Vol 95, No 1 (2023)

Cover Page

Full Issue

Editorial

Possibilities of dispensary observation in reducing mortality from coronary heart disease

Boytsov S.A., Provatorov S.I.

Abstract

Dispensary observation of patients with coronary artery disease can significantly reduce the likelihood of cardiovascular complications onset. Active outpatient monitoring allows to correct the main risk factors for cardiovascular complications, to estimate the risk of unfavorable cardiovascular events onset and to identificate patients who will get benefit of coronary revascularization. The introduction of a comprehensive assessment of cardiovascular risk and the development of remote monitoring technologies will improve the long-term results of outpatient follow-up of patients with coronary artery disease at high cardiovascular risk.

Terapevticheskii arkhiv. 2023;95(1):5-10
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Original articles

Comorbid status of patients with hypertension

Osmanov E.M., Reshetnikov V.A., Manyakov R.R., Garaeva A.S., Korkmazova L.K., Demenkova V.V.

Abstract

Aim. To establish age and gender characteristics, nosological structure of comorbidity among persons 20–99 years with hypertension.

Materials and methods. The study is based on data from 21 514 electronic health records of the population (20–99 years old) with hypertension, mean age 63.0 years, 68.2% women. Diseases associated with hypertension with a frequency above 10% were analyzed.

Results. In the sample of people with hypertension, concomitant diseases were detected in 82.7% of cases, 1 disease accompanies 21.0% of the sample with hypertension, 2 diseases 17.9%, 3 diseases 14.0%, 4+ diseases 29.8%. The frequency of association of hypertension with ≥1 concomitant disease at the 20–29 years is 60.8% of cases, at 30–39 years – 65.1%, at 40–49 years – 73.9%, at 50–59 years – 81.1%, 60–69 years – 85.8%, 70–79 years – 87.3%, 80+ years – 86.2% of cases. Among women with hypertension, the average number of concomitant diseases is higher compared to men (3.47 vs 2.4 cases; p<0.001). Among young and middle-aged people, hypertension in most cases is associated with osteochondrosis, osteoarthritis, chronic pancreatitis, gastritis and duodenitis, retinal diseases, thyroid diseases, the female with hypertension accompanied by benign breast disease and menopausal disorders. Hypertension in the elderly is most often associated with cerebrovascular disease, coronary heart disease, diabetes mellitus, senile cataract, but osteochondrosis and osteoarthritis also do not lose their relevance.

Conclusion. The existing system of organization of medical care cannot meet the needs of patients with comorbidity, which indicates the need to reorient medical care towards patient-centered care.

Terapevticheskii arkhiv. 2023;95(1):11-16
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Obstructive sleep apnea syndrome and cardiovascular risk factors in the antihypertensive therapy “escape” phenomenon

Mikhailova O.O., Elfimova E.M., Litvin A.Y., Chazova I.E.

Abstract

Aim. To assess the role of obstructive sleep apnea and other cardiovascular (CV) risk factors in the development of the antihypertensive therapy (AHT) efficacy “escape” phenomenon in patients with arterial hypertension (AH).

Materials and methods. The data of 75 patients with AH stage I–II, grades 1–3 were proceeded. All patients included in the study underwent night respiratory monitoring. After AHT prescription, blood pressure (BP) was monitored by three measurement methods (office, daily monitoring and self-control of blood pressure) – initially, in 1, 3 and 6 months after the inclusion – in order to confirm the initial therapy efficacy and to identify or exclude the “escape” phenomenon.

Results. In 36.0% of patients, the “escape” phenomenon was diagnosed in 1 or 3 months of observation. When comparing the group with the “escape” phenomenon, an initially higher level of systolic BP was revealed according to office measurements, 24-hour monitoring and self-control BP monitoring (134.0±4.7 mmHg vs 126.0±8.5 mmHg; 129.0±2.3 mmHg vs 121.0±7.7 mmHg; 131.0±8.2 mmHg vs 121.5±6.2 mmHg resp.; р<0,05). There were no differences in sleep apnea and CV risk factors between the groups. However in patients with a minimal SpO2≤85% during sleep, there were a higher levels of office systolic BP both before the AHT prescription, and during its use (157.6±10.4 mmHg vs 152.4±8.1 mmHg resp., р<0,05; 132.0±6.8 vs 127.1±8.9 mmHg resp.; р<0,05), and mean 24-hour systolic BP (125.7±5.9 vs 121.6±8.2 mmHg resp.; р<0,05) – compared with patients with a minimum SpO2>85%.

Conclusion. The higher BP level in patients with lover nocturnal hypoxemia does not allow us to exclude the delayed negative impact of obstructive sleep apnea, especially severe, on the BP profile in case of initially successful AH control.

Terapevticheskii arkhiv. 2023;95(1):17-22
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Clinical and diagnostic value of including PCR blood test in the traditional algorithm for identifying causative agents of infective endocarditis: a cohort study of 124 patients

Kotova E.O., Domonova E.A., Kobalava Z.D., Moiseeva A.Y., Pisaryuk A.S., Silveystrova O.Y., Karaulova J.L., Akimkin V.G.

Abstract

Background. If infective endocarditis (IE) is suspected, the determination of the etiology is of fundamental importance for the verification of the disease and the appointment of effective therapy. Microbiological diagnostic features are important, but they often need to be supplemented by culture-independent studies of pathological agents.

Aim. To investigate of the diagnostic advantage and value of quantitative analysis of molecular biological methods (polymerase chain reaction – PCR, sequencing) in addition to microbiological examination of whole venous blood in IE.

Materials and methods. We examined 124 patients with suspected or significant IE (DUKE 2015) hospitalized in the Vinogradov City Clinical Hospital (2015–2021). All patients underwent parallel microbiological (cultural) and molecular biological (PCR or PCR followed by sequencing) examination of venous whole blood samples.

Results. The introduction of an early parallel PCR study into the algorithm for the etiological diagnosis of IE made it possible to obtain an additional advantage in 43/124 (34.7%) patients, which made it possible to exclude unreliable results in the determination of CoNS skin commensals and pathogens atypical for IE or contamination and identify the true pathogens, and also for the first time to isolate the etiopathogenetic pathogen with a negative microbiological study. It was shown that in IE associated with CoNS, the association with the disease was confirmed by PCR in 21.4% (3/14) and refuted in 71.4% (10/14). The coincidence of the results of microbiological and PCR studies of blood samples was obtained only in 35/95 (36.8%). Positive results of PCR analysis of blood of biological material with negative results of culture were obtained in 22/51 (43.1%), of which 2/22 (9.0%) were able to confirm the presence of Bartonella spp DNA. The presented complex algorithm made it possible to significantly increase the possibility of intravital identification of the pathogen in the blood from 58.9 to 76.6%. IE with unknown etiology was present in 29/124 (23.4%) patients. A parallel PCR study allowed timely correction of antibiotic therapy in 43/124 (34.7%) patients.

Conclusion. Expansion of indications for the use of PCR studies, primarily whole venous blood samples, is justified, not only in IE with negative results of microbiological examination, but also as a control method for the reliability of the results of traditional (cultural) diagnostic methods.

Terapevticheskii arkhiv. 2023;95(1):23-31
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Anemia and quality of life of chronic kidney disease patients on renal replacement therapy by programmed hemodialysis

Kotenko O.N., Abolyan L.V., Kuteinikov V.I., Vinogradov V.E., Fomin V.V.

Abstract

Aim. To study relationship between anemia and health-related quality of life (HRQOL) of chronic kidney disease stage 5 patients (CKD) undergoing renal replacement therapy by programmed hemodialysis.

Materials and Methods. The study was conducted on the basis of dialysis centers/departments in Moscow. The Russian-language version of the KDQOL-SFTM questionnaire, validated in Russia, was used to assess the HRQOL of patients on hemodialysis. A total of 723 patients were interviewed. Hemoglobin (Hb) levels were assessed in 442 patients based on outpatient records. To identify the relationship between Hb level and HRQOL scales, a correlation analysis was performed, as well as a HRQOL analysis in the three groups differing in hemoglobin levels (<100; 100-120 and >120 g/l). Statistical data processing was carried by SPSS.22 and using parametric and nonparametric statistical methods.

Results. Correlation relationship was revealed between Hb and HRQOL of patients on hemodialysis on the scales "symptoms/problems", "pain", "vital activity, energy" and "total physical component of health". According to the scales "symptoms/problems" and "vital activity, energy", higher rates were noted among patients with Hb higher than the target level, which confirms the recommendations concerning the possibility of achieving higher Hb among individual patients who have not serious concomitant diseases and cardiovascular complications in order to improve their quality of life.

Conclusion. HRQOL assessment is important tool for planning and evaluating the effectiveness of anemia drug therapy among patients with CKD on hemodialysis.

Terapevticheskii arkhiv. 2023;95(1):32-37
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Irritable bowel syndrome in the Russian Federation: results of the ROMERUS multicenter observational study

Maev I.V., Okhlobystina O.Z., Khalif I.L., Andreev D.N.

Abstract

Background. Irritable bowel syndrome (IBS) is one of the most common functional disorders of the gastrointestinal tract. According to Russian guidelines, a standard examination using laboratory and instrumental evaluation methods, including colonoscopy, should be performed to establish the diagnosis of IBS.

Aim. To characterize the Russian population of IBS patients.

Materials and methods. A multicenter observational prospective study ROMERUS was conducted at 35 clinical centers in the Russian Federation. The study included male and female patients aged 18 to 50 with a diagnosis of IBS based on the Rome IV criteria, with no signs of structural gastrointestinal disease. The follow-up duration was 6 months and included three patients' visits to the study site. During the study, data were collected on patients' demographic and clinical characteristics, medical history, and drug therapy. The secondary parameters included the assessment of the proportion of patients with a diagnosis of IBS confirmed by a standard examination among all patients meeting the Rome IV criteria, the evaluation of the change over time of the IBS symptoms, quality of life (QoL), and adherence to therapy. Characterization of the population was performed using descriptive statistics methods. The standard examination results were presented as the percentage of patients with IBS confirmed by the standard examination among all patients meeting the Rome IV criteria, with a two-sided 95% confidence interval.

Results. The study included 1004 patients with a diagnosis of IBS according to the Rome IV criteria, with 790 (78.7%) patients included in the final analysis. The mean age of patients was 34.0±7.5 years; they were predominantly female (70.4%), Caucasian (99.4%), married (55.1%), urban residents (97.5%) with higher education (64.5%) and a permanent position (74.9%). Patients enrolled in the study have low physical activity and lack a healthy diet. The smoking rate was 26.3%. IBS symptoms with predominant constipation (IBS-C) were observed in 28.1% of patients; 28.9% had IBS with predominant diarrhea (IBS-D), 11.9% had mixed-type IBS, and 31.1% had non-classified IBS. The main IBS symptoms were pain (99.7%), abdominal distension (71.1%), and fullness (36.8%). Biliary tract dysfunction (18.9%) and gastritis (17.2%) were the most frequently reported comorbidities. Prior to enrollment, 28% of patients received drug therapy. The most commonly prescribed drug during the study was mebeverine (54.1%). At 6 months of follow-up, there was a significant reduction of abdominal pain, bloating, and distention, and a twofold reduction in the incidence of constipation and diarrhea in the subgroups of patients with IBS-C and IBS-D, respectively. The overall QoL score measured by the IBS-QoL questionnaire increased from 83.0 to 95.2 points (p<0.05) during the study. In the overall assessment of their condition, 69.6% of patients noted no symptoms and 25.3% reported marked improvement, 35% were asymptomatic according to the physician's overall assessment of the patient's condition, and 51.8% showed significant improvement.

Conclusion. IBS patients in the Russian Federation were characterized. The diagnosis of IBS, established following the Rome IV criteria, is confirmed by the results of a standard examination in 96.3% of patients. The Rome IV criteria for the IBS diagnosis make it possible to establish a diagnosis with a probability of 94.7%. For 6 months of follow-up, there was a clinical improvement with a decrease in the severity of symptoms and a QoL improvement.

Terapevticheskii arkhiv. 2023;95(1):38-51
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New opportunities for complex treatment of oropharyngeal candidiasis in HIV-infected patients in the later stages of the disease

Charushin A.O., Elovikov A.M., Charushina I.P.

Abstract

Treatment of recurrent oropharyngeal candidiasis (OPC) in HIV-infected patients is a serious clinical problem due to the emergence of resistant Candida strains, the risk of invasive disease, and high economic costs, which warrants the need for new treatment regimens.

Aim. To improve the treatment regimen of OPC in the later stages of HIV infection by combining the complex herbal medicinal product Tonsilgon® N with fluconazole and evaluate the effectiveness of this combination.

Materials and methods. A comparative randomized clinical study included 65 patients divided into observation and comparison groups, receiving fluconazole plus Tonsilgon® H and fluconazole monotherapy, respectively, for 7 days. On days 1 and 8, the severity of OPC clinical signs was assessed using a visual analog scale. The secretory immunoglobulin A in saliva was measured as a criterion for changing the level of local mucosal protection of the oral cavity and pharynx.

Conclusion. This treatment regimen for oropharyngeal candidiasis in patients with HIV infection in the later stages of the disease (IVB–IVC) with fluconazole and Tonsilgon® N is effective, which is confirmed by a significantly more pronounced regression of clinical signs (pM–U<0.01), as well as an increase in the level of secretory immunoglobulin A in the oral fluid (from 0.62±0.33 g/L to 0.81±0.18 g/L; p<0.05).

Terapevticheskii arkhiv. 2023;95(1):52-56
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Risk factors for adverse outcomes in elderly patients with asthma and severe COVID-19 at the hospital and early post-hospital stages

Avdeev S.N., Gaynitdinova V.V., Pozdniakova A.A., Vlasenko A.E., Gneusheva T.I., Baytemerova I.V.

Abstract

Background. Mortality and COVID-19 related factors are thoroughly analyzed. Given the large number of hospitalized patients, the potential short- and long-term COVID-19 related complications, further research is needed on the possible consequences of hospitalization, especially in higher-risk patients, after prolonged hospitalization and intensive care admission.

Aim. To study the clinical course and outcomes of severe COVID-19 in elderly patients with asthma at the hospital and early post-hospital stages.

Materials and methods. The study included 131 elderly patients (WHO, 2020) >60 years old, n=131 with asthma, hospitalized for severe COVID-19. Of these, 86 (65.6%) patients survived, 30 (22.9%) died in the hospital, and 15 (14.9%) patients died after discharge from the hospital (in the 90-day post-hospital period). COVID-19 was confirmed by laboratory tests (SARS-CoV-2 PCR RNA test) and/or clinically and radiologically. All patients had a documented history of asthma. Patients were followed up during the hospital stay and for 90 days after discharge.

Results. Comparison of outcomes showed that in the groups of patients with a fatal outcome (regardless of the stage), the Charlson comorbidity index, respiratory rate, extent of lung damage assessed by computed tomography, the absolute leukocyte and neutrophil number and the ratio of neutrophils to lymphocytes were statistically significantly higher. The absolute number of eosinophils was lower in these groups. In the group of patients who died during hospitalization, severe (IV–V) asthma (p=0.03), steroid use during the previous year (p=0.02), chronic heart failure with a reduced ejection fraction (p=0.009) were more common, and atopic asthma phenotype was less common (p=0.02). In those who died after discharge, more common were non-invasive ventilation and diabetes mellitus (p<0.001). The multivariate regression analysis model revealed the most significant predictors of mortality at the hospital and early post-hospital stages.

Conclusion. Adverse outcomes of severe COVID-19 in elderly patients with asthma include hospital and post-hospital mortality. The most significant predictors of mortality are the comorbidity index and low eosinophil count. Hospital mortality is associated with a higher ratio of neutrophils to lymphocytes and lower total protein levels; early (90-day) post-hospital mortality is associated with extensive lung damage shown by computed tomography and diabetes mellitus.

Terapevticheskii arkhiv. 2023;95(1):57-65
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Pharmacoeconomic evaluation of the tixagevimab and cilgavimab combination using for pre-exposure prophylaxis of COVID-19

Zhuravleva M.V., Chulanov V.P., Gagarina J.V., Shabalina E.A.

Abstract

Aim. To evaluate pharmacoeconomic feasibility using of the tixagevimab and cilgavimab combination for pre-exposure prophylaxis of COVID-19 in immunocompromised patients.

Materials and methods. Cost-effectiveness of tixagevimab and cilgavimab in persons ≥12 years old who weigh ≥40 kg and have either a history of allergy that prevents their vaccination against COVID-19 or moderate or immunocompromised was assessed based on PROVENT phase III study results. The quantity of life years or quality-adjusted life years gained was calculated. Direct medical cost associated with prophylaxis of COVID-19, treatment of infected patients and those experiencing long COVID post infection were assessed. Results were compared with wiliness-to-pay threshold, measured as tripled gross domestic product per capita and equal to 2.69 mln RUB in 2022.

Results. Pre-exposure prophylaxis of COVID-19 results in additional 0.0287 life years or 0.0247 quality-adjusted life years. The cost of additional life year gained is equal to 1.12 mln RUB, the cost of additional quality-adjusted life years is 1.30 mln RUB. Both costs of additional life year and cost of quality-adjusted life years appeared to be significantly less compared to wiliness-to-pay threshold.

Conclusion. Pre-exposure prophylaxis of COVID-19 with combination of tixagevimab and cilgavimab is economically feasible and may be recommended for wide use in Russian healthcare system.

Terapevticheskii arkhiv. 2023;95(1):66-77
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Pre-exposure prophylaxis of new COVID-19 coronavirus infection with tixagevimab/cilgavimab in adult Moscow patients with primary immunodeficiencies

Roppelt A.A., Lebedkina M.S., Chernov A.A., Kruglova T.S., Mukhina O.A., Yukhnovskaya Y.D., Samedova F.A., Mаrkina U.A., Andrenova G.V., Karaulov A.V., Lysenko M.A., Fomina D.S.

Abstract

Background. Primary immunodeficiencies (PIDs), now known as inborn errors of immunity, are a group of inherited diseases caused by defects in the genes that control the immune response. Patients with PIDs have risks of developing a severe course and/or death in COVID-19. Passive immunization with long-acting monoclonal antibodies (MABs) to SARS-CoV-2 should be considered as pre-exposure prophylaxis in patients with PIDs. Tixagevimab/cilgavimab is a combination of MABs that bind to the SARS-CoV-2 spike protein.

Aim. To evaluate the efficacy and safety of pre-exposure prophylaxis of new SARS-CoV-2 infection in PIDs with the combination of tixagevimab/cilgavimab.

Materials and methods. Forty eight patients diagnosed with PIDs were included in the study. Median follow-up after drug administration was 174 days. The total number of confirmed coronavirus infections in patients with PIDs as well as 6 months before and after administration of MAT were assessed.

Results. In the analyzed cohort, the overall incidence of COVID-19 from pandemic onset to MABs administration was 75% (36/48), with 31% (11/36) of over-infected patients having had the infection more than once. The incidence of COVID-19 immediately 6 months before the introduction of tixagevimab/cilgavimab was 40%. All patients who had COVID-19 after pre-exposure prophylaxis had a mild infection. The incidence of COVID-19 6 months after tixagevimab/cilgavimab administration significantly decreased compared to the incidence 6 months before administration (7 and 40%, respectively; p<0.001).

Conclusion. The use of tixagevimab/cilgavimab in patients with PIDs is effective as pre-exposure prophylaxis and reduces the risk of severe COVID-19.

Terapevticheskii arkhiv. 2023;95(1):78-84
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Clinical notes

The experience in treatment of dengue fever using antiviral drug riamilovir in the Republic of Guinea (case report)

Maltsev O.V., Kasyanenko K.V., Zhdanov K.V., Malyshev N.A., Kolomoets E.V., Konomou V.K.

Abstract

Dengue fever is classified as one of the most common viral diseases with a transmission mechanism implemented through arthropod vectors. The expansion of of the Aedes aegypti mosquito is leading to a significant increase in the number of cases of dengue fever in more than 100 countries, highlighting the importance of developing and implementing specific prevention and treatment measures. Etiotropic drugs with proven efficacy against the pathogen are not registered, and the use of the vaccine is approved only among seropositive individuals. In this regard, pathogenetic treatment remains the main therapeutic strategy, however, work on the synthesis of antiviral drugs is being actively carried out. Due to the unique functions of non-structural proteins NS3 and NS5 in the viral replication cycle, they have become the main targets for studying the antiviral activity of a number of chemotherapy drugs. Of these proteins, due to the most conserved structure, the NS5 protein is a promising target for inhibition, however, success in obtaining a clinical effect using a number of available antiviral drugs has not been reached. This study describes the positive experience of using the nucleoside analogue riamilovir in the treatment of a patient with dengue fever in the Republic of Guinea.

Terapevticheskii arkhiv. 2023;95(1):85-89
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Reviews

Antibiotic resistance – what can be done? A review

Kisil O.V., Gabrielyan N.I., Maleev V.V.

Abstract

Serious work is being carried out in the world in the field of combating antibiotic resistance: reducing the prescribing of antibiotics, banning the use of antibiotics as stimulators of animal growth, improving infection control. Antimicrobial resistance is systematically monitored not only in every medical center, but also at the national level. The collected data is successfully used to implement local and national recommendations on the optimal use of antibiotics.

Terapevticheskii arkhiv. 2023;95(1):90-95
pages 90-95 views

Functional methods of amyloid cardiomyopathy diagnostic in practice and in expert centers: A review

Dzhioeva O.N.

Abstract

The article is a set of recommendations for the interpretation of electrocardiography and echocardiography data in patients with suspected amyloidosis of the heart. Amyloid cardiomyopathy is a progressive disease characterized by a detailed picture of congestive heart failure, poor quality of life and poor prognosis. Currently, medications have appeared that can improve the prognosis in patients with amyloidosis of the heart. Therefore, raising awareness of specialists about specific instrumental signs of the disease is an important and urgent task.

Terapevticheskii arkhiv. 2023;95(1):96-102
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History of medicine

Activity of N.A. Semashko during the evacuation of the 1st Moscow Order of Lenin Medical Institute to Ufa (1941–1942)

Reshetnikov V.A., Strizhkova Z.A., Kinyabulatov А.U., Khazimanova A.A., Strizhkov A.E.

Abstract

An attempt is made to systematize the main directions of N.A. Semashko’s activity during the evacuation of the 1st Moscow Order of Lenin Medical Institute (MOLMI) during the Great Patriotic War to Ufa (October 1941 – March 1942) is undertaken. The significance of its results for the Bashkir State Medical Institute (now Bashkir State Medical University) is evaluated. It is shown that the joint work of N.A. Semashko with the teaching staff of the 1st MOLMI and Bashkir medical institute improved the pedagogical and scientific qualification of teachers at Bashkir medical institute, improved the existing forms of teaching, scientific and educational work during the period of war and created new ones. Professor N.A. Semashko actively worked in several directions during complicated conditions of evacuation. Besides pedagogical and scientific activities, he was occupied with the training of scientific-pedagogical personnel, took part in advanced training of physicians and medical workers, organized educational work with the population, delivered brilliant lectures to the crowded halls. In addition, as the first People’s Commissar of Health of the RSFSR, he helped the People’s Commissariat of Health of the Bashkir ASSR in organizing the work of evacuation hospitals and rendering assistance to health care institutions located on the territory of the Bashkir ASSR.

Terapevticheskii arkhiv. 2023;95(1):103-107
pages 103-107 views


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