Evidence-based medicine: new in the search for evidence

The review is focused on discussing new trends in DM, rethinking the evidence base medicine with an emphasis on demonstrating the efficacy and safety of new therapeutic agents and medical technologies, from gene editing to AI algorithms. At the same time, clinical trials of drugs are also not standing still, there is active development, new approaches, methods and designs are being developed. The process of drug development, registration and market launch of any drug takes a significant period of time, requires high financial costs and human resources. The gold standard of evidence-based medicine was initially considered to be RCTs, but at the same time, they have objective disadvantages: limited sample, inability to control all factors; insufficient follow-up time,negative impact on participants, inability to determine cause-and-effect relationships; limited measurement methods, limited budget and others. This review discusses the trends in the methodology of clinical research. The active implementation of new designs such as Adaptive Clinical Trials, "Master" protocols including Umbrella Study, Basket Study, Platform Studies, Master Observational Trials and the increased use of Single Patient Trials (N-of-1 trials) are allowing studies to become more efficient, relevant and applicable to real-life health care practice settings and patient-centered. In the review, we also look at both the pros and cons of the expanded use of biomarkers and Digital Endpoints in clinical trials and virtual clinical trials, which use mathematical models to study patient heterogeneity and its impact on various therapeutic questions. The process of expertise and regulatory approval continues to slow down the entry of drugs into the pharmaceutical market. The review considers changes in the approaches of regulators (FDA, EMEA and Russian Ministry of Health) to the drug registration procedure. The COVID-19 pandemic and sanctions have led to the need to expand the list of drugs with authorized accelerated registration. However, accelerated registration raises many questions regarding the sufficiency of the level of evidence and safety. As we can see a deep synthesis and integration of all available data is needed to achieve the next generation of evidence-based medicine. The major challenge in the next two decades will be to exploit the potential of multidimensional evidence generation by extracting, collating and generating large data sets of natural course of disease, genomics and all other omics analyses, all published clinical trials, RWD to provide next generation evidence

Systemic characteristic of safety profile of monoclonal antibodies used in rheumatology practice

Monoclonal antibodies are highly effective medications, which made a breakthrough in medicine. Taking into consideration the properties of monoclonal antibodies safety plays a key role in “risk-benefit” assessment. For monoclonal antibodies this remains studied insufficiently. The article presents a systemic characteristic of safety profile of monoclonal antibodies used in rheumatology, based on the database of spontaneous reports of the Federal Service for the Supervision of Healthcare. Specified greater alertness of Russian practitioners regarding the risk of developing tuberculosis infections in comparison to their foreign counterparts. Spontaneous reports of the development of neoplasms and deviations of laboratory tests, according to our data, on the contrary, are reported less. It is advisable to draw the attention of practitioners to the peculiarities of work with isolated deviations in laboratory tests and keep alert about the safety issues of monoclonal antibodies in general. It is important to continue monitoring to characterize delayed type D adverse drug reactions

Long term instability in the defect assembly in irradiated high resistivity silicon detectors

Different kinetic behavior has been revealed for the two types of irradiated high resistivity silicon detectors in the reactions of the interstitial carbon (C{sub i}) annealing and the formation of the C{sub i}-O{sub i} complex. In the detectors with an increased oxygen contents prolonged growth of the C{sub i}-O{sub i} complex concentration obeyed the second order reaction due to an additional source of C{sub i} atoms which were not detected by DLTS measurements. Transformation of carbon related defects has been analyzed concerning the long term instability of irradiated silicon detectors. 5 refs., 2 figs

Safety issues of monoclonal antibodies used in rheumatology

Success in practical rheumatology of the latest decade achieved mainly due to monoclonal antibodies (MABs) appearance in routine medical practice. At the same time, the experience of practical application of MABs is limited both by observation period and exposure and their clinical and pharmacological properties do not allow to fully characterizing their safety profile with the data from clinical studies. The use of MABs is associated with the risk of delayed adverse drug reactions (ADRs) — types B (immunoallergic reactions), C (new diseases) and D (delayed teratogenic and oncogenic effects). Determination of risk factors in real medical evidence is especially important. The risk factors of ADRs including serious ADRs were studied based on an analysis of the spontaneous reports database of the Federal Service for Supervision in Healthcare and the data from rheumatologic register of patients receiving MABs — the E.E. Eikhvald Clinic in North-Western State Medical University named after I.I. Mechnikov. It was shown that the factors coming from the patient (gender, age group) do not affect the severity of the risk of occurrence of ADR, including serious ADRs, while the risk factor for monoclonal antibodies can be considered the choice of tocilizumab, which increases the risk of serious ADRs

Scanning transient current study of the I-V stabilization phenomena in silicon detectors irradiated by fast neutrons

Investigation of the I-V stabilization phenomena in neutron irradiated silicon detectors has been carried out using scanning transient current technique (STCT) on non-irradiated PP{sup +}-p-n{sup +} detectors. The PP{sup +}-p-n{sup +} detectors were used to simulate the PP{sup +}-n-n{sup +} detectors irradiated beyond the space charge sign inversion (SCSI). Two mechanisms partially responsible for the I- V stabilization have been identified

Factors associated with adverse outcome among hospitalized patients with moderate to severe COVID-19

Aims. To consider factors associated with adverse outcome among hospitalized patients with moderate and severe COVID-19.Materials and methods. Data from 345 case histories of adult patients hospitalized with moderate to severe COVID-19 were analyzed in a single-center retrospective study. Characteristics by sex, age, number of days from disease onset to admission to hospital, duration of hospitalization, duration of disease, population characteristics by medical history of comorbidities and self-medication, outcome of hospitalization and medical technologies used in hospital conditions were given for the whole cohort of patients. All parameters were analyzed using descriptive statistics methods. Qualitative variables are given in absolute (n) and relative (%) values with 95% confidence interval. Continuous variables were presented as median and quartiles. Risk factors for mortality were determined across groups using the χ2  criterion and odds ratio.Results. There was no demonstrated effect of gender, degree of pulmonary tissue lesions on computed tomography data, or time of initiation of respiratory support on disease outcome. At the same time, the age older than 65 years as well as neoplasms, type 2 diabetes mellitus, dementia, Stage 3 arterial hypertension, chronic heart failure, coronary heart disease, myocardial infarction and stroke history, chronic obstructive pulmonary disease, bronchiectatic disease, urogenital diseases were the predictors of unfavorable outcome in patients with moderate and severe COVID-19 form. Prehospital use of antiplatelet agents, direct and indirect oral anticoagulants, drugs affecting the renin-angiotensin system, systemic glucocorticosteroids, antibiotics, antiviral drugs, and analgesics was associated with a decrease in the mortality rate in patients with moderate-to-severe COVID-19, as well as timely use of pronposition and transfer to intensive care unit.Conclusions. Our findings are partially consistent with previous reports on the effect of risk factors on COVID-19 outcomes

Investigation of epitaxial silicon layers as a material for radiation hardened silicon detectors

Epitaxial grown thick layers ({ge} 100 micrometers) of high resistivity silicon (Epi-Si) have been investigated as a possible candidate of radiation hardened material for detectors for high-energy physics. As grown Epi-Si layers contain high concentration (up to 2 {times} 10{sup 12} cm{sup {minus}3}) of deep levels compared with that in standard high resistivity bulk Si. After irradiation of test diodes by protons (E{sub p} = 24 GeV) with a fluence of 1.5 {times} 10{sup 11} cm{sup {minus}2}, no additional radiation induced deep traps have been detected. A reasonable explanation is that there is a sink of primary radiation induced defects (interstitial and vacancies), possibly by as-grown defects, in epitaxial layers. The ``sinking`` process, however, becomes non-effective at high radiation fluences (10{sup 14} cm{sup {minus}2}) due to saturation of epitaxial defects by high concentration of radiation induced ones. As a result, at neutron fluence of 1 {times} 10{sup 14} cm{sup {minus}2} the deep level spectrum corresponds to well-known spectrum of radiation induced defects in high resistivity bulk Si. The net effective concentration in the space charge region equals to 3 {times} 10{sup 12} cm{sup {minus}3} after 3 months of room temperature storage and reveals similar annealing behavior for epitaxial as compared to bulk silicon

Скрытая кадровая проблема российской инновационной экономики: потенциал системы профессионально-педагогического образования

The article is devoted to the necessity of development of the system of vocational pedagogic education from the position of importance of vocational education teacher’s training which can create a real opportunity to solve the problem of understaffing and middle manager supply in Russian innovative economy.Статья посвящена обоснованию необходимости развития системы профессионально-педагогического образования с позиции важности подготовки педагогов профессионального обучения для создания реальной возможности решения проблемы обеспеченности инновационной экономики России рабочими кадрами и специалистами среднего звена.Исследования выполнены при финансовой поддержке РГНФ (грант РГНФ 07-06-00606-а по проекту «Разработка компетентностной модели подготовки специалистов по обучению рабочих кадров для инновационных производственных технологий и инновационных технопарков»)

Новый исходный материал для создания перспективных сортов дыни

Relevance. The creation of varieties with a complex of economically valuable traits, resistant to biotic and abiotic environmental factors, is the main direction in melon breeding. The market for vegetables and melons and gourds is very dynamic, the demands for varieties are constantly changing, therefore, it is necessary to introduce new varieties with high taste and commercial qualities, as well as capable of producing high yields in a changing climate. The aim of the work is to produce a new melon starting material for use in the breeding process.Materials and methods. At the Bikovskaya cucurbits breeding experimental station – branch of the Federal state budgetary scientific institution "Federal scientific vegetable center", research was carried out from 2018 to 2020. The object of research is samples from the collection of VIR, foreign and domestic selection, hybrid combinations obtained as a result of intervarietal hybridization. Collection samples of melon were studied in the nursery of the source material: 84 samples from the VIR collection, 26 samples of domestic and foreign selection were studied.Results. As a result of the research, samples of melon with economically valuable traits were identified that meet the requirements of selection. Paired crosses with zoned varieties of local selection were carried out with them. As a result of hybridization, hybrid combinations F1 were obtained, from which the best ones were selected for further breeding work. The obtained collection samples and hybrid combinations were evaluated in terms of taste, yield, resistance to environmental abiofactors, dry matter content, large-fruited, attractive color of the fruit and pulp As a result received a new source material for the selection of new varieties and hybrids of melons with valuable economic traits. The resulting hybrid combinations of F1 melon were tested against an infectious background. Hybrid combinations with the best performance will be further studied in a breeding nursery.Актуальность. Создание сортов, обладающих комплексом хозяйственно ценных признаков, устойчивых к биотическим и абиотическим факторам среды, является главным направлением в селекционной работе по дыне. Рынок овощной и бахчевой продукции очень динамичен, запросы на сорта постоянно меняются, поэтому требуется внедрение новых сортов, обладающих высокими вкусовыми и товарными качествами, а также способных давать высокие урожаи в условиях изменяющегося климата. Цель работы – создать новый исходный материал дыни, обладающий параметрами, необходимыми селекционеру согласно разработанной модели сорта.Материалы и методы. Объект исследования – образцы из коллекции ВИР, зарубежной и отечественной селекции, гибридные комбинации, полученные в результате межсортовой гибридизации. Исследования проводили на Быковской селекционной опытной станции – филиале ФГБНУ ФНЦО в 2018-2020 годах. В питомнике исходного материала изучали коллекционные образцы дыни: 84 образца из коллекции ВИР, 26 образцов отечественной и иностранной селекции. Оценивали полученные коллекционные образцы и гибридные комбинации по вкусовым качествам, содержанию сухого вещества, урожайности, устойчивости к абиофакторам среды, крупноплодности, привлекательной окраске плода и мякоти.Результаты. Выделены образцы дыни с хозяйственно ценными признаками, которые отвечают требованиям селекции. Провели парные скрещивания с районированными сортами местной селекции. В результате гибридизации получены гибридные комбинации F1, из которых отобраны лучшие для дальнейшей селекционной работы. В итоге исследований получен новый исходный материал для селекции новых сортов и гибридов дыни с ценными хозяйственными признаками. Полученные гибридные комбинации F1 дыни были испытаны на инфекционном фоне. Гибридные комбинации с лучшими показателями в дальнейшем будут изучены в селекционном питомнике