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Background. Achieving a pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) is a predictive factor for improving disease free and overall survival. In triple negative (TN) and HER2-positive breast cancer (BC), the pCR rate exceeds 60 %. Patients with TN and HER2-positive BC who demonstrate an excellent response to NST are like­ly ideal candidates for downsizing surgery. The condition for reducing the volume of surgical intervention is a reliable determination of pathologic complete response using instrumental imaging and biopsy methods.Aim. To further assess the accuracy of post-NST image-guided biopsy to predict pCR.Materials and methods. Sixty one patients with T1-3N0-3 triple negative or HER2-positive BC receiving NST in the Department of Breast Tumors of the NMRC of Oncology named after N.N. Petrov in the period from 2017 to 2019 were enrolled in this single-center retrospective trial. Patients underwent ultrasound-guided core-biopsy of the initial breast tumor region before surgery. Findings were compared with findings on pathologic evaluation of surgical specimens to determine the performance of biopsy in predicting pCR after NST.Results. After neoadjuvant systemic therapy, clinical partial response (cPR) was diagnosed in 47 (77 %) patients, clinical complete response (cCR) in 14 (23 %) patients. pCR in the core-biopsy tissue and surgical material was achieved in 46 (75.4 %) and 37 (60.7 %), respectively. Performance of image-guided core-biopsy: sensitivity 100 % (95 % confldence interval (CI) 90.51-100), specificity 62.5 % (95 % CI 40.59-81.20), false-negative rate (FNR) 0 %, positive-pre­dictive value (PPV) 75.00 % (95 % CI 59.46-85.99), negative predictive value (NPV) 100.00 %.Conclusion. This retrospective trial showed that ultrasound-guided core biopsies are accurate enough to identify breast pCR in patients with triple-negative or HER2-positive BC with good response after NST (FNR 0 %). Based on these results, a prospective clinical trial has commenced in which breast surgery is omitted in patients with a breast pCR after NST according to image-guided biopsy.

Aim. To assess the economic efficacy of a fixed combination tiotropium bromide+olodaterol (T+O) in comparison with other medications, included in the Vital and Essential Drugs List (VEDL), for the maintenance triple therapy of chronic obstructive pulmonary disease (COPD).Materials and Methods. A Markov model was used for the estimation of direct medical costs associated with different medications. Costminimization and budget impact analyses were performed.Results. The drug costs for T+O were the lowest among all compared treatment strategies. The cost savings in favor of T+O were 24.82% [15.86–29.95%]. The application of T+O strategy in 4,101 target patients led to a decrease in the total direct medical costs under the state programs of guarantees of free medical care by 13.13% in 3 years, which will make T+O therapy available to 643 more patients in the first year and 1,624 patients in three years.Conclusion. A fixed combination T+O is a preferred efficient option for maintenance triple treatment for patients with COPD in comparison with other drugs from VEDL, because it is associated with lower total costs and equal efficacy.

Purpose. To evaluate the economic and clinical results of the aflibercept and ranibizumab angiogenesis inhibitors in the treat-and-extend regimen in patients with the “wet” form of age-related macular degeneration (wAMD). Materials and methods. We analyzed cost minimization, impact on the budget and “missed opportunities” for the treatment of patients with wAMD using intravitreal injections (IVI) of aflibercept compared to ranibizumab in the “treat-and-extend” regimen (T & E). Costs were calculated with regard to the budget of the system of compulsory health insurance. To calculate the number of IVI, network meta-analysis data (P. Lanzetta, et al., 2019), including a matching-adjusted indirect comparison of aflibercept and ranibizumab in wAMD patients in the T & E regimen, were taken into account. The budget impact analysis involved a cohort of 1,000 wAMD patients. To assess the stability of the results, a one-factor multicomponent sensitivity analysis was used. Results. Network meta-analysis data showed that aflibercept and ranibizumab used in the T & E regimen revealed comparable changes in the maximum corrected visual acuity; however, the use of aflibercept required a significantly lower (by 6 procedures in two years) number of IVI compared to ranibizumab. Analysis of cost minimization showed that the use of aflibercept can reduce costs by 36 % in two years compared to ranibizumab in the T & E regimen. The use of aflibercept in the T & E regimen with wAMD will reduce the cost of compulsory medical insurance by 281 million rubles in two years of therapy per 1,000 patients. The analysis of “missed opportunities” showed that budget savings of the compulsory medical insurance as a result of transferring 1,000 patients from ranibizumab to aflibercept will allow an additional 563 patients to be treated in two years. A sensitivity analysis confirmed the robustness of the study results. Conclusion. Treating wAMD with aflibercept in the T & E regimen saves a significant part of health protection resources compared to using ranibizumab in the same regimen.

Aim: a prognosis of clinical-economic efficacy of the fixed combination of insulin glargine and lixisenatide (Soliqua SoloStar®) in comparison with standard therapy with focus on micro- and macrovascular complications of Diabetes Mellitus type 2 (T2DM) in the real practice.Materials and Methods. Model of Burden of T2DM has been created in Microsoft Excel 2010 program. Direct (costs of medicines, treatment of main T2DM complications — myocardial infarction, stroke, etc.) as well as indirect costs (GPD losses, disability related payments, etc.) were calculated. Complications’ rate was took from Federal Diabetes Register. Influence on Burden of T2DM was tested with the additional model which can calculate expenditures with different drugs including Soliqua SoloStar® usage.Results. Direct medical costs with Soliqua SoloStar® usage were less in compare with insulin glargine 100 UI/ml on 23,5 % per year due to decreasing level of severe hypoglycemia and possible protective effect on complications of T2DM (better control). Total expenditures for Soliqua SoloStar® were less on 2,5 % annually, in the same time insulin glargine led to total cost increase by 18,4 % per year. So, difference between expenditures in case of Soliqua SoloStar® were less on appr 21 % vs insulin glargine 100 UI/ml. Budget saving is expected as 6,78 ml RUR per year / 1 000 patients in case of Soliqua SoloStar® usage.Conclusion. Soliqua SoloStar® has economic benefits due to T2DM complications and severe hypoglycemia reduction risks.

Background. Experimental data suggest that tumor growth depends on angiogenesis. Once the tumor reaches a size of up to a 1 mм in diameter, a further increase in the population of tumor cells requires the growth of new blood vessels. In contrast to benign lesions, a rapid growth of cancer cells results in the formation of pathological vessels of different diameter and chaotic distribution. therefore, determination of the type of vascularization of lesions is an important criterion in the diagnosis of breast cancer (Bc). color Doppler mapping (cDM) is an ultrasound technology that evaluates blood floor through a blood vessel; however, according to data from a variety of literature sources, cDM is not sensitive to slow (week) blood flow as it allows the visualization of only large vessels with a diameter of at least 100 µm. The purpose of the study was to evaluate the diagnostic value of cDM in determining the type of vascularization of malignant and benign breast tumors, as well as to detect their statistically significant Doppler characteristics by comparing with histological findings. material and methods. From 2017 to 2019, a total of 277 women with complaints of breast lump or pain underwent ultrasound examination using cDM. Results. statistically and diagnostically significant us characteristics of benign lesions included the presence of avascular or hypovascular types of blood flow. the most significant characteristic of malignant lesions was the presence of hypervascular mixed blood flow. the diagnostic value of ultrasound B-mode in combination with cDM in differential diagnosis of breast tumors was as follows: 77.6 % sensitivity, 51.7 % specificity and 58.8 %. accuracy. Conclusion. statistically and diagnostically significant signs observed by cDM allow one to use this ultrasound technology in the early diagnosis of breast cancer. However, low diagnostic efficiency of cDM dictate the need to search for new ultrasonic signs.

Objective: to assess the economic outcomes of using anidulafungin (Eraxis®) in comparison with the recommended treatment regimens in adult patients with invasive candidiasis.Materials and methods. The economic impact assessment was carried out using “cost–effectiveness” analysis and “budget impact” analysis. “Cost–effectiveness” and “budget impact” analyses were performed in Microsoft Excel model.Results. An analysis of the effectiveness showed that the use of anidulafungin is characterized by higher survival (79.25 % vs 66.17 % for caspofungin and 60.84 % for mikafungin). The cost of anidulafungin was 377.7 thousand rubles, which is comparable with the course of caspofungin and 61 % lower than the cost of micafungin therapy. “Cost–effectiveness” analysis showed that the use of the anidulafungin in the treatment of invasive candidiasis is pharmacoeconomically effective and has a “cost–effectiveness” ratio comparable to caspofungin in terms of the effectiveness of therapy for 7 days and exceeds it in terms of the cost of preserving the patient»s life by 14.5 %. Compared to micafungin, anidulafungin is both more economical and more effective in terms of preserving the patient's life, reaching an advantage of up to 45 %. An analysis of the impact on the budget showed that with the complete replacement of the currently used treatment regimens in the target population of 11,840 patients with invasive candidiasis with anidulafungin, it is possible to reduce the burden on the budget of the healthcare system to 17 % or 1458.6 million rubles in year. The average savings in the 3‑year study horizon, taking into account the gradual switching of 25, 50 and 75 % of the target patient population, amounted to 1277.9 million rubles per year or 14.4 %. A sensitivity analysis confirmed the results.Conclusion. Based on results, it can be concluded that the use of the drug anidulafungin (Eraxis®) in patients with invasive candidiasis is economically the preferred option compared to the use of current antibiotic therapy regimens.

Aim: to assess the economic outcomes of using ceftazidime + avibactam (compared with the recommended treatments) in adult patients with sepsis caused by carbapenem-resistant enterobacteria.Methods. The economic assessment was made using the cost-effectiveness analysis and budget impact analysis. The cost-effectiveness and budget impact analyses were performed using the Microsoft Excel software.Results. The treatment efficacy analysis showed that patients treated with the fixed-dose combination ceftazidime + avibactam had fewer days spent in the ICU and higher clinical cure rates than patients receiving the reference drug combinations (8 vs 18 days and 75% vs 34.8%, respectively, p=0.031). The cost of treatment with ceftazidime + avibactam amounted to 228.3 thousand rubles, which was lower than the cost of using the alternative treatment regimens by 34.5-229.5 thousand rubles or 13.12-50.14%. According to the cost-effectiveness analysis, the use of ceftazidime + avibactam is pharmacoeconomically effective as it reduces the cost of patient clinical cure case by 61-72% (depending on the treatment regimen used); in addition, the ceftazidime + avibactam allows for managing the hospitalized patient at a cost lower by 76270 thousand rubles or 16-40% than the compared treatment. The median economic benefit from using the fixed dose combination ceftazidime + avibactam is 154 thousand rubles (28% savings compared with the current practice). The budget impact analysis showed that the reduction in the health budget burden would reach 29% or 34.3 million rubles in year. The sensitivity analysis confirmed the above results.Conclusion. Based on the obtained results, we conclude that the ceftazidime + avibactam combination in patients with sepsis caused by carbapenem-resistant bacteria is economically preferable as compared with the current antibiotic therapy regimens.

Aim. To assess the possibility of azilsartan medoxomil to achieve target blood pressure (BP) (less than 130/80 mm Hg), to study angioprotective features and reduction of adipokines levels and inflammatory markers in patients with hypertension and previous therapy with other ARBs.Material and methods. In open observational study with 24 weeks follow-up were included 60 patients with previous therapy (losartan or valsartan or telmisartan).All patients underwent ambulatory BP monitoring, applanation tonometry (determination of the augmentation index and central BP), measurement of the pulse wave velocity, laboratory tests (lipid profile, uric acid, fasting glucose, Homeostasis Model Assessment, homocysteine, leptin, adiponectin, highly sensitive C-reactive protein, tumor necrosis factor alpha, interleukin-6).Results. Azilsartan provided the systolic BP (29,05%, 22,5% and 8,9%) and diastolic BP reduction 18,82%, 20,46% and 8,54% (p

Te purpose of the study is to assess the economic consequences of the use of various anti-VEGF drugs in patients with diabetic macular edema (DME).Materials and methods. Te cost–effectiveness analysis and budget impact analysis was conducted from the payer perspective (health insurance system).Results. In accordance to the results from RCT (Protocol T) aflibercept required a lower number of intravitreal injections (IVI) and laser coagulations for frst year and it has tendency for lower number of IVI for the second year of treatment that resulted in lower costs for aflibercept therapy by 122,819 rubles (12.7 %) per patient within frst 2 years (1st year – 66,632 rubles, 2nd year – 61,186 rubles) in comparison with ranibizumab. Te cost–effectiveness analysis showed that aflibercept is a “cost–effective” method of treating patients with DME compared to ranibizumab in Pro Re Nata (PRN) mode. Te budget impact analysis has shown savings for the health insurance system (12 million rubles) for the analyzed patient cohort (n = 100) with aflibercept in 2 years (1st year – 6.163 million rubles; 2nd year – 6.119 million rubles). Te analysis of “lost opportunities” in a cohort of 100 patients showed that the use of aflibercept in DME can free up to 216 hospitalizations within 2 years (109 cases in the 1st year and 107 in the 2nd year). As a result, about 14 patients with DME can be additionally treated with aflibercept for two years within a fxed budget.Conclusion. Treatment of DME with aflibercept can save resources of health insurance system compared to use of ranibizumab.

Aim. To assess azilsartan medoxomil (AZM) in achieving the target blood pressure (BP) (

Aim. To study the effect of various classes of glucose-lowering agents (dipeptidyl peptidase-4 (DPP-4) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors) on the vascular stiffness in patients with type 2 diabetes (T2D) and high cardiovascular risk.Material and methods. The open-label, prospective 24-week study included 120 patients with T2D and high cardiovascular risk. We evaluated the effect of modern glucose-lowering medications, empagliflozin at a dose of 25 mg/day (SGLT-2 inhibitor) and sitagliptin at a dose of 100 mg/day (DPP-4 inhibitor), on vascular elasticity, central hemodynamic and laboratory parameters.Results. After 24-week therapy, the target glycated hemoglobin level reached 71% and 80% of patients in the sitagliptin and empagliflozin groups, respectively. In both groups, vascular stiffness and central hemodynamic parameters were improved. However, significant changes were recorded only in the empagliflozin (carotid-femoral pulse wave velocity decreased by 14,4%, augmentation index — by 6%, central pulse pressure — by 7,8%) (p

On the basis of multicriteria analysis, a pilot complex system for evaluating medicinal products (MP) used in the therapy of oncohematological diseases has been developed. The obtained results allow to rank MPs by priority of choice when making decisions on procurement of drugs or inclusion in MP lists in the framework of programs of preferential drug provision of the population. It has been shown that, according to the set of criteria, ibrutinib in treatment of chronic lymphocytic leukemia (CLL) has the highest priority, followed by obinutuzumab (CLL treatment) and ruxolitinib (treatment of myelofibrosis).

Aim. Evaluation of the ability of fixed combination of perindopril and indapamide (Noliprel Bi Forte) to achieve additional angioprotection in patients with arterial hypertension already reached target blood pressure (BP) at previous antihypertension therapy with losartan and hydrochlorothiazide (HCT).Material and methods. To open observational study, lasting 12 weeks, 25 patients included, those who had been taking losartan+HCT 100/12,5 mg. Results. During the study, all patients underwent 24 hour BP monitoring, applanation tonometry (augmentation index assessment and of central BP), measurement of pulse wave velocity (PWV), laboratory tests (lipids, fasting glucose, HOMA index, homocystein, leptin, adiponectin, high-sensitive C-reactive protein (hsCRP), vascular age assessment). After shifting the therapy with losartan and HCT to combination perindopril and indapamide, BP decreased additionally by 3,9%, and diastolic BP — 5,4% (p

Aim. Evaluation of the ability of the fixed combination of lisinopril, amlodipine and rosuvastatin (Equamer) in achievement of additional angioprotection in patients with systemic arterial hypertension (AH) and high pulse wave velocity (PWV), regardless of previous antihypertensive therapy (AHT).Material and methods. To the open multicenter observational study 24 weeks duration, 60 patients included, taking double AHT during 6 months. All participants underwent ambulatory 24 hour blood pressure (BP) monitoring, applanation tonometry (augmentation index and central BP), pulse wave velocity assessment, laboratory tests (lipids, fasting glucose, insulin resistance index (HOMA), leptin, high sensitive C-reactive protein (hsCRP) before and after transition to the fixed combination of lisinopril, amlodipine and rosuvastatin (Equamer).Results. By the data from office BP measurement, after transition of patients from the double combinations to fixed combination of lisinopril, amlodipine and rosuvastatin, there was additional decrease of systolic BP (SBP) by 14,3% and diastolic BP (DBP) by 18,5%. By the data from ABPM, decrease of SBP was 16,1%, and DBP — 21,8%. Combination of lisinopril, amlodipine and rosuvastatin decreased PWV by 14,4%, augmentation index by 14,5%, central SBP by 8,1% (p

Aim. To compare cost-effectiveness of the use of direct factor Xa inhibitors rivaroxaban and apixaban in patients with non-valvular atrial fibrillation (AF) and to assess the impact of the both therapies on the healthcare budget of Russian Federation.Material and methods. Pharmacoeconomic analysis with "decision tree" modeling is performed. The costs of regimens using rivaroxaban and apixaban were calculated. Assessment of the likelihood of cerebrovascular complications during anticoagulant therapy was performed, and the average additional costs in development of adverse clinical effects were calculated. The average costs of treatment regimens used in view of the probability of occurrence of all the clinical effects, were calculated as a result of the modeling.Results. The results of the pharmacoeconomic analysis shown, that the strategy of the use of rivaroxaban for stroke prevention in patients with non-valvular AF is less costly 49558.43 rubles for one patient per year. The strategy of apixaban application costs higher by 0.15% (50027.57 rubles). Cost reduction for the year of rivaroxaban therapy in a cohort of 1000 patients was 469140 rubles due to decrease in the incidence of cerebrovascular complications in comparison with apixaban therapy.Conclusion. When choosing pharmacotherapy strategy to prevent the stroke in patients with non-valvular AF rivaroxaban use is more effective, than the use of apixaban, from the clinical and pharmacoeconomic points of view.

Aim. To compare effectiveness of metformin monotherapy (Mf) and combination of metformin with slow release melatonine (MfM) from the perspective of correction of anthropometric, hemodynamical parameters, premature vascular ageing and somnological status in patients with metabolic syndrome (MS).Material and methods. An open label prospective comparative study conducted, in 3 parallel groups: 238 MS patients (IDF, 2005) having, at the moment of prescreening, sleep disorders (less than 19 points in Questionnaire of self sleep evaluation), were randomized to 3 groups. During 12 weeks all patients underwent life style correction that included regimen of meal intake, normalization of “sleepwakefulness” rhythm, physical activity. In addition to this, first group patients (n=80) received Mf, and second (n=78) — combination MfM (Circadin 2 mg). Controls (n=80) were patients without pharmaceutical interventions. Groups were comparable by the baseline clinical and demographic characteristics. Sleep quality, anthropometric and metabolic parameters, adipocytokine level and vascular elasticity parameters were assessed at baseline and in 12 weeks after treatment.Results. The results of the study performed have proved the feasibility of melatonine slow release addition to standard MS therapy in circadian disorders (CD). MfM no only normalizes the rhythm “sleep-wakefulness”, but also retards vascular ageing, has positive profile of cardiovasular and metabolic effects, acting on insulin resistance as trigger of MS development. Serious adverse events were not marked during the study. Conclusion. Combination therapy by MfM is more effective than monotherapy by Mf in correction of body overweight, carbohydrate and lipid metabolism disorders in MS with CD.

Aim. To compare effectiveness of non-drug therapy together with menopausal hormonal therapy (MHT) — estradiol hemihydrate 1 mg/drospirenon 2 mg (Angeliq® Bayer Pharma AG (Germany)) related to normalization of anthropometric and metabolic parameters, elasticity values and vascular age in women with metabolic syndrome (MS) in postmenopause.Material and methods. The open-label prospective comparative controlled randomized study in 2 parallel groups. Sixty female patients (mean age 55,26±5,63 y.) with MS (according to IDF 2005 criteria) were randomized equally 1:1 into 2 groups. During 36 weeks patients of 1st group (n=30) received life style modification recommendations and monotherapy by Angeliq® , patients from 2nd group (controls, n=30) only followed life style modification. Groups were comparable by baseline clinical and demographic parameters. All patients received instructions for diet, physical activity and life style changes. Anthropometric, metabolic and instrumental assessments were done at baseline, in 12 and 36 weeks of therapy.Results. Prescription of MHT in MS patients in postmenopause led to body weight decrease, decrease of percent composition of visceral fat, improvement of metabolic parameters, vascular elasticity and decrease of vascular age. There were no adverse events related to the drug during the study.Conclusion. Angeliq® is effective and safe medication for low-dosage continuous combination MHT in menopausal MS that facilitates improvement of anthropometric parameters, vascular elasticity and vascular ageing.

Objective. Determine if dapagliflozin use is pharmacoeconomically reasonable option for patients with inadequate glycemic control compared with basal insulin.Materials and Methods. The study was conducted according to standard pharmacoeconomic methods: cost-utility analysis (CUA), budget impact analysis (BIA).Results. The use of dapagliflozin as an alternative to basal insulin can reduce health system costs, improves the quality of life of patients, adding 0.73 QALY per patient. Modelling suggests that dapagliflozin introduction could delay the start of insulin treatment by an average of 6.5 years that in turn will allow achieving cost savings and improving the quality of life of patients.Conclusions. Dapagliflozin therapy is the preferred alternative to basal insulins, due to lower costs and improvement in the quality of life of patients.

Background: The metabolic syndrome (MS) is a cluster of hormonal and metabolic abnormalities arising from insulin resistance. It is associated with high risk of diabetes and cardiovascular disease. To reduce this risk, correction of the key pathophysiological factor of MS is recommended, namely, abdominal obesity. However, conventional non-medical treatment approaches (lifestyle changes and diet), as well as medical therapy with metformin frequently do not provide significant and consistent reduction in body weight. With all this, the use of sibutramine, a centrally active anti-obesity agent, looks promising. Being a selective inhibitor of re-uptake of neurotransmitters serotonin and norepinephrine, this agent promotes decreased appetite and weight loss in combination with diet and exercise.Aim: To compare efficacy of lifestyle intervention only to that of lifestyle intervention plus metformin monotherapy or lifestyle intervention plus combination therapy with sibutramine and metformin with regard to anthropometric and metabolic parameters in MS patients. Materials and methods: This was a prospective, open-label, randomized, comparative study in 3 parallel groups. Sixty patients (mean age 45.4 ± 7.5 years) with MS (according to IDF 2005 criteria) were enrolled and randomized into 3 groups at 1:1:1 ratio. For 24 weeks, patients in the group 1 (n = 20) were on metformin monotherapy, those in the group 2 (n = 20) on combined therapy with sibutramine and metformin and patients from the group 3 (control group, n = 20) were given recommendations on lifestyle change only. The groups were matched for baseline clinical characteristics and demographics. All patients were instructed on diet, physical activity, and lifestyle changes. Anthropometric and metabolic parameters were assessed at baseline, weeks 4, 12 and 24. Results: The group on combination therapy with sibutramine/metformin showed the highest mean percentage of decrease in body mass, body mass index and waist circumference. Under combination therapy, waist circumference decreased by 2.3 ±0.57 cm (р < 0.05), waist/hip ratio by 2.72% (р < 0.05). Serum ALT activity in both groups on medical treatment decreased significantly (by 27.5% in group 1 and by 28.07% in group 2, p < 0.05 for comparison with baseline values) which indicates an improvement of liver function in MS patients. At week 24, there were clinically significant improvements of lipid profile in both medical treatment groups. In group 2, there was more advanced decrease in triglyceride levels, compared to group 1 (by 24.5% vs. 11.2%, p < 0.05). There were no serious adverse events related to the drugs during the study.Conclusion: Combination of sibutramine with metformin is effective, safe and well tolerated for correction of excess weight in patients with MS, in whom metformin monotherapy is ineffective.

According to recent guidelines of AASLD, AGA and ACG, NAFLD is a liver disease accompanied by the accumulation of fatty acid content greater than 5% of hepatocytes weight, absence of substantial alcohol consumption (20 g per day for men, 10 g per day for women), absence of hepatitis viruses and other specific causes of liver disease.