Innovative approaches in assessing social and economic damage from road accidents

The article is devoted to the review of approaches and analysis of methods for assessing the cost of social and economic damage from road accidents. The urgency of the problem is determined by the high rates of accidents and deaths. Social and economic consequences of non-underestimation of human life in the country can negatively affect the individual quality of life of Russians, and state level in the form of damage from losses of the economically active population and the state's compensation for damages to the families of victims. Therefore, the development of new theoretical approaches to assess social and economic damage from accidents, which meet modern conditions, has become of particular relevance in Russia. The article considers methodological peculiarities of accounting and assessment of the consequences of road accidents both within the framework of international experience and within the framework of the Russian Federation, which has allowed developing scientifically grounded approach to assessing damage from road accidents in our country, this in its turn contributes to reducing mortality rates through development and financial support of road safety programs. Based on the author's research, an innovative approach to assessing social and economic losses from road accidents in the Russian Federation has been formed, which focuses on damage resulting from death and injury of people, taking into account age and gender structure of the deceased, wounded people and regional characteristics, damage as a result of damage to vehicles and goods, damage as a result of damage to roads and road structures, as well as moral damage.peer-reviewe

Innovation activity of Russian business entities and its determinants

Market growth prospects of the entities during the innovation activity could not be sized up due to lack of systematized and shared view at factors defining the innovation activity of business entities. The paper presents key factors of innovation activity along with its classification by levels (macro, meso, and micro). Authors suggested a specific innovation activity evaluation framework as well as multivariate regression model of assessing the structure and key-factors’ effect on business activity is developed.peer-reviewe

Development of an Approach to the Assessment of Changes to Approved Biological Products

The need to strengthen the post-approval regulation of biological products stems from their increasing role in the treatment of serious human diseases. Until recently, there were open questions on the classification of changes and supporting data necessary to confirm the comparability of a biological medicinal product before and after any changes, as well as on the procedures and deadlines for the submission and approval of variations. In October 2017 the WHO Expert Committee on Biological Standardisation developed and published the «Guidelines on procedures and data requirements for changes to approved biotherapeutic products». The WHO recommendations are primarily aimed at resolving the complexities and current problems in the global life cycle management of biotherapeutic products. Guidelines suggest approaches that ensure continued quality, efficacy, and safety of this group of products, as well as continuity in supply and access. The purpose of this paper was to analyse the WHO recommendations on post-approval changes to biotherapeutic products in order to develop harmonised approaches to the assessment of post-approval changes to biological medicinal products in the Russian Federation. The categories of quality changes, supporting data, conditions to be fulfilled, procedures and deadlines set forth in this paper can serve as a basis for further improvement of the national regulatory and methodological framework

Planning of clinical trial programmes for medicines for the treatment of obesity

Scientific relevance. Obesity is a significant public health problem. Currently, the Russian Federation and the other Member States of the Eurasian Economic Union (EAEU) do not have regulatory documents and recommendations for planning clinical trials (CTs) of new (original) medicines for the treatment of obesity.Aim. The study aimed to provide recommendations on the basic principles of planning and conducting CTs of medicines for the treatment of obesity.Discussion. The authors reviewed the requirements for conducting CTs of medicines for the treatment of obesity set forth by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). In addition, the authors analysed approaches to CTs providing for a reliable evaluation of the efficacy and safety of medicines for the treatment of obesity. The primary endpoint of such CTs is a statistically significant loss of at least 5% of the baseline weight after 12 months of treatment. Secondary endpoints include assessments of abdominal obesity reduction, subcutaneous and visceral fat reduction, and the medicinal product’s effect on maintaining a reduced body weight.Conclusions. In addition, CTs should investigate the effects of treatment on cardiovascular risk factors and cardiovascular morbidity/mortality. A CT protocol should define the intercurrent events that should be considered in the analysis of trial results. When investigating the safety of medicines for the treatment of obesity, studies should focus on neuropsychiatric safety, the potential for abuse/addiction and withdrawal reactions, and the development of valvulopathy and pulmonary hypertension. These recommendations may be of use to experts evaluating clinical development programmes or marketing authorisation submissions for medicines for the treatment of obesity

Formation of the investment portfolio on the basis of adaptive-discrete model, considering globalization effects

The article implements the idea of usage of universal properties of an adaptive regression modeling procedure in the processes of making investment solutions with predictor optimality. The necessity of using of universal properties is that the same value in the stock market can be predicted on the basis of inertial changes, and on the basis of discrete, discontinuou

INFLUENZA AND ACUTE VIRAL RESPIRATORY INFECTIONS IN THE PRACTICE OF THE EMERGENCY CREWS OF MOSCOW

Influenza and acute viral respiratory infections have a great social significance during epidemic rise of morbidity and demand differential diagnosis of pneumonia with bacterial etiology and consultation with an infectious disease doctor in case of seeing patients in non-core hospitals. This article highlights the problem of influenza and acute respiratory viral infections’ early diagnosis. Clinical manifestations of influenza and other respiratory extremely similar. The differential diagnosis must take into account the presence of mixed infection in the same patient. According to the results of consultative infectious ambulance teams in 2014-2016, quality of diagnostics of this infectious pathology was examined. Observed deaths in persons later seeking medical treatment, not receiving timely antiviral therapy and related to high-risk groups: patients with obesity, chronic alcohol intoxication, diabetes, pregnant women. Influenza and acute viral respiratory infections, more complicated by pneumonia, people in the older age group, indicating the need for timely medical evacuation of patients older than 60 years. In some cases, in the diagnosis of influenza was helped by the results of laboratory studies (especially the trend to leukopenia) and a positive rapid test. It should be noted that a negative rapid test for influenza was not a reason for exclusion of the diagnosis “influenza”

Regulation of acetylcholinesterase activity by nitric oxide in rat neuromuscular junction via N-methyl-d-aspartate receptor activation

Acetylcholinesterase (AChE) is an enzyme that hydrolyses the neurotransmitter acetylcholine, thereby limiting spillover and duration of action. This study demonstrates the existence of an endogenous mechanism for the regulation of synaptic AChE activity. At the rat extensor digitorum longus neuromuscular junction, activation of N-methyl-d-aspartate (NMDA) receptors by combined application of glutamate and glycine led to enhancement of nitric oxide (NO) production, resulting in partial AChE inhibition. Partial AChE inhibition was measured using increases in miniature endplate current amplitude. AChE inhibition by paraoxon, inactivation of NO synthase by Nω-nitro-l-arginine methyl ester, and NMDA receptor blockade by dl-2-amino-5-phosphopentanoic acid prevented the increase in miniature endplate current amplitude caused by amino acids. High-frequency (10 Hz) motor nerve stimulation in a glycine-containing bathing solution also resulted in an increase in the amplitude of miniature endplate currents recorded during the interstimulus intervals. Pretreatment with an NO synthase inhibitor and NMDA receptor blockade fully eliminated this effect. This suggests that endogenous glutamate, released into the synaptic cleft as a co-mediator of acetylcholine, is capable of triggering the NMDA receptor/NO synthase-mediated pathway that modulates synaptic AChE activity. Therefore, in addition to well-established modes of synaptic plasticity (e.g. changes in the effectiveness of neurotransmitter release and/or the sensitivity of the postsynaptic membrane), another mechanism exists based on the prompt regulation of AChE activity. NO molecules depress AChE activity in the neuromuscular junction thereby enhancing endplate current amplitude. Endogenous glutamate, released into the synaptic cleft as a co-mediator of acetylcholine, is capable of triggering the NMDA receptor-/NO synthase-mediated pathway that modulates synaptic AChE activity. In addition to well-established modes of synaptic plasticity another mechanism exists based on the prompt regulation of AChE activity. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd

A thorny pathway of macrophage activating factor (GcMAF): from bench to bedside

Vitamin D3 Binding Protein (DBP) is a multifunctional glycoprotein whose main role is to transport vitamin D3 and its metabolites, but it also is the precursor of the macrophage activating factor (GcMAF). DBP is converted to GcMAF as a result of site-specific selective deglycosylation under the action of β-galactosidase and sialidase, localized on activated B and T cells, respectively. GcMAF exerts its biological activity primarily as the capability of activating macrophages by enhancing their phagocytic function and producing ROS. Activation results in elevated expression of the specific macrophageal surface receptors involved in the recognition of tumor-associated antigens, as well as in the implementation of direct anticancer activity by inducing the apoptosis or necrosis of tumor cells. Increased interest in GcMAF is associated with its potential to be used in the clinic as a new antitumor drug. Besides its anti-tumor activity, GcMAF exerts a potential against a number of viral and neurodegenerative diseases associated with increased activity of N-acetylgalactosaminidase (nagalase) in the blood serum of patients. Nagalase is an enzyme that completely (rather than selectively) deglycosylates DBP so it cannot be converted to GcMAF, leading to immunodeficiency. Circulating DBP is composed of unmodified and O-glycosylated molecules with the glycosylation degree being dependent on the allelic variants of the gene encoding DBP. The role of DBP in the resistance of organism against a number of diseases is supported by the increased risk of a variety of severe illnesses (amyotrophic lateral sclerosis, colorectal cancer etc.) in patients deficient for GcMAF due to homozygosity for defective DBP alleles. In this review, we also will examine in detail the current data i) on the structure and functions of DBP, as the main precursor of GcMAF, ii) on the main mechanisms of GcMAF anticancer effect, iii) on the tumor strategy for neutralizing GcMAF activity, iv) on the results of GcMAF clinical trials in various cancers; and will discuss the available controversies regarding the positioning of GcMAF as an effective antitumor drug

Рекомендации по программе клинических исследований лекарственных препаратов для профилактики и лечения сахарного диабета

Diabetes is a serious public health problem and one of the major chronic noncommunicable diseases. A lengthy stepwise treatment, and the need for an individualised approach to antidiabetic therapy, pose serious challenges for medicine developers. For all new hypoglycaemic medicines, there has been a centralised authorisation procedure in the European Union (EU) since 2005, which ensures a unified approach to efficacy and safety assessment. The aim of the study was to analyse current requirements for planning clinical trials of hypoglycaemic medicines containing new active substances (except for insulin products). The recommendations for diagnosis and treatment of type 2 diabetes, prepared by the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) in 2019, suggest a step-by-step approach to intensification of treatment to maintain glycaemic targets, which takes account of concomitant cardiovascular or other diseases, and clinical characteristics of patients. The analysis of EASD/ADA documents and scientific literature helped to develop recommendations on the basic principles of planning and conducting clinical trials at the final stages of hypoglycaemic medicine development. The paper describes new approaches to clinical trials, which allow for a more reliable assessment of the treatment effectiveness. The strategy for the assessment of therapeutic effect should be carefully planned, justified, and reflected in variables of interest, clinical trial design, and statistical analysis of the trial results. The main efficacy criterion in confirmatory clinical trials of hypoglycaemic medicines should be the demonstration of benefits in improving glycaemic control. The medicine’s effect on the body weight may be considered as a secondary endpoint. An essential requirement is confirmation of the medicines’ cardiovascular safety, while potential additional benefits are reduction or prevention of risks of cardiovascular disease development. The clinical trial protocol should provide definitions for intercurrent events and hypoglycaemia. A comprehensive safety study of a new hypoglycaemic medicine should involve identification of anticipated or known side effects characteristic of a particular pharmacological class. The provided recommendations may be helpful for medicine developers, and for experts who perform assessment of clinical trial programmes and regulatory submissions for hypoglycaemic medicines.           Сахарный диабет представляет собой значимую проблему общественного здравоохранения, является одним из основных хронических неинфекционных заболеваний. Длительность лечения, поэтапность и необходимость индивидуального подхода при проведении терапии сахарного диабета ставят серьезные задачи перед разработчиками новых препаратов. На территории Европейского союза с 2005 г. действует централизованная процедура регистрации новых гипогликемических препаратов, что обеспечивает единство подходов к оценке их эффективности и безопасности. Цель работы – анализ актуальных требований к планированию клинических исследований гипогликемических препаратов, содержащих новые действующие вещества (исключая препараты инсулина). Рекомендации Консенсуса Европейской ассоциации по изучению сахарного диабета (EASD) и Американской диабетической ассоциации (ADA) по диагностике и лечению сахарного диабета 2 типа 2019 г. предлагают пошаговый подход к интенсификации терапии для достижения гликемической цели, который учитывает наличие у пациента сердечно-сосудистых и других заболеваний, функциональных особенностей организма. На основании проведенного анализа документов EASD/ADA и научной литературы предложены рекомендации по основным принципам планирования и проведения клинических исследований на завершающих этапах разработки гипогликемических лекарственных препаратов. Описаны новые подходы к проведению клинических исследований, позволяющие наиболее достоверно оценить эффективность терапии. Стратегия оценки терапевтического эффекта препарата должна быть тщательно спланирована, обоснована, отражена в переменных интереса, дизайне клинического исследования и статистическом анализе его результатов. Основным критерием эффективности в подтверждающих клинических исследованиях гипогликемических лекарственных препаратов должна быть демонстрация преимуществ в отношении улучшения контроля гликемии. В качестве вторичной конечной точки может рассматриваться влияние препарата на массу тела. Обязательным требованием является подтверждение сердечно-сосудистой безопасности препарата и возможные дополнительные преимущества в отношении уменьшения риска развития сердечно-сосудистых заболеваний. В протоколе клинического исследования требуется представить определение интеркуррентных событий и гипогликемии. Всестороннее изучение безопасности нового гипогликемического препарата должно включать выявление предполагаемых или известных эффектов соответствующего класса лекарственных препаратов. Представленные рекомендации могут использоваться разработчиками лекарственных препаратов, а также экспертами, осуществляющими оценку программы клинической разработки гипогликемических препаратов и экспертизу с целью регистрации.