Search

The aim of the work was to conduct an analysis of the current state and current trends in the approval of drugs, as well as some aspects of the methodology for their development based on biological molecules and registration.Materials and methods. The material for the analysis was taken from the abstract databases of PubMed, Google Scholar and e-library.ru. The search was carried out using publications for the period from 2008 to 2023, the keywords were as follows: “biologicals”, “new drug approval”, “drug authorization”, “drug development”, “biosimilar”, taking into account various spellings.Results. Over the past 15 years, scientists have been observing revolutionary trends and processes in the field of the drug development, especially biopharmaceuticals. Significant advances have been made in gene, immune and cell therapies, resulting in the approval of such drugs more than doubling over the past ten years. The development of biological drugs includes the identification and testing of molecular targets and requires a deep understanding of the structure and functioning of the polypeptides involved in the development of the effect. The features of these active pharmaceutical substances are a high molecular weight, a complex three-dimensional structure and a high immunogenic potential. Preclinical and clinical studies of biologics have unique challenges. Selecting appropriate animal species, understanding the immunogenicity, and assessing pharmacodynamics and toxicological properties require a multilevel, detailed approach. The article discusses the regulatory framework under which these drugs are registered, summarizing the guidelines provided by international organizations such as the International Council for Harmonization and various national agencies.Conclusion. The analysis highlights the current advances and prospects in the development of biologics, highlighting their key role in future transformations in the treatment of rare diseases and oncology, approaching the era of personalized medicine. Monitoring the development directions and technological approaches, as well as the commitment to global methodological and regulatory aspects can become a catalyst in the development of the Russian pharmacology.

Modern approaches to the treatment of type 2 diabetes mellitus (T2DM) are aimed not only at glycemic control, but also at reducing cardiovascular risks. The increasing prevalence of the disease and the need for effective treatment options highlight the importance of glucagon-like peptide-1 (GLP-1) receptor agonists in the pharmacotherapy structure.The aim of the work was to review the literature regarding the physiology of GLP-1 and the therapeutic potential and development trends of its agonists.Materials and methods. The search for the review materials was carried out using the abstract databases of PubMed, Google Scholar and e-Library. The search was carried out for publications from 2000 to 2023, using the following keywords: “GLP-1”; “GLP-1R agonists”; “GIP”; “exenatide”; “liraglutide”; “dulaglutide”; “semaglutide”; “lixisenatide”; “albiglutide”; “taspoglutide” taking into account various spellings.Results. The interaction of almost all food components with enteroendocrine cells of the intestine leads to the secretion of incretins (primarily GLP-1) into the blood, triggering a complex of physiological reactions aimed primarily at the rapid utilization of incoming glucose (regulation of insulin and glucagon secretion), as well as the central regulation of dietary behavior (slowing gastric emptying and the formation of a feeling of satiety). A wide distribution of the GLP-1 receptor in various tissues and organs, its connection with intracellular signaling cascades aimed at launching energy-consuming remodeling (recovery) processes in endothelial cells, heart, neurons, beta cells, etc., is the basis for a wide range of pleiotropic effects of GLP-1 unrelated to its hypoglycemic effect. The discovery of synthetic GLP-1 receptor agonists with a long period of action has made it possible not only to therapeutically influence various parts of carbohydrate metabolism disorders, but also to increase the functional reserves of the target diabetes organs, reducing the risk of developing complications of the disease. Incretin-like drugs are well tolerated, with nausea being the most common side effect. The factors limiting a wider use of the drugs include their high cost and the preferred form of a subcutaneous solution. The current research is focused on the development of long-acting, oral, dual and triple agonists, fixed-dose combinations, and small molecule drugs.Conclusion. GLP-1 receptor agonists are a class of effective and safe drugs for the treatment of diabetes and obesity, which is rapidly developing in the most advanced areas of pharmacy. A further development of this group and the solution of the identified problems will open up new opportunities for the treatment of diabetes and its complications.

The aim of the work is to conduct a review of medications approved by the FDA in 2022.Materials and methods. In searching for the materials to write this review article, bibliographic databases including PubMed, Google Scholar and e-library.ru were utilized. The search was conducted for the publications spanning the period from 2008 to 2023. Herewith, the following keywords and word combinations were used: new drug approval, NDA, drug authorization, approval package, breakthrough medicine.Results. The discovery and development of medications are among the most crucial scientific processes in healthcare. Developing a new drug is a highly intricate, expensive, and time-consuming process. Nowadays, the problem of costs reduction and the process of expedited discovering of new medications are particularly pertinent. To optimize the search for active compounds, virtual and high-throughput screenings, machine learning, artificial intelligence, cryo-electron microscopy, and drug repurposing are employed. Simultaneously, the search for original molecules to serve as the basis for innovative drugs continues. This article presents a review of medications approved by the FDA in 2022 for the treatment of various pathologies.Conclusion. A drug development is a complex and resource-intensive process, with only a small fraction of candidates advancing to clinical trials. A drug design evolves in tandem with societal needs, and this review highlights some of the medications approved by the FDA in 2022. Technological advancements are expected to expedite drug development, potentially reducing the time to the market. Biotechnology, including cell therapy, holds significant prospects, and achievements in genetic mapping and chip technologies will enhance the accessibility of personalized pharmacology.

Background. The available comparative studies on issues of choosing antibiotic regimen in dental implantation are often observational and describe only visible postoperative signs. More objective assessment of postoperative period and comparison of approaches requires laboratory tests. One of the methods to be used at a dental appointment is to study examination of the biochemical properties of saliva.Objective. To carry out comparative evaluation of single and prolonged regimens of amoxicillin/clavulanate administration after dental implantation indicated by nonspecific immunity in mixed saliva.Methods. A randomized uncontrolled trial of 30 partially edentulous patients was conducted. The clinical phase of the study was performed at the Department of Propaedeutics of Surgical Dentistry, MSUMD; the laboratory phase — at the Pharmacology and Biological Chemistry Departments, MSUMD, in 2021–2022. The study included patients aged 18 to 75 years, anatomically suitable for dental implant placement. Patients with somatic diseases in the decompensation stage were excluded from the study. Patients were randomized into 2 groups. The group 1 was prescribed to take amoxicillin/clavulanate pills (875+125 mg) 30 minutes before surgery. The group 2 was to take amoxicillin/clavulanate (875+125 mg) 30 minutes before surgery and then 1 pill of Amoxicillin/ Clavulanate (500+125 mg) 2 times a day for 7 days after surgery. To evaluate the efficacy of the applied antibiotic therapy, unstimulated mixed saliva was collected from all patients on an empty stomach, 1 ml before surgery and on the third day after surgery. The amount of immunoglobulins of G, M, A classes (mg/l) and б-amylase activity (IU/l) were determined spectrophotometrically in the saliva samples. Statistical processing of laboratory data was performed using Welch's t-test by means of Statistica 10 Pro (StatSoft, USA). Intergroup and intragroup differences were considered significant at p ≤ 0.05.Results. Based on the saliva proteins examined, the most pronounced difference between the patient groups was obtained for IgA. For other studied parameters of saliva, no significant difference between the groups was obtained on the third day after the surgery. However, despite the absence of a statistical difference, a tendency to a stronger increase in the amount of IgA, G, IgM, salivary amylase activity was noted for all indicators; moreover, a high correlation between immunoglobulins of class A, G, immunoglobulins of class G, M, and immunoglobulins of class A, M was revealed.Conclusion. Among patients with the prolonged regimen, the groups did not differ significantly in such saliva parameters as immunoglobulins G and M and salivary б-amylase activity, however, a tendency to a stronger increase of the mentioned immunoglobulins in the saliva of group 1 patients was revealed. The most significant difference was recorded for immunoglobulin A in saliva, the amount of which was significantly lower in the group of prolonged antibiotic administration (p < 0.05).

Currently, functional dyspepsia (FD) and irritable bowel syndrome (IBS) are among the most common nosological units in the structure of functional gastrointestinal diseases in adults. An important problem of treatment of these diseases at the current stage of medicine is low efficiency of monotarget drugs, which is determined by multicomponent pathogenesis. Indeed, the currently available methods of drug treatment of FD and IBS have suboptimal efficacy, as illustrated by recent meta-analyses demonstrating high rates of NNT (the average number of patients who need to be treated to achieve a certain favorable outcome). In addition, the frequent “overlap” of these diseases forces clinicians to prescribe several drugs with different pharmacological actions to the patient, which inevitably leads to a decrease in compliance. The optimal strategy for managing patients with FD and IBS is the tactics of multitarget drugs that act on several links in the pathogenesis of these pathologies and have a significant evidence base in the effectiveness and safety of use. STW 5 (Iberogast®), included in the clinical guidelines of the Russian Gastroenterological Association on the diagnosis and treatment of patients with FD, published in 2017, has the above-mentioned characteristics, as well as the clinical guidelines of the Russian Gastroenterological Association in collaboration with the Russian Association of Coloproctologists on the diagnosis and treatment of IBS, published in 2021. The clinical effectiveness of Iberogast in the treatment of FD and IBS has been demonstrated in a number of randomized trials, the results of which showed high efficacy of the drug and its good tolerability.

Proton pump inhibitors (PPIs) are baseline drugs for induction and maintenance of remission in gastroesophageal reflux disease (GERD). PPIs have proven to be highly effective in healing esophageal mucosal lesions and relieving the symptoms of the disease in most cases. However, according to the literature data, the incidence rate of clinical ineffectiveness of PPIs in the form of partial or complete persistence of current symptoms during administration of standard doses of PPIs ranges from 10 to 40%. Optimization of GERD therapy in PPI refractory patients is a significant challenge. In most cases, experts advise to increase a dose / dosage frequency of PPIs, switch to CYP2C19-independent PPIs (rabeprazole, esomeprazole, dexlansoprazole), add an esophagoprotective or promotility agents to therapy. At the same time, these recommendations have a limited effect in some patients, which opens up opportunities for looking for new solutions related to the optimization of GERD therapy. Today there is growing evidence of the relevance of the role of disruption of the cytoprotective and barrier properties of the esophageal mucosa in the genesis of GERD and the formation of refractoriness. Intercellular contacts ensure the integrity of the barrier function of the esophageal mucosa to protect it from various exogenous intraluminal substances with detergent properties. Acid-peptic attack in patients with GERD leads to alteration of the expression of some tight junction proteins in epithelial cells of the esophageal mucosa. The latter leads to increased mucosal permeability, which facilitates the penetration of hydrogen ions and other substances into the submucosal layer, where they stimulate the terminals of nerve fibers playing a role in the induction and persistence of the symptoms of the disease. The above evidence brought up to date the effectiveness study of the cytoprotective drugs with tropism to the gastrointestinal tract, as part of the combination therapy of GERD.

The review article presents current data on functional disorders of the biliary system, taking into account the latest recommendations of experts of the Rome Foundation (Rome Criteria IV, 2016) and the Russian Gastroenterological Association (specialized clinical recommendations, 2018). According to modern concepts, biliary dysfunction is a group of functional disorders of the biliary system caused by motor disorders and increased visceral sensitivity. According to the literature data, the prevalence of functional disorders of GB and OS is 10-15%, and violation of OS function is revealed in 30-40% of patients who underwent cholecystectomy (CE). The presence of biliary pain is an obligatory condition in the diagnosis of functional disorders of GB and OS. Bilirubin and serum transaminases (AST, ALT) levels may increase in biochemical blood analysis in patients with functional OS disorder of biliary type, and pancreatic amylase and lipase in case of functional OS disorder of pancreatic type. Ultrasound examination of abdominal organs is considered to be the priority among instrumental methods. This technique allows to exclude organic lesions of both the GB and visualized ducts, and adjacent organs (GSD, biliary tract, liver and pancreas neoplasms). Magnetic resonance cholangiopancreatography (MRCP) is used as a clarifying method, which allows to visualize the state of biliary ducts throughout. Ultrasonic cholecystography is used to assess the contractile activity of the GB. When duct dilation is detected and/or when liver/pancreatic enzyme levels are elevated in the absence of changes according to MRCP data, it is reasonable to perform an endoscopic ultrasound examination. According to the latest recommendations of the Russian Gastroenterological Association (2018), the foundation of pharmacotherapy for this group of diseases are antispasmodics and ursodeoxycholic acid (UDCA).

Aim. This paper presents guidelines on the diagnostics and treatment of eosinophilic esophagitis, which can be used by practitioners in their everyday practice.Summary. Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized by the symptoms of esophageal dysfunction and a pronounced eosinophilic infiltration of the esophageal mucosa. The EoE diagnostics is based on the clinical manifestations of the disease (dysphagia, food impaction, chest pain regardless of swallowing), as well as on the combination of endoscopic and histological signs. The diagnostic criterion is the eosinophilic infiltration of the esophageal mucosa with an eosinophil density of ≥ 15 per high power field (×400) in at least one of the biopsy specimens (about 60 eosinophils in 1 mm2). Total IgE levels, peripheral blood eosinophilia and skin allergy tests are considered to be additional diagnostic means. Several approaches are used for the treatment of EoE, including proton pump inhibitors (PPIs) and topical glucocorticosteroids (GCS), as well as elimination diets. The choice of therapy should be individualized, with the mandatory assessment of the treatment efficacy after 6–12 weeks using esophagogastroduodenoscopy with biopsy sampling. Endoscopic dilatation should be considered in patients suffering from severe dysphagia due to esophagus stricture.Conclusion. Increased incidence of EoE predominantly among children and young people, as well as its chronic character requiring long-term maintenance therapy, make EoE a significant issue to the practice of gastroenterology.

Aim of investigation. To study association interleukin-1 (IL-1) gene (rs16944), interleukin-6 (IL-6) gene (rs1800795), interleukin-10 (IL-10) gene (rs1800896) polymorphisms with development of acute pancreatitis (AP) in the Russian population. Material and methods. Whole blood samples were received from 297 AP patients and 238 healthy controls. Genotyping of IL-1 gene (rs16944) polymorphisms, IL-6 gene (rs1800795), IL-10 gene (rs1800896) was carried out by polymerase chain reaction with allele discrimination by TaqMan-probes. Results. The genetic polymorphism combination 511СТ×174GC of IL-1 and IL-6 genes was associated to high risk of AP development (OR=2.25, 95%-CI 1.45-3.49; p=0.0018). According to stratification analysis smoking patients with 511CT genotype had higher AP risk, then the patients with other genotypes (OR=2.22, 95%-CI 1.3-3.79; p=0.003). Paired combination of genotypes to disease risk analysis demonstrated that at 511СT×174GС genotype combination the AP risk is highest at alcohol abuse history for over 10 years (OR=2.88, 95%-CI 1.59-5.23; p=0.0004). Conclusion. Interleukin genetic polymorphism investigation may be useful at assessment of cytokine status in AP patients to predict the outcomes and to develop the personalized approach to treatment and prophylaxis.

Aim of review. To present the modern concept of functional gastrointestinal diseases (FGID) and to analyze the basic clinically relevant changes made in Rome IV criteria (2016) in comparison to the previous edition. Summary. According to the due definition that was proposed by the Rome IV advisory council, FGID are the brain-gut axis interaction disorders. It was proposed to exclude the term «functional» from the definition. The new nosological entities with known causative factor (opioid-induced gastrointestinal hyperalgesia, opioidinduced constipation, cannabinoid induced hyperemesis syndrome), hypersensitive reflux syndrome, nausea and vomiting syndrome (that encompasses previously separate nosological forms: chronic idiopathic nausea and functional vomiting) were added to the new version of the classification. In the new edition of Rome criteria the management approach to patients with sphincter of Oddi dysfunction is specified, along with diagnostic criteria of functional dyspepsia and irritable bowel syndrome. Conclusion. The classification of FGID is revised in updated Rome criteria, diagnostic features of several nosological entities were specified.

The article provides a systematic review of modern literary data on the basics of gastric acid secretion. It describes the ionic transport systems of the parietal cell involved in the hydrochloric acid synthesis. The molecular structure of H +, K + -ATPhase (proton pump) is discussed. The article characterizes various ways of regulation of gastric acid secretion (neural, hormonal and paracrine) and intracellular signal transduction processes of a parietal cell.

Purpose: to carry out pharmacoeconomic modeling for an early economic evaluation of the generic pegylated liposomal doxorubicin (PLD) drug.Materials and methods: a Markov model and Decision tree model were developed to simulate and to compare the costs and effects of new generic PLD versus doxorubicin. Using the threshold criteria for economic value (willingness to pay threshold (WTP) for Russia), we determine value-based pricing for new generic PLD.Results: pharmacoeconomic modeling can be used for an early economic evaluation of new medicines to determine value-based pricing for new pharmaceuticals and its financial impact on Russian health care system.

The publication examines the doctrinal principles on the forms of direct democracy and the existing problems regarding the exercise of power by the people. Based on the historical perspective of the analysis of European legislation in this area, ways of improving the Basic Law of Ukraine are proposed. It was established that, despite the insignificant and contradictory support of the thinkers of the ancient world and the Middle Ages regarding the need to recognize the right of the people to cancel the legislative acts of the representative bodies of the state, this idea received significant development precisely in the era of the New Age, when the proclamation of people's rule was accompanied by the establishment of parliamentarism, the authority and trust of which is constantly fell among the common people. It has been proven that the essence of such judgments was that modern democracy is based on the idea of popular sovereignty, that is, on the need to create such a system of state-legal relations that would ensure the primacy of law in all spheres of social relations and enable the people to exercise their right to be the source and basis state power precisely because of various forms of political participation in the state management of the country, one of which is participation in the exercise of judicial power. It has been determined that the views of thinkers in support of forms of people's power boil down to the fact that the right to limit state power is recognized as an inalienable, natural human right that belongs to them from birth. Therefore, people's power itself is one of the means related to the system of checks and balances, and therefore helps not only the normal functioning of state authorities by exercising control over the actions of their representatives, but also the direct exercise of power by the people, which thereby helps to ensure the principle of popular sovereignty. It has been established that today the practice of applying forms of direct democracy is significantly ahead of theoretical developments in this area. This very issue is voluminous, and at the same time there are a large number of gaps and contradictions in the possibility of constitutional consolidation of new forms of people's rule. [ABSTRACT FROM AUTHOR]

Summary: Antimicrobial resistance poses a serious threat to global public health. The COVID-19 pandemic underscored the need to monitor the dissemination of antimicrobial resistance genes and understand the mechanisms driving this process. In this study, we analyzed changes to the oropharyngeal and fecal resistomes of patients with COVID-19 undergoing therapy in a hospital setting. A targeted sequencing panel of 4,937 resistance genes was used to comprehensively characterize resistomes. Our results demonstrated that the oropharyngeal resistome is homogeneous, showing low variability over time. In contrast, fecal samples clustered into two distinct resistotypes that were only partially related to enterotypes. Approximately half of the patients changed their resistotype within a week of therapy, with the majority transitioning to a less diverse and ermB-dominated resistotype 2. Common macrolide resistance genes were identified in over 80% of both oropharyngeal and fecal samples, likely originating from streptococci. Our findings suggest that the fecal resistome is a dynamic system that can exist in certain “states” and is capable of transitioning from one state to another. To date, this is the first study to comprehensively describe the oropharyngeal resistome and its variability over time, and one of the first studies to demonstrate the temporal dynamics of the fecal resistotypes.

Aim. To study overall drug resistance genes (resistome) in the human gut microbiome and the changes in these genes during COVID-19 in-hospital therapy. Materials and methods. A single-center retrospective cohort study was conducted. Only cases with laboratory-confirmed SARS-CoV-2 RNA using polymerase chain reaction in oro-/nasopharyngeal swab samples were subject to analysis. The patients with a documented history of or current comorbidities of the hepatobiliary system, malignant neoplasms of any localization, systemic and autoimmune diseases, as well as pregnant women were excluded. Feces were collected from all study subjects for subsequent metagenomic sequencing. The final cohort was divided into two groups depending on the disease severity: mild (group 1) and severe (group 2). Within group 2, five subgroups were formed, depending on the use of antibacterial drugs (ABD): group 2A (receiving ABD), group 2AC (receiving ABD before hospitalization), group 2AD (receiving ABD during hospitalization), group 2AE (receiving ABD during and before hospitalization), group 2B (not receiving ABD). Results. The median number of antibiotic resistance (ABR) genes (cumulative at all time points) was significantly higher in the group of patients treated with ABD: 81.0 (95% CI 73.8–84.5) vs. 51.0 (95% CI 31.1–68.4). In the group of patients treated with ABD (2A), the average number of multidrug resistance genes (efflux systems) was significantly higher than in controls (group 2B): 47.0 (95% CI 46.0–51.2) vs. 21.5 (95% CI 7.0–43.9). Patients with severe coronavirus infection tended to have a higher median number of ABR genes but without statistical significance. Patients in the severe COVID-19 group who did not receive ABD before and during hospitalization also had more resistance genes than the patients in the comparison group. Conclusion. This study demonstrated that fewer ABR genes were identified in the group with a milder disease than in the group with a more severe disease associated with more ABR genes, with the following five being the most common: SULI, MSRC, ACRE, EFMA, SAT.

Acotiamide is a prokinetic with a novel mechanism of action an antagonist of muscarinic M1 and M2 receptors and an acetylcholinesterase inhibitor. Acetylcholine is the central mediator of the tone of the muscular components of the gastrointestinal tract, increasing its motor activity. Blockade of presynaptic M1 and M2 receptors neutralizes the inhibitory effect of the feedback mechanism on the acetylcholine synthesis, while inhibition of acetylcholinesterase in the synaptic cleft reduces the acetylcholine degradation. Currently, the clinical efficacy of acotiamide in the population of patients with functional dyspepsia is demonstrated in more than 10 clinical studies in different regions of the world, demonstrating a reduction of the symptoms of the disease during treatment with this agent and an improvement in the quality of life of patients. In addition, the combination of acotiamide with proton pump inhibitors optimizes the management of patients with gastroesophageal reflux disease.

IntroductionThe new coronavirus disease, COVID-19, poses complex challenges exacerbated by several factors, with respiratory tissue lesions being notably significant among them. Consequently, there is a pressing need to identify informative biological markers that can indicate the severity of the disease. Several studies have highlighted the involvement of proteins such as APOA1, XPNPEP2, ORP150, CUBN, HCII, and CREB3L3 in these respiratory tissue lesions. However, there is a lack of information regarding antibodies to these proteins in the human body, which could potentially serve as valuable diagnostic markers for COVID-19. Simultaneously, it is relevant to select biological fluids that can be obtained without invasive procedures. Urine is one such fluid, but its effect on clinical laboratory analysis is not yet fully understood due to lack of study on its composition.MethodsMethods used in this study are as follows: total serum protein analysis; ELISA on moderate and severe COVID-19 patients’ serum and urine; bioinformatic methods: ROC analysis, PCA, SVM.Results and discussionThe levels of antiAPOA1, antiXPNPEP2, antiORP150, antiCUBN, antiHCII, and antiCREB3L3 exhibit gradual fluctuations ranging from moderate to severe in both the serum and urine of COVID-19 patients. However, the diagnostic value of individual anti-protein antibodies is low, in both blood serum and urine. On the contrary, joint detection of these antibodies in patients’ serum significantly increases the diagnostic value as demonstrated by the results of principal component analysis (PCA) and support vector machine (SVM). The non-linear regression model achieved an accuracy of 0.833. Furthermore, PCA aided in identifying serum protein markers that have the greatest impact on patient group discrimination. The study revealed that serum serves as a superior analyte for describing protein quantification due to its consistent composition and lack of organic salts and drug residues, which can otherwise affect protein stability.

Aim. To evaluate the efficacy of Saccharomyces boulardii (S. boulardii) CNCM I-745 probiotic drug in preventing and treating diarrhea in hospitalized patients with COVID-19. Materials and methods. A prospective comparative study was conducted in two parallel groups. The study included males and females aged 18 to 60 with the following diagnosis confirmed by polymerase chain reaction: U07.2 Coronavirus infection COVID-19, caused by SARS-CoV-2 virus (grade 13 pneumonia according to CT scan). All patients received antibiotic therapy. The patients were subdivided into two equal groups (n=60) depending on the administration of S. boulardii CNCM I-745 probiotic drug in addition to standard treatment. The probiotic was prescribed by the attending physician; the dose was 2 capsules per day (500 mg/day) 30 min before the meal for 10 days. All patients were monitored for main clinical, laboratory, and instrumental parameters during the study. In addition, the symptom of diarrhea (stool with a frequency of more than 3 times a day of type 6 and 7 according to the Bristol stool scale), including its frequency, duration, and the number of bowel movements of loose stool per day were precisely evaluated in both groups. Results. In the overall patient pool, diarrhea was reported in 21.7% of in-patients during the observation period (95% confidence interval [CI] 14.229.1) with a mean duration of 4.6154 days (95% CI 3.7910-5.4398). The incidence of diarrhea in group 1 was 13.3% (95% CI 4.522.2), and in group 2, it was 30.0% (95% CI 18.141.9). Relative risk showed that the use of the S. boulardii CNCM I-745 probiotic drug leads to a significant reduction in the risk of diarrhea in hospitalized patients with COVID-19 infection receiving antibiotic therapy (odds ratio [OR] 0.3590, 95% CI 0.14210.9069; p=0.0303). In group 1, the duration of diarrhea was 3.1250 days (95% CI 2.58923.6608) versus 5.2778 days (95% CI 4.22906.3265) in group 2, p=0.0112. The mean daily frequency of loose stools in patients with diarrhea in group 1 was 3.2500 (95% CI 2.65883.8412) versus 4.3889 (95% CI 3.72525.0525) in group 2, p=0.0272. The secondary endpoint, duration of hospital stay, was also significantly shorter in group 1 patients 11.6833 days (95% CI 11.204212.1625) versus 12.7333 days (95% CI 12.135713.3309) in group 2, p=0.0120. Conclusion. The present prospective comparative study demonstrated that adding S. boulardii CNCM I-745 probiotic drug into the standard treatment regimen of patients with new coronavirus infection COVID-19 receiving antibiotic therapy helps reduce the incidence of diarrhea and its severity during hospitalization, as well as the duration of hospital stay.

The author explores the stage of development of Ukrainian institute of advocacy in 1917-1992, which was given the name of «Soviet» («post-revolutionary») period in the legal literature. The conclusion is that this period is characterized by a significant number of events which influenced the development of the national Institute of the Bar Association. The article notes that this period features the first reference to terms «lawyer» and «advocacy» in the legal acts, and the first cases to provide a legal definition of «advocacy». It is pointed out that during the period the legal profession was officially recognized by a constitutional body for the first time.