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

Рекомендации по программе клинических исследований лекарственных препаратов для лечения гриппа

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.Последствия вспышек эпидемий гриппа, связанных с высококонтагиозным характером инфекции, а также ограничения существующих методов лечения и возникновение лекарственной резистентности обуславливают актуальность разработки новых лекарственных препаратов для лечения этого заболевания. Надлежащее планирование программы и проведение клинических исследований, гарантирующих получение корректных данных об эффективности и безопасности разрабатываемых препаратов, обеспечивается соблюдением рекомендаций регуляторных органов. На данный момент в Российской Федерации и Евразийском экономическом союзе отсутствуют документы, содержащие рекомендации по проведению клинических исследований противогриппозных препаратов. Существует потребность в разработке отечественного руководства, отражающего порядок проведения клинических исследований, а также регламентирующего необходимый объем данных, которые должны быть представлены при регистрации новых противогриппозных препаратов. Цель работы — изучение основных возможных регуляторных подходов к планированию программ клинических исследований лекарственных препаратов для лечения гриппа. Особое внимание уделено клиническим исследованиям III фазы как основным исследованиям, подтверждающим эффективность и безопасность препарата. Описана стратегия клинических исследований препарата, требования к объему и качеству данных по эффективности и безопасности. Материал подготовлен на основе действующих рекомендаций к планированию и разработке лекарственных средств в Российской Федерации, руководства по экспертизе лекарственных средств и рекомендаций Управления по контролю за качеством продуктов питания и лекарственных средств США. В результате проведенного анализа показана необходимость разработки отечественных рекомендаций по проведению клинических исследований препаратов для лечения гриппа с учетом специфики юридических норм и традиций российской клинической практики. Разработка таких рекомендаций приведет к ускорению ввода в практику новых эффективных препаратов против гриппа

Анализ функциональных показателей респираторной системы в разные сроки после перенесенной COVID-19

The objective: to define the type and evaluate the severity of respiratory functional disorders after COVID-19. \Subjects and Methods. A retrospective observational study was conducted. The following parameters were analyzed: demographic data, data from chest computed tomography during the acute period of the disease (CTmax), parameters of pulmonary function tests (PFT) – spirometry, body plethysmography and diffusion test. Those data were collected in 341 patients, 262 (76.8%) of them were men (median age – 48 (41.5–57) years, median durtaion of Period A (onset of COVID-19 before PFT) made 53 (28.5–111) days). Depending on duration of Period A, patients were divided into three groups: Group 1 – up to 90 days (n=221), Group 2 – 90-180 days (n=80), and Group 3 – more than 180 days (n=40). In patients of Groups 1, 2 and 3, in 68.3%, 47.5% and 32,5% of cases, respectively, disorders of diffusing lung capacity were recorded, which were associated to a greater extent with CTmax, and to a lesser extent with duration of Period A. The restrictive type of ventilation disorders was observed in 33.5% and 11% of cases in Groups 1 and 2, no restriction was detected in Group 3, airway obstruction was detected in 8%, 5%, 7.5% of cases in Groups 1, 2 and 3 respectively.Conclusion. Disorder of diffusing lung capacity was the most common functional disorder of the respiratory system after COVID-19, and therefore it is advisable to include a diffusion test along with spirometry to the examination plan of such patients.Цель исследования: определение типа и оценка выраженности функциональных нарушений респираторной системы после перенесенной COVID-19.Материалы и методы. Выполнено ретроспективное обсервационное исследование. Были проанализированы демографические данные; данные компьютерной томографии органов грудной клетки в острый период заболевания (КТмакс); показатели легочных функциональных тестов (ЛФТ) – спирометрии, бодиплетизмографии и диффузионного теста 341 пациента, их них 262 (76,8%) – мужчины (медиана возраста – 48 (41,5-57) лет, медиана срока А (начало COVID-19 до проведения ЛФТ) – 53 (28,5-111) дней). В зависимости от срока А пациенты были разделены на три группы: группа 1 – до 90 дней (n=221); группа 2 – 90-180 дней (n=80); группа 3 – более 180 дней (n=40). У пациентов 1, 2 и 3 групп в 68,3%, 47,5% и 32,5% случаев соответственно регистрировалось нарушение диффузионной способности легких, которое в большей степени зависело от КТмакс, в меньшей – от срока А. Рестриктивный тип вентиляционных нарушений был в 33,5% и 11% случаев в группах 1 и 2, в группе 3 рестрикции выявлено не было, обструкция дыхательных путей была выявлена в 8%, 5%, 7,5% случаев в группах 1, 2 и 3 соответственно.Заключение. Нарушение диффузионной способности легких является наиболее частым функциональным нарушением респираторной системы после перенесенного COVID-19, в связи с чем в план обследования таких пациентов целесообразно наряду со спирометрией включать диффузионный тест

Dopaminergic D1 receptor signalling is necessary, but not sufficient for cued fear memory destabilisation

Rationale. Pharmacological targeting of memory reconsolidation is a promising therapeutic strategy for the treatment of fear memory-related disorders. However, the success of reconsolidation-based approaches depends upon the effective destabilisation of the fear memory by memory reactivation. Objectives. Here, we aimed to determine the functional involvement of dopamine D1 receptors in cued fear memory destabilisation, using systemic drug administration. Results. We observed that direct D1 receptor agonism was not sufficient to stimulate tone fear memory destabilisation to facilitate reconsolidation disruption by the glucocorticoid receptor antagonist mifepristone. Instead, administration of the nootropic nefiracetam did facilitate mifepristone-induced amnesia, in a manner that was dependent upon dopamine D1 receptor activation, although. Finally, while the combined treatment with nefiracetam and mifepristone did not confer fear-reducing effects under conditions of extinction learning, there was some evidence that mifepristone reduces fear expression irrespective of memory reactivation parameters. Conclusions. The use of combination pharmacological treatment to stimulate memory destabilisation and impair reconsolidation has potential therapeutic benefits, without risking a maladaptive increase of fear

Treatment of recurrent vulvovaginal candidiasis -systemic or topical therapy

Despite a certain breadth of expertise and simplicity in diagnosis of candidal vaginitis, current monitoring of the etiological disease structure and a variety of drugs for treatment, the problem of therapy for recurrent forms of this nosology is still unresolved.Among the problematic non albicans (C. glabrata, C. kruzei) species, the strains mainly had a dose-dependent sensitivity to the main antimycotics (fluconazole, itraconazole, miconazole, ketoconazole,), i.e. their efficacy in vivo if taken at doses safe for humans is directly associated with the ability of the drug to accumulate in the mucous membrane, creating the necessary concentration for non albicans. In this regard, determining sensitivity of fungi in clinical practice is currently more justified for non albicans species. The studies of recent years arguing against assumptions concerning pathogenesis associated with the biofilm formation by fungi of the genus Candida on the surface of the vaginal mucosa may allow come closer to the pathogenetic substantiation of the use of local and systemic etiotropic therapy.In this case, at least two factors should be taken into account: the yeast fungus may be resistant to the used antimycotic agent, which is characteristic mainly of non-albicans species, especially C. glabrata and C. krusei, and the invasion of the fungus pseudomycelium into the vaginal mucosa.The article discusses the issues of etiotropic therapy for vulvo-vaginal candidiasis based on the current medical data. The authors provide recommendations for the use of systemic and local antimycotics and substantiated the expediency of their separate and combined use in certain clinical situations

MASS-SPECTROMETRY IN MICROBIOLOGICAL PRACTICE OF SCIENTIFIC CENTRE OF OBSTETRICS, GYNECOLOGY AND PERINATOLOGY

Aim. Comparative evaluation of species identification of microorganisms by MALDI-TOF mass-spectrometry and automatic biochemical analyzer VITEK2 Compact30. Materials and methods. Species identification of18 400 isolates of microorganisms (staphylococci, streptococci, enterococci, enterobacteria, nonfermenting gram-negative bacteria, lactobacilli, anaerobes, yeast fungi, neisseriae), isolated from vagina of pregnant and non-pregnant women and from newborns, was carried out. Identification of the isolated microorganisms was carried out by automatic bac-teriologic analyzer VITEK2 Compact30 (BioMerieux, France) and MALDI-TOF-MS analysis method on AutoflexIII (Bruker Daltonics, Germany) mass-spectrometer. Results. Comparative identification of 2005 isolates of microorganisms was carried out. Sequencing of ribosomal RNA was used as a reference method. Authenticity of species identification my MALDI-TOF-MS analysis method was: for staphylococci (95.8%), enterococci (97.5%), enterobacteria (98.4%), nonfermenting gram-negative bacteria (93.6%), P-hemolytic staphylococci (93.8%), lactobacilli (92.8%), yeast fungi (99.9%). Conclusion. Introduction of MALDI-TOF-MS analysis technology into practical work of microbiological laboratories exceeds previously used methods of microbiological testing in terms of speed, cost and authenticity of identification of a wide spectrum of microorganisms

Barium Titanate Synthesis in Water Vapor: From Mechanism to Ceramics Properties

A facile and environmentally benign method for single-phase barium titanate synthesis in a water vapor medium was studied to reveal the mechanism of phase transformation of the initial simple oxide mixture and estimate the capability of the product to be used as a raw material for low-frequency dielectric ceramics. The composition and structure of the reactants’ mixture, treated in vapor at 130–150 °C as well as at 230 °C for various time periods, were investigated by means of XRD, SEM, TEM, EDX, and FTIR methods. The kinetics of the occurring phase transformation can be described using the Johnson–Mehl–Avrami–Erofeev equation. The reaction between the initial oxides was considered as a topochemical process with an apparent activation energy of 75–80 kJ mol−1. A crucial role in this process belonged to the water vapor medium, which facilitated the generation of the reaction zone and the spreading inward of the solid particles. The synthesized tetragonal barium titanate powder (mean particle size of 135 nm) was sintered using a conventional technique at 1250 °C to obtain ceramics with grains of about 2 μm. Capacitance measurements identified a permittivity and dielectric loss factor of the ceramics that reached 3879 and 6.7 × 10−3, respectively, at 1 kHz and room temperature

STATUS OF THE DESIGN AND TEST OF SUPERCONDUCTING MAGNETS FOR THE NICA PROJECT

Abstract NICA is a new accelerator complex being under design and construction at the Joint Institute for Nuclear Research in Dubna. The actual design and the main characteristics of superconducting magnets for the NICA booster and collider are given. The magnets are based on a cold window frame iron yoke and a single-layered superconducting winding made from a hollow NbTi composite superconductor cable cooled with the forced two-phase helium flow. The first results of cryogenic tests of the magnets for the NICA project are presented