The aim of the study was to evaluate the possibility of achieving control of severe bronchial asthma (BA) using genetically engineered biological therapy with Dupilumab. Materials and methods. The study included 32 patients with severe bronchial asthma (8 (25 %) men, mean age 58 [28; 65]) years, 24 (75 %) women, mean age 50 [26; 62] years) who received additional therapy with Dupilumab for 12 months. The endpoint of the study was 12 months of therapy with Dupilumab. The allergic phenotype of the disease was recorded in 19 (60 %) patients, a quarter of patients had non-allergic phenotype, and 5 (15 %) patients had mixed BA. Results. Before the introduction of genetically engineered biological therapy, patients had an extremely high daily need for emergency medications — about 9 times a day, 4 or more exacerbations were recorded during the previous 12 months before inclusion in the study. After 12 months of additional therapy with Dupilumab, a significant reduction in symptoms was noted — 22 (70 %) patients did not have asthma attacks at all. In 6 patients (19 %), 1 exacerbation of bronchial asthma developed during the next 12 months, which the patients coped with independently using nebulizer therapy at home. Before the start of genetically engineered biological therapy, 10 people (31 %) received systemic glucocorticosteroids (OCS) at a dose of 10 to 5 mg of prednisolone. After 4 months, 22 (70 %) patients receiving hormonal drugs managed to stop them. After 12 months, no patients took OCS. Conclusion. During 12 months of additional therapy with Dupilumab, patients managed to completely stop taking OCS. Exacerbations requiring hospitalization were absent in all patients included in the study. Complete control was achieved by 22 (69 %) subjects, partial control was achieved by 10 (31 %). There was no need for short-acting beta-agonists (SABA) in 27 (85 %) subjects.

Bronchial asthma (BA) is one of the most common respiratory diseases. The primary purpose of BA treatment is to achieve disease control on a case-to-case basis. The disease control concept refers to not only the current control over symptoms, but also the risk of adverse outcomes in the future. Inhaled glucocorticosteroids (ICS) remain the mainstay of treatment for adult patients with AB. Long-acting e2-agonists (LABA) are recommended to all patients who continue to experience symptoms as add-on therapy to medium- or high-dose ICS as the preferred option for controlled treatment at stages 4 and 5. However, despite LABA / ICS therapy, some patients may still exhibit uncontrolled asthma, in which case long-acting anticholinergics (LAMA) should be included in the treatment regimen. Concurrent use of multiple and often different medications poses a significant burden for patients with BA. The presence of LABA / LAMA / ICS in a single inhaler can ensure the best medication adherence in patients with asthma. This therapy option is indicated for patients with persistent asthma uncontrolled with medium- or high-dose ICS + LABA and patients receiving medium- and high-dose ICS / LABA / tiotropium bromide in multiple inhalers. This will enhance BA control, which has been proven in a number of clinical studies. In the clinical case under discussion, a patient with severe BA had to be prescribed a disease-modifying drug in the form of a triple fixed-dose combination in a single inhaler to improve disease control, which led to increased tolerance of physical activities, absence of asthma attacks, shortness of breath, night symptoms, the need for short-acting e2-agonists (SABA), and calls for emergency medical service.

The purpose of the study was to assess the clinical and functional parameters of patients with severe asthma to optimize drug therapy in order to improve the control. Methods. We examined 45 patients diagnosed with severe asthma: 34 (75%) women and 11 (25%) men. The median age was 56 (30; 70) years. 37 (82%) respondents had an allergic asthma phenotype, while 8 (18%) patients had non-allergic asthma. As for the comorbidities, allergic rhinitis was the most common (56%), intolerance to NSAIDs was observed in a third of the studied patients, and chronic polypous rhinosinusitis (CPRS) was diagnosed in 20 (44%) patients. Results. Each respondent was diagnosed with at least 1 marker of T2 immune response. Before the initiation of biologics, the patients experienced frequent asthma attacks daily, and a high need for SABA was determined. None of the patients had asthma symptoms under control. After 4 months, the control indicator, AST test score, improved to 22 [20; 25] points. The low FEV 1 of 65.5% (48.6; 76.8) and FEV 1 /FVC of 61.4% (43.9; 72.1) before the initiation of biological therapy should be noted. However, the pulmonary function parameters improved after 4 months – the FEV 1 increased to 82% (51.0; 93.4), and FEV 1 /FVC raised to 71.3% (51.2; 74.4). Conclusion. All patients were diagnosed with at least 1 marker of T2 immune response. Thus, the correct selection of patients with T2 immune response markers makes it possible to prescribe personalized drug therapy, which, in turn, ensures the achievement of control over asthma. After 4 months biological therapy, the patients noted the absence of exacerbations, a decrease in the need for SABA, and an improvement in pulmonary function.

Asthma is a global health problem affecting countries worldwide. Currently, there is an increasing prevalence of patients with asthma who also suffer from concomitant cardiovascular pathology. The most common comorbidity is the coexistence of asthma and chronic heart failure (CHF). Given the overlap in clinical symptoms, differential diagnosis of these diseases at onset can be quite challenging. This raises the question of the possibility of early diagnosis of CHF in patients with asthma and the need to continue searching for etiopathogenic markers, as most laboratory indicators do not have 100% pathognomonic value. An analysis of available literature data on potential CHF markers in patients with a history of asthma was conducted. Information queries included the following set of keywords: "markers of chronic heart failure, bronchial asthma, N-terminal pro-brain natriuretic peptide (NTproBNP)." It was found that NTproBNP, currently considered the "gold standard" for diagnosing CHF, does not have absolute prognostic value, indicating the need for further search for highly sensitive and more specific markers. The article presents new biological markers, such as the fibrosis marker galectin-3, gamma-glutamyltransferase, growth stimulating factor, pentraxin 3, and tenascin C, which could be used for forecasting and risk stratification of heart failure development. It is concluded that the search for new biological markers would facilitate earlier diagnosis of CHF, thereby enabling timely therapy initiation, which could help reduce hospitalizations and improve the quality of life of patients.

Приступообразный кашель, одышка, свистящее дыхание часто встречаются в практике врача-аллерголога и в первую очередь требуют исключения диагноза бронхиальной астмы. В качестве начального исследования для выявления и оценки степени тяжести обструкции дыхательных путей у всех пациентов с подозрением на астму рекомендуется проводить спирометрию, однако не всегда выявление положительной пробы с бронходилататором подтверждает именно этот диагноз. Несмотря на то что многие пациенты являются коморбидными, необходимо тщательно анализировать результаты обследования не только в данный момент времени, но и в динамике и всегда иметь онкологическую настороженность, особенно в отношении пожилых пациентов. Представлен клинический случай пациентки, госпитализированной в аллергологическое отделение с клиникой бронхообструктивного синдрома, который нарастал после перенесенных повторных пневмоний. Однако, согласно анализу данных мультиспиральной компьютерной томографии легких в динамике, причиной симптомов явилось новообразование легких. Представленный случай демонстрирует необходимость персонифицированного подхода к каждому пациенту с учетом того, что правильная и как можно более ранняя диагностика является основой повышения эффективности терапии и улучшения качества жизни.

Aim. The study of clinical and functional characteristics, features of pharmacotherapy and the level of adherence in severe and difficult-to-treat bronchial asthma in real clinical practice to optimize pathogenetic therapy measures.Materials and methods. 143 patients diagnosed with severe bronchial asthma were examined. Patients were divided into 2 groups: difficult-to-treat bronchial asthma and severe bronchial asthma. Examination methods included: anamnestic method, physical examination, filling out the ACQ-5 questionnaire, AST, the Morisky-Green questionnaire, instrumental (spirography with bronchodilator), laboratory methods.Results. Most of the studied patients were patients with difficultto-treat bronchial asthma (55%), while patients with severe bronchial asthma accounted for 45% of the total number of patients. We noted that patients of the 1st group were more often hospitalized due to an exacerbation of the disease. There were no significant differences in clinical and functional parameters and in the structure of comorbidity. All patients received the amount of basic therapy corresponding to stages 4 and 5 in accordance with GINA 2022. According to the results of the Morisky-Green questionnaire, lack of adherence was recorded in 79% of cases. Incorrect inhalation technique among patients of the 1st group was recorded in 32% of cases, while an uncontrolled course of concomitant pathology was detected in a third (33%) of cases. In group 2, 94% of patients had at least one marker of T2 inflammation.Conclusions. Among patients with difficult-to-treat asthma, truly severe bronchial asthma was confirmed in 45% of cases, bronchial asthma difficult-to-treat - in 55% of cases. Lack of adherence (79% of cases), uncontrolled course of comorbidity (33%), and incorrect inhalation technique (32% of cases) are the main factors hindering the achievement of control in the difficult-to-treat asthma group. For patients with difficult-to-treat asthma, it is necessary to take measures aimed primarily at improving adherence to treatment.

The medical and social significance of cardiovascular diseases remains high. One of the factors that determine cardiovascular risks is metabolic syndrome. As a result of excessive accumulation of lipid and carbohydrate metabolism products in metabolic syndrome, oxidative (oxidative) stress develops. The article considers both domestic and foreign scientific studies, which highlight various aspects of the influence of reactive oxygen and nitrogen species, as well as other free radicals on the formation of oxidative stress in pathological conditions that are part of the metabolic syndrome complex. This describes the mechanisms of the formation of chronic inflammation through excessive secretion of pro-inflammatory cytokines and adipokines, activation of the transcription factor NF-kB, as well as damage to the antioxidant system in obesity. Separately, a number of mechanisms of the stimulating effect of adipokines: leptin, adiponectin, chimerine, omentin 1, resistin, on the formation of oxidative stress have been noted. The ways of activating the polyol pathway, as well as diacyl-glycerol — protein kinase C — the signaling pathway of oxidative stress, the formation of mitochondrial dysfunction is described. As a result of which there is an excessive production of free radicals in insulin resistance, diabetes mellitus and macroand microvascular complications of diabetes. In addition, the influence of oxidative stress directly on the formation of cardiovascular diseases of atherosclerotic genesis, as well as arterial hypertension, has been shown.

The paper considers the publications that reports endocrine changes in patients with SARS-CoV-2 and SARS-CoV. In the electronic database PubMed, the investigators sought by using the terms of subject headings (MESH) associated with SARS-CoV, SARS-CoV-2 and different hormones. To search for the publications, the interval was taken from January 2002 and to the present time, since the outbreak of SARS-CoV occurred in 2002. The articles dealing with the outbreaks of both viruses were considered. The viruses of the family SARS-CoV(-2) cause systemic diseases involving many organs. The patients are observed to have hormonal and metabolic disorders. There are data on the damaging effect of both SARS-CoV and SARS-CoV-2 on the pancreas and thyroid, adrenals and gonads.

BACKGROUND: Bronchial asthma is one of the most common and socially remarkable diseases in humans. The uncontrolled course of asthma remains a leading problem in the management of patients with this disease. Patients who cannot achieve control include a special group with severe asthma. AIM: Comprehensive assessment of clinical, functional, and immunological features and the pharmacotherapy of severe bronchial asthma in real clinical practice to optimize basic pathogenetic therapy. MATERIALS AND METHODS: In all, 83 patients diagnosed with severe asthma were examined. Patients with severe asthma were divided into two groups: patients with and without fixed airway obstruction. Plasma concentrations of interleukin (IL)-4, IL-5, IL-9, IL-13, periostin, cathepsin S, and transforming growth factor (TGF)- were determined via solid-phase enzyme immunoassay. Immune status was investigated using a NAVIOS flow cytometer. RESULTS: Both groups of severe bronchial asthma patients showed a decrease in helper T-cell and immunoregulatory index levels with simultaneous increases in cytotoxic T lymphocytes, natural killer T cells, naive T lymphocytes, activated T and B lymphocytes, and phagocytic index compared with the controls. No differences were observed in the immune status between the groups, and the resulting changes were independent of the presence or absence of fixed obstruction. Both study groups exhibited increases in the levels of cathepsin S and TGF- in the plasma compared with the controls. We identified two remarkable risk factors for forming fixed obstruction: taking SABA more than four inhalations per day (odds ratio (OR)=4.2) and FeNO concentration 20 ppb (OR=6.0). A remarkable improvement was observed in the clinical condition of patients with severe asthma with fixed obstruction while receiving genetically engineered biological therapy for a year. CONCLUSIONS: To date, no unambiguous explanation is available for the mechanisms of implementation of pathobiochemical reactions in the bronchial wall in severe asthma, leading to the development of fixed airway obstruction. Severe asthma is variable and depends on the correct choice of management tactics.

Bronchial asthma and obesity are showing a steady increase in incidence worldwide, incurring significant economic losses for society. There is no doubt about the pathogenetic role of obesity in the development of cardiovascular events. The purpose is to analyze the current data that demonstrate the impact of asthma and obesity association on the increased risk of cardiovascular disease. The critical role of obesity is noted as a risk factor for the development and progression of both bronchial asthma and cardiovascular diseases. The review emphasizes importance of determining cardiovascular and cardiometabolic risks according to generally accepted scales specified in clinical guidelines. As part of the review, the combination of bronchial asthma and cardiovascular diseases was analyzed, and their etiopathogenetic interdependence was noted. The role of metabolic processes in adipose tissue is shown, which can increase both inflammation in bronchial asthma and lead to the progression of cardiovascular diseases. Understanding the mechanisms of mutual influence will allow for personalized treatment, as well as the prevention of cardiovascular accidents in patients with bronchial asthma and obesity.

Patients with severe bronchial asthma, which remains uncontrolled despite the optimal basic therapy, carry a significant healthcare burden and require substantial financial investments. Severe asthma is a heterogeneous airway disease with complex pathophysiological mechanisms that can be broadly divided into inflammatory pathways with eosinophilic and non-eosinophilic inflammation. Aim. This study aimed to analyze the literature data on the use of targeted genetic engineering therapy in patients with severe bronchial asthma, as well as to analyze the organization of immunobiological therapy in the Krasnoyarsk Territory. The addition of targeted drugs for severe eosinophilic bronchial asthma based on phenotyping has proven to be effective and is recommended by all current guidelines. Today, several biologics targeting specific endotypes and phenotypes has been approved for the treatment of severe eosinophilic asthma worldwide. These are antibodies binding immunoglobulin E (omalizumab), antagonists of interleukin-5 (mepolizumab, reslizumab) and its receptor (benralizumab), as well as antibodies selectively binding to the IL-4 and IL-13 receptors (dupilumab). Eosinophilic inflammation therapy is a relatively new direction of asthma treatment, and understanding its long-term efficacy and safety is important. Conclusion. It is essential to differentiate patients with severe eosinophilic asthma from the general cohort of asthma patients, timely refer them to specialists who can prescribe this therapy and have experience with it, select the drug correctly, and monitor the patients during the treatment. This article describes organization of biological therapy for patients with severe eosinophilic bronchial asthma in the Krasnoyarsk Territory.

Кратко описаны основные причины медиастинальной лимфаденопатии, представлен клинический случай, который демонстрирует трудности дифференциальной диагностики медиастинальной лимфаденопатии у пациента, имеющего неспецифические проявления заболевания. Особенностью данного случая является обнаружение во внутригрудных лимфатических узлах гранулематозного воспаления, характерного для туберкулеза, при интактной легочной ткани и отсутствии специфического поражения бронхов и трахеи, а также при отсутствии анамнестических и клинических данных о вероятном туберкулезе. Только гистологическое исследование лимфатических узлов в данном случае явилось ключевым методом для определения диагностической и лечебной тактики.

The review analyzes the role of microRNAs in the pathogenesis of bronchopulmonary diseases. The universality of the mechanisms underlying epigenetics causes a continuously growing interest in research in this field in various fields of medicine. Research in the field of epigenetics not only allows us to expand knowledge in the field of etiology and pathogenesis, but also helps to explain the heterogeneity of the disease. Currently, biomarkers used in determining the phenotype of bronchial asthma or COPD are not able to display the variety of pathological processes involved in the pathogenesis of the disease at the molecular level. It is noteworthy that microRNAs retain their stability in various body environments, are resistant to high temperatures, pH fluctuations, and freeze-thaw cycles, which greatly simplifies the process of detecting these molecules in biological fluids. The amount of detected microRNA is highly specific for a particular pathological process occurring intracellularly. Currently, biomarkers used in determining the phenotype of bronchial asthma or chronic obstructive pulmonary disease are not able to reflect the variety of pathological processes involved in the pathogenesis of the disease at the molecular level. For both diseases, the key links are known to be inflammation, airway remodeling, and an abnormal response of epithelial cells to external stimuli. Thus, there is a great potential for using microRNAs in clinical practice: as noninvasive biomarkers reflecting key points of pathogenesis, as a prognostic biomarker predicting response to therapy, and possibly in the future as new therapeutic targets.

Low awareness of doctors of various specialties about such an initial defect in immunity as hereditary angioedema leads to poor detection of this disease, as a result of which patients often receive ineffective drugs for a long time and are at risk of developing life-threatening complications. A clinical case was presented of a patient whose diagnosis of hereditary angioedema was first established at the age of 65 despite a long history of edema. There were no urticarial rashes. For edema for 3 years, the patient took Loratadine, systemic glucocorticosteroids were repeatedly administered. In addition, for many years she was worried about abdominal syndrome with an episode rate of up to several times a week, for the purpose of stopping which she used Tempalgin. There is a burdened family history of angioedema. This hospitalization was due to the development of edema of the lower lip and left cheek, the appearance of which is associated with a bite of the inner side of the cheek in sleep, there was no effect from the use of systemic glucocorticosteroids and antihistamines. The examination revealed a decrease in both the amount and functional activity of the C1-inhibitor, thus, hereditary angioedema of type I was diagnosed. Genetic examination revealed a previously undescribed variant of mutations in the SERPING1 gene. The pathogenesis of edema in hereditary angioedema is due to the accumulation of bradykinin, therefore, the use of glucocorticosteroids and antihistamines is ineffective. Currently, there are modern highly effective and safe means, both for stopping and for the prevention of such edema. It is important to inform specialists of various profiles about this disease and the principles of its therapy.

Chronic spontaneous urticaria is an urgent health problem. Recurrent urticarial rashes, angioedema and severe itching reduce the quality of life of patients. The ineffectiveness of standard therapy requires the search for new modern methods of treating this disease. Taking into account the current data on the pathogenesis, the third line of therapy for chronic spontaneous urticaria is the addition of anti-IgE therapy (omalizumab) to antihistamines of the 2nd generation. The presented clinical case is devoted to the experience of long-term use of omalizumab in a patient with chronic spontaneous urticaria. Having a disease duration of about a year, the patient was thoroughly examined, all concomitant diseases were identified and compensated, parasitic invasion was treated, but this did not lead to a regression of symptoms. Antihistamines of the 2nd generation in standard and increased doses (up to 4 times) did not control the disease, systemic glucocorticosteroids stopped the symptoms for a short time, and therefore, in the future, the patient began to use them independently and uncontrollably. Almost daily use of corticosteroids for 6 months caused the development of complications in the form of weight gain and Cushing’s syndrome. Omalizumab completely stopped all the symptoms during the first day, no side effects were detected. The clinical effect lasted from 3 to 4 weeks. Thus, omalizumab therapy allowed the patient to almost completely get rid of the symptoms of CSC, which significantly improved the quality of life and made it possible to cancel systemic glucocorticosteroids. The peculiarity of the presented case is the duration of the use of omalizumab (more than 2 years) with the inability to cancel due to the return of urticarial rashes and itching.

Today, the world is actively engaged in the selection of new markers that correlate with severity of the condition after recovery from COVID-19. For a more detailed understanding of the changes caused by SARS-CoV-2 virus in the human body, and assessment of the factors correlating with long-term persistence of symptoms after a new coronavirus infection, one should evaluate the relationships between the severity of the disease and the indices of clinical and biochemical blood tests. The purpose of the work was to reveal prognostic markers based on clinical blood testing which correlate with severity of the patients condition after a new coronavirus infection. The study included 372 patients in the post-COVID period. Initial course of the disease was assessed using the WHO Clinical Progression Scale. The patients were divided into groups according to the Post-COVID-19 Functional Status Scale (PCFS). When performing clinical blood analysis of subjects, critical points of laboratory parameters were identified and analyzed for presence of relationships with severity of the syndrome. Qualitative analysis of distinct types of immune reactions was carried out using the Protist software. The more pronounced statistically significant changes were found for the group 1. The NLR, LMR, SII coefficients were lower when compared with group 1, 2, 3. The PLR index was lower when compared with group 0. There were no other statistical differences between the groups. Therefore, the study of qualitative indexes is of interest. Suppressed immune respose (71-92%) was revealed, mainly, in groups 0, 1, 2. Activation of innate immunity, increased adaptive immunity and immunodeficiency (immune suppression) in groups 3 and 4 are observed in a half of the cases. The patients from group 2 took an intermediate position. Over the post-COVID period, general hematological disorders are not pronounced and sufficient for making a diagnosis. Therefore, one should bring more attention to complex qualitative indicators. It makes sense to use the Methods for determining the type of immune response by a comprehensive blood test as one of the main qualitative parameters in patients in the post-COVID period. At the same time, assessing the type of immune response allows not only to identify patients with post-COVID syndrome, but also to select patients who require anti-inflammatory and detoxication therapy.

Introduction. In the pathogenesis of a number of diseases, a significant role is played by redox imbalance, which is referred to as oxidative (oxidative stress) stress. Aim. The aim of the study is to review current information on the pathophysiological mechanisms of the influence of oxidative stress on the development of cardiovascular pathology. Material and methods. A review of current published studies on the effect of oxidative stress on the development and course of cardiovascular pathology was carried out. Results and discussion. Oxidative stress, disorders of the antioxidant system, and inflammation are considered the leading links in the pathogenesis and progression factors of atherosclerotic cardiovascular diseases, heart failure, arterial hypertension, and others. Conclusion. By maintaining the physicochemical parameters of biological membranes regulating intracellular homeostasis and protein kinase activity, free radicals take part in key biological reactions, such as differentiation, proliferation, and apoptosis. Strengthening reactions of free radical oxidation of lipids leads to damage to membranes and enzymatic systems, acting as a trigger factor for hidden genetically determined changes. Inflammation is a pathological process inextricably linked with oxidative stress, which develops in tissues in response to their damage due to the action of agents of an infectious and non-infectious nature. Maladaptive inflammation leads to systolic and diastolic dysfunction through cardiovascular remodeling. Oxidative stress due to damage to the endothelial lining leads to the formation of endothelial dysfunction. The combination of the described pathological processes leads to cardiovascular diseases.

Bronchial asthma is a current problem of health care in connection with high prevalence and heterogeneity of a disease. Development and deployment in clinical practice of genetically engineered biological medicines for treatment of patients with severe eosinophilic bronchial asthma allowed to change cardinally the course of a disease and to considerably improve quality of life of such patients. The presented clinical case focuses on the experience of using benralizumab, an interleukin-5 receptor antagonist in a patient with T2-endotype of severe bronchial asthma in combination with polypous rhinosinusitis. The diagnosis of bronchial asthma was established to the patient in 36 years. The patient had the burdened allergological personal and family anamnesis, intolerance of nonsteroid anti-inflammatory medicines, polyps in a nose were revealed later. It is known that the clinical phenotype of a combination of bronchial asthma to a polypous rhinosinusitis is difficult for treatment in connection with the inflammation which was more expressed, difficult giving in to control in airways. Over time the course of a disease was made heavier, control of symptoms was lost and, despite the therapy volume corresponding to the 5th step on GINA, including reception of system glucocorticosteroids, an exception of all factors interfering achievement of control regular symptoms and frequent aggravations remained. In accordance with the Federal Guidelines, the patient was prescribed targeted therapy with benralizumab, which suppresses eosinophilic inflammation in the respiratory tract. During the treatment, a rapid significant improvement in the patient’s condition was noted in the form of a decrease in asthma symptoms, normalization of spirography indicators, and cessation of exacerbations. The persistent clinical effect allowed to abandon the use of systemic glucocorticosteroids without losing control of the disease. There were no adverse reactions to the drug administration. Thus, therapy with benralizumab in patients with the T2-endotype of severe bronchial asthma in combination with polypous rhinosinusitis is safe and highly effective and allows it to be recommended for widespread use in clinical practice.

To date, the study of the role of proteases in the pathogenesis of various diseases remains relevant. The variety of cathepsin functions is associated with the peculiarities of their localization, expression, and regulation, due to which cathepsins are involved in development of many pathologies. Dysregulation of proteases, their inhibitors, and substrates can lead to the development of multiple organ dysfunction. The review presents data on the characteristics of the entire family of cathepsins and cathepsin S, in particular. The pathophysiological role of cathepsin S in the formation of bronchopulmonary pathologies, as well as in bronchial asthma is described, and intra- and extracellular implementation mechanisms are considered. The authors believe it is this enzyme that could be targeted in targeted asthma therapy to prevent airway wall remodeling at the earliest stages of the disease. The literature search was carried out in the search engines Medline, eLibrary, Scopus, the Cochrane Library, and RSCI.