[Development of early diagnosis of Parkinson's disease and comprehensive economic analysis of the effect of its implementation]. / Razrabotka rannei diagnostiki bolezni Parkinsona i kompleksnyi ekonomicheskii analiz effekta ot ee vnedreniya.

The paper summarizes the literature and author's data on the development of early (preclinical) diagnosis of Parkinson's disease (PD). Implementation of this diagnosis will promote the use of preventive therapy and change investments in diagnosis and treatment of patients. The paper declares that at present the only approach to early diagnosis of PD is positron-emission tomography of the nigrostriatal dopaminergic system, but it cannot be used for preventive examination due to its high cost. The authors consider that a less specific, but more promising approach to the development of early diagnosis of PD is the search for markers in body fluids, mainly in the blood, in patients at the prodromal stage of PD. Indeed, a number of markers as changes in the level of metabolites of monoamines, sphingolipids, urates, and indicators of oxidative stress were found in patients selected for the risk group of the prodromal stage of PD, according to characteristic premotor symptoms. In addition, it is assumed that the search for blood markers at an earlier - pre-prodromal stage is possible only in animal models of PD at the early preclinical stage. This approach can also be used to verify blood markers identified in patients at the clinical stage of PD. It is also evident that the complex socio-economic factors influencing the incidence of PD is different in developed versus developing countries. The societal and medical costs of Parkinson's are huge and efforts to improve early preclinical diagnosis of PD will lead to considerable economical and societal benefits. For instance this will allow efficient selection of patients for preclinical diagnostic tests. To assess the effectiveness of this strategy considering the uncertainty of socio-economic issues, a modification of the «cost-utility¼ analysis is proposed. For the first time, a Markov model of PD including preclinical diagnostic tests and possible neuroprotective therapy was developed and studied. Analytical outcomes of this process suggest that the idea of developing a new multimodal strategy is promising from a socio-economic point of view.

[Steroid pulse -therapy in patients With coronAvirus Pneumonia (COVID-19), sYstemic inFlammation And Risk of vEnous thRombosis and thromboembolism (WAYFARER Study)].

Introduction Coronavirus pneumonia not only severely affects the lung tissue but is also associated with systemic autoimmune inflammation, rapid overactivation of cytokines and chemokines known as "cytokine storm", and a high risk of thrombosis and thromboembolism. Since there is no specific therapy for this new coronavirus infection (COVID-19), searching for an effective and safe anti-inflammatory therapy is critical.Materials and methods This study evaluated efficacy and safety of pulse therapy with high doses of glucocorticosteroids (GCS), methylprednisolone 1,000 mg for 3 days plus dexamethasone 8 mg for another 3-5 days, in 17 patients with severe coronavirus pneumonia as a part of retrospective comparative analysis (17 patients in control group). The study primary endpoint was the aggregate dynamics of patients' condition as evaluated by an original CCS-COVID scale, which included, in addition to the clinical status, assessments of changes in the inflammation marker, C-reactive protein (CRP); the thrombus formation marker, D-dimer; and the extent of lung injury evaluated by computed tomography (CT). Patients had signs of lung injury (53.2 % and 25.6 %), increases in CRP 27 and 19 times, and a more than doubled level of D-dimer (to 1.41 µg/ml and 1.15 µg/ml) in the active therapy and the control groups, respectively. The GCS treatment group had a more severe condition at baseline.Results The GCS pulse therapy proved effective and significantly decreased the CCS-COVID scores. Median score difference was 5.00 compared to the control group (р=0.011). Shortness of breath considerably decreased; oxygen saturation increased, and the NEWS-2 clinical status scale scores decreased. In the GCS group, concentration of CRP significantly decreased from 134 mg/dl to 41.8 mg/dl (р=0.009) but at the same time, D-dimer level significantly increased from 1.41 µg/ml to 1.98 µg/ml (р=0.044). In the control group, the changes were nonsignificant. The dynamics of lung injury by CT was better in the treatment group but the difference did not reach a statistical significance (р=0.062). Following the GCS treatment, neutrophilia increased (р=0.0001) with persisting lymphopenia, and the neutrophil/lymphocyte (N/L) ratio, a marker of chronic inflammation, increased 2.5 times (р=0.006). The changes in the N/L ratio and D-dimer were found to correlate in the GCS pulse therapy group (r =0.49, p=0.04), which underlined the relationship of chronic autoimmune inflammation with thrombus formation in COVID-19. No significant changes were observed in the control group. In result, four patients developed venous thromboembolic complications (two of them had pulmonary artery thromboembolism) after the GCS pulse therapy despite the concomitant antiplatelet treatment at therapeutic doses. Recovery was slower in the hormone treatment group (median stay in the hospital was 26 days vs 18 days in the control group, р=0.001).Conclusion Pulse therapy with high doses of GCS exerted a rapid anti-inflammatory effect but at the same time, increased the N/L ratio and the D-dimer level, which increased the risk of thromboembolism.

[Development of early diagnosis of Parkinson's disease based on the search for biomarkers such as premotor symptoms and changes in blood]. / Razrabotka rannei diagnostiki bolezni Parkinsona na osnove biomarkerov v vide premotornykh simptomov i izmenenii v krovi.

OBJECTIVE: To determine changes in the chemical composition of blood plasma in subjects at risk of Parkinson's disease (PD) at the prodromal stage compared with age control. MATERIAL AND METHODS: Subjects at risk were selected for the presence of characteristic premotor symptoms, including impairments of sleep, olfaction and constipation.The risk group included 12 people, the control group - 8 people. RESULTS: Among seven catecholamines and their metabolites detected in the blood, only the concentration of L-dioxiphenylalanine (L-DOPA) changed (decreased) in subjects at risk compared with the control. A decrease in the concentration of L-DOPA is considered as a manifestation (marker) of selective degeneration of central and peripheral catecholaminergic neurons in PD. In contrast to L-DOPA, the concentration of seven of the twelve detected sphingomyelins in the blood of the subjects at risk increased. Given that a change in the metabolism of sphingomyelins is associated with processes such as apoptosis, autophagy, and synucleinopathy, an increase in their concentration in the blood of patients at risk is considered as a manifestation of systemic general degeneration of central and peripheral neurons. Finally, in the blood of subjects at risk, we found a trend towards a decrease in the concentration of urates, which are endogenous neuroprotectors. CONCLUSION: The changes in the level of L-DOPA, sphingmyelins and urates in the blood of subjects at risk may serve as diagnostic markers of PD at the prodromal stage.

[Early Stages of Parkinson's Disease: Comparative Characteristics of Sleep-Wakefulness Cycle in Patients and Model Animals].

The results of study of sleep-wakefulness cycle in experimental models of pre-clinical and early clinical stages of Parkinson's disease present and compared to some clinical examples. The conclusion is, the increase in activity level and decrease in total amount of slow wave and paradoxical sleep in model animals are taking place at the same circadian period of the secretion of pineal melatonin as sleep disorders in patients.

[The diagnostic efficiency of the methods of separate and combined registration of oronasal airflow and pulse oximetry for detection of the obstructive sleep apnea/hypopnea syndrome].

The diagnostic efficiency of the methods of separate and combined registration of oronasal airflow and pulse oximetry in order to identify the obstructive sleep apnea/hypopnea syndrome (OSAHS) is studied in this work. Patients with cardiovascular diseases with complaints on sleep disorders were included in the study. Combined registration of oronasal airflow and pulse oximetry during sleep were performed for all examined patients (diagnostic system ApneaLink with pulse oximetry, ResMed). Registration results of oronasal airflow and pulse oximetry were analyzed separately and together. Apnea/hypopnea index (classic, recommended), desaturation index with a threshold of desaturation of 4% and 3% were evaluated as the diagnostic criteria for the identification of OSAHS. Also, in this paper the "apnea/hypopnea combined index" summarizing hypopnea episodes, which are associated with significant desaturation and without desaturation, was tested. As a method of comparison, polysomnography (Embla N7000, MedCare Flaga), which was carried out simultaneously with the main study, was used. The diagnostic efficiency of test methods and their criteria assessed by ROC-analysis (receiver operator characteristic, the characteristic curve analysis). The results of the study showed that combined registration of respiratory oronasal airflow and pulse oximetry during sleep was most effectively identified OSAHS and can be used as a screening method. The most accurate diagnostic criterion for identification of OSAHS is an "apnea/hypopnea combined index".

[The use of screening methods in diagnosis of disturbances of respiration during sleep in patients with cardiac pathology].

Disturbances of respiration during sleep especially those of obstructive character are sufficiently widespread phenomena. In addition to worsening of the quality of sleep itself they facilitate formation and development of concomitant pathology of cardiovascular system, endocrine system, cognitive sphere. This results in lowering of quality of life and its duration. At present standard method of diagnosis of disturbances of respiration during sleep is polysomnographical examination. At the same time more accessible screening methods are also actively used with the aim of detection of subjects with high probability of respiratory disturbances during sleep. Among them cardiorespiratory monitoring, nocturnal pulsoximetry, registration of oro-nasal flow during sleep, are questionnaires most widely-spread.

Marinobufagenin in hypertensive patients with obstructive sleep apnea.

Although obstructive sleep apnea (OSA) is an independent risk factor for hypertension, the underlying mechanisms are not clearly understood. Apnea and hypopnea episodes during sleep lead to sympathoactivation, decrease plasma pH, and predispose to sodium and volume retention. We hypothesized that, the latter could stimulate digitalis-like natriuretic/vasopressor hormones, endogenous ouabain (EO) and marinobufagenin (MBG). Overnight polysomnography (Embletta) and 24 hrs blood pressure monitoring (SpaceLab 90207) was conducted in 52 consecutive patients with OSA (51 +/- 8 years; 40 males, 12 females) and in 48 age-matched hypertensive subjects without OSA. According to the polysomnography data, 17 patients had a mild degree of OSA (apnea/hypopnea index (AHI) 5-15), 17 patients-moderate (AHI 15-30) and 18 -severe OSA (AHI >30). Levels of MBG excretion co-varied with OSA severity (0.5 +/- 0.1, 0.9 +/- 0.04 and 1.2 +/- 0.06 nmoles per 24 hrs, respectively), while excretion of EO did not differ in patients with different degrees of OSA severity. Our observations suggest that MBG may be involved in the pathogenesis of hypertension in OSA, and may be a marker of OSA severity.

[Polysomnographic results of surgical treatment of obstructive apnea syndrome]. / Rezul'taty khirurgicheskogo lecheniia sindroma obstruktivnogo apnoé sna po dannym polisomnografii.

The study was made of 20 patients suffering from mild, moderate and severe snore and obstructive sleep apnea. The patients were treated surgically but because their upper respiratory pathology varied the intervention consisted of several one-stage operations in the nasal cavity, nasopharynx and oropharynx. To remove nasal obstruction, operations on the nasal septum and/or turbinated bones were made. Pharyngeal surgery varied from uvulotomy and volumetric reduction of the soft palate thickness to uvulopalatopharyngoplasty with tonsillectomy. The results of polysomnography performed after surgical intervention confirmed efficacy of surgical treatment. A more than 2-fold decrease of the index apnea/hypopnea was registered in 75% patients with moderate and in 83% patients with a severe form of obstructive sleep apnea syndrome.

[Efficiency of intraoral applicator UPLH-01 in snore and obstructive sleep apnea]. / Otsenka éffektivnosti primeneniia vnutrirotovogo applikatora UPLKH-01 pri khrape i sindrome obstruktivnogo apnoé sna.

Tolerance, subjective and objective effectiveness of domestic intraoral applicator UPLH-01 were studied in the treatment of snoring and obstructive sleep apnea (OSA). In 44 patients with uncomplicated snoring the above parameters were assessed using questionnaire, in 20 patients with uncomplicated snoring and OSA paired polysomnographic investigations were made. Tolerance of the treatment was 50%. Subjective positive effect was registered in 65% of the patients. The applicator was found effective in the majority of patients with uncomplicated snoring. In mild and moderate OSA the applicator was effective only in a few cases. In severe OSA no effect was found. Patients with chronic disorders of nasal breathing exhibited deterioration of respiration and blood saturation with oxygen. Thus nasal obstruction is a contraindication to applicator use.