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Idiopathic thrombocytopenic purpura (ITP), or primary immune thrombocytopenia, is an orphan disease associated with thrombocytopenia. One of the most recent and promising approaches to ITP treatment is the use of thrombopoietin receptor agonists (TPO-RAs). The scope of TPO-RA use is expanding rapidly, which stimulates the development of both innovator and generic (or biosimilar) medicines. The aim of the paper was to assess TPO-RA role in ITP treatment, methodological approaches to TPO-RA development, and feasibility of using the platelet count as a pharmacodynamic marker in bioequivalence studies of peptide TPO-RAs in healthy volunteers. Clinical development of new medicines for the treatment of thrombocytopenia includes comparative, parallel-group trials lasting about a year. The standard approach to bioequivalence studies, which is based on the results of comparative pharmacokinetic studies, can be used in marketing authorisation applications for generic non-peptide TPO agonists, while peptide TPO agonists have to comply with specific requirements for biosimilar products. The orphan status of ITP does not affect the development strategy and study design, but it limits the number of patients that could be included into the study. In the absence of valid surrogate biomarkers of efficacy, demonstration of comparable clinical efficacy of the biosimilar and reference drug is usually required in a randomised, parallel, preferably double-blind comparative study. On the other hand, clinical comparability of the biosimilar and reference drug can also be demonstrated in comparative pharmacodynamic studies, if the selected biomarker is a well-established and valid surrogate marker which correlates with patient clinical outcome. Platelet count is a key parameter in both diagnosis of diseases associated with low platelet levels and assessment of treatment efficacy. Therefore, it can be used as a pharmacodynamic marker in bioequivalence studies of biosimilar peptide TPO-RAs. It was concluded that such studies could be performed in healthy volunteers, and not in patients, whose participation in clinical trials is limited due to the orphan status of ITP.

Objective : to analyze the dynamics of quality of life (QOL) in patients with prior osteoporotic vertebral compression fracture during an 18-month follow-up study. Subjects and methods . The investigation enrolled 219 patients (mean age, 67.6 years) with vertebral fracture from seven centers of the Russian Federation. QOL was assessed four times using the EQ-5D (EuroQoL-5D) and TTO (Time Trade-Off) questionnaires during an 18-month prospective follow-up study. The work was done within the framework of the International Multicenter Study ICUROS (The International Costs and Utilities Related to Osteoporotic Fractures Study) organized by the International Osteoporosis Foundation (www.icuros.org). Results and discussion . The patients with vertebral compression fracture showed a statistically significant decrease in QOL throughout the follow-up period. Immediately after the fracture, there was a dramatic decrease in the total EQ-5D score, followed by its gradual increase. However, the emerging trend in QOL recovery proved to be unstable, and by the end of the 18th month, it was significantly lower than that before the fracture. On the contrary, the TTO questionnaire showed that QOL drastically decreased immediately after fracture, but at month 4 it reached the level that was before the fracture, and remained stable until the end of the follow-up period. Conclusion . The performed investigation enabled us to obtain data on QOL using the EQ-5D (QOL assessment from the social point of view) and TTO (individual QOL assessment) in the population of residents of the Russian Federation, in men and women aged 50 years and older with osteoporotic vertebral compression fracture.

Backgraund. MiсroRNA are small regulatory factors that regulate gene expression by post-transcriptional regulation of mRNA, playing an important role in numerous cellular processes including organogenesis, apoptosis, cell proliferation and differentiation. Acromegaly causes bone fragility, but the pathogenetic mechanism is generally unknown. Aim. To evaluate levels of microRNA related to bone remodeling regulation in plasma samples from patients with acromegaly Materials and methods. Fasting plasma samples were taken and stored in aliquot at -80C from consecutive subjects with clinically evident and biochemically confirmed active acromegaly and healthy volunteers matched by age, sex and body mass index (BMI). miRNeasy Serum/Plasma Kit, TaqMan Advanced miRNA cDNA Synthesis Kit, TaqMan Advanced miRNA Assays were used to assay plasma miRNA expression. Insulin-like growth factor 1 (IGF1) was measured by immunochemiluminescence assay (Liaison). Results. We enrolled 40 subjects 22 patients suffered from acromegaly and 18 matched healthy controls) matched by sex, age and BMI. The median age of patients with acromegaly was 42 years (Q25;Q75 37;43) with no difference among the groups, p=0.205; BMI 28 (24;32) kg/m2, p=0.253. The median IGF1 in subjects with acromegaly 622 (514;1000) ng/ml was significantly higher as compared to the control group (p0.001). Patients with acromegaly had significantly higher expression of microRNA-100-5р (p=0.051), microRNA-550а-5р (p=0.048), microRNA-7b-5р (p=0.005) and microRNA-96-5р (p=0.042) among 27 bone-specific microRNA tested in plasma Conclusions. This study reveals that several microRNAs, known to regulate bone remodeling can be detected in plasma samples of patients with acromegaly and may be suggested as biomarkers for skeletal involvement in patients with acromegaly.

191 consecutive unselected children with acute lymphoblastic leukemia aged from 1 to 16 years were enrolled in the study. Bone marrow samples were obtained at the time of initial diagnostics as well as at days 15 (n = 188), 36 (n = 191), and 85 (n = 187) of remission induction. Minimal residual disease (MRD) was assessed by 6–10-color flow cytometry. Flow cytometry data at day 15 allowed distinguishing three patients groups with significantly different outcome (p ˂ 0.0001): 35.64 % patients with MRD < 0.1 % represented 5-year event-free survival (EFS) of 100 %; 48.40 % cases with 0.1 % ≤ MRD< 10 % had EFS 84.6 ± 4.2 %; 15.96 % patients with very high MRD (≥ 10 %) belonged to group with poor outcome (EFS 56.7 ± 9.0 %). At the end of remission induction (day 36) 36 children (18.85 %) with MRD higher than 0.1 % had significantly worse outcome compared to remaining ones (EFS 49.4 ± 9.0 and 93.5 ± 2.1 % respectively; p ˂ 0.0001). From a clinical standpoint it is relevant to evaluate both low-risk and high-risk criteria. Multivariate analysis showed that day 15 MRD data is better for low-risk patients definition while end-induction MRD is the strongest unfavorable prognostic factor.

Objective. To study prevalence of knee joints osteoarthritis (OA) in menopausal women and its influence on menopausal syndrome severity and quality of life of pts. Material and methods. A random sample (673 pts) from the general population of pts (6734 women) consulted by specialists due to menopausal problems was examined. History evaluation, physical examination by a rheumatologist, calculation of body mass index (BMI) and waist/hips circumference ratio (WHR) were performed. Pain (VAS), Lequesne index, modified menopausal index (MMI), depression presence and severity and quality of life (QL) with SF-36 questionnaire were assessed. OA was diagnosed according to common clinical and radiological criteria. Results. 73% of examined persons complained of joint pain. 45,1% of cases fulfilled OA criteria. 932 women with knee OA were analyzed (mean age 51,6±5,5 years). Control group included 372 women without OA (mean age 50,1+5,7 years). Frequency of manifest knee OA in women visited a specialized center due to menopausal problems was higher than in general population. Obesity doubled risk of knee OA development in menopause. Pts with knee OA had decreased QL according to physical functioning and pain scales. QL restriction on social and emotional functioning scales, general and mental health in OA pts was associated with presence of comorbid depression.

Dynamic electroneurostimulation (DENS) is a type of percutaneous electroneurostimulation with a differentiation approach to choosing exposure areas and to optimizing electrocutaneous therapeutic action on the reflexogenic areas and acupuncture points for analgesia and for the treatment of functional disorders. Objective: to study the clinical efficiency and safety of therapy using a DiaDENS-PC apparatus in the treatment of knee osteoarthritis (OA). Subjects and methods. A multicenter randomized double-blind placebo-controlled study was conducted in 132 knee OA patients with pain value above 40 mm on visual analogue scale (VAS) and Lequesne’s index of 4–12. In a study group (n = 66), DENS was carried outwith a DiaDENS-PC apparatus using a trailing electrode applicator to the knee target in a Therapy stimulation mode at a frequency 77 Hz, a power of 15 units. In the placebo group, the similar procedure was performed with a switched-on placebo apparatus that did not differ in appearance from the working apparatus; but produced no electrical pulses. The treatment cycle consisted of 10 sessions lasting 30 min. Changes in Lequesne’s algofunctional index were primary end point. The results of the Get-Up to Go test (in seconds) and changes pain on VAS and WOMAC were used as secondary end points. Results and discussion . Both groups showed a statistically significant reduction of painand improvement of Get-Up and to Go test results by the end of the treatment course (p < 0.0001). Therewas a statistically significant difference in pain in the compared groups after a treatment session during the first (p = 0.037) and second (p = 0.010) visits. The analgesic effect of therapy was observed to persist in the DENS group 2 weeks (p = 0.006) and 1 month (p = 0.070) after treatment termination. After 10 sessions, there was a statistically significant difference between the groups in the Get-Up and Go test (p = 0.033) and Lequesne’s index (p = 0.022). Both groups exhibited a significant decrease in the total WOMAC scores. In the DENS group, positive changes in all subscales were statistically significant starting from the second visit whereas in the control group, the total WOMAC scores improved only at the expense of the pain subscale.

Alexander G Chuchalin,1 Nikolai Khaltaev,2 Nikolay S Antonov,1 Dmitry V Galkin,3 Leonid G Manakov,4 Paola Antonini,5 Michael Murphy,5 Alexander G Solodovnikov,6 Jean Bousquet,7 Marcelo HS Pereira,8 Irina V Demko9 1Institute of Pulmonology, Federal Medical and Biological Agency, Moscow, Russia; 2Global Alliance Against Chronic Respiratory Diseases (GARD), Genève, Switzerland; 3GlaxoSmithKline, Moscow, Russia; 4Far Eastern Scientific Center of Physiology and Pathology of Respiration RAS (Russian Academy of Sciences), Blagoveshchensk, Russia; 5Worldwide Clinical Trials, King of Prussia, PA, USA; 6Worldwide Clinical Trials, Ekaterinburg, Russia; 7Institut National de la Santé et de la Recherche Médicale, Montpellier, France; 8Research and Development Chief Medical Office, International Medical, GlaxoSmithKline, London, United Kingdom; 9Krasnoyarsk State Medical University, Krasnoyarsk, Russia Background: Estimation suggests that at least 4 million people die, annually, as a result of chronic respiratory disease (CRD). The Global Alliance against Chronic Respiratory Diseases (GARD) was formed following a mandate from the World Health Assembly to address this serious and growing health problem. Objectives: To investigate the prevalence of CRD in Russian symptomatic patients and to evaluate the frequency of major risk factors for CRD in Russia. Methods: A cross-sectional, population-based epidemiological study using the GARD questionnaire on adults from 12 regions of the Russian Federation. Common respiratory symptoms and risk factors were recorded. Spirometry was performed in respondents with suspected CRD. Allergic rhinitis (AR) and chronic bronchitis (CB) were defined by the presence of related symptoms according to the Allergic Rhinitis and its Impact on Asthma and the Global Initiative for Obstructive Lung Disease guidelines; asthma was defined based on disease symptoms; chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume per 1 second/forced vital capacity ratio

Direct current breaker of a modular design is developed for the strong field tokamak power supply system. The power supply system comprises four 800 MW alternative current generators with 4 GJ flywheels, thyristor rectifiers providing inductive stores pumping by a current up to 100 kA for 1 - 4 sec. To form current pulses of various shapes in the tokamak windings current breakers are used with either pneumatic or explosive drive, at a current switching synchronously of not worse than 100 mks. Current breakers of these types require that the current conducting elements be replaced after each shot. For recent years vacuum arc quenching chambers with an axial magnetic field are successfully employed as repetitive performance current breakers, basically for currents up to 40 kA. In the report some results of researches of a vacuum switch modular are presented which we used as prototype switch for currents of the order of 100 kA.

The reliability and efficiency of cryogenic storage tanks and their liquefying and refrigerating systems were studied in the context of a helium cyrogenic system. The purpose was to assess the feasibility of adding such accumulators to production lines in chemical and petroleum processing to guarantee continuous operation of the line. Reliability was assessed by using such parameters as production achieved before failure, production at failure, and the time required for restoration. The probability of trouble-free operation as a function of the unit restoration time was determined. It was established that in the case of an exponential distribution function the average restoration time was independent of the amount of product in the tank. Tests show increased reliability depending on the time when the system can be supplied from a spare storage tank in the case of failure and repair of the liquefying unit.

A modern submersible centrifugal electric pumping system (SCEPS) for oil production consists of a submersible part which includes a centrifugal pump, an electric motor, a hydroprotection arrangement, a cable line, and an aboveground part that includes a control station and a transformer. The author discusses the mean service life of the submersible part of the SCEPS as the most important parameter of reliability of the SCEPS. The effect of the operating factors is assessed by calculating the mean service life of the submersible part of the typical SCEPS, making allowance for failures resulting from all causes. The mean operating time until failure of the submersible part of the new SCEPS due to design and technological error was determined.