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Meditsinskiy sovet = Medical Council

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No 17 (2020)
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Actual problem

9-16 2764
Abstract

A severe course of bronchial asthma develops in 5–20% of patients with bronchial asthma. The use of key disease-modifying agents for the treatment of severe bronchial asthma (SBA) is not always effective due to the possible uncontrolled course of the disease and persistence of signs of eosinophilic airway inflammation. Therefore, the isolation of phenotypes/ endotypes is important for an individual approach to the treatment of such patients. This method permits to get better control over the disease and reduces the risks of exacerbations, airway remodelling and unwanted adverse reactions to the therapy particularly with systemic glucocorticosteroids. The use of biological therapy among other drugs can greatly contribute to the achievement of good control over management of patients with uncontrolled severe asthma. There are currently 5 registered immunobiological drugs in Russia that belong to the group of SBA phenotype-based treatment modalities: anti-IgE therapy, anti-IL-4/13 therapy, anti-IL-5 therapy and anti-IL5Rα therapy. Depending on the disease history, clinical features of bronchial asthma course, the presence of hypersensitivity to one of the year-round allergens and the levels of laboratory markers, the medical professional establishes the exact diagnosis indicating a disease phenotype (allergic BA, eosinophilic or non-allergic BA) and addresses an issue of an appropriate drug for a patient with BA. Benralizumab (Fazenra), a humanized monoclonal antibody, generates considerable interest. Benralizumab has a slightly different principle of action: it blocks not interleukin-5 itself, but the alpha subunit of the interleukin-5 receptor (IL-5Rα), triggers active apoptosis of eosinophils, reducing their level in sputum and blood. The results of clinical studies showed the efficacy of the drug, which resulted in the significant reduction of bronchial asthma exacerbations and a dose of systemic glucocorticosteroids.

19-24 615
Abstract

The literature review is devoted to the discussion of the role of respiratory viral infections in the development of exacerbations of bronchial asthma. Despite significant advances in the development of new approaches and means of treating bronchial asthma, an insufficient level of control of the disease remains, one of the consequences of which is an exacerbation of asthma, which causes significant damage both to the health of patients and leads to high costs of the healthcare system for treatment. The article provides data on the leading causal role in the development of exacerbations of bronchial asthma in children, as well as adult respiratory viruses, among which rhinoviruses are most often detected during exacerbations, especially rhinovirus C. Based on the research results, the mechanisms of predisposition of patients with bronchial asthma to virus-induced exacerbations are considered in detail., including at the gene level, associated both with the suppression of the production of cytokines suppressing the replication and spread of viruses, in particular alpha-interferon, and the stimulation of the production of T2 cytokines, such as IL5. An important role in the development of asthma exacerbations in viral infections of allergic sensitization is indicated, the role of allergen-specific IgE antibodies in the pathogenesis of asthma exacerbations caused by viruses is discussed. The data on the role of plasmacytoid dendritic cells in the formation of the pathological process in virusinduced exacerbations in patients with atopic bronchial asthma are presented. The results of studies obtained both in real clinical practice and in experimental rhinovirus infection in patients with asthma, testifying to the high therapeutic efficacy of the preparation of monoclonal antibodies against IgE – omalizumab – in the prevention and treatment of exacerbations of bronchial asthma caused by respiratory viruses are presented.

27-32 11314
Abstract

The article deals with the issues of epidemiology and pharmacotherapy of acute bronchitis in adults. Acute bronchitis is one of the most pressing challenges in modern pulmonology, which is associated with a high incidence reaching 30–40 ‰ every year. The data on the prevalence of the disease, current ideas on the etiology of acute bronchitis, and trends of pharmacotherapy are presented. Acute bronchitis is a disease of viral etiology and it is inappropriate to use antimicrobial drugs to treat this disease. The widespread use of antibiotics, on the contrary, is accompanied by several adverse events, increased cost of treatment and the rise of antibiotic resistance. A special attention is paid to the markers of inflammatory response such as C-reactive protein and procalcitonin, their role in deciding on the need for antibacterial therapy for this disease. The article provides a critical analysis of the options for using inhaled bronchodilators and steroids to treat acute bronchitis. The clinical picture of acute bronchitis may include an acute onset, the presence of symptoms caused by upper and lower respiratory events, symptoms of intoxication of varying severity. The primary symptom of acute bronchitis is a cough, which is usually productive, with the discharge of a small amount of mucous and, sometimes, purulent sputum. Among the recommended drugs to treat acute bronchitis are mucoactive drugs, as cough is the main symptom of this disease. The results of presented studies showed that the combination drugs had the most pronounced mucoactive effect in acute bronchitis. For example, a drug containing bromhexine hydrochloride, guaifenesin and salbutamol demonstrated greater efficacy in reducing the duration of cough than mucoactive drugs being compared in the study in patients with acute respiratory viral infections and a long history of smoking.

35-39 904
Abstract

The purpose of the article is to determine the place of the combined bronchodilator fenoterol + ipratropium bromide in the treatment of exacerbations of bronchial asthma, COPD and recommendations on various delivery methods. The treatment of exacerbations of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) is of interest to a general practitioner. Although this concept has lost most of its gloomy colors in the last decade thanks to the new concept of diagnosing and treating patients, the problem of providing qualified timely assistance at the time of an exacerbation remains acute and not always solvable. Often the basis for the treatment of exacerbation of asthma and COPD is repeated administration of a fast-acting inhaled short-acting b2-agonist or an anticholinergic drug, or their combination, early administration of systemic corticosteroids and oxygen inhalation. Exacerbation therapy should be as safe as possible for patients. Following the recommendations for the treatment of asthma and COPD exacerbations both on an outpatient basis and in a hospital can significantly reduce the frequency of asthma and COPD exacerbations. Medical care that a patient can receive at home depends on the experience of the physician and the patient, as well as on the possibilities of medicine and instrumental provision. Ideally, the level of peak expiratory flow (PEF) should be a measure of control over one’s well-being, both in remission and in an exacerbation.

40-49 569
Abstract

Introducrion. Due to the peculiarities of the Krasnoyarsk krai (a huge territory, low population density, different levels of health development in the districts, personnel shortage), there is a need to increase the availability and quality of medical care to district patients. For this purpose, since 2016, the Regional telemedicine system has started functioning online monitoring for patients with severe pneumonia, which provides full-fledged curation of patients from all over the region.

Objective. To evaluate the results of RTS monitoring of patients with severe pneumonia.

Materials and methods. 770 cases of severe community-acquired pneumonia registered in RTS from 2016 to 2018 were analyzed. Statistical data processing was performed using variational statistics using the “Excel-7” software package. For all values, the minimum significance level (p) of 0.05 was taken into account.

Results. The risk factor for severe flow was male. Among comorbid diseases, cardiovascular and bronchopulmonary diseases, diabetes, alcoholism and HIV infection prevailed. The lack of flu vaccination in 97% of patients increased the number of deaths by 4.5 times. The greatest need for consultation arose in the Central district hospitals of low capacity. The majority of patients are registered in the system on the first day of hospitalization and are consulted by a pulmonologist of the Regional clinical hospital within 2 hours. Air ambulance of the Regional clinical hospital evacuated 174 patients, the need for flights decreased by 3.5 times. The main mistakes of district hospitals in the management of patients were the irrational selection of antibacterial drugs, the volume of detoxification therapy, the late start of antiviral therapy and ventilators, and the lack of prescription of anticoagulants.

Conclusions. Along with the presence of comorbidities, the outcome of the EAP is affected by the quality of medical care, which depends on the professional training of medical workers, continuity in the work of regional medical institutions and air ambulance, which causes difficulties, given the specifics of the region. RTS allows you to solve this problem at minimal cost.

50-55 648
Abstract

The simplicity of converting medicinal solutions and suspensions into aerosols using mechanical and thermal energy, convenient delivery to the airways allows nebulizers to take a worthy place in the treatment of hospitalized and outpatient patients. Different types of nebulizers are available for use in the home and in medical settings (jet, ultrasound, membrane), and researches show that the performance and characteristics of the aerosol vary between different devices and manufacturers. Jet nebulizers are still the most used devices that do not require coordination of inhale and delivery of aerosol to the respiratory tract. To reduce the consumption of medicinal aerosol and optimize the air flow, virtual valve technology (V.V.T.) is being improved, and breath-actuated nebulizers are being created. The advantage of nebulizer therapy is the ability to apply large doses of medications, use substances that exist only in inhaled form. The choice falls on the nebulizer in cases where the patient can not use other delivery devices, for example, if the patient is unable to coordinate the inhalation and intake of the drug into the respiratory tract, with a severe exacerbation of obstructive disease, in the presence of motor disorders. The optimal delivery device for children of any age, including newborns, is a nebulizer. The most common indication for nebulizer therapy is the delivery of bronchodilators and inhaled corticosteroids for asthma or chronic obstructive pulmonary disease, as well as the treatment of upper respiratory tract diseases, in particular croup in children. An important place is given to nebulizers when it is necessary to prescribe certain mucolytics and antibiotics. In the treatment of emergency conditions, inhalation administration of drugs may be required, including situations when the patient is on mechanical ventilation or has a tracheostomy installed. The significance of nebulizers in the treatment of cystic fibrosis, pulmonary arterial hypertension, and alpha-1-antitrypsin deficiency is being studied. The possibilities of endobronchial delivery of heparin, insulin, and monoclonal antibodies are evaluated.

57-64 1761
Abstract

T2-associated diseases are a group of heterogeneous immune-mediated diseases such as bronchial asthma (BA), chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis (AD), based common pathogenetic mechanisms with the type 2 immune response (T2 inflammation). Interleukins 4 and 13 (IL-4, IL-13) play a key role in T2 inflammation, activating multiple mediators and types of cell, participating in the differentiation of T-lymphocytes and switching B-lymphocytes to the production of specific immunoglobulin E (IgE), promote migration eosinophils in tissue and airway remodeling. Taking into account pathogenesis of the T2-related diseases and presence of comorbid diseases is a strategically important goal for the optimal targeted therapy. The article discusses the contemporary terminology of T2 inflammation, key cytokines involved in the pathogenesis of atopic diseases, biomarkers of T2 inflammation as criteria for proving T2 inflammation, the place of anti-IL-4/IL-13 targeted biological therapy in international Guidelines for the treatment of severe BA GINA 2020 and EACCI 2020 recommendations, the effect of dupilumab on such clinically significant outcomes as a decrease in the frequency of severe exacerbations and an improvement in lung function, a decrease in the need for oral glucocorticosteroids (GCS) in patients with BA, the evidence base for dupilumab in patients with CRSwNP and AD, as well as further promising research directions for use antiIL-4/IL-13 targeted therapy.

COVID-19

66-73 900
Abstract

The review examines the clinical and epidemiological links between COVID-19 and pneumonia. At the same time, both general patterns linking viral respiratory infections and bacterial infections of the lower respiratory tract are discussed, as well as recent data relating directly to COVID-19. The clinical aspects of secondary infections, the peculiarities of their etiology, course and outcomes are analyzed separately. The publication provides a short essay on the history of the development of vaccines against pneumococcal infection. The current vaccines against pneumococcal infection are described, their brief characteristics and individual characteristics are given, their clinical and immunological advantages and disadvantages are analyzed. The data on the effectiveness of vaccine prophylaxis using pneumococcal vaccine are presented. The specific and nonspecific effects of vaccine prophylaxis both at the population level and at the level of an individual organism as a whole and in particular when using vaccines against pneumococci are considered separately. Data on the putative biochemical and molecular mechanisms of these effects are presented. Based on the data presented, the need for the use of pneumococcal vaccines in the prevention of the spread of the SARS-Cov2 virus, the prevention of complications of COVID-19 and the rehabilitation of patients who have undergone this infection is substantiated. When considering the role of pneumococcal vaccines in the rehabilitation of patients who have undergone COVID-19, their potential is analyzed both in accelerating the restoration of the normal functioning of the immune system and in the prevention of superinfections. The ways of further research in this direction are outlined, which include the development of protocols for certain groups of patients with concomitant diseases and immuno-compromised contingents. In this direction, the role of a thorough and comprehensive study of the immunological and clinical indicators of this category of persons is emphasized.

75-80 1994
Abstract

The article presents a comparative retrospective analysis of clinical, laboratory data and outcomes in 39 patients with severe COVID-19 complicated by acute respiratory distress syndrome, who received high-flow oxygen therapy. Of which, 19 patients additionally received 75 mg of inhaled surfactant BL twice daily for 5 days using a nebulizer. As a result, mortality rate in the group of patients receiving surfactant was 10.5%, while in the standard therapy group — 50%; the number of patients transferred to the mechanical ventilation was 21% and 70%, respectively. As the patients receiving the surfactant were injected with COVID-19 hyperimmune convalescent plasma and monoclonal antibodies to interleukin-6 receptors more often than those from the control group, we recalculated the results regardless of these patients. However, a significant difference between the mechanical ventilation rate (2.5 times less often in the surfactant group) and mortality rate (3.5 times less in the surfactant group) was observed. The duration of hospitalization and stay at the intensive care unit was not significantly different between patients with and without surfactant treatment. Inhalation therapy with surfactant BL was well tolerated even by patients with chronic obstructive pulmonary disease. In no case did therapy have to be stopped due to side effects, the most common of which was coughing during inhalation. This retrospective analysis shows that the prescription of an inhaled surfactant prior to transferring patients to mechanical ventilation can prevent the progression of respiratory failure, put down mechanical ventilation, and improve survival.

82-90 1578
Abstract

Introduction. In the context of a high load on all links in the structure of providing medical care to patients with COVID-19, solving the issue of effective triage of patients seems to be extremely urgent. The duration of inpatient treatment is one of the most objective and unambiguously interpreted indicators that can be used to indirectly assess the severity of the patient’s condition.

Objective. Develop a machine learning model to predict the duration of inpatient care for patients with COVID-19 based on routine clinical indicators assessed at the prehospital stage.

Materials and methods. A total of 564 patients were examined with diagnoses: U07.1 COVID-19, virus identified (n = 367) and U07.2 COVID-19, virus not identified (n = 197). The study included 270 patients, of whom in 50.37% of patients the duration of inpatient treatment did not exceed 7 days, in 49.63% of patients the duration of inpatient treatment was more than 10 days. Eleven clinical parameters were chosen as the most important predictors for predicting the duration of inpatient treatment: age, height and weight of the patient, SpO2 level, body temperature, body mass index, pulse rate, number of days from the onset of illness, respiratory rate, systolic and diastolic arterial pressure.

Results. The accuracy of our machine learning model for predicting the duration of inpatient treatment more than 10 days was 83.75% (95% CI: 73.82–91.05%), sensitivity — 82.50%, specificity — 85.00%. AUC = 0.86.

Conclusion. The method developed by us based on machine learning is characterized by high accuracy in predicting the duration of inpatient treatment of patients with COVID-19, which makes it possible to consider it as a promising new tool to support medical decisions on further tactics of patient management and to resolve the issue of the need for hospitalization.

Tuberculosis

91-97 837
Abstract

Current trials are underway to design chemotherapy regimens that include bedaquiline to treat children with rifampicin and isoniazid resistant mycobacterium tuberculosis. This clinical observation is interesting from the viewpoint of experience of the potential effective and safe use of the new anti-tuberculosis drug bedaquiline (Sirturo) in children under 12 years of age, as the publications of clinical trials of the drug use in children is limited. The female patient was diagnosed with primary tuberculosis complex complicated by infusional pleurisy based on the epidemiological anamnesis (family contact with tuberculosis patients), immunodiagnostic tests – a positive ATR-test result (Diaskin-test), pathological changes in the lung tissue and intrathoracic lymph nodes found on the chest CT scans. The diagnosis was confirmed by detection of MBT in pleural effusion by PCR and liquid culture method (BACTEC MGIT-960), which are resistant to isoniazid and rifampicin (multidrug resistance, MDR). The girl was enrolled in a clinical trial and treated according to chemotherapy regimen IV including a new anti-tuberculosis drug, which she received for 6 months. There was a positive clinical and X-ray dynamics of the tuberculosis process with minimal residual changes throughout the entire course of chemotherapy followed by confirmed clinical cure of TB (after 24-month follow-up). Based on the example of this clinical observation, it can be concluded that bedaquiline is safe and showed good clinical efficacy in the chemotherapy regimen to treat MDR MBT in children under 12 years of age.

Interstitial lung disease

99-106 756
Abstract

A number of patients with interstitial lung diseases (ILD) of various etiologies, including hypersensitive pneumonitis, diffuse connective tissue diseases (rheumatoid arthritis, systemic scleroderma, dermatomyositis), sarcoidosis, idiopathic non-specific interstitial pneumonia (NSIP) and unclassified ILD develop rapid deterioration of lung ventilation function due to the progression of fibrotic changes, accompanied by a decrease in physical performance and quality of life. It is proposed to distinguish a progressive fibrotic phenotype from those with similar pathogenetic mechanisms, radiologic pattern, clinical course, and prognosis. The progressive course of the fibrotic process is assessed by reducing the forced vital capacity of the lungs (FVC), increasing the severity of signs of pulmonary fibrosis according to computed tomography (CT) and worsening respiratory symptoms. There are several risk factors for the progression of ILD, such as male gender, older age, lower initial pulmonary function, and radiological or pathological picture of usual interstitial pneumonia (UIP). Currently, the role of antifibrotic drugs in the treatment of this pathology is being actively studied. Previously, the common approach was to use this group of drugs in patients with idiopathic pulmonary fibrosis (IPF) and immunosuppressive drugs in patients with other fibrotic subtypes of IL. However, the results of clinical studies have shown a favorable response to antifibrotic therapy for a wider range of fibrotic ILD, manifested in a decrease in the annual rate of FVC reduction. And in 2020, the use of the first anti-fibrotic drug was approved for the treatment of patients with advanced pulmonary fibrosis, NOT related to idiopathic pulmonary fibrosis (IPF).

Rational pharmacotherapy

109-112 944
Abstract

This article is a review of published studies on the clinical application of thiamphenicol glycinate acetylcysteinate (TGA) in the treatment of acute and chronic upper and lower respiratory tract diseases. Search for literature in Medline and eLibrary databases was performed. The special place that the drug holds in clinical practice, due to the specific properties of its components - mucolytic N-acetylcysteine (NAC) and antibiotic tiamphenicol. In addition to the usual mucolytic effects, NAC has antioxidant properties, which extends the range of its clinical effectiveness. The antibiotic thiamphenicol has antimicrobial activity against staphylococci, streptococci and gram-negative microorganisms. TGA can be administered by parenteral and inhalation routes. Inhalation route of drug injection is preferable in the treatment of acute and chronic bronchopulmonary diseases, because it allows to create a higher concentration of the drug in the respiratory tract, is associated with much less systemic effects and less often accompanied by the development of side effects. The results of TGA application in the treatment of both acute and chronic upper respiratory diseases (rhinosinusitis, otitis, pharyngotonsillitis) and bronchopulmonary diseases (chronic obstructive pulmonary disease, bronchoectasis) are considered in this review. It has been shown that the drug is quite effective in most patients and its effectiveness sometimes exceeds that of standard oral antibiotics. TGA also allows you to effectively combat biofilms, which have high antibacterial resistance. Thus, the published data allow us to speak about the high antibacterial effectiveness of TGA in acute and chronic infectious diseases of the upper and lower respiratory tract, including cases with the formation of biofilms.

114-122 1237
Abstract

The article investigates the causes and mechanisms of coughing and the treatment choice. Phytotherapy has a special role in the treatment of acute respiratory infections. Biologically active substances of plants integrate into metabolic processes more naturally, treatment with herbal medicines is distinguished by better tolerance, lower frequency of side effects and complications. High biological activity and a wide therapeutic index (the relationship between toxic and therapeutic dosing) can also be designated as advantages of medicinal plants. The article presents research data showing the miscellaneous effects of herbal medicines on the pathogenesis of cough: sputum production, improving the drainage function of the bronchi, as well as antimicrobial effect. The article discusses the pharmacological properties of drugs containing combinations of herbal extracts as active ingredients: thyme, ivy and primrose. Thyme has anti-inflammatory, antiviral and antibacterial effects due to blocking the growth of various strains of bacteria and fungi. Ivy leaf extract is characterized by similar properties. Primrose root extract has expectorant, secretolytic, anti-inflammatory and antiviral properties. It is important to note that the use of a combination of extracts provides a more significant clinical effect compared to the sum of the effects of the individual ingredients. A review of key clinical studies confirming the effectiveness of the use of combinations of thyme, ivy and primrose extracts (approved for medical use in the Russian Federation in the form of drugs Bronchipret and Bronchipret TP) in adults and children for cough and other symptoms of acute respiratory infections treatment. The compatibility of herbal medicines with other drugs for the treatment of respiratory pathology has been noted.

124-131 1530
Abstract

Cough is one of the most common symptoms and is present in diseases of the respiratory, cardiovascular, digestive, endocrine and other systems. Cough is a reflex act, therefore it is caused by stimulation of cough receptors due to pathological influences. The diagnosis takes into account the nature of the cough, its duration, the results of laboratory and instrumental examination methods. The most attention is required to diagnose chronic cough and exclude life-threatening causes. Symptoms of anxiety are hemoptysis, prolonged resistant cough, prolonged intoxication syndrome, weight loss, etc. In diagnostically unclear cases, the examination schedule must include computed tomography of the chest, magnetic resonance imaging and bronchoscopy. A dry, painful intense cough can lead to the development of complications: a decrease in the quality of life, hemorrhages, pneumothorax, etc., therefore, requires symptomatic treatment. A common cause of unproductive cough is viral diseases, whooping cough, diseases leading to overactive cough receptors. The variety of coughs determines a differentiated approach to its therapy. The main efforts should be directed to the treatment of the underlying disease. In the case of a productive cough, mucoactive drugs are used. To stop unproductive cough, antitussive drugs of central and peripheral action are used. The recommendations of the European Respiratory Society present the results of clinical trials assessing the efficacy and safety of antitussive drugs with morphine-like action. The study identified side effects that limit their use. One of the most effective and safe drugs is a non-opioid drug with a central action Sinekod. The effectiveness and safety of the drug is confirmed by clinical studies.

Allergology

132-140 1737
Abstract

Rhinitis can be of various etiologies. More often it is an infectious process (bacterial, viral) or clinical manifestations of an immediate allergic reaction. Other factors that provoke the development of rhinitis, for example, irritating substances, a number of drugs, hormonal imbalance, neurovegetative dysfunction, viruses are known. Doctors of various specialties are familiar with allergic rhinitis (AR) in their practice. In a number of cases there can be some difficulties in the differential diagnosis of rhinitis, the correct diagnosis and the appointment of adequate therapy. The COVID-19 epidemic (“coronavirus disease 2019”) has already been imprinted in the global history as an emergency of international importance. Scientific medical communities continue to study the characteristics of this epidemic, which is regarded by WHO as a pandemic. In a short period (from January 2020), there has been accumulated enough information about the etiology, features of the clinical manifestations of this disease, diagnostic methods have been developed, and clinical approaches and treatment regimens continue to be developed. The pandemic coincided with successive pollen seasons of trees, grasses and weeds. At the beginning of the pollen season, doctors were concerned about the possible difficulty in differential diagnosis of allergic rhinitis, manifestations of coronavirus and other viral infections. In the process of monitoring patients, more and more data has been accumulated, indicating the features of the clinical characteristics of COVID-19, influenza, acute respiratory infections, seasonal allergic rhinitis (rhinoconjunctivitis). Undoubtedly, information is still being accumulating and enriching day by day. AR is not only the most common form of rhinitis, but one of the most common diseases in children and adults. It is known about the pronounced negative effect of AR symptoms on the patient’s quality of life: normal daily activity, cognitive functions, mood, sleep. The severity of AR symptoms varies from minimal clinical manifestations to severe. Therapy should be directed towards the general control of AR symptoms. Over the past decades, the concept of phenotyping (definition of a disease by its clinical manifestations) and endotyping (based on the pathobiological mechanisms of the disease) has been developed. The belonging of AR in a particular patient to a certain phenotype plays a key role in choosing the most effective therapy and requires a personalized approach to treatment. The article provides frequently asked questions regarding AR treatment during the COVID-19 pandemic. The role of intranasal corticosteroids (InHCS), which are the most effective drugs in AR therapy, is discussed, due to their pronounced anti-inflammatory effect and influence on all stages of the pathogenesis of the disease. Mometasone furoate nasal spray has the widest indications among all InHCS drugs registered in our country.



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ISSN 2079-701X (Print)
ISSN 2658-5790 (Online)