[Cost-effectiveness of pneumococcal vaccination among patients with chronic heart failure].

Aim      To analyze the cost-effectiveness of pneumococcal vaccination in 40- and 65-year-old patients with chronic heart failure (CHF).Material and methods  Analysis was performed by Markov modeling from the perspective of the healthcare system. The evaluation was based on Russian epidemiological data taking into account results of international studies. The analyzed schedule of vaccination included one dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent polysaccharide vaccine (PPSV23) after one year and vaccination with only one dose of PCV13. The time horizon of the study was 5 years. Costs and life expectancy were discounted at 3.5% per year.Results The cost-effectiveness of vaccination for both 65-year-old and 40-year-old CHF patients is very high: the incremental cost of one additional QALY (Quality-Adjusted Life Year) for PCV13+PPSV23 vaccination is 113.24 thousand rubles, while vaccination with PCV13 entails a reduction in costs by 556.50 rubles per one vaccinated patient. For vaccination of 40-year-old CHF patients with PCV13+PPSV23, the incremental costs per 1 QALY will be 519.72 thousand rubles, while for vaccination with PCV13 it will be 99.33 thousand rubles.Conclusion      Pneumococcal vaccination of CHF patients reduces the associated morbidity and mortality and is highly cost effective.

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine administered concomitantly with other paediatric vaccines in toddlers: a phase III randomised study.

Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12-23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.

[The prevention of disability as a leading priority of caring of mother and child health].

The prevention of disability in children and support of families fostering disabled children and children with limited capacities in health are included into number of main priorities of the state social policy of the Russian Federation. Thereupon, the project "Childhood Decade" is an important stage that includes social care of disabled children and children with limited capacities in health and their integration in modern society according the Decree of the President on implementation of state policy in the field of family and children care. The underestimation of children disability is supposed to be present produced by such causes as social motivation of family, complicacy of legal official registration, harsh requirements of medical social expertise services, inadequate awareness of medical staff about criteria of disability. According the WHO European Regional Bureau, in Russia there are 250 000 children with limitations of life activity mainly caused by somatic pathology, who have no status of disabled person and no state social support. The prevention of children disability is considered as a system of measures of caring mother and child health all along childhood. The priority directions of prevention considering causes of development of disability and its structure according particular disease are marked. The data is presented related to modern technologies of decreasing genetic load on population from position of prevention of hereditary, inborn and orphan diseases. In particular studies non-infectious pathology acquiring greater significance in development of disability in children of various age groups since neonatal period is considered. The new directions of research are proposed to affect the processes of incapacitation of child on more profound pathogenic level and to develop organization of preventive activities in this area.

[Clinical case of congenital cleft palate in 22q11.2 deletion syndrome]. / Vrozhdennaia rasshchelina neba pri sindrome deletsii 22g11.2. Klinicheskii sluchai.

The paper presents a clinical case of congenital cleft palate as a manifestation of 22q11.2 deletion syndrome accompanied by other systemic disorders having direct impact on functional indicators and perioperative period during cleft surgery. Specific for 22q11.2 deletion syndrome endocrine disorders affect the facial development. Multidisciplinary approach contributes to the early optimal treatment outcome and prevents further postoperative disturbances in maxillofacial development.

[Efficacy and safety of botulinum toxin type A (IncobotulinumtoxinA) in the treatment of patients with cerebral palsy]. / Éffektivnost' i bezopasnost' primeneniia botulinicheskogo toksina tipa A (IncobotulinumtoxinA) pri lechenii patsientov s detskim tserebral'nym paralichom.

AIM: To assess the safety and clinical and neurophysiological efficacy of xeomin in children with spastic equinus and equinovarus foot deformity in cerebral palsy. MATERIAL AND METHODS: Sixty-four patients with spastic forms of cerebral palsy (levels I-IV on the GMFCS) were enrolled into this multi-center open-label comparative randomized trial. The patients were administered xeomin or botox once, each drug being administered to 32 patients. Efficacy was evaluated based on clinical characteristics (the modified Ashworth scale, goniometry) and electromyography data. The subjects were observed for 3 months (90±7 days) after injections. The incidence, severity and intensity of adverse events (AE) was also determined. RESULTS: Treatment with xeomin according to the suggested protocol has proven its high clinical efficacy. The efficacy was demonstrated by significant, stable and long-term decrease in the gastrocnemius muscle tone: in the xeomin group, the score on the modified Ashworth scale decreased from 2.6±0.49 points at baseline to 1.8±0.54 points (р<0.000001, paired t-test; р<0.000004, Wilcoxon test). In the botox group, this score decreased from 2.4±0.56 points to 1.6±0.45 points (р<0.000001, paired t-test; р<0.000002, Wilcoxon test). The increased range of ankle joint movements at passive and voluntary feet extension. In the xeomin group, the significant proportion of patients (45.1%) moved to the group of lower spasticity defined as less than two score points on the modified Ashworth scale. The clinical data fully matched the changes in electromyography parameters, which were characterized by the lower amplitude and area of the target muscle (lateral and medial gastrocnemius heads) M-responses. AE developed in three patients (9.4%) administered xeomin and in two patients (6.3%) administered botox. The AE recorded in the study are described in the recommendations on the use of xeomin and botox. In three cases (50.0%), AE intensity was determined as mild, in the remaining three cases (50.0%) as moderate. CONCLUSION: The results have shown the safety and efficacy of xeomin in the treatment of gastrocnemius spasticity in pediatric patients with cerebral palsy. These data are confirmed by the lack of significant differences in any clinical or electromyography parameters with the results in the reference group administered botox.

[The evaluation of quality of implementation of preventive medical examinations of underage persons in the Russian Federation].

The analysis was implemented concerning informational statistic data characterizing health of children population of different age groups in the Russian Federation on the basis of results of dispensarization in its federal okrugs and subjects in 2014. The purpose of the study was to discover ways and modes of developing and increasing efficiency of preventive examinations of underage population. The following indices were analyzed: coverage of children population by preventive medical examinations, distribution according health groups and medical groups for physical culture involvement, level and stricture of established total and primary morbidity, rate of dispensary registration, requirements in additional consultations, examinations and treatment in out-patient condition, day hospital, day-and-night hospital and also coverage with all these medical services. In the most of the subjects of the Russian Federation a high level of coverage of underage population with preventive medical examinations is registered. The percentage of healthy children population in the Russian Federation comprises more than one third of all covered by dispensarization. The significant variations in indices of rate of healthy children and children with functional disorders and chronic diseases in subjects of the Russian Federation is determined by quality and accessibility of medical care at the regional level. The established total and primary morbidity of children population in significant percentage (more than one third) of the subjects has a level higher than a national one. The leading causes of morbidity in children are diseases of respiratory system, musculoskeletal system, nervous system. In adolescents, these causes are diseases of musculoskeletal system, eye diseases and diseases of respiratory system. Despite high prevalence of chronic pathology in children population of the Russian Federation, the guidelines concerning treatment and rehabilitation on the basis of results of preventive medical examinations were developed in inadequate scope. The regional characteristics of the results of dispensarization are established. These results made it possible to sort out the most unfavorable territories and to determine defects in its organization and absence of continuity between medeical institutions providing the given type of medical services.

[The mode of evaluation of sensibilization of children to grain herbs under respiratory allergy.]

The sensibilization of patients to allergens of grain herbs is characterized by expressed crossed allergic reactions to pollen of various representatives of the given family. The investigation of antibody response to allergens of grain herbs and also data of epidemiological studies, results of world and national studies permitted to develop and propose a new mode of diagnostic of allergy with evaluation of level of sensibilization of patient and also qualitative detection in blood serum the level of specific immunoglobulins E (IgE) to allergens of grain herbs. The parameter «concentration of IgE to allergens of cocksfoot¼ - IgE(g3) - is a key one for evaluating in blood serum of patients content of IgE to allergens of grain herbs matched to cocksfoot: randall, timothy, Kentucky bluegrass, field brome, meadow foxtail, French ryegrass. To calculate concentration of IgE to allergens of the mentioned grasses detection of IgE(g3) is necessary and sufficient. The elaborated prognostic table permits evaluating degree of ensibilization of patient to various grain herbs and also detecting concentration of IgE expressed in units kE per l without application of additional serological analyses. Therefore, the elaborated technique permits reducing number of «in vitro¼ tests and minimizing number of blood sample of patient and also speeding up receiving of information concerning sensibilization profile of patient.

[The diagnostic detection of sIgE to allergens of trees' pollen by rest-system «Alkor-Bio¼ and Immunocap technique.]

The article presents the results of preliminary analysis of 320 pair results of testing of children with bronchial asthma and/or allergic rhinitis conditioned by tree pollen. The imported and national test-systems ImmunoCAP and Alkor-Bio were applied. The detailed analysis of study results of the mentioned tests demonstrated that detection of levels of allergen-specific IgE in patients using test-systems Alkor-Bio and ImmunoCAP shows high degree of data matching related to a number of tree allergens. The application of national test-system Alkor-Bio can be considered as an alternative to import methods in evaluation of levels of sIgE to allergens of alder tree, birch, hazel, willow, poplar, pine.

[Technologies for Complex Intelligent Clinical Data Analysis].

UNLABELLED: The paper presents the system for intelligent analysis of clinical information. Authors describe methods implemented in the system for clinical information retrieval, intelligent diagnostics of chronic diseases, patient's features importance and for detection of hidden dependencies between features. Results of the experimental evaluation of these methods are also presented. BACKGROUND: Healthcare facilities generate a large flow of both structured and unstructured data which contain important information about patients. Test results are usually retained as structured data but some data is retained in the form of natural language texts (medical history, the results of physical examination, and the results of other examinations, such as ultrasound, ECG or X-ray studies). Many tasks arising in clinical practice can be automated applying methods for intelligent analysis of accumulated structured array and unstructured data that leads to improvement of the healthcare quality. AIMS: the creation of the complex system for intelligent data analysis in the multi-disciplinary pediatric center. MATERIALS AND METHODS: Authors propose methods for information extraction from clinical texts in Russian. The methods are carried out on the basis of deep linguistic analysis. They retrieve terms of diseases, symptoms, areas of the body and drugs. The methods can recognize additional attributes such as "negation" (indicates that the disease is absent), "no patient" (indicates that the disease refers to the patient's family member, but not to the patient), "severity of illness", disease course", "body region to which the disease refers". Authors use a set of hand-drawn templates and various techniques based on machine learning to retrieve information using a medical thesaurus. The extracted information is used to solve the problem of automatic diagnosis of chronic diseases. A machine learning method for classification of patients with similar nosology and the methodfor determining the most informative patients'features are also proposed. RESULTS: Authors have processed anonymized health records from the pediatric center to estimate the proposed methods. The results show the applicability of the information extracted from the texts for solving practical problems. The records ofpatients with allergic, glomerular and rheumatic diseases were used for experimental assessment of the method of automatic diagnostic. Authors have also determined the most appropriate machine learning methods for classification of patients for each group of diseases, as well as the most informative disease signs. It has been found that using additional information extracted from clinical texts, together with structured data helps to improve the quality of diagnosis of chronic diseases. Authors have also obtained pattern combinations of signs of diseases. CONCLUSIONS: The proposed methods have been implemented in the intelligent data processing system for a multidisciplinary pediatric center. The experimental results show the availability of the system to improve the quality of pediatric healthcare.

[Nutritional management of kidney diseases in children].

The prevalence of various kidney diseases in children remains high in recent decades. Adequate nutrition management can enhance the effectiveness of drug treatment, slow the frequency of relapses andprevent the progression of the disease. The article is devoted to modern approaches to diet therapy in various kidney diseases in children with the defeat of tubular and glomerular appa ratus. For the first time the therapeutic diets for children with various kidney diseases are presented. Particular attention is paid to diet therapy in nephrotic syndrome (steroid-responsive and steroid-refractory). Dietary approaches with modern formulas for enteral nutrition in cases of steroid therapy complications in children with renal insufficiency (in predialysis stage and on dialysis) are described. Differentiated nutritional approaches for patients with different types of crystalluria are separately presented.

[The First Russian Consensus on the Multilevel Abobotulinumtoxin A Injections in Spastic Forms of Cerebral Palsy]. / Pervyi Rossiiskii konsensus po primeneniyu mnogourovnevykh in''ektsii abobotulinumtoxin A pri lechenii spasticheskikh form detskogo tserebral'nogo paralicha.

Spasticity treatment is one of the key aspects of the contemporary cerebral palsy (CP) rehabilitation that influences on the effectiveness of other methods. The paper presents the first Russian document that unites the recommendations for the BTA treatment of CP and could be used as the guideline for the multilevel injections. The Russian consensus on the multilevel botulinum toxin A (BTA) treatment of spastic CP is based on the international data and the results of national studies. The authors describe typical CP spasticity patterns in the upper and lower extremities, give recommended intervals for the BTA (Abobotulinum toxin A) dosages for the whole injection procedure and for the separate muscles. The method of dosage calculation for functional segments is also described. Attention is paid to the frequency, optimal intervals between the repeated injections and the whole duration of BTA treatment. The authors discuss effectiveness and safety of BTA, factors that potentially influence the results of the injections, including ultrasound and electromyography control, and indications for the continuation and termination of treatment.

[The non-invasive diagnostic of fibrosis and cirrhosis of liver under chronic viral hepatitis: publications review].

The chronic viral hepatitis is characterized by progressing course. In connection with this fact, there is a risk of development of fibrosis of liver. The diagnostic of this disease biopsy is applied as main technique. However, this invasive procedure is not always safe for patient. Therefore, it is applied only in specialized institutions, requires special training of medical personnel and has a number of contraindications. In recent years, in the capacity of noninvasive diagnostic of different stages of fibrosis of liver a number of serum markers are considered. Among them, the most number of studies concerns hyaluronic acid, collagen type IV, matrix metalloproteinase and their tissue inhibitors, transforming growth factor ß. The review presents actual information concerning possibilities of application of these serological indices in practical medicine in patients with chronic viral hepatitis.

[Pediatric Health Quality Assessment in Different Regions of Russian Federation].

Background: The quality of pediatric healthcare is a cornerstone for good maternal and infant health. Aims: To evaluate the quality of healthcare in secondary and tertiary regional pediatric hospitals in the Russian Federation. Methods: Healthcare quality assessment was performed in 21 pediatric hospitals (tertiary, n=5; secondary, n=16) of four regions. The WHO recommendations were used. Results: In all regions, similar traits of inpatient pediatric healthcare determining a poor quality were observed. These included low preparedness for emergent care at admission departments; a high rate of unjustified hospitalization due to lack of clear indications for inpatient care; a widespread polypharmacy and unnecessary painful procedures and treatment; inadequate unjustified antimicrobial and parenteral therapy. Conclusions: The revealed identity of problems in different regions of the country allows to consider a common strategy to overcome them, which, obviously, should primarily involve education of medical personnel, restructuring of hospital beds to increase day care beds, increasing the clinical expert work in hospitals.

[Nutritional and Hormonal Status of Premature Infants Born with Intrauterine Growth Restriction at the Term Corrected Age].

Background: Inadequate nutrition supply during the period of intrauterine growth and the first year of life leads to persistent metabolic changes and provokes development of various diseases. Aims: Тo compare physical development, body composition, and hormonal status (insulin, insulin-like growth factor-1 (IGF-1), somatotropic hormone (STH), C-Peptide, cortisol) indices in premature infants born with intrauterine growth restriction (IUGR) at the term corrected age with the same indices in mature infants with IUGR and premature infants with weight appropriate for their gestational age (GA). Materials and Methods: А crossover study of anthropometric measures, body composition and growth hormones changes assessment was carried out. It included 140 premature infants with weight appropriate for their GA, 58 premature infants with IUGR and 64 mature infants with IUGR. Anthropometric measures were assessed with Fenton and Anthro growth charts (WHO, 2009); body composition was studied with the air plethysmography method (РЕA POD, LMi, USA). Level of hormones in blood serum was assessed with biochemical methods. Results: It is found that anthropometric measures in premature infants with weight appropriate for their GA and premature infants with IUGR at the term corrected age did not have any significant differences while premature infants with IUGR tended to have lower weight. Studying body composition we found that both groups of premature infants had slightly higher level of fat mass in comparison with mature infants. High concentration of insulin, cortisol, IGF-1, and C-peptide was found in premature and mature infants with IUGR. Instead, lower levels of STH was found in infants with IUGR. Formula fed premature infants (comparing to breastfed ones) had higher levels of fat mass, insulin, IGF-1, and C-peptide. Mature infants with IUGR did not tend to have the correlation between levels of fat mass, insulin, IGF-1, C-peptide, and type of feeding. Conclusions: Not only insufficient intrauterine growth but also nutrition pattern plays important role in development of body composition disbalance and hormonal shifts in premature infants.

[Sanfilippo Syndrome].

Sanfilippo syndrome (mucopolysaccharidosis type III) is a lysosomal disorder caused by a defect in the catabolism of heparan sulfate. Mucopolysaccharidosis type III is the most common type of all mucopolysaccharidoses. The pathogenic basis of the disease consists of the storage of undegraded substrate in the central nervous system. Progressive cognitive decline resulting in dementia and behavioural abnormalities are the main clinical characteristics of Sanfilippo syndrome. Mucopolysaccharidosis type III may be misdiagnosed as otherforms of developmental delay, attention deficit/hyperactivity disorder and autistic spectrum disorders because of lack of somatic symptoms, presence of mild and atypical forms of the disease. Patients with Sanfilippo syndrome may have comparatively low urinary glycosaminoglycans levels resulting in false negative urinary assay. Definitive diagnosis is made by enzyme assay on leucocytes and cultured fibroblasts. There is currently no effective treatment of mucopolysaccharidosis type III, though ongoing researches of gene, substrate reduction and intrathecal enzyme replacement therapies expect getting curative method to alter devasting damage of central nervous system in near future.

[Medical and Social Problems of Assisted Reproductive Technologies from the Perspective of Pediatrics].

The article presents a literature review over the last few years devoted to the health status and development peculiarities of children born using assisted reproductive technologies (ART) procedures. The statistics shows an explosive increase in the frequency of ART application as a fertility treatment method. The presented data analysis reflects the perinatal outcomes after ART in children, the frequency of congenital malformations and genetic diseases in this population, possible long-term malconditions and pathologies in children born using ART. The overwhelming majority of investigators consider the adverse effect of ART on a child's body to be the result of prematurity and multiple pregnancy (transfer multiple embryos followed by partial reduction). It is stated that the widespread introduction of ART may contribute to the vertical transmission of parental infertility factors in the population. The application of ARTprocedures in some cases is associated with controversial ethical and legal issues (surrogacy, oocyte donation). Further improvements in ART procedures (preimplantation training, medical and genetic diagnosis, reducing the frequency of multiple pregnancy) cannot be stated as an alternative to the general medical and social prevention of reproductive disorders in adolescents and youth.

[Selection of a dose of the botulinum toxin A in spastic forms of cerebral palsy]. / Vybor dozy preparata botulinicheskogo toksina tipa A pri lechenii spasticheskikh form detskogo tserebral'nogo paralicha.

AIM: To analyze the efficacy and safety of dose ranges of abobotulinum toxin A (BTA) for multilevel injections into upper and lower extremity muscles in children with spastic forms of cerebral palsy (CP). MATERIAL AND METHODS: We analyzed retrospectively multilevel BTA injections for 216 patients, aged from 2 to 17 years. Children received 1-6 repeated injections and complex physiotherapy. Patients were classified according to the GMFCS. Treatment results were evaluated with the modified Ashworth and Tardieu scales. RESULTS: Multilevel BTA injections were indicated for the most (89/8%) of the patients with spastic forms of CP, and in most of them the total dosage exceeded 30 U/kg. In the bilateral forms of CP, the total dosage (U and U/kg) was higher compared to the unilateral forms. Doses for each muscle in U/kg were similar in all CP forms. The total doses of BTA and the intervals between the repeated injections were stable for each patient. CONCLUSION: The dose ranges suggested for CP are effective and safe for the reduction of spasticity in several functional segments of upper and lower extremities in one treatment session.

[Obstructive sleep apnea syndrome in children as a risk of cardiovascular pathology development].

OBJECTIVE: Our aim was to examine the predictors of cardiovascular disorders in children affected by obstructive sleep apnea syndrome (OSAS) based on the results of polysomnography and continuous monitoring of blood glycose. METHODS: Before the examination, parents filled in questionnaires concerning their children sleep quality. The procedure was followed by the study of the sleep by means of polysomnography (Embla s 7000, USA). A system of continuous monitoring of blood glucose was applied (Guardianreal-time, Medtronicminimed, USA) by means of which a glycemic profile tissue fluid was studied. RESULTS: A night sleep research of 120 children aged 3-16 y.o. is presented. There were 4 groups depending on the pathology: diseases of the nervous system (n = 31), ENT-pathology (n = 18), bronchial asthma (n = 24) and overweight and obesity (n = 34). The comparison group consisted of 13 apparently healthy children. The study has shown that the parents of every second child with sleep disorders did not know about the fact. The 60 % of the patients with high body mass index (BMI) had a snore, which was significantly higher the in children with normal body mass index--35% (p = 0.012). The index of apnea-hypopnea (AHI) was higher in the patients with ENT-pathology 17 times (p < 0.001) and the patients with obesity 7 times (p < 0.001) in comparison to the comparison group. In the analysis of the overall sample (n = 120) was obtained significant negative correlation with heart rate variability and heart rate (r = 0.405; p < 0.001). It is also shown that among 14 investigated children with OSAS only 8 had episodes of hypoglycemia (less than 3.3 mmol/l) during night sleep. All of them were with a high body mass index and with above average stature (>1sd). CONCLUSION: Children with ENT-pathology and with high high body mass index have high risk of cardio-vascular diseases. Children with above average stature and with increased body mass index affected by OSAS have additional backgrounds for cardiovascular diseases develop- ment as a result of the latent periods of hypoglycemia at night.

[Topical issues of food allergy diagnosis in pediatric practice].

Food allergy (FA) in children, especially in infancy, is still a significant public health problem. The severity and prognosis of disease progression associated with FA considerably depends on the correct and early diagnostics of this pathology, as well as on the following management of a child. At the same time delayed elimination diet administration, unreasonable or overlong dietary intervention might have become abuse management of a patient and have a negative impact on the development of a child and reduce the quality of life. The article summarizes the current practical approaches to the diagnosis of FA based on evidence-based medicine and adopted European and Russian national consensus documents, as well as on our own experience of management of patients with this pathology. FA diagnosis in a child usually includes clinical laboratory tests and clarification of clinical and anamnestic data. Unfortunately, it is a fact that preference is given to laboratory methods for diagnosis based on specific IgE determination or skin samples. However, the basis for cause-significant allergen identifying is detecting detailed medical history and clinical picture of a disease which still appears to be the most reliable tool for FA diagnosis.

[Risk management of a patient on the basis of remote health monitoring: current situation and prospects].

Review is dedicated to the problem of remote monitoring of health status. Existing approaches to the organization of an outdoor monitoring of a patient using telemedicine technologies are reviewed and analyzed. A new approach to risk management of a patient which meets the requirements of pediatric hospital is provided.