Planning a clinical trial programme for direct-acting antivirals for chronic viral hepatitis C

Scientific relevance. Direct-acting antivirals have significantly improved the effectiveness of treatment for hepatitis C. However, Russia and the Eurasian Economic Union lack recommendations for the clinical development of medicinal products from this pharmacotherapeutic group.Aim. The study aimed to analyse the requirements and recommendations for planning safety and efficacy clinical trials of direct-acting antivirals for chronic viral hepatitis C, outlined in the regulatory documents of the European Union and the United States.Discussion. Upon analysing the requirements and recommendations, the authors explained the reasons behind choosing the target population and the design for the efficacy and confirmatory studies. The article covers the clinical development of direct-acting antivirals in special populations, including patients with hepatitis C and HIV co-infection, a liver transplant, and prior treatment experience. According to the authors, patients who achieved a sustained virological response should be followed up for a full year after the end of treatment in order to confirm the durability of their response. A dose-finding study should first identify a suitable dose range for monotherapy and, subsequently, for combined therapy. Current treatment regimens should be optimised, and studies should be conducted to reduce treatment duration.Conclusions. The authors outlined the main approaches and a methodology for clinical trial programmes that should take into account the degree of correlation between the efficacy of direct-acting antivirals and the genotype/subtype of hepatitis C virus

Особенности применения вертебральных методик массажа в оздоровительных и профилактических целях = Features of vertebral massage techniques in wellness and prevention

Samosyuk I. Z., Gubenko V. p., Samosyuk N. I., Tkalina A. V., Zachatko T. M., Fedorov S. M., Chuhraeva E. N., Zukow W. Особенности применения вертебральных методик массажа в оздоровительных и профилактических целях = Features of vertebral massage techniques in wellness and prevention. Journal of Education, Health and Sport. 2015;5(1):171-202. ISSN 2391-8306. DOI: 10.5281/zenodo.14834http://ojs.ukw.edu.pl/index.php/johs/article/view/2015%3B5%281%29%3A171-202https://pbn.nauka.gov.pl/works/533672http://dx.doi.org/10.5281/zenodo.14834Formerly Journal of Health Sciences. ISSN 1429-9623 / 2300-665X. Archives 2011 – 2014 http://journal.rsw.edu.pl/index.php/JHS/issue/archive Deklaracja.Specyfika i zawartość merytoryczna czasopisma nie ulega zmianie.Zgodnie z informacją MNiSW z dnia 2 czerwca 2014 r., że w roku 2014 nie będzie przeprowadzana ocena czasopism naukowych; czasopismo o zmienionym tytule otrzymuje tyle samo punktów co na wykazie czasopism naukowych z dnia 31 grudnia 2014 r.The journal has had 5 points in Ministry of Science and Higher Education of Poland parametric evaluation. Part B item 1089. (31.12.2014).© The Author (s) 2015;This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland and Radom University in Radom, PolandOpen Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited.This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercialuse, distribution and reproduction in any medium, provided the work is properly cited.The authors declare that there is no conflict of interests regarding the publication of this paper.Received: 20.10.2014. Revised 18.01.2015. Accepted: 25.01.2015.  ОСОБЕННОСТИ ПРИМЕНЕНИЯ ВЕРТЕБРАЛЬНЫХ МЕТОДИК МАССАЖА В ОЗДОРОВИТЕЛЬНЫХ И ПРОФИЛАКТИЧЕСКИХ ЦЕЛЯХ FEATURES OF VERTEBRAL MASSAGE TECHNIQUES IN WELLNESS AND PREVENTION Самосюк И.З., Губенко В.П., Самосюк Н.И., Ткалина А.В., Зачатко Т.М., Федоров С.М., Чухраева Е.Н., Жуков В.А. Samosyuk I. Z., Gubenko V. p., Samosyuk N. I., Tkalina A. V., Zachatko T. M., Fedorov S. M., Chuhraeva E. N., Zukow w. Національна медична академія післядипломної освіти імені П.Л. Шупика, Kyiv, UkraineUniwersytet Kazimierza Wielkiego, Bydgoszcz, PolskaNational Medical Academy of postgraduate education named after P.L. Shupyk, Kyiv, UkraineKazimierz Wielki University, Bydgoszcz, Poland Ключевые слова: позвоночные массажные техники; оздоровительный массаж. keywords: vertebral massage techniques; wellness. резюме Есть средство, которое уже многие века приносит людям пользу, укрепляет их здоровье, поднимает жизненный тонус, делает мышцы сильными и упругими. Одним оно продлевает молодость, другим возвращает бодрость и хорошее самочувствие. Средство это – массаж (Бирюков А.А., 1977).Массаж – это метод дозированного механического воздействия на ткани и органы больного с помощью рук массажиста в виде определенных приемов или специальных аппаратов.Вопросы, связанные с назначением массажа, требуют соблюдения медицинской этики, такта.При назначении массажа врач должен указать, в каком сочетании с другими процедурами следует применять его разновидности, должен постоянно наблюдать за больным, а массажист должен сообщать врачу обо всех отклонениях. Такой подход к применению массажа делает этот метод наиболее эффективным при лечении различных заболеваний и повреждений. abstract There is a tool that brings people for many centuries, strengthens their health benefits, raises a vitality that makes the muscles strong and supple. one it prolongs youth, the other gets the vivacity and good mood. this tool-massage (Biryukov A., 1977).Massage is a method of measured mechanical impact on the patient's tissues and organs through the hands of the masseur in the form of certain techniques or special apparatus.Issues relating to the appointment of massage require adherence to medical ethics, quantum.When a massage therapist should indicate in which combined with other procedures should apply its variety, must constantly monitor the patient and the therapist should inform your doctor about all deviations. Such an approach to the application of massage makes this method is most effective in the treatment of various diseases and injuries

Recommendations for the Programme of Clinical Trials of Medicinal Products for the Treatment of Influenza

The development of new medicinal products to treat influenza is motivated by the limitations of existing treatment options, the emergence of drug resistance, and the health consequences of influenza epidemics associated with the highly contagious nature of the virus. Proper planning and implementation of clinical programmes providing reliable data on the efficacy and safety of medicinal products under development requires adherence to recommendations of the regulatory authorities. At the moment, the Russian Federation, the Eurasian Economic Union, and the European Union lack documented recommendations on conducting clinical trials of anti-influenza medicines. There is a need in national guidelines that will reflect the procedure for conducting clinical trials and establish the required amount of data to be submitted with marketing applications for new anti-influenza products. The aim of this study was to analyse possible regulatory approaches to planning clinical development programmes for anti-influenza medicinal products. The article pays particular attention to phase III studies, as the main studies confirming efficacy and safety. The authors described a clinical development strategy and the requirements for the volume and quality of efficacy and safety data. This article is based on the current Russian recommendations for the design and development of medicinal products and guidelines on their evaluation, as well as the recommendations by the U.S. Food and Drug Administration (FDA). The analysis results demonstrate the necessity for elaborating Russian recommendations for clinical studies of medicinal products for the treatment of influenza that will take into account the national legislation and clinical development practices. Such recommendations will streamline the implementation of new effective anti-influenza medicinal products

Improving the accuracy of modeling surface roughness profiles with regular microrelief

В данной статье рассматриваются вопросы повышения точности моделирования профиля шероховатости поверхности при регулярном характере микрорельефа. В качестве исходных данных для рассмотрения взяты поверхности, обработанные чистовой токарной обработкой и алмазным заглаживанием с жесткой фиксацией индентора. Модель шероховатости поверхности основана на использовании методологического аппаратафрактальной геометрии. Построение модели основано на использовании алгоритма случайного сложения. Исходными данными являются фрактальная размерность профиля и параметры закона распределения. Показано, что использование традиционных законов распределения случайных величин: нормального (Гаусса), Рэлея и Вейбуля не позволяет получить требуемую точность моделей.This article discusses the issues of improving the accuracy of surface roughness profile modeling in case of regular microrelief character. As initial data for consideration, surfaces treated with finishing turning and diamond smoothing with rigid fixation of the indenter are taken. The surface roughness model is based on the use of themethodological apparatus of fractal geometry. The construction of the model is based on the use of a random addition algorithm. The source data is the fractal dimension of the profile and the distribution law parameters. It is shown that the use of traditional laws of distribution of random variables: normal (Gauss), Rayleigh and Weibul does not allow obtaining the required accuracy of models

Reconstruction of internal gravity wave parameters from radio occultation retrievals of vertical temperature profiles in the Earth's atmosphere

A new method for the reconstruction of internal gravity wave (IGW) parameters from a single vertical temperature profile measurement in the Earth's atmosphere has been developed. This method does not require any additional information not contained in the profile and may be used for the analysis of profiles measured by various techniques. The criterion for the IGW identification has been formulated and argued. In the case when this criterion is satisfied, then analyzed temperature fluctuations can be considered as wave-induced. The method is based on the analysis of relative amplitude thresholds of the temperature wave field and on the linear IGW saturation theory in which amplitude thresholds are restricted by dynamical (shear) instability processes in the atmosphere. When the amplitude of an internal gravity wave reaches the shear instability limit, energy is assumed to be dissipated in such a way that the amplitude is maintained at the instability limit as the wave propagates upwards. In order to approbate the method we have used data of simultaneous high-resolution balloon measurements of the temperature and wind velocity in the Earth's stratosphere over France where a long-period inertia-gravity wave has been detected. Using the radiosonde temperature data only, we have reconstructed all wave parameters, which were determined by radiosondes, with relative deviations not larger than 30%. An application of the method to the radio occultation (RO) data has given the possibility to identify the IGWs in the Earth's stratosphere and to determine the magnitudes of key wave parameters such as the intrinsic frequency, amplitudes of vertical and horizontal perturbations of the wind velocity, vertical and horizontal wavelengths, intrinsic vertical and horizontal phase (and group) speeds, kinetic and potential energy, vertical fluxes of the wave energy and horizontal momentum. The obtained results of internal wave studies in the Earth's stratosphere deduced from the COSMIC and CHAMP GPS occultation temperature profiles are presented and discussed

Description of radiation conditions and evaluation of the date of ¹³⁷Cs release to the atmosphere using the radionuclide transfer model coupled with the forecasts by the mesoscale hydrodynamic model

© 2016, Allerton Press, Inc.The estimates of 137Cs emissions from the accident happened in Elektrostal at the beginning of April 12, 2013 are presented. The transport of radionuclides and their dry and wet deposition on the surface are computed using the Lagrangian stochastic model of the NOSTRADAMUS software package worked out by Nuclear Safety Institute of Russian Academy of Sciences. Prognostic fields of wind (horizontal and vertical components) in the lower troposphere, precipitation, and vertical and horizontal turbulence diffusivity coefficients in the lower atmosphere (up to 4 km) were used as input data. Prognostic fields were obtained using the WRF-ARW numerical mesoscale model

ИМПОРТОЗАМЕЩЕНИЕ И МИГРАЦИОННАЯ ПОЛИТИКА

International migration has become an integral part of the globalization process and came to the fore on the agenda of world politics. During the given research a large amount of statistical material has been processed and visualized to assess capacity and  nature of labor markets in Russia and countries - members of the Shanghai Cooperation Organization. The basic trends, forming the key aspects of the State migration policy in this sector of economy, which are the factors of competitiveness and implementation of the program of import substitution are identified.Международная миграция стала неотъемлемой частью процесса глобализации и вышла на первый план в повестке дня мировой политики. В ходе данного исследования был обработан и визуализирован большой объем статистического материала для оценки емкости и характера рынков труда России и государств – членов ШОС. Выявлены основные в данном секторе экономики тренды, формирующие ключевые аспекты миграционной политики государства, которые являются факторами обеспечения конкурентоспособности и реализации программы импортозамещения

Organisational and methodological challenges of CAR-T manufacturing in the Russian Federation

Despite their widespread clinical implementation, chimeric antigen receptor T-cell (CAR-T) therapy products, including those manufactured by industrial processes, are still not legally available or used in the Russian Federation.The aim of the study was to describe the current challenges associated with specific aspects of CAR-T manufacturing in the Russian Federation and the potential ways to overcome them.This article discusses the regulatory, legal, organisational, and methodological challenges of CAR-T manufacturing. It analyses differences in the interpretation of CAR-T therapy products under national and supranational law. According to Russian Federal Law No. 180-FZ “On Biomedical Cell Products” of 23 June 2016, CAR-T therapy products are considered biomedical cell products. However, according to Decision No. 78 of the Council of the Eurasian Economic Commission “On the Rules of Marketing Authorisation and Assessment of Medicinal Products for Human Use” of 3 November 2016, CAR-T therapy products are considered advanced therapy medicinal products (ATMPs). This article provides a detailed overview of the difficulties in obtaining starting biological materials (i.e. the inability to consider the patient as a donor) and transferring the materials for CAR-T manufacturing (i.e. the inapplicability of national law). In addition, this article describes export aspects specific to biological materials. The authors reckon that CAR-T therapy products should be categorised as ATMPs and that the corresponding active pharmaceutical ingredients, genetically modified autologous lymphocytes, should be defined as starting materials. Therefore, genetically modified autologous lymphocytes should be regulated under the requirements for starting materials for the manufacturing of active pharmaceutical ingredients that are set forth in Decision No. 77 of the Council of the Eurasian Economic Commission “On the Adoption of the Rules of Good Manufacturing Practice of the Eurasian Economic Union” of 3 November 2016. In conclusion, the authors recognise the need for national and supranational law harmonisation. For this task, it is necessary to establish expert groups that will include clinicians, legal experts, and representatives from the relevant authorities and the pharmaceutical industry

Планирование программы клинических исследований препаратов прямого противовирусного действия для лечения хронического вирусного гепатита С

Scientific relevance. Direct-acting antivirals have significantly improved the effectiveness of treatment for hepatitis C. However, Russia and the Eurasian Economic Union lack recommendations for the clinical development of medicinal products from this pharmacotherapeutic group.Aim. The study aimed to analyse the requirements and recommendations for planning safety and efficacy clinical trials of direct-acting antivirals for chronic viral hepatitis C, outlined in the regulatory documents of the European Union and the United States.Discussion. Upon analysing the requirements and recommendations, the authors explained the reasons behind choosing the target population and the design for the efficacy and confirmatory studies. The article covers the clinical development of direct-acting antivirals in special populations, including patients with hepatitis C and HIV co-infection, a liver transplant, and prior treatment experience. According to the authors, patients who achieved a sustained virological response should be followed up for a full year after the end of treatment in order to confirm the durability of their response. A dose-finding study should first identify a suitable dose range for monotherapy and, subsequently, for combined therapy. Current treatment regimens should be optimised, and studies should be conducted to reduce treatment duration.Conclusions. The authors outlined the main approaches and a methodology for clinical trial programmes that should take into account the degree of correlation between the efficacy of direct-acting antivirals and the genotype/subtype of hepatitis C virus.Актуальность. Разработка и применение препаратов прямого противовирусного действия существенно повысили эффективность лечения пациентов с инфекцией гепатита С. Однако рекомендации по клинической разработке данной группы препаратов в России и странах Евразийского экономического союза на данный момент отсутствуют.Цель. Анализ требований и рекомендаций к планированию клинических исследований эффективности и безопасности противовирусной терапии хронического гепатита С препаратами прямого противовирусного действия на основании нормативной документации регуляторных органов Европейского союза и США.Обсуждение. В результате проведенного анализа обоснован выбор целевой популяции пациентов и дизайна клинических исследований эффективности и подтверждающих исследований, а также особенности разработки на клиническом этапе в особых группах пациентов, в том числе с коинфекцией гепатитом С и вирусом иммунодефицита человека, пациентов с трансплантатом печени и наличием предшествующего опыта лечения. Отмечено, что за пациентами, достигшими устойчивого вирусологического ответа, требуется наблюдение в течение одного полного года после завершения терапии для подтверждения длительности эффекта. В исследованиях по подбору дозы рекомендовано сначала изучить достаточный диапазон доз в режиме монотерапии, а затем проводить исследования комбинированного применения препарата. Показана необходимость совершенствования существующих схем лечения и изучения возможности сокращения продолжительности курса лечения.Выводы. Сформулированы основные подходы и определена методология программы клинических исследований с учетом высокой степени корреляции эффективности указанных препаратов с генотипом и подтипом вируса гепатита С, которым инфицирован пациент