Characteristics of mukoviscisidosis in the southern regions of Russia

Introduction. Cystic fibrosis (CF) is a  hereditary disease with genetic heterogeneity and clinical polymorphism. Expanding the range of knowledge about the characteristics of the course of the disease in different regions is important to achieve the goal of improving the quality and life expectancy.Purpose. Comparative analysis of the features of the course of CF in the subjects of the Southern Federal District, Stavropol Territory.Methods. Data from the National Register of Patients of the RF MV 2016 were used. Results: there are clinical and genetic features between the regions of the Southern Federal District and the Stavropol Territory of the North Caucasus Federal District and in general with the Russian Federation. Analysis of the data showed differences in indicators: the proportion of patients aged ≥ 18 is the lowest in the Republic of Crimea (14.9%), in the Rostov region the lowest average age of patients (9.0 ± 6.3), and the lowest age of diagnosis 2.2 ± 3.1 years. Late terms of diagnosis were revealed in the Stavropol Territory (4.0 ± 8.0 years), but here there is one of the highest average age of CF patients (14.1 ± 11.5), the proportion of adult patients (23.3%) and the lowest allelic frequency of F508del, which is determined by the high number of patients with a “soft” genotype. There is a high proportion of patients with an undetermined genotype. A low proportion of two identified genetic variants of the CFTR gene is registered in patients of the Republic of Crimea. A low frequency of Burkholderia cepacia complex and Achromobacter spp was revealed, and a high infection with non-tuberculous mycobacteria was revealed in the Rostov region. FEV1 in children and adults was lower in Rostov Region and Stavropol Territory. In all regions, there is a discrepancy between the seeding of flora and azithromycin therapy and the severity of the genotype with the use of pancreatic enzymes.Conclusions. Analysis of the data of the registry, which allows substantiating the need to study the regional characteristics of the course of CF in order to differentiate the planning of measures to improve the quality of medical care for patients with CF

Изучение эффективности, безопасности и оценка удовлетворенности ингаляционной терапией препаратом Тобрамицин-Гобби при синегнойной инфекции у детей с муковисцидозом

Study of efficacy, safety, and patient satisfaction with inhaled tobramycin (Tobramycin-Gobbi) in children with cystic fibrosis and pseudomonas infectionAim of the study was to assess efficacy and safety of Tobramycin-Gobbi in CF, as well as the patients’ satisfaction with the treatment.Methods. 35 children from 6 to 18 years with CF were enrolled in this non-interventional prospective cohort multicenter study. All children had P. aeruginosa in the respiratory tract (newly diagnosed, recurrent, or chronic infection). The children received inhalation treatment with Tobramycin-Gobbi in the following cycles: 28-day treatment/28-day break, for 6 months. The studied parameters included respiratory function, bacterial cultures of the respiratory tract with a bacterial count, growth and body weight, antibiotic therapy for the respiratory episodes. The children and parents filled in a questionnaire “Treatment satisfaction assessment” and assessed their state of health on the visual-analog scale before and after each treatment cycle.Results. P. aeruginosa was eradicated in 17.7% of cases (6 patients, including 2 newly diagnosed, 3 recurrent infections, and 1 chronic infection), reduced bacterial count, decreased number of courses of antibiotic therapy, improvement of FEV1. Adverse reactions were reported by one patient.Conclusion. The efficacy, safety, and tolerability of Tobramicine Gobbi were confirmed in the patients with newly diagnosed, recurrent, and chronic infection caused by P. aeruginosa.Антибактериальная терапия (АБТ) синегнойной инфекции при муковисцидозе (МВ) остается основным фактором, определяющим функцию легких и продолжительность жизни больных. Основным патогеном, который определяет степень тяжести течения МВ, продолжительность и качество жизни пациентов, является Pseudomonas aeruginosa.Целью исследования явилось изучение эффективности, безопасности и оценка удовлетворенности ингаляционной терапии препаратом Тобрамицин-Гобби при синегнойной инфекции у детей с МВ.Материалы и методы. В неинтервенционном проспективном когортном многоцентровом исследовании принимали участие дети (n = 35; возраст – 6–18 лет) с установленным диагнозом МВ, наличием синегнойной инфекции (первый высев, рецидивирующая и хроническая инфекция), наблюдавшиеся в 8 российских центрах МВ. В течение 6 мес. дети получали ингаляционную терапию указанным препаратом циклами по 28 дней ингаляций / 28 дней перерыв. Контролировались показатели респираторной функции, бактериальная флора дыхательных путей с оценкой степени обсемененности, показатели массы тела и роста, применяемая АБТ по поводу респиратор- ных эпизодов. Дети и их родители заполняли анкету пациента «Оценка удовлетворенности препаратом», при этом отмечалось самочувствие по визуальной аналоговой шкале до начала лечения и после каждого цикла приема препарата.Результаты. На фоне терапии в 6 (17,7 %) случаях (2 – с первичным высевом, 3 – с рецидивирующим, 1 – с хронической синегнойной инфекцией) выявлено отсутствие высева P. аeruginosa, уменьшение степени обсемененности, сокращение числа курсов АБТ, улучшение показателей объема форсированного выдоха за 1-ю секунду. Зарегистрированы нежелательные побочные реакции (n = 1).Заключение. Показана эффективность препарата Тобрамицин-Гобби при первичном высеве, интермиттирующей и хронической инфекции, вызванной P. аeruginosa, его безопасность и хорошая переносимость

Генетическая характеристика больных муковисцидозом в Российской Федерации по данным Национального регистра (2014)

The aim of this study was to investigate genetic features of patients with cystic fibrosis (CF) according to the National Register findings in Russia. Methods. The study involved 2,131 CF patients living in 74 regions of Russia who were included in the National Register of CF patients in 2014. Results. Genetic testing was performed in 89% of patients. The total mutant allele frequency was 81.2%. One hundred and twenty two mutations were found which comprised 173 genotypes; «mild» mutations took 23%. The most common mutant allele frequencies in the descending order were as follows: F508del, 51.53%; СFTRdele2,3, 5.93%; E92K, 2.62%; 3849+10kbC>T, 2.14%; 2184insA, 1.80%; W1282X, 1.80%; 2143delT, 1.69 %; N1303K, 1.43%; G542X, 1.16%; 1677delTA, 0.98%; L138ins, 0.95%; R334W, 0.85%; 394delTT, 0.85%; 3821delT, 0.42%; 2789+5G>A, 0.37%; S466X, 0.37%; S1196X, 0.37%; 3272-16T>A, 0.34%; W1282R, 0.29%; 3944delGT, 0.21%. Typical features of CFTR mutation distribution in Russian CF patients were lower frequency of mutations which are predominant worldwide, such as F508del, G542X, N1303K, and scarce G551D, 1717-1G>A, 2183AA>G mutations. On contrary, СFTRdele2,3, E92K, 2184insA, 2143delT, 1677delTA, L138ins mutations which are quite rare in Western Europe were encountered more often in Russia. «Mild» mutations were more common in Russian population of CF patients compared to European countries and have being increasing last years. Conclusion. Genetic features of Russian CF patients could be provided by Slavic, Turkic and Finno-Ugric genetic influence on Russian population.Генетическому разнообразию больных муковисцидозом (МВ) в России посвящены единичные работы на ограниченной выборке больных. Цель. Выявление особенностей генетического профиля больных МВ в России по данным Национального регистра (2014). Материалы и методы. Данные пациентов с МВ (n = 2 131) из 74 регионов России, включенные в Национальный регистр больных МВ (2014). Результаты. Генетическое обследование проведено у 89,0 % больных, суммарная аллельная частота выявленных мутаций составила 81,2 %. Выявлено 122 мутации, которые сформировали 173 различных генотипа, среди которых доля «мягких» генотипов составила 23,0 %. Аллельная частота самых распространенных мутаций представлена в порядке убывания: F508del – 51,53 %, СFTRdele2,3 – 5,93 %, E92K – 2,62 %, 3849+10kbC>T – 2,14 %, 2184insA – 1,80 %, W1282X – 1,80 %, 2143delT – 1,69 %, N1303K – 1,43 %, G542X – 1,16 %, 1677delTA – 0,98 %, L138ins – 0,95 %, R334W – 0,85 %, 394delTT – 0,85 %, 3821delT – 0,42 %, 2789+5G>A – 0,37 %, S466X – 0,37 %, S1196X – 0,37 %, 3272-16T>A – 0,34 %, W1282R – 0,29 %, 3944delGT – 0,21 %. Выявлено, что особенностями распределения мутаций. CFTRсреди российских больных МВ являются меньшая частота доминирующих в мире мутаций, таких как F508del, G542X, N1303K, единичная встречаемость мутаций G551D, 1717-1G>A, 2183AA>G и наоборот – более высокая частота мутаций, являющихся относительно редкими в западноевропейских странах: СFTRdele2,3, E92K, 2184insA, 2143delT, 1677delTA, L138ins. Другой особенностью является более высокая встречаемость «мягких» мутаций в России по сравнению со странами Европы. Выявлено, что доля «мягких» мутаций в популяции больных МВ на протяжении последних лет увеличивается. Заключение. При формировании населения России особенности генетического профиля российских больных МВ определяются славянскими, тюркскими и финно-угорскими влияниями

Prediction of 5-year survival in patients with heart failure and implanted cardiac resynchronization therapy devices

Aim. Based on clinical parameters and diagnostic investigations, to create a complex model of personalized selection of patients with heart failure (HF) for cardiac resynchronization therapy (CRT). To establish the diagnostic value of the created model in predicting 5-year survival.Material and methods. The study included 141 patients with HF (men, 77,3%; women, 22,7%). The mean age of patients at the time of implantation was 60,0 [53,0; 66,0] years. All patients had New York Heart Association (NYHA) class II-IV HF, left ventricular ejection fraction (LVEF) ≤35%, and QRS ≥130 ms. Patients were randomly divided into training (n=95) and test (n=36) samples, which were comparable in main clinical and functional characteristics.Results. The index included parameters that had a significant relationship with 5-year survival according to the Cox regression: male sex, prior myocardial infarction, hypertension, QRS <150 ms, no left bundle branch block, PR ≥200 ms with sinus rhythm/absence of radiofrequency ablation in atrial fibrillation, NYHA class III, IV HF, LVEF <30%, left ventricular end-diastolic volume ≥235,0 ml, NT-proBNP ≥2692,0 ng/ml. All variables were scored based on the в-coefficients. In the training sample, a value ≥45 points demonstrated a sensitivity of 82,4% and a specificity of 67,2% in predicting 5-year survival (AUC, 0,873; p<0,001). The index use on the test sample showed comparable results (AUC, 0,718; p=0,020; sensitivity — 71,4%, specificity — 62,5%). Also, in the training sample, the index ≥45 points was associated with1-year survival (sensitivity — 84,6%, specificity — 58,1%, AUC, 0,811; p<0,001).Conclusion. An index of personalized selection for CRT has been created, which makes it possible to accurately predict the 5-year survival rate, as well as the 1-year survival rate, regardless of the current selection criteria

Sanatorium rehabilitation effects on vegetative test dynamics in myocardial infarction patients

Aim. To study dynamics of vegetative reflex tests (VRT) during sanatorium rehabilitation in patients with noncomplicated myocardial infarction (MI).Material and methods. In total, 106 men (mean age 48,6±1,0 years) were examined 44,3±3,2 days after MI, beforeand after sanatorium6based rehabilitation. Heart rate variability (HRV) was assessed during 24-hour electrocardiography (ECG), ECG at rest, active orthostatic test (AOT) and controlled breath rate test (CBRT). Physical stress tolerability (PST) and echocardiography parameters were also assessed.Results. After rehabilitation course, low frequency HRV component was increased in rest ECG (by 19 % for absolute values (p=0,06), by 5 % for normalized values (p=0,08)) and during AOT (by 27,3 % (р=0,015) and 6,2 % (р=0,011), respectively). CBRT results remained the same. Veloergometry PST increased by 10,1 %, end-systolic and end-diastolic left ventricular (LV) volumes decreased by 8,7 % and 6,6 %, respectively, asynergic area reduced by 6,0 %, and LV ejection fraction increased by 6,1 %. Rehabilitation adequacy was also confirmed by some decrease in mean HR and ventricular extrasystole rate during 246hour ECG monitoring.Conclusion. The results obtained could facilitate HRV data use in physical rehabilitation effectiveness assessment,optimizing and individual tailoring of rehabilitation programs

Vitamin d status during winter months among children and adolescents with cystic fibrosis living in southern Russia

The article presents the results of vitamin D tests in children with cystic fibrosis and in healthy children living in the South of Russia. The study showed the high prevalence of vitamin D deficiency and inadequate levels in patients with cystic fibrosis (86.7%). 25(OH) D level characterizing the vitamin D status decreases progressively in patients and healthy children. With regard to the above mentioned, it is significantly lower in patients with cystic fibrosis than in healthy children in all age periods. The correlation between the serum calcidiol level and the age of patients with cystic fibrosis was r = -0.44 (p = 0.015). Intake of prophylactic (500--1000 IU/day) and therapeutic (1500--3000 IU/day) doses of cholecalciferol results in a less significant increase in calcidiol levels in patients with cystic fibrosis compared with healthy children. A significantly lower 25(OH)D level was detected in patients with cystic fibrosis infected with Staph. aureus. The 25(OH)D levels are significantly lower in children with cystic fibrosis and hypocholesterolemia, than in patients with normal cholesterol levels. Risk factors for the development of severe hypovitaminosis D in children with cystic fibrosis are age, physical developmental delay, exocrine pancreatic insufficiency, presence of chronic Staph. Aureus bronchopulmonary infection. Given the conducted study, the dosage of cholecalciferol in patients with cystic fibrosis should be at least 2 times higher than that in healthy children

A Comparative Cross-Sectional Study Assessing the Psycho-Emotional State of Intensive Care Units’ Physicians and Nurses of COVID-19 Hospitals of a Russian Metropolis

Working in intensive care units (ICUs) is stressful and potentially leads to various psychoemotional disorders. Today, this issue represents a serious concern to the healthcare sector and affects the quality of healthcare provided. This study aimed to assess and compare the psycho-emotional state in COVID-19 and non-COVID-19 hospitals’ ICU healthcare workers (HCWs). From January to July 2021, we conducted an anonymous cross-sectional web survey of ICU physicians and nurses (N = 1259) of various hospitals in a metropolis with a population of over 10 million people. The statistical distributions of non-COVID-19 ICU HCWs showed the following results: Emotional exhaustion levels (low 14.6%, average 30.8%, and high 54.6%); depersonalization levels (low 11.6%, average 16.5%, and high 71.9%); and reduced personal accomplishment levels (low 23.5%, average 40.3%, and high 36.2%). The statistical distributions of COVID-19 ICU HCWs showed the following results: Emotional exhaustion levels (low 16.5%, average 31.5%, and high 52%); depersonalization levels (low 7.4%, average 9.4%, and high 83.1%); and reduced personal accomplishment levels (low 25.4%, average 45.4%, and high 29.1%). This study found a strong correlation between emotional exhaustion, aggression, and depersonalization in non-COVID-19 ICU HCWs and also found a correlation between their age, aggression, emotional exhaustion, and occupational stress. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Role of vitamin D in pre-school children’s health

Vitamin D has pleiotropic effects, including maintaining calcium and phosphate homeostasis, and affecting the immune and endocrine systems. The article summarizes data on the expected biological effects of vitamin D on children’s health. The results of randomized clinical trials evaluating the effect of vitamin D supplementation on the incidence of acute respiratory tract infections are reviewed in detail. It has been shown that daily intake of vitamin D at a dose of 10 to 25 mcg/day (400–1000 IU/day) compared with placebo leads to a significant decrease in the proportion of children and adolescents who have had at least one episode of acute respiratory infection. The criteria for the provision of calciferol and the gradation of the status of vitamin D deficiency and deficiency in different countries are discussed. It has been shown that in the interpretation of the 25 (OH) D results there is a consensus on two points: calcidiol levels below 12 ng/ml (30 nmol/L) are considered clearly insufficient, and levels above 30 ng/ml (75 nmol/L) are considered sufficient in all regions. The incidence of hypovitaminosis D has been reported in children aged 3 to 7 years, where the overall combined assessment, regardless of age group, ethnic composition and breadth of the studied populations, showed that 13% of European children had a serum calcidiol concentration of less than 12 ng/ml (<30 nmol/L), and about 40% had a level of less than 30 ng/ml (<75 nmol/L). The data on the physiological need and the recommended daily dose of vitamin D for preschool children have been analyzed. In each country, the recommended intake of vitamin D is set (from 400 to 4000 IU), depending on the target concentration of serum calcidiol, the level of insolation, and nutritional characteristics. The necessity of conducting clinical studies in the age group from 3 to 7 years to determine an adequate, effective and safe preventive dose of vitamin D for preschool children in the Russian Federation is emphasized