Effects of CYP2C19 genetic polymorphism on the steady-state concentration of citalopram in patients with major depressive disorder.

Citalopram is commonly prescribed to patients suffering from major depressive disorder. Some of them do not respond adequately to therapy with citalopram, while many of them experience type A adverse drug reactions. Current research revealed that CYP2C19 isoenzyme is involved in the biotransformation of citalopram. The objective of our study was to investigate the impact of 681G>A polymorphism of the CYP2C19 gene on the efficacy, safety and the concentration/dose indicator of citalopram. Our study enrolled 130 patients with major depressive disorder and comorbid alcohol use disorder (average age-38.7 ± 14.1 years). Therapy regimen included citalopram in an average daily dose of 31.1 ± 14.4 mg per week. Therapy efficacy and safety were evaluated using the international psychometric scales. For genotyping, we performed the real-time polymerase chain reaction. Our findings revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMD scores at the end of the treatment course): (GG) 8.0 [8.0; 9.0] and (GA) 10.0 [9.0; 11.0], p < 0.001. In the safety profile (the UKU scores), the statistical significance was also obtained: (GG) 3.0 [3.0; 4.0] and (GA) 5.0 [4.0; 5.0], p < 0.001. We revealed a statistical significance for concentration/dose indicator of citalopram in patients with different genotypes: (GG) 2.543 [1.659; 4.239] and (GA) 4.196 [2.643; 5.753], p < 0.001). The effect of CYP2C19 genetic polymorphism on the efficacy and safety profiles of citalopram was demonstrated in a group of 130 patients with major depressive disorder.

[Socio-economic aspects of neurogenic dysfunctions in urology].

AIM: to evaluate the medico-economic significance of neurogenic lower urinary tract dysfunction (NLUTD) in the Russian Federation, to calculate the economic burden of NLUTD in patients with targeted entities and to prepare suggestions for improving the methods of payment for the provision of medical care to patients with NLUTD in inpatient practice. MATERIALS AND METHODS: an analysis of the literature and an expert assessment of the prevalence of NLUTD in the Russian Federation were performed. Due to the various etiology of NLUTD, the following entities were considered: craniocerebral trauma, acute stroke, multiple sclerosis, spinal cord injury (hereinafter referred to as targeted entities), characterized by the highest rate of NLUTD and high social significance (damage to the working-age population): traumatic brain injury, acute stroke, multiple sclerosis, spinal cord injury. The calculations of the economic burden of NLUTD and its main complications (stage 5 of chronic kidney disease (CKD), urinary tract infection) in the Russian Federation (using mainly the normative method) were carried out, based on national statistics, regulatory legal acts and expert assessments of healthcare specialists. Proposals have been prepared for improving the reimbursement (tariffs of the KSG) for payment of NLUTD in the inpatient practice. RESULTS: according to the study, the number of patients with NLUTD due to the group of targeted entities is estimated at 910 000. The economic burden (excluding indirect and unaccounted costs) of the NLUTD is 33.3 billion rubles per year. The burden associated with secondary complications (stage 5 CKD, urogenital infection) due to ineffective diagnosis and treatment of NLUTD is 51.6 billion rubles. The total costs on the NLUTD is estimated at 84.9 billion rubles. Direct costs, calculated by the normative method based on the analysis of standards of medical care per patient are 36,546 rubles per year. Provision of medical care to patients with NLUTD in accordance with federal guarantees within the framework of the compulsory medical insurance is provided in accordance with the tariffs of KSG st30.005 (profile "urology"). The KSG tariff for 2019 (taking into account the established standards of financial costs for one case of hospitalization in the inpatient department and the established cost-intensity coefficients (CZ) established by the CG is 21,495.07 rubles, which is 58% of the minimum need, excluding the cost of treatment of complications, according to the normative method of calculation. The real estimate of the tariff for the payment of treatment of NLUTD in the constituent entities of the Russian Federation is 35-38% of the minimum need, excluding the cost of treatment of complications, according to the normative method of calculation. The real estimate of the costs for the treatment of NLUTD in regions is 35-38% of the minimum need, excluding the cost of treatment of complications, according to the normative method of calculation. To provide effective specialized urological care in the framework of compulsory medical insurance at the rates of the CSG for neuro-urological care (st30.005), expert calculations of the actual cost of NLUTD therapy were made. The proposed average cost of the CSG and the values of the cost intensity factors: CSG (min) st30.005.1 - 39,936 rubles, CZ - 1.65; CSG (max) st30.005.2 - 68,531 rubles, CZ - 2.75. The weighted average savings while expanding the availability of complex neuro-urological care for patients with NLUTD in accordance with the proposed payment rates is 9.4 billion rubles per year. CONCLUSIONS: Evaluation of the prevalence and burden of NLUTD showed the high medical and economic significance of NLUTD in the Russian Federation. The results of the study indicate a significant discrepancy between the requirements and the real costs within federal guarantees for the organization of medical care for patients with NLUTD. To provide effective specialized urological care in the compulsory medical insurance at the rates of CSG for neuro-urological care, it is necessary to increase funding, through the correction at the federal level of the cost-intensity coefficient from 1.65 to 2.75 for the CSG st30.005, which will ensure the increase in the cost for a case of treatment in inpatient department in form 39 936 to 68 531 rubles. The weighted average savings while expanding the availability of complex neuro-urological care for patients with NLUTD in accordance with the proposed payment rates is 9.4 billion rubles per year.

[ECONOMIC BURDEN AND CURRENT STATUS OF THE DRUG SUPPLY MANAGEMENT FOR IMMUNE INFLAMMATORY DISEASES (BY EXAMPLE OF ULCERATIVE COLITIS AND CROHN'S DISEASE)].

AIM: to estimate the quality and availability of medical care for patients with ulcerative colitis (UC) and Crohn's disease (CD), to assess the impact of the economic burden of these diseases on the healthcare budget of Russia and to systematize the main problems in the organization of medical care and drug supply for patients with inflammatory bowel diseases (IBD). Regional IBD databases (2016-2018), official statistical databases, costs of treatment and results of expert interviews with specialists in IBD were used in the study. The analyzed databases showed 104,668 patients with UC in Russia in 2018 (prevalence rate 71 per 100,000 people) and 66,647 patients with CD (prevalence rate of 45 per 100,000 people). The economic burden including agents for biologic therapy (ABT) for the UC was 39.54 billion rubles a year (495 rubles per capita), and CD - 32.98 billion rubles a year (378 rubles per capita). It requires an additional 9.87 billion rubles annually for UC and 9.20 billion rubles annually for CD patients to provide the complete supply with ABT. The annual burden of IBD is 72.52 billion rubles, which is comparable to the costs of other socially significant diseases, including malignant tumors. It shows the high social and economic value of IBD for the country. The main problems of medical care and drug supply for IBD patients are the mismatch of official statistical data and real IBD prevalence in Russia due to absence of comprehensive register and the insufficient supply with ABT due to limited funding. A federal center for IBD should be founded for better quality of registration, for the precise monitoring and for the active management of personal drug supply.

[Clinical, neurophysiological and hemodynamic effects of a new nondepolarizing myorelaxant mivacurium in heart surgery patients]. / Klinicheskie, neirofiziologicheskie i gemodinamicheskie éffekty novogo nedepoliarizuiushchego miorelaksanta mivakuriuma u kardiokhirurgicheskikh bol'nykh.

Thirty patients aged 23 to 65 years with ASA class III operated on the heart under total intravenous anesthesia were examined after the Good Clinical Practice protocol. Mivacurium in bolus dose of 0.2 mg/kg was injected for intubation of the trachea; neuromuscular blocking (NMB) was maintained by a repeated injection of the drug in a dose of 0.15 mg/kg, after which it was infused at a rate of 1 to 10 micrograms/kg/min. Accelerometric control of neuromuscular conduction was carried out by the Organon (Belgium) TOF-Guard device. Central and peripheral hemodynamics was monitored. Side effects of the drug were recorded. Bolus injection of mivacurium in a dose of 0.2 mg/kg caused T1 suppression (90%) after 2.6 +/- 0.7 min. Maximal (97.7 +/- 4.5%) suppression was observed after 4.17 +/- 2.5 min. The conditions of intubation of the trachea after 3.9 +/- 1.8 min in the presence of 78 to 100% T1 suppression (97.7 +/- 4.5%) were considered excellent or good in 96.6% of cases. Clinically and neurophysiologically sufficient muscle relaxation after the first injection of the drug persisted for 27.7 +/- 7.3 min. Minimal rate of infusion for maintaining the NMB at 95 +/- 4% level of T1 suppression was 6.3 +/- 1.7 micrograms/kg/min. Bolus injection of mivacurium in a dose of 0.2 mg/kg for 60 sec involved a 1-3-min drop of the mean arterial pressure by 10.5% and a 10.3% decrease of heart rate. Repeated bolus injection of the drug in a dose of 0.15 mg/kg and its infusion did not change the peripheral and central hemodynamics. The most typical side effect of the drug in a dose of 0.2 mg/kg is short-term reversible reddening of the skin of the face and neck, observed in 20% of patients. The results permit us to consider mivacurium as an effective, safe, and controllable agent, which can be used in cardiosurgical patients.