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FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology

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ORIGINAL ARTICLES

218
Abstract

Objective: to conduct clinical and economic analysis of nosocomial pneumonia antibacterial therapy in a multidisciplinary hospital in Moscow.

Material and methods. The medical records of patients admitted to Yudin City Clinical Hospital in Moscow in 2019–2021 were analyzed retrospectively. Pharmacoepidemiological analysis included the structure of prescriptions of antibacterial drugs (ABDs), features of empirical and etiotropic therapy, duration of using ABDa and other parameters. In total, 110 cases of severe nosocomial pneumonia caused by ESKAPE pathogens were selected for analysis. Direct medical costs and cost-effectiveness coefficients were calculated based on real world data.

Results. It was established that nosocomial pneumonia is the most common complication among hospitalized patients in the intensive care unit (ICU). The etiology of nosocomial pneumonia was mostly presented by K. pneumoniae, A. Baumanii, and P. aeruginosa. The administered ABDs included 31 international nonproprietary names of the group J01 Systemic antibacterial drugs. The direct medical costs of empirical antibacterial therapy averaged for 9367 rubles (2118 rubles [1462; 3525]). Comparative cost-effectiveness analysis was performed based on surrogate and endpoints. It was found that direct medical costs associated with ESKAPE pathogens spend about 70% of the budget of established tariff to pay for medical care of the compulsory health insurance program for the patient's stay in the ICU.

Conclusion. Antibacterial therapy costs for nosocomial pneumonia significantly increase the total cost of a patient's hospital stay. Сlinical and economic assessment of drug use help optimize therapy costs and develop a hospital formulary of antimicrobial drugs.

960
Abstract

Objective: to investigate the antitumor effects of various forms of vitamin B12 in combination with various synergistic vitamins and evaluate the prospects for clinical applications.

Material and methods. Cell lines BT-474 (breast ductal carcinoma) and A549 (lung carcinoma) were used as an in vitro cell model, and transplantable epidermoid Lewis lung carcinoma (LLC) was used as an in vivo animal tumor model. Animal studies of LLC were carried out on 25 male F1 hybrid mice (age 2.5–3 months, body weight 23–26 g). In silico research was conducted as a systematic computer analysis of 9,326 scientific sources.

Results. In vitro studies on cultures of two human tumor cell lines (BT-474 and A549) confirmed the cytotoxic effect of vitamin B12 (aquacobalamin). It has been shown that vitamin B12 has weak cytotoxic properties in the concentration range of 3.125–200 μg/L (IC50>200 nM), and its hydrophobic derivative (heptamethyl cyanoquacobyric acid ester) significantly reduces the survival of tumor lines. BT-474 and A549 cells at high concentrations (100–200 µg/l, IC50~100 nM). Experimental animals with an in vivo LLС model easily tolerated a drug based on vitamin B12. Exposure to the drug up to the 21st day of LLС development was accompanied by an increasing tendency to inhibit tumor growth by 10–20% (р=0.059). The results of a systematic in silico review of the literature show that clinical data confirmed the significant antitumor effect of vitamin B12.

Conclusion. The cellular model indicated the antitumor properties of vitamin B12 and its hydrophobic derivative. With subchronic intragastric administration of B12 to tumor-bearing animals, a steady tendency to inhibit the LLС growth was observed. Analysis of clinical data confirmed the feasibility of the antitumor use of vitamin B12 individually and in combination with synergistic vitamins.

112
Abstract

Objective: To identify potential predictors of CKD based on the analysis of relationships between somatometric (including bioimpedance), biochemical and clinical parameters of patients with chronic kidney disease (CKD).

Material and methods. The values of 58 parameters describing the condition of 357 participants were collected: 128 patients with CKD and 229 participants in the control group (without kidney pathology). Demographic, anthropometric, anamnestic data (a total of 19 diagnoses according to the International Classification of Diseases, 10th revision), bioimpedance values, results of general and biochemical blood tests (a total of 19 parameters), and diet parameters according to the CINDI questionnaire were studied. New mathematical approaches were used to establish intervals of informative values of numerical parameters, find metric concentrations in the space of biomedical research parameters and construct metric maps.

Results. In the CPP group, there was a predominance of older patients (mean age 54.1±13.1 years) compared to the control group (48.78±9.75 years), as well as overweight people (82.18±19 versus 74.7±17.45 kg). Patients with CPP had impaired adipose tissue metabolism, decreased active and reactive resistance of bioimpedance, high systolic blood pressure, and multiple organ pathology.

Conclusion. The analysis of the cluster of interactions of indicators allowed us to formulate promising areas for further research: it is necessary to study in more detail the informativeness and "strength" of CPP predictors, conduct a comprehensive assessment of the effectiveness of therapy, identify differences between subgroups of patients with different nosologies and stages of CPP, evaluate the effectiveness of various approaches to therapy, as well as the role of physical activity and micronutrient supply. 

93
Abstract

Background. Gastroenterological side effects (esophageal, gastric, and intestinal erosions) with the use of drugs from the group of nonsteroidal anti-inflammatory drugs (NSAIDs) dictate the need to explore new candidate molecules with reduced ulcerogenic effects. The zinc-containing molecule-candidate рilim-1 may exert an anti-inflammatory effect and possibly improve the regenerative properties of the gastric mucosa.

Objective: To explore the anti-inflammatory, ulcerogenic, analgentic and antivitamin effects of the рilim-1 molecule using cheomreactomics techniques.

Material and methods. The chemoreactome assessment of the pharmacological properties of рilim-1 and zinc derivatives of known NSAIDs (ketorolac, diclofenac and nimesulide) was carried out using the methods of chemoinformation analysis of molecules developed at the scientific school of Academician Yu.I. Zhuravlev.

Results. Pilim-1 has a distinct anti-inflammatory effect realized through modulation of cytokine activity, prostaglandin and leukotriene metabolism. The most important feature of the рilim-1 molecule is its neutrality with respect to vitamin metabolism, with comparability in potency of anti-inflammatory action to zinc-containing NSAID derivatives. The analgesic effect of рilim-1 is based on the inhibition of kinine and histamine receptors. The nociceptin receptor ORL1 can be inhibited by pilim-1 more effectively (IC50 198–214 nM) than zinc-NSAIDs (IC50 361–1093 nM). In the phenylquinone analgesia test in rats, pilim-1 demonstrated a slightly higher percentage of analgesia (44%; zinc-NSAIDs: 21–43%). The incidence of gastric ulcers at a dose of 100 mg/kg orally was estimated at 35% (other molecules - 75%). Compared with other zinc-derived NSAIDs, рilim-1 minimally interferes with vitamin and mineral metabolism.

Conclusion. Chemoreactome analysis of рilim-1 indicates promising prospects for its application as an anti-inflammatory drug.

51
Abstract

Objective: Analysis of competition and the level of dominance in the cosmetics market within pharmacy sales, identification of trends in three key segments: selective, mass market and active (medicinal) cosmetics.

Material and methods. The materials used were the annual reports on the Russian pharmaceutical market of the DSM Group company. The Linda and Herfindahl–Hirschman indices, as well as the strength/variety (SV) matrix, including concentration coefficients and the modified Hall–Tideman index, were used as analysis tools. The level of concentration in the market was assessed, the presence of dominant groups was determined. The paper includes an analysis of the market structure and the dynamics of the rating of major players.

Results. In the Russian cosmetics market, both similarities and significant differences between segments are observed within pharmacy sales. In the selective cosmetics segment, where foreign players dominate (except for domestic Librederm®), a transformation has occurred from high brand differentiation to a state close to a natural oligopoly. This trend is accompanied by a strengthening positions of Russian brands after 2014. In contrast to the selective cosmetics segment, the mass-market cosmetics market, characterized by high dynamism and competition, demonstrates low concentration and more blurred leadership positions, while the ambiguity of the dynamics of international players after 2014 is accompanied by the growth of domestic brands, for example, Moe Solnyshko®, which indicates the influence of geopolitics not only on the selective cosmetics segment, but also on mass-market cosmetics. Active (medicinal) cosmetics, where Russian manufacturers are market leaders, show relative stability of individual brands, such as Alerana®, against the background of high market volatility. The absence of a dominant group confirms the high level of competition.

Conclusion. There are differences in the development of cosmetic segments within pharmacy sales: the most concentrated is the selective cosmetics segment, in contrast to the mass market and active (medicinal) cosmetics segments, which are characterized by a high level of competition. The significance of domestic brands increased after the introduction of sanctions.

535
Abstract

Background. Omega-3 polyunsaturated fatty acids (ω3-PUFA) are an important factor in somatic and reproductive health. Micronutrient and pharmaceutical preparations based on ω3-PUFA are widely used for cardioprotection (prevention of atherosclerosis, endothelial dysfunction, chronic inflammation, excessive thrombus formation), support of reproductive function during pregnancy and improvement of neurological development of children. The effectiveness of ω3-PUFA preparations is determined by their fatty acid composition: the amounts of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and other types of unsaturated and saturated fatty acids.

Objective: To analyze the fatty acid composition of micronutrient and pharmaceutical preparations of ω3-PUFA.

Material and methods. The fatty acid composition of 16 ω3-PUFA preparations was studied. The method of quantitative chromatographic determination of more than 50 fatty acids, their derivatives and other compounds was used.

Results. Previously obtained pharmacomarkers of fatty acid composition were confirmed and new ones were obtained, allowing with high reliability to separate drugs with a high degree of standardization for ω3-PUFA (Omacor®, NFO Omega-3 Premium®, NFO® Omega-3 Strong DHA, NFO® Omega-3 Ultima, etc.) from less standardized drugs (Fish oil-Teva®, Omeganol®, etc.). New, more effective criteria for assessing the quality of the fatty acid composition of ω3-PUFA drugs were proposed. In particular, the feasibility of the criteria "ω11<3%", "EPA+DHA>55%" corresponds to more standardized drugs with better purification quality. The usefulness of our proposed "standardization coefficient" of preparations, assessing the compliance of measured ω3-PUFA levels with the content declared by the manufacturer, has been confirmed.

Conclusion. The feasibility of the criteria “ω11<3%”, “EPA+DHA>55%” corresponds to more standardized preparations. Preparations with a very high degree of standardization for ω3-PUFA (NFO® Omega-3 Ultima, NFO® Omega-3 Strong DHA, Omacor®) have been identified. The identification of highly standardized preparations allows physicians and patients to make informed choices when considering ω3-PUFA supplementation. 

REVIEW ARTICLES

236
Abstract

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.



ISSN 2070-4909 (Print)
ISSN 2070-4933 (Online)