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In the ongoing transport and logistics researches, a coefficient of railway line non-straightness is introduced, by means of which, for the considered loading stations, the specifics of the location of the railway network in a given region are taken into account. The use of this coefficient makes it possible to increase the efficiency and practical expediency of applying the method of economic and geographical delimitation of the «influence areas» of the loading stations. As a result, it is possible to construct a mathematically substantiated geometric routing model of the territorial oligopolistic market for freight transportation formed by the considered loading stations. As an effective tool in the research process, a system of analytical calculations is used.

The issues of optimizing the functioning of logistical-type cargo distribution center (LFDC) are considered from an economic point of view. The research is carried out in order to identify the intensity of competition between the indicated centers in the oligopolistic market of transport and logistics services performed using road transport. A modification of the method of economic-geographical delimitation of «influence areas» of distribution centers has been developed for its application in cases where the supply chains include rail freight. Using the system of analytical calculations, a mathematically justified analysis of the territorial expression of the competitive environment created by the indicated centers in the transport hub was performed.

A multi-agent approach has been developed for solving the optimization transport-type problems. As an object of application, a multimodal system of transportation of grain cargoes with cost indicators is considered. The egalitarian principles of welfare theory implemented in the form of the Pareto criterion are used as the methodological basis of the research. A significant role belongs to the mathematical experiment as an effective tool for simulation modeling. The optimization algorithm developed in a mathematically oriented software environment makes it possible to effectively manipulate the values of cost indicators and constraints in the problem.

A multi-agent approach is proposed in the complex researches time and cost indicators of multimodal freight transportation on the railway loop, carried out in the direction of the port unloading stations. Along with the traditional subjects of the transportation process, such as the infrastructure owner, the carrier, the operator company (the rolling stock owner), the logistics company and clients (consignors and cargo’s owners), a “green logistics” agent is introduced. This agent is a concept that accumulates forms of manifestation of a conscious attitude of society to the environment in transport and logistics activities. Based on the assessment of the transport and technological railway loop infrastructure and the cost of transport services, a mathematical model of the freight transportation process is built, which is a multi-criteria transport problem. The choice of objective functions and constraints in the task is aimed at, first of all, taking into account the diverse interests of the agent “green logistics”. The algorithm for solving the problem, presented in the form of an integer programming problem, is based on the fundamental principles of the egalitarian and utilitarian approaches in the welfare theory. The implementation of the corresponding calculations for the grain transportation is performed in the environment of the computer mathematics system.

Aim: The study was aimed at assessing efficacy and safety of micronized purified flavonoid fraction (MPFF, Detralex) in comprehensive treatment of chronic venous oedema induced by lower limb varicose veins., Patients and Methods: We performed a post hoc analysis of the results of treatment of 708 patients included into the observational programme VAP-PRO-C3 (ClinicalTrials.gov. NCT03722836). These patients, depending on the type of treatment, were divided into 8 subgroups: MPFF (n=32); MPFF + compression (n=145); MPFF + compression + topical treatment (n=158); MPFF + compression + topical treatment + endovasal laser coagulation (n=197); MPFF + endovasal laser coagulation (n=3); MPFF + compression + endovasal laser coagulation (n=152), patients not receiving MPFF (n=16); MPFF + topical treatment (n=2). Due to paucity of the participants, from the subsequent analysis we excluded the groups MPFF + endovasal laser coagulation, patients not receiving MPFF (n=16) and MPFF + topical treatment. All further statistical data are shown for the remaining 687 patients., Results: Comparing the groups of patients undergoing conservative treatment alone and those subjected to surgical intervention demonstrated no statistically significant differences in dynamics of crural oedema. In both groups at every subsequent visit there was a statistically significant decrease in the ankle volume (p<0.001). During the whole period of follow up the crural volume in patients from the group of conservative treatment totally decreased by 0.201±0.158 L and in the operated patients by 0.236±0.189 L (p=0.021). The QOL assessed by the CIVIQ-14 global index score statistically significantly improved in the unoperated patients from 31.5±19.2 to 12.0±10.1 (p<0.001). In the operated patients, the baseline and final values of the QOL of the global index score amounted to 33.4±17.8 and 7.7±9.2, respectively (p<0.001). In the groups with and without topical treatment, the baseline values of the QOL assessed by CIVIQ-14 global index score amounted to 28.5±17.4 and 36.2±18.6, respectively. During the follow-up period, we observed statistically significant positive dynamics of all parameters of quality of life. The final visit demonstrated improvement of the CIVIQ-14 global index score to 9.4±9.2 in patients without topical treatment and 10.1±10.4 in those receiving topical treatment (p=0.367), with the mean value of this parameter during treatment in both groups decreased significantly (p<0.001). A statistically significant decrease in the ankle volume in both groups was registered at every visit, finally amounting to 0.223±0.166 L and 0.248±0.174 L (p=0.118) for patients not receiving and receiving topical treatment, respectively. In groups of patients not receiving and those receiving compression therapy, the baseline values of the QOL assessed by CIVIQ-14 global index score amounted to 21.4±14.2 and 33.1±18.5 (p<0.001), respectively. At the final visit, these indices statistically significantly (p<0.001) decreased to 7.3±9.1 and 9.9±9.9 (p=0.106). Compared with the baseline values, the ankle volume at the final visit in groups of patients with and without compression therapy statistically significantly decreased by 0.187±0.14 L and 0.238±0.17 L respectively (p=0.204). During the study, there were no adverse events related to the administration of MPFF and use of Detragel., Conclusion: MPFF and Detragel appear to be effective and safe components of comprehensive conservative therapy of chronic oedema induced by primary varicose veins of lower extremities.

Aim: This study was undertaken to evaluate efficacy of Actovegin in the composition of comprehensive therapy in patients presenting with post-thrombotic disease of lower extremities free from trophic disorders., Patients and Methods: The study included a total of 60 patients (28 men and 32 women) diagnosed as having post-thrombotic disease of lower limbs without trophic disorders (C1-C3 according to the CEAP classification), induced by previously endured iliofemoral phlebothrombosis. The duration of the disease varied from 1 year to 10 years. All patients for 10 days received Actovegin intravenously in drips at a dose of 1200 mg (30 ml of the drug reconstituted in 400 ml of normal saline) followed by continuing taking the drug orally in a daily dose of 1200 mg for 30 days. During the whole follow up period the patients wore class 2 compression stockings (RAL standard). The results of the carried out treatment in relation to the subjective complaints (pain, feeling of heaviness, convulsions, pruritus and paresthesias) were assessed by the visual analogue scale and based on the CIVIQ-20 questionnaire, with additionally measuring the malleolar circumference., Results: On the background of the carried out therapy the patients demonstrated a significant decrease in the oedematous syndrome in the area of the ankles. This parameter decreased form 26.88±0.39 cm to 25.02±0.35 cm (p<0.05). The patients' complaints of tingling decreased form 5.73±0.79 to 2.32±0.68 points (p<0.05), the incidence and intensity of convulsions fell from 6.51±1.39 to 3.2±0.98 points (p<0.05). The intensity of the oedematous syndrome (swelling) decreased significantly from 8.11±1.75 to 4.33±1.20 points (p<0.05), the pain syndrome fell from 7.92±1.88 to 3.12±1.45 points (p<0.05), the feeling of heaviness in the lower limbs decreased from 8.52±1.73 to 3.91±1.48 points (p<0.05). Also, improvement of the general quality of life of patients was observed (the integral parameter decreased from 63.27±1.8 to 44.33±1.19 points, p<0.05).

Aim: The purpose of the study was to assess efficacy and safety of using in real clinical practice micronized purified flavonoid fraction (Detralex) in patients with chronic venous oedema., Patients and Methods: The study enrolled a total of 708 patients presenting with chronic venous disease, belonging to C3EpAsPr according to the CEAP classification (chronic venous oedema), who. depending on the accepted clinical practice by expert physicians were prescribed compression and phlebotropic therapy, as well as undergoing surgical interventions. The main criteria for efficacy of the micronized purified flavonoid fraction included the dynamics of chronic venous oedema, vein-specific symptoms, as well as the main parameters of quality of life. Assessment was made using visual analogue scales, the vein-specific questionnaire CIVIQ-14, and the method of discs for measuring the volume of the crus., Results: The obtained findings demonstrated significant positive dynamics of the main vein-specific symptoms assessed by a visual analogue scale. When comparing between the visits of recruitment into the study and its termination the feeling of heaviness in calves decreased form 5.38±2.19 cm to 1.56±1.56 cm (p<0.001), pain in the calf diminished from 4.24±3.39 cm to 1.12±1.37 cm (p<0.001), feeling of oedema dropped from 5.68±2.44 cm to 1.38±1.59 cm (p<0.001), severity of nocturnal cramps fell from 2.46±2.30 cm to 0.43±1.01 cm (p<0.001), and intensity of skin inching from 1.46±2.06 cm to 0.43±1.01 cm (p<0.001). Positive dynamics of venous-specific symptoms appeared to be accompanied by significant improvement of all dimensions of quality of life according to the CIVIQ-14 scale: by the pain scale from 41.0±19.1% to 12.8±11.6% (p<0.001), by the physical condition scale - from 31.6±23.8% to 11.1±15.4% (p<0.001), by the psychological state scale - from 24.5±21.1% to 5.7±9.0% (p<0.001). The global index of quality of life also improved significantly from 32.4±18.5% to 9.9±9.9% (p<0.001). The results of the intervention along all the examined parameters (external appearance, possibility of wearing various clothes and increasing the quality of the self-performed work, to improve both interactions with surrounding people and the social activity and rest) turned out better than expectations form an intervention. The volume of the crus as the main criterion over the period of follow up averagely by the group decreased from 3.07±0.84 to 2.78±0.80 litres (p<0.001). A significant decrease in the calf volume from 3.03±0.87 to 2.77±0.85 litres was observed in 288 patients who during the follow up period were not subjected to surgical interventions, with no significant differences in the dynamics of chronic venous oedema revealed between the operated patients and those having received conservative treatment alone., Discussion: According to a meta-analysis, the micronized purified flavonoid fraction (Detralex) turned out to possess better parameters in relation to therapy of chronic venous oedema as compared with other phlebotropic agents. Therefore, it appears absolutely logical to predominantly use the micronized purified flavonoid fraction in real clinical practice in patients with the CEAP C3 clinical class, which was registered in our study. An important result was also the fact that within the specified terms of follow up surgical intervention demonstrated no significant advantage over conservative therapy alone in treatment of chronic venous oedema. Moreover, conservative treatment in the form of a combination of compression and phlebotropic therapy demonstrated a dynamic decrease in the volume of the affected extremity with a probable transition of the CEAP C3 clinical class to C2., Conclusion: The micronized purified flavonoid fraction (Detralex) at a standard daily dose of 1000 mg in a combination with compression therapy irrespective of the surgical intervention performed resulted in a significant dynamic decrease in the volume of the calf in patients with chronic diseases of lower limb veins (C3EpAsPr according to the CEAP classification). An anti-oedematous effect of the micronized purified flavonoid fraction (Detralex) in a combination with compression manifests itself during the entire period of treatment.

Aim: The purpose of the study was to assess efficacy and safety of heparin sodium gel 1000 IU/g and Detragel® in decreasing the incidence and treatment of the most common local adverse reactions in patients after endured sclerotherapy of reticular veins and telangiectasias., Patients and Methods: Our open prospective observational study included a total of sixty 18-to-35-year-old female patients who after undergoing standardized sclerotherapy of reticular veins and telangiectasias on symmetrical portions of lower limbs were given a tube of heparin sodium gel 1000 IU/g or Detragel® to be applied onto the skin of one (left) lower limb in the projection of the sclerotherapy-exposed vessels 2-3 times daily for 10 days followed by putting on a compression class 2 (RAL standard) stocking. The women were allowed to use only the paired stocking on the contralateral extremity. Efficacy and safety of heparin sodium gel 1000 IU/g and Detragel® were evaluated based on the incidence of typical adverse reactions (ecchymoses, phlebitides, hyperpigmentation and neovasculogenesis), as well as on the patient's subjective perceptions., Results: The use of heparin sodium gel 1000 IU/g and Detragel® in addition to compression after sclerotherapy of reticular veins and telangiectasias significantly and comparably decreased the incidence and accelerated the resolution of ecchymoses and phlebitides associated with phlebosclerosing treatment. The Detragel® group patients were found to develop hyperpigmentation or neovasculogenesis significantly less often as compared with the heparin sodium gel 1000 IU/g group women. What is more, using Detragel® was not accompanied by hyperkeratosis, pruritus or formation of a sticky film, the events, however, observed while applying heparin sodium gel 1000 IU/g., Conclusion: The use of Detragel® or heparin sodium gel 1000 IU/g for 10 days additionally to compression significantly decreased the incidence of typical undesirable reactions associated with sclerotherapy of reticular veins and telangiectasias. The Detragel® group women turned out to have lower incidence of hyperpigmentation and neovasculogenesis. Besides, Detragel® demonstrated better organoleptic properties.

Aim: The study was aimed at assessing efficacy and safety of using a micronized purified flavonoid fraction in the perioperative period in patients scheduled for endovascular surgical intervention for CEAP clinical class C2 lower limb varicose veins., Patients and Methods: This study enrolled a total of 1519 patients with CEAP C2a,sEpAs (primary varicose vein with valvular incompetence of the great and/or small saphenous vein) who were subdivided into two groups. Group One included 1039 patients who in the perioperative period were prescribed a micronized purified flavonoid fraction at a daily dose of 1000 mg and who continued therapy, including visit 4. Group Two was composed of 480 patients taking no venoactive agents. The main criterion for assessing efficacy of the micronized purified flavonoid fraction was the incidence rate of typical adverse events in the compared groups of patients after surgical intervention., Results: The patients receiving the micronized purified flavonoid fraction were found to have adverse events significantly less often as compared with those in the control group: ecchymosis 7.1 versus 11.0% (p=0.01), haematoma 0.5 vs 1.3% (p=0.1), paresthesia 0.5 vs 1.7% (p=0.02), thrombophlebitis 0.2 vs 0.6% (p=0.2), pigmentation 0.6 vs 3.3% (p=0.001), heat-induced thrombosis 0.3 vs 1.3% (p=0.02). The total incidence rate of adverse events in patients receiving and those not receiving the micronized purified flavonoid fraction amounted to 7.6 vs 15.0%, respectively (<0.001)., Discussion: The micronized purified flavonoid fraction prescribed in the perioperative period, owing to a pluripotent mechanism, adapts the venous system and microcirculatory bed of the lower extremities to operative stress, decreasing the anti-inflammatory response to endovascular intervention, lowering thereby the incidence of undesirable events., Conclusion: Prescription of the micronized purified flavonoid fraction in the perioperative period ensures a significant decrease in the incidence of typical adverse events developing after endovascular surgical treatment for CEAP clinical class C2 varicose veins and may be recommended for real clinical practice.

Presented herein are the results of the observational follow up study programme dedicated to the assessment of appropriate use of adjuvant therapy with Detralex while carrying out phlebosclerosing treatment in patients suffering from dilated intradermal veins (clinical class C1 according to the CEAP classification). A conclusion was drawn that administration of Detralex for 60 days decreased the incidence rate of typical undesirable side events after phlebosclerosing therapy, thus making the use of this drug appropriate in routine clinical practice.

Compression serves as an important component for carrying out successful and safe phlebosclerosing treatment. At the same time, the necessity of wearing compression hosiery or bandages is associated with known limitations and objections of patients, especially in a hot season. We comparatively assessed efficacy of usual compression stockings and a short-term pneumatic bandage with cryoelements while carrying out sclerosing treatment of dilated intradermal veins. Our open prospective observational study included a total of fifty 18-to-35-year-old women. After performing standardized sclerotherapy of reticular veins and telangiectasias on the symmetrical portions of the lower limbs, a pneumatic cryocompression bandage with a pressure of 50 mmHg was applied onto one of the limbs for 15 minutes, with a class 2 compression (RAL standard) medical stocking put on the other limb to be worn by the patients at daytime for 10 days. We assessed completeness of obliteration of the target veins, frequency of the development of typical undesirable events (ecchymoses, phlebitides, hyperpigmentation and neovasculogenesis), as well as the composite discomfort score according to an 11-point visual analogue scale. It was determined that using the pneumatic bandage with cryoelements as compared with the traditional compression stockings significantly decreased the frequency of the development of typical undesirable events after phlebosclerosing treatment, such as formation of ecchymoses, phlebitides, hyperpigmentation and neovasculogenesis. Significance of differences was revealed as early as 7 days after sclerotherapy, to be increasing during further dynamic follow up. By convenience for the patients, the use of the short-term pneumatic cryobandage was four times better than wearing the compression stockings. A conclusion was drawn that while carrying out sclerotherapy of reticular veins and telangiectasias short-term pneumatic cryocompression by efficacy and safety was not inferior to the traditional medical stockings (RAL standard) and made it possible to significantly decrease the incidence of the known undesirable events after phlebosclerosing treatment.

Objective: The purpose of our study was to evaluate both clinical and laboratory efficacy of sulodexide given at a daily dose of 500 lipasemic units (LSU) in patients presenting with class C3-C4 chronic venous insufficiency (CVI) according to the CEAP classification., Patients and Methods: The study included a total of 25 patients diagnosed with C3-C4 CVI and prescribed to receive sulodexide at a daily dose of 500 LSU for 90 days. Efficacy was comprehensively controlled by the following tools: the disease-specific Chronic Venous Insufficiency Quality of Life Questionnaire (CIVIQ), visual-analogue methods of assessment separate symptoms; the Venous Clinical Severity Score (VCSS), as well as ultrasonographic determination of the thickness of subcutaneous fat and crural fascia. Amongst the key laboratory indices determined by means of the ELISA test were the levels of interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), matrix metalloproteinases-2 and -9 (MMP-2, MMP-9), vascular endothelial growth factor A (VEGF-A), vasopressin and endothelin., Results and Discussion: Of the initially enrolled 25 subjects, twenty-two patients completed the study and were taken as 100%. The 90-day treatment yielded favourable results manifesting themselves in complete disappearance of convulsions in the calf muscles detected at the first visit in 22.7% of patients (p=0.0485), a significant reduction in the frequency of complaints of decreased tolerance to static loads from 27.3 to 9.1% (p=0.2404). The volume of the crus of the control lower extremity decreased from 134.18±14. 92 to 128.42±12.46 cm3 (p=0.0006), subcutaneous fat thickness at the fixed point decreased from 1.50±0.53 to 1.32±0.46 cm (p=0.0007), and fascial thickness decreased from 0.14±0.7 to 0.11±0.04 (p=0.0359). Pain syndrome according to the visual analogue scale (VAS) decreased from 36.45±25.60 to 17.50±19.27 mm (p=0.0002). The global index of quality of life (GIQoL) according to the CIVIQ-20 increased by 27.7% compared with the baseline level (p = 0.0001), the VCSS index decreased from 6.00±1.83 to 4.86±2.05 points (p=0.0002). as for the laboratory markers of endothelial dysfunction, there was a significant decrease in the levels of MMP-2 - from 178.53±36.30 to 176.35±36.67 ng/ml (p=0.0152), MMP-9 - from 90.84±20.41 to 89.78±20.32 ng/ml (p=0.0394), and that of endothelin - from 0.42±0.10 to 0.39±0.10 fmol/ml., Conclusion: Sulodexide exerting a statistically significant clinical and endothelium-protecting effect turned out to be an effective drug for treatment of initial forms of chronic venous insufficiency of lower limbs.