Material and methods. The analysis of 7(OH)MR was carried out by chemoinformatic approach using the combinatorial theory of solvability and the topological theory of recognition. The postgenomic approach makes it possible to assess the effect of drugs on genome transcription (transcriptome) and on the proteome as a whole.

Results. 7(OH)MP has anti-inflammatory (inhibition of 5-lipoxygenase, matrix metalloproteinase 2, mitogen-activated kinase p38-alpha, leukotriene В4 receptor, prostacyclin receptor), and oncoprotective (antioxidant effect due to inhibition of heme oxygenase-2, inhibition of cyclin-dependent kinases 3 and 4, epidermal growth factor, mTOR protein) pharmacological effects.

Conclusion. By reducing the expression of proliferative genes and genes involved in chronic inflammation, the 7(OH)MP molecule inhibits the proliferation of tumor cells. Pharmacoinformatic modeling showed that the anti-inflammatory effects of 7(OH)MR may contribute to increased lifespan in animal models.

Objective: to evaluate the effectiveness and safety of rehabilitation programmes in patients with vulvovaginal atrophy (VVA).

Material and methods. The study involved 350 patients with VVA in surgical (n=140) and natural (n=140) menopause, the control group included 70 women without VVA. Patients with VVA were distributed into groups receiving complex “active” rehabilitation (surgical menopause: group 1A, natural menopause: group 2A) and “passive” rehabilitation (surgical menopause: group 1B, natural menopause: group 2B). Body mass index (BMI), vaginal pH, carbohydrate profile with calculation of insulin resistance index (HOMA-IR), inflammatory markers leptin, interleukin-6, tumour necrosis factor alpha, serum magnesium, and safety profile with evaluation of adverse events related to rehabilitation measures were assessed over 24 months.

Results. BMI decreased significantly in groups 1A and 2A. Vaginal pH at 1-year follow-up decreased in groups 1A and 2A, but increased in groups 2A and 2B. BMI was higher than normal in all patients with VVA, as well as in the control group, demonstrating preobesity (groups 1A, 2A, control group) or first-degree obesity (initially in group 1B and throughout follow-up in group 2B). HOMA-IR initially reflected postoperative insulin resistance in groups 1A and 2A, but in those receiving complex “active” rehabilitation the dynamics of its reduction was the most pronounced. The concentration of inflammatory markers was initially increased compared to the control group and decreased over time in groups 1A and 1B, but only leptin levels reached the control group values by the end of the study. Serum concentration of magnesium levels was 0.71±0.12 mmol/l in group 1A, 0.71±0.10 mmol/l in group 2A, 0.76±0.08 mmol/l in group 1B, 0.72±0.17 mmol/l in group 2B (magnesium deficiency). When organic magnesium salts in combination with pyridoxine were supplemented in groups 1A and 1B, serum magnesium levels were restored to normal from the 3^rd month of follow-up. No adverse events were registered.

Conclusion. The personalised programme of complex “active” rehabilitation in patients with VVA is more effective than “passive” rehabilitation with comparable safety profile. Its implementation into routine practice will contribute to the improvement of the quality of health care for such patients.

Objective: to study the antitumor effects of organic lithium salt (lithium ascorbate) in different doses in comparison with inorganic lithium salt (carbonate).

Material and methods. Two series of experiments were carried out on the effect of lithium preparations on the dynamics of transplantable Lewis lung carcinoma (LLC) growth and metastasis in F1 mice (CBA × C₅₇Bl/6j). In the first series, a comparative study of the effects of different lithium ascorbate doses (1 and 10 mg/kg/day based on elemental lithium) was performed, and in the second series, a comparison was made of the effects of lithium ascorbate and carbonate when used at the same dose (5 mg/kg/day).

Results. Significant antitumor effects were found for lithium ascorbate lower doses (1 and 5 mg/kg/day). A statistically significant antitumor effect of lithium ascorbate was observed from Day 10 throughout the entire observation period (tumor growth inhibition index (TGII) 30–40%). The antitumor effect of lithium carbonate in this experiment was less pronounced and stable (TGII 20–30%). No antimetastatic effect was observed with both preparations.

Conclusion. Subchronic intragastric administration of lithium ascorbate and carbonate to tumor-bearing animals at a daily dose of 5 mg/kg, an antitumor effect is observed, manifested by LLC growth inhibition. Effective and safe antitumor doses of lithium ascorbate are in the range of 1–5 mg/kg.

Acute kidney injury (AKI) is a life-threatening condition that occupies one of the leading places in the structure of mortality in intensive care units. AKI markers common in clinical practice are characterized by a number of disadvantages: serum creatinine – late response to damage to the kidney tubules, an increase in damage to more than 50% of nephrons; urine volume – limited diagnostic value and overdiagnosis of AKI in dehydration, the impossibility of assessing on the basis of a single measurement, as well as the need for regular and frequent dynamic monitoring. The review considers the diagnostic and prognostic possibilities of cystatin C (CysC) in AKI. The results of 55 researches were analyzed. The influence of a number of physiological conditions and non-renal diseases on blood serum and urinary CysC levels were shown. These indicators proved to be highly sensitive and specific biomarkers for AKI diagnosis and prognosis, allowing the specialists to verify renal dysfunction at an early stage of development, ahead of structural changes, and thereby to timely correct treatment, including withdrawal of nephrotoxic drugs and initiation of nephroprotection therapy.

Background. Determining the cost of laboratory tests is a significant factor in the context of economic analysis and management of clinical diagnostic laboratories. Information about costs allows medical organizations to plan operational activities more efficiently, optimize resource utilization, and exercise control over expenditures. These measures are aimed at improving the financial position and enhancing the operational efficiency of the laboratories.

Objective: to review various methods for calculating the cost of laboratory tests.

Material and methods. The study included the collection and analysis of publications on calculating cost of laboratory tests, determining their prime cost in PubMed/MEDLINE and Google Scholar databases, as well as in Google and Yandex search engines for similar “cost laboratory test” query. The regulatory documents of the Russian Federation in this area were considered.

Results. For calculating the prime cost of laboratory tests such methods as direct costing, regulatory prime costing, total prime costing, activity-based costing (ABC), standard costing, costing for base service, department costing, cost-volume analysis are used. The ABC and standard cost methods provide the most accurate assessment of the impact of various factors.

Conclusion. The approaches established by regulatory documents do not contradict each other and represent the implementation of total costing method. At the same time, a medical organization may use other methods for calculating the cost of laboratory tests, depending on the objectives of the analysis, the specifics of the laboratory and the cost accounting method adopted in accounting policy, the management accounting system.

The article is devoted to analysis of the stages of development and current directions of research and practical application of artificial intelligence (AI) in the field of healthcare and medicine based on scientific publications in PubMed/MEDLINE, Scopus, Web of Science, Embase, eLibrary and CyberLeninka. The dynamics of scientific publications on AI in healthcare and medicine is shown, and an analysis of the growth of investments in software development based on AI in recent years is provided. AI can achieve comparable accuracy in the diagnosis of diseases in comparison with human decisions. However, future research should focus on comparing the clinical results of diagnosis and treatment performed by doctors who make decisions based on AI with the results of clinical work by doctors who do not use AI. The importance of training specialists able to combine knowledge in the field of medicine with the skills of using AI is emphasized.

On March 15, 2024, in Moscow, the Russian Phlebological Association and the National Association of Specialists in Thrombosis, Clinical Hemostasiology and Hemorheology organized a meeting of the Council of Experts during the Russian Forum on Thrombosis and Hemostasis on the acute issues of venous thromboembolism (VTE) primary prevention using low molecular weight heparins (LMWH) in surgical patients with different body weight. The participants reviewed the relevance and prevalence of this problem in surgical practice, discussed risk factors and the frequency of VTE development, including bleeding in the postoperative period, and the Caprini risk score for complications. The discussion also focused on standard and personalized LMWH doses for primary prophylaxis of VTE in the perioperative period in surgical patients, depending on body weight, and the role of laboratory tests, including assessment of LMWH anti-Xa activity for monitoring the efficacy and safety of VTE primary prevention in clinical practice.