[The effectiveness of tele-rehabilitation for patients with multiple sclerosis during the COVID-19 pandemic in 2020-2021 was evaluated in this study]. / Effektivnost' telereabilitatsii patsientov s rasseyannym sklerozom v usloviyakh pandemii koronavirusnoi infektsii v 2020­2021 gg.

OBJECTIVE: To evaluate the effectiveness of telerehabilitation (TELEREBT) of patients with multiple sclerosis (MS) in the context of the coronavirus pandemic 2020-2021. MATERIAL AND METHODS: The study included 37 patients with MS who underwent a course of teleRBT. The course included 10 classes of 60 minutes for 10 days with a two-day break. Various questionnaires and scales were used to assess the effectiveness, as well as an assessment of the neurological status. RESULTS: 19 patients refused to participate in the program. The level of disability on the EDSS scale decreased from 4.86±1.19 at the initial level to 4.73±1.12 after the course of teleRBT, while no statistically significant changes were found. CONCLUSION: TeleRPT in patients can be an effective way to correct existing disorders. Further research is required to establish the effectiveness of teleRBT.

[Assessment of the efficacy and safety of alemtuzumab in patients with highly active relapsing-remitting multiple sclerosis in Russian population]. / Otsenka effektivnosti i bezopasnosti alemtuzumaba u patsientov s vysokoaktivnym techeniem rasseyannogo skleroza v rossiiskoi populyatsii.

OBJECTIVE: To evaluate the severity and frequency of infusion reactions (IR) in patients with highly active relapsing-remitting multiple sclerosis (MS) In Russian population receiving alemtuzumab therapy. MATERIAL AND METHODS: In retrospective study, we analyzed data from 50 patients with highly active relapsing-remitting multiple sclerosis (MS) from six Regional MS Centers in the Russian Federation who received two courses of alemtuzumab between 2018 and 2022. RESULTS: Among all IRs, the most frequently reported were hives-like rashes, which were registered in 27 people, mostly of mild severity (70.6%). Headaches were the second most common IR, observed in 17 patients (34%). When comparing the group of patients who underwent music therapy (MT) with those who received alemtuzumab therapy without MT, no statistically significant difference was found in the frequency and severity of IRs. CONCLUSION: All patients experienced IRs of varying degrees of severity. A decrease in the score on the EDSS disability scale was noted. MT did not affect the occurrence or severity of IRs.

[Efficacy, tolerability and safety of the treatment with teberif: the results of a 2-year randomized clinical trial of treatment naïve patients with remitting multiple sclerosis, who have not received DMT, after switching from other interferon ß-1a]. / Éffektivnost', perenosimost' i bezopasnost' terapii preparatom teberif: rezul'taty dvukhletnego klinicheskogo issledovaniia u patsientov s remittiruiushchim rasseiannym sklerozom, ranee ne poluchavshikh PITRS, i pri perekliuchenii s drugogo interferona ß-1a.

OBJECTIVES: To evaluate efficacy, safety, and tolerability of the treatment with teberif/interferon ß-1a, to analyze safety, tolerability and dynamics of key efficacy variables after switching from referent drug rebif to biosimilar teberif in patients with remitting multiple sclerosis (RMS). MATERIAL AND METHODS: During the main period of the international multicenter randomized study patients were randomized to receive treatment with teberif for 52 weeks, or rebif for 52 weeks, or placebo for 16 weeks to evaluate efficacy and safety of treatment. After the main study period, patients were group-independently switched to take open-label teberif treatment during the next 48 weeks. RESULTS AND CONCLUSION: The analysis of multiple evaluation parameters of the efficiency during the 1st study period (blinded) and the 2nd study period (open-label) has shown that teberif and rebif demonstrate equivalent efficacy and stable 2-year efficacy of teberif was proven. There were no significant differences between teberif and rebif for all safety, and tolerability parameters. Switching from rebif to teberif didn't influence treatment efficacy. The 2-year study results confirmed a biosimilar teberif's benign tolerability and expected safety profile to other interferons ß-1a in patients with RMS.

[Sensitivity and specificity of urinary and serum neurotrophins in the diagnosis of neurogenic detrusor overactivity in multiple sclerosis].

Lower urinary tract dysfunction is common among neurological patients. Traditionally, the basic method of diagnosis is a complex urodynamic study. In recent years, many studies have focused on the search for new non-invasive diagnostic modalities. In particular, neurotrophins are considered as potential biological markers of a neurogenic bladder. AIM: To estimate the sensitivity and specificity of the serum and urinary nerve growth factor (NGF) and brain neurotrophic factor (BDNF) in MS patients as markers of detrusor overactivity. MATERIALS AND METHODS: The study comprised 20 patients with multiple sclerosis, who complained of voiding problems. The control group consisted of 20 people without neurological diseases, lower urinary tract symptoms and detrusor overactivity estimated by filling cystometry. Apart from standard laboratory tests, diagnostic evaluation included a complex urodynamic study, ultrasound of the urinary tract, cystoscopy, testing serum and urinary NGF and BDNF using the enzyme immunoassay. The diagnostic significance of neurotrophins was evaluated using ROC analysis. RESULTS: According to the ROC analysis, the diagnostic sensitivity and specificity of serum NGF as a marker of detrusor hyperactivity was 57% and 93%, respectively (for serum NGF more or equal 26 pg/ml). The quality of the test according to the expert scale of AUC values was "very good" (AUC=0.806). Detecting NGF in patients urine was less effective. The sensitivity and specificity were 52% and 40%, respectively (for NGF more or equal 6 pg/ml). The quality of the test according to the expert scale of AUC values was "average" (AUC=0.64). The serum BDNF demonstrated high sensitivity (90%) and low specificity (23%), AUC=0.56. The urinary BDNF was more informative, (AUC=0.65). The combination of all four markers provides a sensitivity of 85.7% and a specificity of 66.7% (AUC=0.824). CONCLUSIONS: Testing serum and urinary neurotrophins in patients with multiple sclerosis can be used to diagnose detrusor overactivity. The NGF is a highly specific biomarker, while the BDNF is highly sensitive. Combined testing for serum NGF and BDNF is most informative.

[Russian version of the neurogenic bladder symptom score (NBSS)].

AIM: The Neurogenic Bladder Symptom Score (NBSS) is widely used now for the bladder symptoms assessment in neurogenic low urinary tract dysfunction. It is suitable for all patients, regardless of a bladder management method. NBSS contains 24 questions, which focus on incontinence, storage and voiding symptoms, urinary complicationsand life quality.With the permission of the authors (Dr.Welk et al.), NBSS had been translated into Russian according to the cultural and lingual adaptation algorithm. OBJECTIVES: Validate the Russian version of NBSS for multiple sclerosis patients. DESIGN, SETTING, AND PARTICIPANTS: The study included 80respondents: group A - 40 multiple sclerosis (MS) patients with neurogenic bladder, group B - 40 multiple sclerosis (MS) patients without bladder dysfunction, group C - healthy controls. All participants filled out the NBSS two times with an interval of two weeks. They also completed other measurement tools (IPSS,OAB Awareness Tool, WHOQOL BREF).Data were used to determine the internal consistency (Cronbachs alfa), external validity (Pearson correlation), and test-re-test reliability with interclass correlation coefficient. RESULTS: The mean of the NBSS total in the group A was 22.56+/-12.6, which significantly (p<0.001) exceeded score in comparable groups B (6.42+/-2.3) and C (5.31+/-1.9). The Cronbachs alfa of the total and the in continence, storage/voiding, and consequences domains was 0.939, 0,965, 0,801 and 0.712 respectively, which confirms the high internal consistency of the Russian version of the NBSS. External validity was verified by the relevant correlations with other questionnaires. Test-retest reliability was excellent. The interclass correlation coefficients were >0.85 (p<0.001) for all subdomains and the overall score. CONCLUSION: The Russian version of the NBSS demonstrated good validity and reliability and may be recommended for use in clinical practice.

[Polymorphic variants of the immune response genes as risk factors for primary progressive multiple sclerosis]. / Polimorfnye varianty genov immunnogo otveta kak faktory riska razvitiia pervichno-progressiruiushchego rasseiannogo skleroza.

AIM: To analyze the involvement of immune response genes in the pathogenesis of primary progressive multiple sclerosis (PPMS). MATERIAL AND METHODS: This multicenter study included 111 patients with PPMS from the Russian ethnic group. The association of PPMS with genes of immune system was analyzed by the study of polymorphic variants of genes of cytokines and genes of antigen-presenting cells. RESULTS AND CONCLUSION: The genotypes of IL-4 (rs2243250)*C/C and CLEC16A (rs6498169)*G/G were associated with PPMS in Russians. The association between the HLA-DRB1*15 and PPMS found out in other populations was confirmed in Russians.

[A comparative placebo-controlled clinical study on the efficacy and safety of interferon beta-1a for subcutaneous injections in patients with remitting multiple sclerosis: results of the first year of observations]. / Sravnitel'noe platsebo-kontroliruemoe klinicheskoe issledovanie éffektivnosti i bezopasnosti preparatov interferona beta-1a dlia podkozhnogo vvedeniia u patsientov s remittiruiushchim rasseiannym sklerozom: rezul'taty pervogo goda nabliudeniia.

AIM: To prove the equivalent efficacy of teberif (BCD-033, interferon beta-1) and rebif (interferon beta-1a) in patients with remitting multiple sclerosis (RMS). MATERIAL AND METHODS: A multicenter double blind placebo-controlled comparative randomized III phase study included 163 patients with RMS. Patients were randomized into three equal groups (teberif, rebif or placebo). RESULTS AND CONCLUSION: After 52 weeks, the equivalent efficacy of teberif and the brand drug rebif was shown. The result of assessment of the primary endpoint, which was combined unique active (CUA) lesion (the total of MRI T1-weighted lesions and new or newly enlarging T2-weighted lesions, without double counting of lesions with both activities), showed no significant differences (0.727±1.042 and 0.652±1.059 (p=0.7354, t-Student test) in the teberif and rebif groups, respectively. No between-group differences were found for other MRI indices and clinical parameters related with relapses. Teberif was shown to have a favorable safety and tolerability profile comparable to that of rebif. The results suggest the therapeutic equivalency of the drugs and form the basis for using the bioanalogue of interferon-beta 1 in patients with RMS.

[Primary progressive multiple sclerosis: current issues of timely diagnosis]. / Pervichno-progressiruiushchii rasseiannyi skleroz: sovremennoe sostoianie problemy svoevremennoi postanovki diagnoza.

This article presents a review of international data on primary progressive multiple sclerosis (PPMS) and an analysis of factors influencing timely diagnosis of PPMS in a number of regions of the Russian Federation.

[The results of the multicenter pharmaco-epidemiological observational project on the use of mydocalm in the treatment of pain syndromes with the muscle spasm].

The prospective multicenter open noncomparative pharmaco-epidemiological observational project on the use of mydocalm in real clinical practice has been completed in 2013. The project has been performed in 2090 clinical/rehabilitation settings in 284 cities of 13 countries using the results of 35,383 patients. The project aimed to assess the safety of treatment (percentage of patients with adverse-effects) and pain relieving efficacy as well as patient's satisfaction with the treatment. In total, 6603 (19%) adverse-effects were recorded. Their severity was evaluated as mild in 84,48%, no serious adverse-effects were noted. The high efficacy of mydocalm in the treatment of pain syndromes with the muscle spasm has been demonstrated. The high level of tolerability and absence of the clinically significant increase of adverse effects in the combination with nonsteroidal anti-inflammatory drugs have been confirmed.

[Organization of medical care for patients with cardiovascular diseases].

Morbidity with cardiovascular diseases in Sverdlovsk region has increased nearly twice over 10 years. Cardiovascular diseases are main causes of disablement and death, taking over a half of the total population losses over recent years. The article was aimed to specify approaches to manage risks of population losses with cardiovascular diseases. Structuring main blocks in organization of medical care for cardiovascular patients was attempted.

[Pathomorphological characteristics of unstable bronchial asthma (brittle phenotype)].

AIM: To ascertain morphological features of severe uncontrolled bronchial asthma (BA) of brittle phenotype. MATERIAL AND METHODS: Standard bronchofibroscopy was made in 10 patients with severe BA (brittle phenotype) and 9 patients with moderate BA. Cell composition of bronchial lavage and morphological indices of bronchial mucosa biopsies were studied. RESULTS: Patients with brittle BA had low total cytosis of lavage fluid compared to patients with moderate BA patients (1.73 +/- 0.10 and 2.84 +/- 0.21 x 10(6) in 1 ml, respectively, p = 0.001). Bronchobiopsy samples from patients with brittle BA were characterized by reduced cubic density of tegmental epithelium, ciliary and goblet epithelyocytes, height of epithelial layer and relative gland volume, increased thickness of basal membrane (18. 77 +/- 2.74 mcm), relative volume of connective tissue, hyperplasia of smooth muscle cells in the proper mucous plate. Infiltrate of bronchial mucosa in brittle BA contained a predominant amount of histiomacrophagal elements (65.80 +/- 3.83 in 1 mm2) and lymphocytes (52.94 +/- 4.38 in 1 mm2), moderate count of easinophils and neutrophils (15.35 +/- 2.13 and 19.04 +/- 2.23 in 1 mm2, respectively). CONCLUSION: Patients with severe brittle BA had atrophic alterations, inflammatory mucosal infiltration, marked bronchial remodeling in spite of therapy with high doses of inhalatory corticosteroids.

[Polymorphism of APOE gene and risk of development of the multiple sclerosis at ethnic Russians].

The multiple sclerosis is a complex disease of the central nervous system with the pronounced hereditary predisposition. The purpose of our research consisted in acknowledgement of the assumption on importance of apolipoprotein E gene (APOE) polymorphism in exon 4 in development of the multiple sclerosis in ethnic Russians. Research was lead on the samples independently collected in Moscow (106 patients and 189 persons of control group), Sverdlovsk area (54 and 109, accordingly) and republic Bashkortostan (119 and 285, accordingly). 2059C/T and 2197C/T polymorphisms of APOE gene, which determine aminoacid substitutions C112R and R158C in apolipoprotein E, were determined by polymerase chain reaction with the following restriction analysis of amplicons. There was not detected statistically significant distinctions on genotypes frequencies and alleles frequencies between control group and group of patients with multiple sclerosis. APOE*4 allele is not assosiated with risk of development of the multiple sclerosis at ethnic Russians.

[Pneumonia: errors in outpatient diagnosis and treatment].

AIM: To reveal errors in diagnosis and treatment of pneumonias in outpatients. MATERIAL AND METHODS: The analysis of 345 case records of outpatients. RESULTS: It is demonstrated that initially most of the patients had no symptoms and physical data pointing to pneumonia. This may be one of the causes of late diagnosis (29.7%). The first visit to the doctor brought out misdiagnosis--acute respiratory viral infection (ARVI)--in 96.6% cases. The choice of starting antibacterial therapy did not correspond to recommendations of the Standards of Diagnosis and Treatment of Patients with Nonspecific Diseases of the Lungs in 22.8% cases. 20.6% patients of this group demanded change of antibiotics. Unnecessary long-term therapy had place in 11.5% patients. 24-h underdose of antibiotic was given in 18.6%, inadequate dose regimen was registered in 5.6%. Instead of 13.3% patients, 51.3% were hospitalized. Control x-ray examination was performed in 75.9%. Lesions in the lungs remained in 36.5% patients. CONCLUSION: Quality of pneumonia diagnosis and treatment in outpatient setting must be updated.

Efficacy of supplemental anti-inflammatory therapy with fenspiride in chronic obstructive and nonobstructive bronchitis.

OBJECTIVE: The objective of this randomised, nonblind study was to assess the efficacy of fenspiride as complementary anti-inflammatory therapy in combination with ipratropium bromide in patients with chronic bronchitis (CB). A comparison was made with ipratropium bromide alone, the generally accepted standard therapy for CB. METHODS AND SUBJECTS: The study population comprised 20 patients with chronic obstructive bronchitis (COB) and 60 patients without signs of obstruction. Fifty-one males (64%) and 29 females (36%) aged from 25 to 65 years were studied over a 6-month treatment period. Combined therapy with fenspiride (160 mg/day) and ipratropium bromide (160 mug/day) was prescribed to 39 patients (28 with CB and 11 with COB) for 6 months, and monotherapy with ipratropium bromide (160 microg/day) was prescribed for 41 patients (32 with CB and nine with COB). RESULTS: The combined therapy group had a reduced intensity of dyspnoea, improvements in sputum nature and quantity of exudation, and a reduced intensity of coughing. The monotherapy group showed reductions in sputum exudation and cough intensity. Improvements in lung respiratory function were observed in both groups, but were greater in the combined therapy group of patients. Reduced cytosis, percentage and absolute content of neutrophils, and absolute content of lymphocytes and eosinophils in induced sputum were observed with CB patients in the combined therapy group. A reduced content of lymphocytes and an increase in macrophages were observed with CB patients in the monotherapy group. A significant decline in tumour necrosis factor (TNF)-alpha content in sputum was observed with both therapeutic regimens, although a statistically significant decline in serum TNFalpha (10.85 ng/L to 5.58 ng/L; p = 0.03) and reduced interleukin-8 in sputum (311.94 ng/L to 122.02 ng/L; p = 0.027) were observed with patients given combined therapy. CONCLUSION: The study showed greater efficacy of long-term treatment with fenspiride and ipratropium bromide compared with ipratropium bromide alone in patients with CB. This combination regimen can be recommended for the reduction of inflammation and prevention of disease progression in patients with CB and may also be useful in patients with COB.

[Efficacy of a complementary antiinflammatory treatment with erespal in chronic obstructive and nonobstructive bronchitis]. / Effektivnost' dopolnitel'noi protivovospalitel'noi terapii érespalom pri khronicheskom obstruktivnom i neobstruktivnom bronkhite.

AIM: To compare efficacy of atrovent alone and in combination with erespal in patients with chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: Of 80 participants of the trial (51 male and 29 female--63.75 and 36.25%, respectively) who had CB or COPD, 39 patients (28 with CB and 11 with COPD) received 6-month combined treatment with erespal (160 mg/day) and atrovent (160 mcg/day) and 41 patients (32 with CB and 9 with COPD) received atrovent monotherapy in the same dosage. RESULTS: Combined therapy produced positive changes in dyspnea, sputum characteristics and its discharge, cough, monotherapy improved sputum discharge and relieved cough; pulmonary ventilation improved in both groups especially in those on monotherapy. CB patients showed low cytosis, percentage and absolute count of neutrophils, absolute count of lymphocytes and eosinophils in induced sputum. In CB patients percentage of lymphocytes reduced while count of macrophages went up. Combined treatment including erespal also promoted a significant fall of serum and sputum TNFalpha and IL-8 reduction in the sputum. CONCLUSION: Erespal+atrovent treatment proved more effective than atrovent alone. It is recommended for both CB and COPD patients without marked disorders of external respiration function.

[Clinicomorphological assessment of budesonide efficiency in patients with bronchial asthma]. / Kliniko-morfologicheskaia otsenka éffektivnosti budesonida u bol'nykh bronkhial'noi astmoi.

AIM: to study clinicomorphological efficacy of inhalation glucocorticosteroid budesonide (benacort, Pulmomed, Russia) in bronchial asthma. MATERIAL AND METHODS: Twenty patients with bronchial asthma were treated with budesonide. RESULTS: A response to budesonide was manifest to the end of treatment week 1. Budesonide reduced frequency of acute asthma episodes and the need in inhalations of short-acting beta 2-agonists. The peak expiratory velocity (PEV) rose by 12% in three months, variability of PEV lowered by 13%, in 6 months by 21%, in 12 months by 31% compared to pretreatment values. In 12 months hypersecretion and thickness of basal membrane decreased. Three-month treatment also reduced eosinophil and lymphocyte epithelial count and cell density of stromal infiltrate in bronchial mucosa. In 12 months cell density of stromal infiltrate diminished. CONCLUSION: Bronchial asthma treatment with budesonide for 12 months reduces 24 hour rate of acute asthma episodes, the need in the disease exacerbations, improves functional indices of respiration but morphological composition of bronchial mucosa does not normalize completely this showing the necessity of longer budesonide administration.

[Results of a multicenter study of Rebif-22 mcg administration in Russia]. / Rezul'taty multitsentrovogo issledovaniia éffektivnosti preparata Rebif-22 mkg v Rossii.

The results of multicenter study of Rebif 22 micrograms in Russia have been reported. 167 multiple sclerosis patients have received Rebif 22 micrograms three times a week for 1 year. This study provides evidence for reduction of the relapse rate in patients with relapsing/remitting and secondary progressive multiple sclerosis. The tendency to the decrease of the severity of relapses, less need for steroid use and the decrease of EDSS score in patients with relapsing/remitting multiple sclerosis have been shown. In general Rebif 22 micrograms was tolerated well.