Clinical Practice In Russia Research Articles

КЛИНИЧЕСКИЕ И ПРАВОВЫЕ АСПЕКТЫ ПРИМЕНЕНИЯ НИЗКОМОЛЕКУЛЯРНЫХ ГЕПАРИНОВ В ПЕДИАТРИИ

The acceptability and effectiveness of low-molecular-weight heparin (LMWH) use in paediatrics has been confirmed by established Russian and foreign clinical practice. However, at present, the only LMWHs that are legally allowable for children are those with the international nonproprietary name of «dalteparin sodium», since this is directly stated in it’s Package Insert Leaflet (PIL). Prescribing the rest of the LMWHs for children will, in fact, be an off-label prescription. In addition, there are currently no standards of medical care, procedures for its delivery and regulations on the organization of medical care that would allow for the possibility of assigning LMWHs to children. This situation makes it difficult to introduce into the Russian pediatric practice the choice of administration of LMWHs in children where necessary. The use of LMWH in pediatrics may become available even without making changes to PIL, but subject to the establishment of such a recommendation in the new clinical guidelines. The latter is the only legal mechanism in force allowing legal and legally secure off-label appointment.

The effectiveness and safety of eribulin therapy in HR-positive HER2-negative metastatic breast cancer post-CDK4/6 inhibitor therapy in Russian clinical practice.

e13035 Background: EMPOWER trial demonstrated the benefit of eribulin administrated post CD4/6i in patients (pts) with HR+ HER2-negative (HR+HER2-) metastatic breast cancer (MBC). There are several important limitations to this trial: > 60% of pts were stage IV at the time of treatment initiation, eribulin used in late lines (2L only in 30% pts) and follow-up data were immature. Current study aimed to provide additional data on the real-world effectiveness and safety of eribulin monotherapy in this setting. Methods: Observation study of eribulin monotherapy in standard regimen enrolled 54 pts (median age 56; range 29-79 years) with HR+ HER2- MBC received at least one dose of eribulin post CDK 4/6i in metastatic settings; 24% pts had de novo metastatic BC, 76% - recurrent BC; 77% received palbociclib, 21% ribociclib, 2% both drugs; 49% pts received CDK4/6i with fulvestrant and 51% with AI. CDK4/6i was used: 49% pts in 1L, 36% in 2L, 16% in 3L. Median DOR of CDK4/6i treatment was 9.07 months (range 2-38). 94% pts received anthracyclines and taxanes, eribulin was used in 2L in 60%, 30% in 3L, 8% in 4L, 2% in 5L. The most common sites of metastases (Mts) were bones (78%), liver (73%), lung (56%) and brain (8%); visceral Mts were seen in 90% pts. Median follow-up – 11,5 months (range 3-36). Results: Median cycles of eribulin therapy was 10,5 (range 1-44); objective response rate was seen in 24%, stabilization - 67%, progression - in 9%. Median PFS was 10.0 months, there were no significant differences in the different subgroups (visceral/no visceral; recurrent/de novo BC; age; CDK4/6i as 1L vs 2L, fulvestrant vs AI), p > 0,05. Median PFS was higher in pts with lung Mts vs non-lung (24 vs 9,1 months, p = 0.056). Most common AEs all grades were neutropenia (26%), anemia (9%), asthenia (9%), polyneuropathy (11.1%). AE did not affect the effectiveness of eribulin (p = 0.648). Dose reduction was in 19% pts and did not affect the effectiveness of eribulin (p = 0.612). At median follow-up of 11.5 months, 92.5% of patients still alive. Conclusions: As post-CDK4/6i therapy, eribulin in HR+HER2- MBC pts was effective and well tolerated, regardless of age, line of CDK4/6, CDK 4/6i combination partner. Patients with metastasis to the lung have better mPFS. Results in this real-world population of pts with HR+HER2- MBC were consistent with the EMPOWER study, and support administration of eribulin in 2-3 lines as an effective option for post-CD4/6i pts.

Correlation of Objective Endpoints and Subjective Patient-Reported Outcomes in NAFLD Treatment with Essential Phospholipids: Real-World Data Based on Pooled Analysis of Observational Studies.

BackgroundWhile no “gold-standard” pharmacotherapy for nonalcoholic fatty liver disease (NAFLD) is yet established, essential phospholipids (EPLs) are reported to decrease steatosis and improve laboratory parameters.ObjectiveThis analysis evaluated adherence and satisfaction with EPL treatment as patient-reported outcomes and their relationship with changes in laboratory and ultrasound parameters among Russian patients with NAFLD.MethodsData were pooled from three observational Russian studies—MANPOWER (2015–2016), LIDER 1 (2012–2013), and LIDER 2 (2013)—in which EPLs were used for at least 12 weeks in the treatment of liver diseases and which measured both subjective and objective endpoints. Only patients who had NAFLD were included in this analysis. The main endpoints were to determine treatment adherence and satisfaction with 12 weeks of EPL therapy, relationship between adherence/satisfaction and changes in the laboratory and ultrasound parameters. A secondary subgroup analysis was performed to identify patients with NAFLD who responded better (or worse) to 24 weeks of adjunctive EPL treatment.ResultsOverall, 3384 patients were included. A total of 82.2% of patients were adherent to 12 weeks of EPL treatment; high/very high satisfaction was reported by 15.3%/65.9% of clinicians and 15.9%/64.4% of patients. There was positive correlation between patients’ adherence and satisfaction and significant improvement in laboratory (transaminases, lipid profile; p < 0.001) and ultrasound (steatosis, p < 0.001) parameters, and improvement in symptoms (p < 0.001) after 24 weeks of EPL. Male patients, patients with unhealthy lifestyles, and those with more comorbidities showed a better response in laboratory and ultrasound parameters.ConclusionsPatients with NAFLD treated with adjunctive EPL therapy in real-world clinical practice in Russia showed good treatment adherence and treatment satisfaction. Improvements in laboratory and ultrasound parameters, as well as dynamics of patient symptoms, were positively correlated with adherence and satisfaction.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-021-00250-x.

First Experience of Using Russian Sulfacrylate Glue Clinical and Morphologic Study (In Vivo)

Russian adhesive sulfacrylate was synthesized in 2000, in contrast to foreign analogues it is based on ethyl ether of α-cyanoacrylic acid, not butyl. Two additional plasticizers were added to the glue, which reduced the brittleness of the compound. In 2010 it was approved for use in clinical practice in Russia. From May 2019 till July 2020 an endovasal catheter obliteration of the main trunks of the great saphenous vein (GSV) and small saphenous vein (SSV) was performed using the sulfacrylate glue in 48 patients with varicose disease (C2-C4). The diameter of the target vein varied from 9 to 13 mm. The dose of VenoGlue depends on the diameter of the target vein. For vein diameter 0.8-1.0, 0.1 mL glue is used for every 5 cm treated. For vein diameter greater than 1.0 cm, 0.2 mL is used for every 5 cm treated. We evaluated pain, thrombophlebitis, and local and general allergic reactions. Ultrasound control was carried out at days 3 and 60, as well as month 6. Immediately after the intervention and on the first day, the possible spread of the glue in the proximal and distal direction of the GSV and SSV was monitored. A histologic study of morphologic changes (in vivo) was performed with the consent of patients to conduct the study. We studied the parts of GSV (n = 11) and SSV (n = 4) taken from 15 patients within the period from 7 to 180 days after procedure. Pain after 48 hours was observed in 10 patients (21%) with visual analogue scale scores ranging from 0.86 to 2.2. In six cases (12%), the visual analogue scale scores were a 4 of 5. A postprocedural phlebitic reaction took place in 25% only a self-limited inflammatory response over the treated vein, and no cases with classic superficial venous thrombosis. There were no cases of glue extension into deep veins and no allergic reactions in the patients. In six patients when the glue reached the subcutaneous fat there were signs of aseptic inflammation. During the histologic examination starting from day 7, there was a gradually relieving aseptic inflammation in the vein wall. Within 180 days, the lumen of all veins was completely obliterated by mature connective tissue, in the absence of glue particles, which was indicative of its complete biodegradation. The anatomical success rate was 100% after 3 and 6 months of follow-up, respectively. Cyanoacrylate adhesive embolization of incompetent truncal veins using the Russian glue cyanoacrylate is a safe and effective procedure. The high adhesive ability of the glue contributes to the absence of extension into the deep system. The glue is biodegradable and was not detected in the vein after 12 months. The Russian glue is a low-cost treatment which can easily be performed as an office-based procedure.

Results of a clinical trial of the efficacy and safety of vildagliptin and metformin fixed combination in real clinical practice in Russia (MASTER study)

BACKGRAUND: The widespread prevalence of type 2 diabetes mellitus (T2DM), high mortality and disability of such patients are the reason for the constant active search for effective approaches to hypoglycemic therapy. Recent years have been marked by a change in the strategy for treatment initiation of T2DM. In clinical studies, evidence has been obtained about the benefits of prescribing combination therapy from the time of diagnosis. It seems important to study this treatment option also in real clinical practice.AIMS: To evaluate the effectiveness and safety of the initiation with Galvus Met® as compared with any other combination therapy approaches used in everyday clinical practice.MATERIALS AND METHODS: multicenter prospective observational study in 15 regions of Russia lasting 6 months. Patients were included in the study after the endocrinologist made a decision on the appointment of therapy. Of the men and women over 18 years of age with first diagnosed or previously untreated type 2 diabetes and a level of glycated hemoglobin &gt;7.5%, two groups were formed. The first group included patients who received vildagliptin + metformin (Galvus Met®) in a fixed dose of 50/1000 mg, n=729, the second — another double combination (with the exception of insulin and GLP-1), n=669. The primary endpoint was defined as the proportion of patients (%) who achieved the level of HbA1c &lt;7.0% without proven hypoglycemia at the end of the observation. The NHPQ questionnaire was used to assess the frequency of hypoglycemia.RESULTS: 1385 patients completed the study. For the other combination therapy group, metformin and sulfonylurea derivatives were most often selected (66.5%). In the Galvus Met® group, 68.7% of patients achieved an HbA1c level of &lt;7.0% without proven hypoglycemia, which is significantly better compared to the group of other combinations (40.7%, p &lt;0.001). Galvus Met® therapy contributed to a significantly greater decrease in HbA1c levels by the end of the study compared to other combinations (delta HbA1c -1.6 ± 0.8% versus -1.4 ± 0.9%, p &lt;0.001). In the same group, the average level of HbA1c reached 6.7 ± 0.6% by the end of the study versus 7.1 ± 0.8% in the comparison group, p &lt;0.001. In the Galvus Met® group, body weight decreased by 3.2 ± 3.9 kg, and in the comparison group by 1.3 ± 4.8 kg, p &lt;0.001. The frequency of hypoglycemia episodes in the Galvus Met® group by the end of the study was significantly lower than in the comparison group: 0.8 ± 0.7 episodes per person, versus 1.4 ± 0.8, p = 0.037. In the Galvus Met® group, there were significantly fewer adverse events (4.9% versus 17.7%, p &lt;0.001).CONCLUSIONS: In real clinical practice, Galvus Met® starting therapy has shown better efficacy and safety in terms of achieving glycemic control, HbA1c dynamics, effects on body weight, the frequency of hypoglycemic conditions compared with other combined oral hypoglycemic therapy.

Russian clinical practice guidelines for the management of c1 clinical class of chronic venous disorders (reticular veins and telangiectasias)

Recently collated scientific data on the management of C1 clinical class of chronic venous disorders; wide prevalence of the disease and high variability amongst medical practitioners in relation to managing this category of patients and absence of any regulatory documents has prompted the development of clinical guidelines for the treatment of patients with reticular varicose veins and telangiectasias of the lower extremities and various parts of the body. These guidelines have been developed by a self-regulated organization Association “The National College of Phlebology”. The purpose of the de novo guidelines is to systematize the existing evidence and offer minimal standards of care for chronic venous disorders in C1 patients.

CDK4/6 inhibitors in the treatment of metastatic breast cancer. Choosing optimal therapy for estrogen-receptor-positive HER2-negative metastatic breast cancer: analysis of doctors’ preferences (“Prometheus”) in Russia – first results of the survey

The emergence of a new class of drugs – inhibitors of cyclin-dependent kinases 4/6 (CDK4/6) – has changed the paradigm of treatment of patients with luminal HER2 negative metastatic breast cancer. Their effectiveness is confirmed not only by randomized, but also observational studies on a wide heterogeneous population of patients from daily clinical practice; the use of these drugs in the 1 st line is significantly expanding in the world. On the territory of the Russian Federation, an observational study of Prometheus was carried out, the purpose of which was to assess the frequency of prescribing CDK4/6 inhibitors, as well as other types of treatment in 1–2 nd lines in real clinical practice in Russia, as well as factors and preferences of doctors influencing the choice of therapy. A survey of the target audience, whose answers can be considered reliable and reflecting today’s Russian clinical practice in the treatment of breast cancer, showed that, despite the fact that the overwhelming majority of doctors (78 %) believe that the maximum benefit from the appointment of CDK4/6 inhibitors is expected for the 1 st line therapy, in real clinical practice, only 35 % of doctors practice 1 st line prescription. In the 2nd line of therapy, CDK4/6 inhibitors are prescribed by 45 % of experts, in the 3 rd (or more) line – 20 %. According to the respondents, the main obstacle to the appointment of CDK4/6 inhibitors is the unresolved issues of the availability of therapy (44 %) and its cost (34 %). Among all the proposed clinical criteria, only the criterion “visceral metastases with impaired function of internal organs” influences the decision not to prescribe a combination of hormonal therapy and a CDK4/6 inhibitor in 1–2 nd lines of therapy. Criteria such as ECOG status, menopause status, tumor subtype preceding chemotherapy, timing of progression do not determine the choice when deciding not to prescribe combination therapy.

«Criminal» local anesthesia in dentistry: a deliberate risk or a game without rules?

The effectiveness and safety of drug treatment are the main criteria for its success. Local anesthetics, used in all medical fields, in some cases can cause a wide variety of undesirable side reactions, but in recent years, such manifestations that have arisen in Russian clinical practice tend to qualify as anaphylactic shock. This article presents the types of adverse reactions and global statistics of anaphylaxis to local anesthetics, as well as analyzes the possible reasons for the erroneous diagnosis of fatal outcomes of anaphylaxis. The purpose of the review was to clarify information about reliable markers of clinical and postmortem anaphylaxis, providing unambiguousness and objectivity of forensic medical examination. Attention is focused on the specific postmortem signs of immediate allergic reactions and the sequence of professional interpretation of all the circumstances associated with a fatal adverse reaction against the background of the use of local anesthetics.

The revised pancreatitis etiology-based classification system TIGAR-O, version 2: adaptation for the Russian clinical practice

The discoveries in molecular genetics and breakthrough visualization techniques in the last 20 years have changed our understanding of the pancreatitis causes and biomarkers, expanded our knowledge on the pathophysiology of the disease, and promoted the development of new additional conservative treatments. From the practical perspective, the physician's comprehension of the etiology is of particular importance. It is for this reason that the activities to elaborate an etiology-based classification of pancreatitis have been already started since long ago. The first internationally acknowledged system was TIGAR-O checklist, introduced in 2001. Being innovative at the time, it structured our understanding of the etiology of chronic pancreatitis. The revised version (version 2) was published in 2019 and is less known to the Russian medical community, although from the authors' point of view, it has been substantially extended and structured to be maximally convenient and useful for physicians in routine medical practice. The review presents key provisions of the TIGAR-O, version 2 and recommendations for its adaption to the Russian clinical setting.

The efficacy and safety of nusinersen within the expanded access program in Russia

Introduction.Spinal muscular atrophy is a severe neuromuscular disease characterized by rapid progression of muscle weakness and earlydeath. Pathogenetic therapy with nusinersen can significantly change the course of the disease and enable the patient to acquire new skills.The study of the efficacy and safety of nusinersen therapy in patients with type 1 spinal muscular atrophy should be continued.Theaim of the studywas to assess the safety and efficacy of nusinersen therapy in patients with type 1 spinal muscular atrophy for 6 monthsas part of an expanded access program at federal and regional healthcare facilities.Materials and methods.Patients with type 1 spinal muscular atrophy received nusinersen therapy under the expanded access program(NCT02865109). Patients were evaluated before starting treatment and 6 months after starting treatment. Overall motor development andmotor function was assessed using the Hammersmith Infant Neurological Status Scale Part 2 and the Philadelphia Pediatric Hospital Neonatal Motor Scale.Results.41 children aged 6 to 38 months received nusinersen therapy between July 2019 and March 2020. At the time of analysis, all patients were alive and continued treatment. The average improvement on the Hammersmith Hospital Neurological Status Scale was 3.7 pointsafter 6 months of therapy compared to baseline (n = 39, p &lt;0.001). The mean improvement on the Children’s Hospital of PhiladelphiaScale for the Diagnosis of Motor Function in Newborns was 9.8 after 6 months of therapy from baseline (n = 30, p &lt;0.001).Conclusion.The efficacy and safety of nusinersen have been demonstrated in real clinical practice in Russia in the treatment of early-onsetspinal muscular atrophy.

Bladder cancer: treatment after progression. Results of the second retrospective analysis of data on the efficacy of vinflunin in patients with metastatic urothelial cancer in real clinical practice in Russia

Objective. There is the second generalized analysis of administration of vinflunine in real clinical practice in Russia.Materials and methods. This analysis gathered 15 patients with urothelial carcinoma treated using this medicine in 8 cancer centers in Russia. We assessed efficacy, safety profile of vinflunine in this subset of patients.Results. Clinical efficacy of vinflunine (complete response + partial response + stable disease) was 73.3 %, one patient demonstrated complete response. Median of response duration accounts for 3.8 months. Six-month and 1-year survival rate made up 93.3 %. Adverse events were observed in 53.5 %, with only one episode of neutropenia 4 grade.Conclusion. In our second analysis vinflunine was more effective than in randomized clinical trial and other studies from real practice in Europe. Thus, we confirm expediency to administer of vinflunine for metastatic urothelial carcinoma.

Triple fixed-dose combination in the treatment of hypertension: the results of the Russian observational study TRICOLOR

The article presents the main results of the Russian post-marketing multicenter open-label program TRICOLOR (Triple fixed-dose combination in the treatment of hypertension).Aim.To evaluate the antihypertensive efficacy and tolerability of the triple amlodipine/indapamide/perindopril fixed-dose combination, as well as the adherence of hypertensive (HTN) patients to this therapy in actual clinical practice.Material and methods.The program enrolled 1247 outpatients aged 18 to 79 of both sexes with essential HTN. All patients included in the study receive amlodipine/ indapamide/perindopril fixed-dose combination. The patient’s condition was assessed according to four visits: visit 1 — at inclusion, visit 2 — after 2 weeks, visit 3 — after 4 weeks, visit 4 — after 12 weeks of follow-up. At each visit, the achievement of the target blood pressure (BP) &lt;140/90 mm Hg and &lt;130/80 mm Hg. At enrollment and visit 4, quality of life was analyzed using the SF-36 questionnaire and adherence to therapy using a validated 6-question questionnaire.Results. After 12 weeks, a significant decrease in systolic and diastolic BP was recorded — by 33,5 and 14,3 mm Hg, respectively (p&lt;0,001). Target BP &lt;140/90 mm Hg after 12-week follow-up was achieved by the overwhelming majority (93,4%) of patients. After 12 weeks, the proportion of patients with good medical adherence increased from 18,8% to 49,0%, while the proportion of patients with low adherence, on the contrary, decreased from 46,3% to 5,1%.Conclusion.The results of the TRICOLOR program demonstrate a high antihypertensive efficacy, good tolerance and medical adherence of triple amlodipine/indapamide/perindopril fixed-dose combination in patients with essential HTN in actual clinical practice in Russia.

Bleeding risk scales in patients with acute coronary syndrome: place of the ORACUL scale

Aim . To compare the diagnostic value of different bleeding risk scales in patients with acute coronary syndrome (ACS). Material and methods . The study included 1502 patients with ACS from the observational, open-label, multicenter trial ORACUL II. The mean age was 65,7±12,9 years. At follow-up visits (hospital discharge, 25, 90, 180 and 360 days from the index event), all cases of bleeding were recorded with a description of bleeding characteristics, source, severity, treatment, and classification according to the BARC, TIMI, and ISTH scales. Results. During the follow-up period, bleeding was recorded in only 170 (11,3%) patients: within the index hospitalization — in 39 (2 б 6%), within a year after the index hospitalization — in 131 (8,6%). In 19 (1,2%) patients, recurrent bleeding at several visits was recorded. In comparison with such scores as CRUSADE, ACTION-ICU, ACUITY, PARIS, the ORACUL scale had the highest predictive value in relation to the in-hospital bleeding risk. The only scale with comparable diagnostic value was the BleeMACS score. It should be noted that the ORBIT and HASBLED scores had a lower predictive value for the in-hospital bleeding risk. In general, all scores were better at predicting major bleeding and slightly worse for clinically relevant ones. Conclusion. The ORACUL scale seems to be the most acceptable tool for assessing the bleeding risk in patients after ACS in actual clinical practice in Russia.

SUPPORTING DEVICES IN THE TREATMENT OF CHRONIC HEART FAILURE IN ELDERLY AND OLD PATIENTS

Chronic heart failure (CHF) is a widespread disease associated with high rates of disability and mortality, as well as a decrease in the quality of life. Moreover, the vast majority of patients are elderly and senile. Modern surgical methods of treating heart failure are able to increase the duration and quality of life of such patients, however, the need far exceeds the volume of this care, and some highly effective methods common in Western countries are still not used in Russian clinical practice.&#x0D; Elderly age is a risk factor for the development of senile asthenia (frailty) and concomitant pathology. Large abdominal surgery is often contraindicated for patients with signs of senile asthenia, and the method of choice in patients with severe heart failure is the implantation of devices for long-term mechanical circulatory support (LT-MCS). After implantation of LT-MCS, a regression of signs of senile asthenia may be observed.&#x0D; The topic of an integrated approach to non-drug treatment of heart failure in elderly and senile patients in Russia has not been studied enough. In particular, the implantation of LT-MCS is not used in Russian clinical practice, while in many Western countries for many years it has been the main and most effective treatment for severe heart failure. Systematization of the available up-to-date information on this topic could help increase the duration and quality of life of patients with severe heart failure.

Diagnostic value of multiparametric ultrasound and the EU-TIRADS system for differentiation of focal thyroid lesions

Background. Over the last 15 years, there have been many recommendations for the management of patients with thyroid nodules, based on the assessment of various ultrasound (US) criteria in B-mode. In 2020, the EUTIRADS system (2017) was included in Russian Clinical Practice Guidelines. Shear wave elastography (SWE) increases the diagnostic efficacy of ultrasonic B-mode examination of thyroid nodules and can be recommended for inclusion in the existing classification system. Objective. To assess the diagnostic efficacy of multiparametric US combining SWE and color flow mapping in differentiating between benign and malignant thyroid nodules to define their stage according to the EUTIRADS system for deciding on the need for fine-needle aspiration biopsy. Material and methods. A total of 150 thyroid nodules from 116 patients were analyzed. Lesions were then classified according to the EU-TIRADS system, SWE with an assessment of the color map and tissue stiffness was performed (Emean). In all tumors, cytological and histological (in operated patients) verification was carried out. Results. After B-mode US with color flow mapping, differentiation of palpable thyroid abnormalities by the EUTIRADS system was carried out. 78 nodules were classified as EU-TIRADS 2 (52%), 42 – EU-TIRADS 3 (28%), 26 – EU-TIRADS 4 (17.3%), 4 – EU-TIRADS 5 (2.7%). On cytological examination 42 tumor nodules were detected. Of these, 6 (14.3%) cases were reported as papillary thyroid carcinoma, 36 (85.7%) as follicular neoplasm, 22 (61%) among the last prove to be follicular carcinoma. Qualitative and quantitative evaluation of elastograms was performed. Benign nodules were colored primarily in blue, while suspicious for malignancy revealed red areas of different size. Elasticity index in benign nodules was 24.3 ± 5.63 kPa for colloid goiter, 27.8 ± 6.35 kPa for cellular goiter; in suspicious for malignancy – 80.9 ± 50.9 kPa for follicular neoplasm, 114 ± 56.8 kPa – for papillary thyroid cancer. The stiffness cutoff value for malignancy indicated with ROC-analysis was estimated as 45.4 kPa. Mean elasticity index (kPa) was significantly higher in suspicious for malignancy nodules than in benign nodules (р &lt; 0.05). Of 120 (80%) nodules, primarily assessed as benign and defined as EU-TIRADS 2 and 3, 18 (12%) nodules after SWE revealed areas of high stiffness exceeding the cutoff value. After that, these nodules were transferred to EU-TIRADS 4 and 5, and these stages require fine-needle aspiration. Of these, 11 (7.3%) cases were reported as follicular neoplasm, 6 (4%) among the last prove to be follicular thyroid carcinoma. Conclusion. Using multiparametric approach with SWE will give the opportunity to classify correctly the nodule according to the EU-TIRADS and to identify greater number of thyroid tumors for fine-needle aspiration. SWE made it possible to increase the specificity of US using the EU-TIRADS system. The characteristics of the SWE score were: sensitivity = 81%, specificity = 90.3%, positive predictive value = 88%, negative predictive value = 91%, and accuracy of comprehensive study = 88.4%.

Pharmacological Management of Osteoarthritis With a Focus on Symptomatic Slow-Acting Drugs: Recommendations From Leading Russian Experts.

This article describes an updated stepwise algorithm for the pharmacological management of osteoarthritis (OA) to establish a treatment method for patients with OA. In step 1, background maintenance therapy includes symptomatic slow-acting drugs for OA, especially prescription crystalline glucosamine sulfate product, for which the high-quality evidence base of efficacy is unequivocal, or prescription chondroitin sulfate. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) or paracetamol only as rescue analgesia is given on top of the background therapy. Step 2: For patients with persistent OA symptoms, the use of oral NSAIDs is mandatory for maintaining supportive therapy with symptomatic slow-acting drugs for OA. It is recommended to properly stratify patients and carefully select oral NSAID therapy to maximize the benefit-to-risk ratio. Intra-articular hyaluronic acid and intra-articular corticosteroids are recommended as well in step 2 of the algorithm, especially for patients who do not respond to the previous therapies. Step 3: Duloxetine is considered along with the previous procedures, especially in patients with pain from central sensitization. Step 4: Total joint replacement is recommended for patients with severe symptoms and poor quality of life. The current guidelines and literature review provide evidence-based recommendations supported by clinical experience on how to organize the treatment process in patients with knee OA applicable in the Russian clinical practice. International evidence-based guidelines lack consensus on different treatments, including the use of prescription crystalline glucosamine sulfate, NSAIDs, and intra-articular hyaluronic acid. The content of this article needs a further discussion about the clinical evidence and harmonization of recommendations for knee OA management.

The first-line therapy of aggressive non-Hodgkin’s lymphomas in russian clinical practice: data from the EQUILIBRIUM study

The objective: evaluation of effectiveness of the first-line therapy with rituximab of B-cell lymphoproliferative diseases in Russian clinical practice in the period from 2014 to 2017.Materials and methods. The EQUILIBRIUM post-registration multicenter study included 1000 patients aged 21 to 91 years old with a verified diagnosis of B-cell non-Hodgkin’s lymphoma, or chronic lymphocytic leukemia, who received at least 4 cycles of rituximab-containing therapy with Acellbia®. The group of aggressive non-Hodgkin’s lymphomas (aNHL), which is the subject of this article, included 295 patients with a median age of 55.9 years: diffuse B-large cell lymphoma – 87 %, primary mediastinal lymphoma – 11 %, Burkitt’s lymphoma – 1 %. Group characterized by the presence of aggressive clinical signs reflecting the poor prognosis: in the majority of patients, generalized stages were diagnosed (61 %), in half of the cases (50.2 %), extranodal localization of tumor foci was detected (in 32.4 % of patients there were 2 or more). The overwhelming majority of patients (84.5 %) received adequate treatment complying with national and international recommendations (R-CHOP, R-CHOEP and R-EPOCH, high-intensity NHL-BFM-R, R-HyperCVAD and R-MACOP-B regimes). The use of R-CVP, FCR, RB, Chl-R, R-monotherapy treatment programs (which received 15.5 % of patients) was considered inadequate for this category of patients.Results. According to the results of the final assessment, high therapy efficacy was established: the overall response exceeded 90 %, complete remission was achieved in most patients with aNHL (68.5 %), partial remission – in every 5th patient (21.8 %). With a median follow-up of 15 months, 16 (5.42 %) deaths and 34 (11.53 %) events were registered. Median of event-free survival and overall survival have not been achieved. Statistically significant differences depending on first-line therapy efficacy were found in overall survival (p = 0.00000) and eventfree survival (p = 0.00000), once again confirming that the main goal of aNHL treatment is to achieve complete remission.Conclusion. Available and compliant with national clinical guidelines treatment of aNHL patients with Russian bioanalogue of anti-CD20 monoclonal antibodies (Acellbia®) demonstrates high immediate efficacy and acceptable long-term results, comparable to a retrospective analysis of previous clinical studies of the original drug rituximab.

First-line therapy of indolent non-Hodgkin’s lymphoma in routine clinical practice

The aim is to evaluate the efficacy of the first-line rituximab-containing therapy of B-cell lymphoproliferative diseases in Russian clinical practice between 2014 and 2017.&#x0D; Materials and methods. In the post-authorisation multicenter study EQUILIBRIUM were included 1 thousand patients aged from 21 to 91 with B-cell non-Hodgkins lymphoma or chronic lymphatic leukemia who had received at least 4 cycles of rituximab-containing therapy using the drug Acellbia. This article was devoted to the group of indolent non-Hodgkins lymphomas and included 253 patients: follicular lymphoma 51% of cases, marginal zone lymphoma 44% of patients, extremely rare were registered lymphoplasmacytic lymphoma and Waldenstrom macroglobulinemia in 3% and in 2% of cases, respectively. The median age in patients with indolent non-Hodgkins lymphomas was 62 years (2191 years). The vast majority of patients were diagnosed with stage IIIIV 190 (75%) of patients. More than 1/2 (53.4%) of patients in routine practice received R-CHOP therapy as a first-line. BR regimen was applied in 15.4% of cases, 14.2% of patients were treated with R-CVP/R-COP. We indicated rare use of rituximab as monotherapy in induction mode only 4.4% of patients. And 2.4% of patients were treated with fludarabine-containing therapy.&#x0D; Results. The final assessment of the effect was carried out after 68 cycles of treatment and as a result the overall effect was more than 90%: the frequency of complete remission was 61%, partial responses 32.9%. The progression admitted only in 17 (6.7%) patients among 253 observed. With a median of 15 months, the median of overall survival and event-free survival was not achieved.&#x0D; Conclusion. The use of the available and appropriate treatment according to the domestic clinical guidelines with the inclusion of the Russian biosimilar anti-CD20 monoclonal antibody Acellbia, demonstrates high direct efficacy and satisfactory long-term treatment results comparable to the retrospective analysis of the previous clinical studies of the original drug rituximab.

Russian clinical practice guidelines for the management of c1 clinical class of chronic venous disorders (reticular veins and telangiectasias)

Recently collated scientific data on the management of C1 clinical class of chronic venous disorders; wide prevalence of the disease and high variability amongst medical practitioners in relation to managing this category of patients and absence of any regulatory documents has prompted the development of clinical guidelines for the treatment of patients with reticular varicose veins and telangiectasias of the lower extremities and various parts of the body. These guidelines have been developed by a self-regulated organization Association “The National College of Phlebology”. The purpose of the de novo guidelines is to systematize the existing evidence and offer minimal standards of care for chronic venous disorders in C1 patients.

Specificities of Approaches to Anticoagulant Therapy in Comorbid Patients with Atrial Fibrillation, Diabetes Mellitus and Impaired Kidney Function

Comorbid patients with atrial fibrillation, diabetes mellitus and chronic kidney disease are at high risk of stroke. The direct oral anticoagulants are indicated for them. The choice of a drug should be based on the results of randomized clinical trials, in which the patients profile corresponds to that in the real Russian clinical practice as much as possible. Taking into account the peculiarities of comorbidity in this category of patients, the requirements for their protection should be considered comprehensively. Along with the prevention of thromboembolic complications, it is necessary that the selected direct oral anticoagulant provides a reduction in the risk of cardiovascular complications, which are typical of diabetes mellitus, and slows down the progression of renal filtration function decline. Rivaroxaban may meet these requirements; its use has significant advantage in high adherence to therapy.