[The problem of comorbid disorders in attention deficit hyperactivity disorder in children and adolescents: clinical cases]. / Problema komorbidnykh rasstroistv pri sindrome defitsita vnimaniya s giperaktivnost'yu u detei i podrostkov i ikh korrektsiya: klinicheskie nablyudeniya.

The problem of comorbid disorders in attention deficit hyperactivity disorder (ADHD) is considered, which occur in at least 60% of patients and lead to additional difficulties in intra-family, school and social adaptation. Children and adolescents with ADHD have a wide range of neurological and somatic disorders caused by complex polygenic pathogenetic mechanisms. Among the pathologies associated with ADHD in this cohort of children, neurotic and anxiety manifestations, motor disorders: dyspraxia, discoordination, impaired gross and fine motor skills, tics, behavioral disorders, enuresis, tension cephalgia are common disorders. Treatment of ADHD should be pathogenetic, taking into account the main symptoms of ADHD and manifestations of comorbid disorders, since it is quite long. When choosing pharmacotherapy, it is preferable to use drugs with verified efficacy not only in the correction of ADHD, but also concomitant behavioral, motor and emotional disorders. Also an important aspect in the pediatric clinic is the use of drugs with a reliable safety profile.

[Treatment of attention deficit hyperactivity disorder in children: results of a multicenter, randomized, double-blind, placebo-controlled clinical trial]. / Terapiya sindroma defitsita vnimaniya s giperaktivnost'yu u detei: rezul'taty mnogotsentrovogo randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo klinicheskogo issledovaniya.

OBJECTIVE: Evaluation of the efficacy and safety of the new drug Prospekta in the treatment of attention deficit hyperactivity disorder (ADHD) in patients aged 7-12 years. MATERIAL AND METHODS: A multicenter (35 clinical centres) double-blind, placebo-controlled, randomized, parallel-group clinical trial enrolled 363 patients. The mean age was 9.3±1.7 years. Children of both sexes aged between 7 and 12 years with a diagnosis of ADHD confirmed by DSM-V diagnostic criteria were included in the study. Patients with a total score of 22 or more on the Attention Deficit Hyperactivity Disorder-Rating Scale-V (ADHD-RS-V) were included in the study. After randomisation, patients in group 1 received Prospekta, 1 tablet twice daily; patients in group 2 received placebo according to the study drug regimen. The primary efficacy criterion was the proportion of patients with a 25% or greater reduction in the overall ADHD-RS-V scale score after 8 weeks of treatment. As additional criteria for efficacy assessment were assessed: change of ADHD-RS-V total score from baseline after 8 weeks of treatment; Clinical Global Impression Efficacy Index (CGI-EI) score after 8 weeks of treatment; side effects. RESULTS: The proportion of patients with a 25% or more reduction in the ADHD-RS-V scale score after 8 weeks of treatment was 55.9% in the Prospekta group, and 43.3% in the placebo group (p=0.0199). There was a reduction of ADHD symptoms in the Prospekta group as a mean ADHD-RS-V score decreased by 10.2±7.7 (in the placebo group by 8.1±7.9); the difference between the mean ADHD-RS-V score reduction during Prospekta and placebo treatment was 2.09±7.81 (p=0.0096). Mean CGI-EI scores calculated on the basis of physician scores were different in the Prospekta group compared to the placebo group at 6.9±3.2 versus 8.0±3.1 (p=0.0012), indicating greater clinical efficacy of the study drug. The frequency of adverse events (AEs) did not differ significantly between the groups. There were a total of 66 AEs in 46 patients, including 31 AEs in 23 (13.2%) Prospekta group participants and 35 AEs in 23 (12.2%) placebo group participants (p=0.87). No cases of serious AEs were reported during the study. Prospekta is compatible with drugs used in pediatric practice. Prospekta did not cause an exciting effect and did not adversely affect the sleep of patients. CONCLUSION: The drug Prospekta is an effective and safe treatment for ADHD in patients 7-12 years old.

Relationship of Nutritional Status and Spirometric Parameters in Children with Bronchial Asthma.

The potential mechanisms of bronchial asthma (BA) negative modification under the influence of obesity are currently being actively studied. However, at present, the effect of nutritional status on bronchial obstruction in children with BA cannot be considered established. In this regard, the purpose of this work was to study the relationship of spirometric parameters reflecting bronchial patency with nutritional status in children with asthma. MATERIALS AND METHODS: The study involved 54 patients with BA at the age of 8 to 17 years, 33 boys and 21 girls with different nutritional status. Assessment of nutritional status was carried out with the calculation of body mass index (BMI), relative body mass index (RBMI), and determination of body fat (% BF). Spirogram parameters were evaluated, including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, maximum expiratory flow at the point of 25% loop flow-volume (MEF 25). RESULTS: Among the children examined, taking into account the BMI Z-score, 9.3% (5/54) had low body weight (group 1), 33% (18/54) had normal body weight (group 2), 31.5% (17/54) overweight (group 3), 25.9% (14/54) obesity (group 4). As the body weight increased, a statistically significant decrease in the FEV1/FVC ratio was observed, amounting to 84.6 [79.3; 90.0], 79.4 [76.6; 82.2], 74.6 [71.7; 77.5], 70.2 [67.0; 73.4]%, respectively, p=0.003; as well as a decrease in MEF 25 (% pred.), which amounted, respectively, to 95.6 [76.1; 115.2], 81.7 [71.4; 92.0], 56.3 [45.7; 66.9], and 48.4 [36.7; 60.1]%, p=0.003. A statistically significant negative relationship was found between indicators of nutritional status, including BMI, RBMI, % BF, and spirometry parameters reflecting bronchial patency, including FEV1/FVC ratio and MEF 25 (% pred.); all p<0.01. CONCLUSIONS: Overweight and obesity in children with BA, estimated both by calculated methods with determination of BMI and RBMI and direct determination of body fat content, are accompanied by a statistically significant decrease in bronchial patency.

Diagnostics of Inherited Metabolic Diseases in Newborns with the Hyperammonemia Syndrome at the Onset of Disease (Pilot Study).

The aim of the study was to develop a diagnostic model that allows with a high degree of probability predicting the development of inherited metabolic disease (IMD) in newborns with the hyperammonemia syndrome at the onset of disease and determine the adequate management tactics for such patients. Materials and Methods: The study included 15 female and 5 male infants with the hyperammonemia syndrome. All the patients underwent a full range of clinical laboratory studies in accordance with the standards of treatment of the underlying disease. Blood ammonia measuring (quantitative assessment) was carried out on the basis of the biochemical laboratory of the Children's City Clinical Hospital No.1 (Nizhny Novgorod, Russia) using a portable PocketChem BA blood ammonia meter (Japan) and Ammonia Test Kit II test strips (Japan) in accordance with the manufacturer's protocol. The confirmation of the IMD diagnosis was carried out using the tandem mass spectrometry (TMS) method and molecular genetic testing (genome sequencing).To check the assumptions, all the patients during the follow-up were randomized retrospectively into two groups depending on the TMS results and molecular genetic testing. Group 1 (n=8) included the patients diagnosed with IMD and group 2 (n=12) included the patients with transient hyperammonemia in the neonatal period. Results: The clinical manifestations of the hyperammonemia syndrome in the neonatal period are most frequently realized in the form of a syndrome of CNS depression of varying degrees up to coma (75%), a convulsive syndrome (55%), vomiting (40%) without significant differences in the frequency of occurrence due to the causes of hyperammonemia. In a third of cases, the onset of the hyperammonemia syndrome occurs in the early neonatal period.The ammonia levels in patients with hyperammonemia caused by IMD are statistically significantly higher than those in patients with transient hyperammonemia (p=0.014) which may serve as the first diagnostic sign of IMD in a newborn.A tendency to a more frequent development of anemia in infants with IMD (p=0.084) has been established which might be due to the compensation of metabolic acidosis. The presence of anemia in combination with clinical features and the level of hyperammonemia increases the risk of IMD.In the course of the study, a diagnostic model was developed for predicting the risk of IMD development in a newborn at the onset of hyperammonemia. Through the discriminant analysis, a statistically significant relationship was established between the level of ammonia at the onset, blood glucose and base deficiency levels, blood lactate, hemoglobin, erythrocyte levels, the average volume of erythrocytes and the pH level (p=0.040) with the risk of IMD development. The sensitivity of the model has amounted to 87.5%, the specificity - 83.3%. The diagnostic efficiency of the model is 85.0%. Conclusion: The proposed model can be used at detecting the debut of the hyperammonemia syndrome in newborns in order to predict the probability of IMD and work out the adequate tactics of the management for these patients.

[Developmental disorders of academic skills in children: the efficacy and safety of Tenoten for children in the multicenter double-blind placebo-controlled randomized study]. / Narusheniya razvitiya uchebnykh navykov u detei: effektivnost' i bezopasnost' Tenotena detskogo po dannym mnogotsentrovogo dvoinogo slepogo platsebo-kontroliruemogo randomizirovannogo issledovaniya.

OBJECTIVE: To evaluate the efficacy and safety of tenoten for children in the treatment of specific developmental disorders of academic skills in children of 1-3 grades. MATERIAL AND METHODS: Two hundred and forty children, aged 7-9 years, (Total set, Safety population) with verified specific reading disorder (F81.0), specific spelling disorder (F81.1), specific disorder of arithmetical skills (F81.2), mixed disorder of scholastic skills (F81.3; F81.2+F81.0, or F81.2+F81.1, or F81.2+F81.0+F81.1), diagnosed with the use of logopedic or psychological testing (15-35 scores in Fotekova T.A. and Akhutina T.V. reading and writing tests; 5-15 scores in arithmetical subscale of the Wechsler Intelligence Scale for Children) were enrolled in the study. CT was conducted in 10 clinical centers in Russian Federation in 2015- 2019. Patients were randomized into two groups. The first one (n=122) received tenoten for children in a dose of 1 tablet 3 times a day, the second one (n=118) was administered placebo in the same dosage regimen. The clinical data on 237 children (121 of the tenoten group and 116 of the placebo group) were used for Intention-to-treat efficacy analysis. Data on 220 children (115 of the tenoten group and 105 of the placebo group) were included in Per-protocol analysis. The duration of study was 12 weeks. The mean total academic skills (reading, spelling, and counting) score in groups after 12 weeks of treatment was set as the primary efficacy endpoint. RESULTS: The mean total academic skills score increased by 18.55±15.87 points. The significant total difference between the median changes in the total score in the tenoten and placebo groups was 5 points. There was a trend towards positive changes in reading and spelling mean scores in tests that didn't reach statistical significance due to lack of normal distribution of points in samples. There were 73 adverse events (AEs) in 42 patients of the tenoten group and 95 AEs in 31 children of the placebo group. No serious or severe AEs were registered in the tenoten group. No AEs definitely related to the study treatment were registered. No negative drug interactions were observed in the tenoten group. CONCLUSIONS: Tenoten for children is an effective and safe treatment for specific developmental disorders of academic skills in primary school children. Tenoten for children is well tolerated. The treatment is characterized by a high level of adherence of children and their parents to therapy.

Effect of Nasal Obstructive Disorders on Sinonasal Symptoms in Children with Different Levels of Bronchial Asthma Control.

Allergic rhinitis (AR) and allergic rhinosinusitis (ARS) are typical upper airway pathologies (UAP) in children with bronchial asthma (BA) frequently accompanied with nasal obstructive diseases (NOD). In order to establish the effect of NOD on correlations between nasal and synonasal symptoms with clinical assessments of asthma control, 82 children, 9.8 [8.9; 10.7] years old, with atopic BA were assessed using ACQ-5 for the BA control level, TNSS for nasal symptoms, and SNOT-20 for synonasal quality of life in combination with rhinovideoendoscopy for NOD. All patients had AR/ARS; in 76.3% (63/82) of children, UAP had a multimorbid character with the presence of NOD. Significant correlations were found between ACQ-5 and TNSS (R=0.40, p < 0.0001) and ACQ-5 and SNOT-20 (R=0.42, p < 0.0001). Correlations between TNSS/ACQ-5 and SNOT-20/ACQ-5 were higher in patients who do not have a combination of AR/ARS with NOD (R=0.67, p=0.0012; R=0.50, p=0.022, resp.) than in patients who have AR/ARS combined with NOD (R=0.30, p=0.015; R=0.26, p=0.04, resp.). Thus, the association of BA control level with the expression of nasal and synonasal symptoms is higher in children who do not have multimorbid UAP.