[Reduction in the need for glucocorticoids on the background of therapy with biologic disease-modifying antirheumatic drugs and Janus kinase inhibitors in rheumatoid arthritis: evidence from real clinical practice].

BACKGROUND: Clinical guidelines for the treatment of rheumatoid arthritis (RA) recommend reducing the use of glucocorticoids (GCs) due to the high risk of associated complications. AIM: To determine the frequency of GC cancellations and dose reductions in real clinical practice, while taking into account active RA therapy. MATERIALS AND METHODS: The study group consisted of 303 patients with RA reliable according to ACR/EULAR criteria (women 79.9%, age 52.8±13.3, disease duration 9 [4; 16] years, DAS-28-CRP 4.9±1.0, RF seropositivity 77.4%, ACPA seropositivity 70.3%), who were prescribed or changed therapy with disease-modifying antirheumatic drugs (DMARDs), biologic disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (iJAK) due to disease exacerbation and ineffectiveness of previous treatment. All patients initially received GC (7.7±3.8 mg/day equivalent of prednisolone). After adjustment of therapy, 42.9% of patients received methotrexate, 27.6% leflunomide, 2.5% sulfasalazine, hydroxychloroquine, or a combination with an Non-steroidal anti-inflammatory drugs, 63.7% bDMARDs, and 7.2% iJAK. The need for GC intake was assessed by a telephone survey conducted 6 months after the start of follow-up. RESULTS: Telephone survey was possible in 274 (90.4%) persons. There was a significant decrease in pain intensity (numerical rating scale, NRS 0-10) from 6.3±1.4 to 4.3±2.4 (p<0.001), fatigue (NRS) from 6.7±2.3 to 5.2±2.1 (p<0.001), and functional impairment (NRS) from 5.4±2.1 to 3.9±2.0 (p<0.001). A positive PASS index (symptom status acceptable to patients) was noted in 139 (50.7%) patients. GC cancellation was noted in 19.7%, dose reduction in 25.9%, maintaining the same dose in 42.7%, and dose increase in 11.7%. CONCLUSION: Against the background of intensive RA therapy, including combination of DMARDs with bDMARDs or iJAK, complete withdrawal or reduction of GC dose was achieved in less than half (45.6%) of patients after 6 months.

[A comparative assessment of microbiocenosis of saliva and oropharynx in patients with migraine]. / Sravnitel'naya otsenka mikrobiotsenoza slyuny i rotoglotki u patsientov s migren'yu.

OBJECTIVE: To identify changes in the microbiome of saliva and to compare it with the microbiome of the oropharynx of patients with migraine. MATERIAL AND METHODS: Sixty patients with migraine (21-56 years old), were examined using a headache diary, MIDAS and VAS. A microbiological examination of saliva and smear from the mucosa of the posterior wall of the oropharynx with evaluation by the method of mass spectrometry of microbial markers (MSMM) with the determination of 57 microorganisms was performed. All patients had comorbid chronic diseases of the gastrointestinal tract and upper respiratory tract (URT), according to anamnestic data and examination by specialists. RESULTS: A significant increase in the content of markers of resident (conditionally pathogenic) microorganisms characteristic of chronic diseases of URT (strepto- and staphylococci); markers of transient microorganisms characteristic of intestinal microflora (clostridia, gram-negative rods, anaerobes) that are normally absent; viral markers of cytomegaloviruses and herpes groups; a decrease in the content of fungi were identified in saliva. A comparative analysis of the microbiome of saliva and oropharynx showed: 1) a significant decrease in the concentration of coccal flora Enterococcus spp., Streptococcus mutans, Staphylococcus aureus, anaerobic bacteria Clostridium difficile and Clostridium perfringens in saliva; enterobacteria Helicobacter pylori; gram-negative rods Kingella spp., fungi and Epstein-Barr virus; 2) an increase in salivary concentrations of Staphylococcus epidermidis, anaerobic Clostridium ramosum and Fusobacterium spp./Haemophilus spp. and gram-negative bacilli Porphyromonas spp. CONCLUSION: A comparative assessment of the microbiota of a smear from the posterior wall of the oropharynx and saliva using MMSM showed the presence of dysbiosis both in the oropharynx and in the saliva of patients with migraine. However, there were fewer deviations from the norm in saliva, therefore, for diagnostic purposes, a smear from the posterior wall of the oropharynx is more significant as a biomarker for patients with migraine.

[Features of fibromyalgia in patients with rheumatoid arthritis]. / Osobennosti fibromialgii u patsientov s revmatoidnym artritom.

OBJECTIVE: To determine the features of fibromyalgia (FM) in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Seventy-six patients participated in the study. The patients were divided into 2 groups: RA+FM (n=55), FM (n=21). Anamnesis of life and disease was carefully collected in all patients. The intensity (according to VAS) and phenotype (Pain DETECT, DN4) of pain syndrome (PS), the presence of symptoms of central sensitization (CSI), fatigue (FSS), signs of anxiety and depression (HADS), sleep quality (PSQI), cognitive functions (DSST) and quality of life (QoL) (EQ-5D, FIQR) were also evaluated. RESULTS: The average age of patients in the FM group was significantly lower (42 [35; 53] vs. 50 [42.5; 59], p=0.042). Patients with «pure¼ FM without RA were more often divorced and had no children (p=0.045 and p=0.02, respectively). The duration of PS in the groups did not differ (11 [7; 17] vs. 8 [5; 13] years, p=0.429), however, patients with «pure¼ FM waited longer for diagnosis (115 [40; 198] vs. 20 [5.5; 59] months, p<0.001), and they also were less likely to be recognized as disabled (p=0.003). Patients of both groups had equally severe fatigue, anxiety, depression, sleep disorders and cognitive functions compared to the norms. Patients of the FM group noted a lower QoL (according to EQ-5D, p=0.041) then in RA+FM group, despite the comparable severity of FM and the intensity of the PS in both groups. CONCLUSION: FM in patients with RA develops at a later age compared to «pure¼ FM. The clinical picture of FM with and without RA does not differ in the main manifestations, however, the QoL of patients with «pure¼ FM is lower. Accounting for fibromyalgia in the treatment of rheumatoid diseases can significantly improve the QoL of patients.

[Botulinum toxin type A (Relatox) in transition from medication overuse to non-overuse status in patients with chronic migraine: a subgroup analysis of phase IIIb randomized single-blind multicenter active-controlled parallel-group trial]. / Botulinicheskii toksin tipa A (Relatoks) v preodolenii lekarstvennogo zloupotrebleniya u patsientov s khronicheskoi migren'yu: podgruppovoi analiz rezul'tatov mnogotsentrovogo prostogo slepogo randomizirovannogo sravnitel'nogo issledovaniya IIIb fazy.

OBJECTIVE: To access the effect of Relatox, the first Russian botulinum toxin type A, in patients with chronic migraine (CM) and medication overuse (MO). MATERIAL AND METHODS: In phase IIIb single-blind randomized multicenter active-controlled parallel-group study, patients with CM were randomized to once intramuscular injections of Relatox (n=101) or onabotulinumtoxin A injections - Botox (n=108). This subgroup analysis evaluated the percentage of patients who transition from medication overuse to non overuse status from baseline; mean changes in the number of headache days, migraine headache days, acute headache medication intakes days, headache intensity, proportion of patients who had a ≥50% reduction in headache days, proportion of the patients with severe (≥60) Headache Impact Test-6 score and with a severe (≥21) MIDAS score in a 28-day periods in each treatment among patients with baseline acute medication overuse via repeated measures. RESULTS: Of 209 patients with CM, 100% met medication overuse criteria. Relatox and Botox demonstrated significant improvement for overall least squares mean change in headache days, migraine headache days, headache intensity; and headache-related disability and quality of life in CM patients with baseline MO, without differences between the groups. 75% and 70% patients in the Relatox and Botox groups, respectively, achieved ≥50% reduction in headache days from baseline (OR 1.58, CI 95% 0.84; 3.02, p=0.155). Furthermore, Relatox and Botox significant reduced average medication overuse rates in patient with CM and MO at baseline. 62% of patients in the Relatox group and 48% of patients in the Botox group transitioned from medication overuse to non overuse status compared from baseline (OR 2.07, CI 95% 0.91; 4.62, p=0.044). Relatox group had greater reductions than the Botox group in the percentage of patients with acute migraine-specific medication (triptan) overuse (p=0.050). CONCLUSION: The results demonstrate highly prevalent of medication overuse among individuals with CM. This analysis provides evidence that the Russian botulinum toxin type A Relatox significantly improves measures of headache symptoms, quality of life and headache-related disability, and also significantly greater, compared to Botox, reduces migraine-specific medication consumption in patients with chronic migraine who overuse acute medications.

Are the Goals of Therapy Achievable in Patients with Rheumatoid Arthritis Receiving Upadacitinib in Real Clinical Practice?

The aim of the study was to evaluate the effectiveness of UPA in RA patients in real clinical practice after 3 and 6 months of therapy. The study included 63 RA patients with high activity of the disease. Activity was assessed according to the DAS28(ESR), DAS28(CRP), SDAI, CDAI; functional ability to HAQ; quality of life to the EQ-5D; disease activity according to the patient's RAPID-3 index; the level of depression and anxiety to the HADS scale. The effectiveness of therapy was evaluated after 3 (n = 45) and 6 (n = 31) months of UPA therapy. Remission or low activity of the disease by 3 months of therapy was achieved by most patients: remission of 69.8% of patients, low activity of the disease-16.3% of patients. Moderate or high activity persisted in 13.9% of patients. By the 6th month of UPA therapy, the number of remissions reached 90%, low activity 3.3%, moderate activity persisted in 6.7% of patients, high activity of the disease was not in any patient. 20% improvement in function was achieved in 71.8% of patients by the 3rd month of therapy and in 77.8% by the 6th month of treatment; the difference in average HAQ values by the 3rd month of therapy was 0.38 points, by the 6th month-0.58 points. After 3 months of follow-up, 31.1% of patients continued taking GC, by 6 months-24.2%. The dose of GC was reduced from an average of 7.23 to 5.6 mg/s. The percentage of patients requiring NSAIDs decreased from 95.2 to 35.6% and 33.3%, respectively. DMARDs continued to be received by 75.6% of patients by 3 months and 69.7% by 6 months of follow-up. Achieving remission or low activity of the disease in patients with RA receiving UPA in real clinical practice is possible in most patients. A rapid decrease in inflammatory activity is accompanied by a significant improvement in the functional state and quality of life of patients. UPA therapy reduces the need for the use of NSAIDs and reduces the dose of GC in a third of patients.

[The role of food allergy as a provoking factor of migraine]. / Rol' pishchevoi allergii kak provotsiruyushchego faktora migreni.

OBJECTIVE: To assess the effect of food allergies on the course of migraine. MATERIAL AND METHODS: Seventy patients with migraine, aged 21-56 years old, were examined using headache diary, MIDAS and VAS, studies of specific antibodies of the IgG4 class (delayed type food allergy) by immuno-enzyme analysis (ELISA), microbiological examination of a smear from the mucous membrane of the posterior wall of the oropharynx with mass spectrometry of microbial markers (MSMM) with the identification of 57 microorganisms. RESULTS: We found an increase in specific IgG4 for a number of food allergens in most patients with migraine, of which 48.5% had a pronounced increase in IgG4 (>150 kEd/l) for at least one allergen (cow's milk - 13% patients, wheat flour - 5%, egg white - 47% or yolk - 26%, quail egg - 15%, sweet pepper - 6%), in 29% of people to several food allergens at once (all of them had chicken egg protein as one of the allergens). There was the association of IgG4 titers to wheat allergen with the severity of headache according to VAS (r-S=0.7; p=0.0046) in patients with the most severe, chronic migraine (17 people) and with an imbalance of the oropharyngeal microbiota, namely, concentration of pathological viruses Herpes spp. (rs=0.29; p=0.02), Epstein-Barr (rs=0.46; p=0.0002) and microscopic fungi (rs=0.39; p=0.0016), detected in these patients. CONCLUSION: We show for the first time the relationship between delayed-type food allergy and redistribution in the microbiome of the oropharynx of patients with migraine and once again confirm the role of delayed-type food allergy as a clinically significant factor influencing the course of migraine (its intensity and chronicity).

[Botulinum toxin type A (Relatox) in the treatment of chronic migraine in adults: results of phase IIIb, randomized, one-blind, multicenter, active-controlled, parallel-group trial]. / Botulinicheskii toksin tipa A (Relatoks) v lechenii khronicheskoi migreni u vzroslykh: rezul'taty mul'titsentrovogo prostogo slepogo randomizirovannogo sravnitel'nogo issledovaniya IIIb fazy.

OBJECTIVE: To access the efficacy and safety of the first Russian botulinum toxin type A (Relatox) as a headache prophylaxis in adult with chronic migraine (CM). MATERIAL AND METHODS: The randomized, one-blind, multicenter, active-controlled, parallel-group trial study involved 209 patients with CM aged from 19 to 65 years. The patients were randomized to injections of the Russian botulinum toxin type A - Relatox (n=101) or onabotulinumtoxinA injections - Botox (n=108). The duration of the study was 16 weeks, which included five visits of patients every 4 weeks. Relatox and Botox were injected once into seven muscle groups of the head and neck at a dose of 155-195 units. Primary efficacy variable was mean change from baseline in frequency of headache days after 12 weeks. Secondary efficacy variables were mean changes from the baseline to week 12 in frequency of migraine days, acute headache pain medication intakes days; headache intensity; proportion of patients achieving ≥50% reduction from baseline in headache days, the proportion of the patients with medication overuse, the proportion of the patients with severe (≥60) Headache Impact Test-6 score and with a severe (≥21) MIDAS score. RESULTS: Analyses demonstrated a large mean decrease from baseline in frequency of headache days, without statistically significant between-group differences Relatox vs Botox at week 12 (-10.89 vs -10.06; p=0.365) and at other time points. Significant differences from baseline were also observed for all secondary efficacy variables at all time points without differences between the groups. The proportion of patients achieving ≥50% reduction from baseline in headache days was 75.0% and 70% in the Relatox and Botox groups, respectively (OR, CI 95% 1.58 [0.84; 3.02], p=0.155). Adverse events (AE) occurred in 15.8% of Relatox patients and 15.7% of Botox patients (p=1.000). No unexpected AE were identified. CONCLUSION: The results demonstrate that the first Russian botulinum toxin type A (Relatox) is an effective prophylactic treatment for CM in adult patients. Relatox led to significant improvements from baseline in multiple measures of headache symptoms, headache-related disability and quality of life. For the first time, a comparative analysis of two botulinum toxin type A products in parallel groups showed no less (not inferior) efficacy and safety of Relatox relative to Botox in the treatment of CM in adults.

[No Effect of the p.Arg230His Variant Of The VCL Protein on the Course of the Hypertrophic Cardiomyopathy In Russian Family Carrying The p.Gln1233Ter Pathogenic Variant In The MYBPC3 Gene].

Aim      To determine specific clinical characteristics caused by a combination of the rs397516037 pathogenic variant in the myosin-binding protein C (MTBPC3) and the rs749628307 polymorphic variant in the vinculin (VCL) gene in a Russian family of carriers and to evaluate the contribution of the rs749628307 polymorphic variant in the VCL gene to the development of hypertrophic cardiomyopathy (HCMP).Material and methods  The family under study included one healthy person and 3 patients with HCMP. A targeted analysis of proband's exome was performed. A structural alignment for both forms of the VCL protein, the canonical form and the form with p.Arg230His substitution, was performed.Results The pathogenic rs397516037 variant and the potentially pathogenic rs749628307 variant were detected in the proband and several family members. A possibly damaging variant rs749628307 was detected in the proband and several family members evaluated in this study. The structural alignment confirmed that the rs749628307 variant did not alter the protein structure significantly and could not cause an impairment or loss of the protein function.Conclusion      This study demonstrated that apparently the rs749628307 variant in the VCL gene does not affect the protein structure in a pathogenetically significant way, neither does it affect the severity and form of the clinical manifestations of HCMP; therefore, it cannot be considered as pathogenic.

[The state of the oropharyngeal microbiome in patients with migraine]. / Sostoyanie mikrobioma rotoglotki u patsientov s migren'yu.

OBJECTIVE: To determine a role of changes in the oropharyngeal microbiome in the development and clinical manifestations of migraine. MATERIAL AND METHODS: Seventy patients with migraine, aged 21-56 years, and 15 healthy subjects matched for age and sex were examined using headache diary, MIDAS and VAS, the Gastrointestinal Symptom Rating Scale (GSRS), microbiological smear examination from the mucous membrane of the posterior wall of the oropharynx with evaluation by the method of mass spectrometry of microbial markers (MSMM) with determination of 57 microorganisms. RESULTS: The following changes in the oropharynx of individuals with migraine compared with the group of healthy individuals (control group) were found: a) a significant increase in the content of markers of resident (conditionally pathogenic) microorganisms characteristic of chronic diseases of the upper respiratory tract (strepto- and staphylococci); b) the appearance of markers of transient microorganisms normally absent, characteristic of the intestinal microflora (clostridia, gram-negative rods, enterobacteria, anaerobes); c) the appearance of viral markers of cytomegaloviruses, Herpes group, Epstein-Barr; d) a significant decrease in the content of bifidobacteria and lactobacilli). All people with migraine had a history or were found on examination to have chronic diseases of the upper respiratory tract (sinusitis in 48%, pharyngitis in 43%, tonsillitis in 25% of people), and gastrointestinal diseases. Dyspepsia was the most frequent and pronounced of the gastrointestinal syndromes on the GSRS in people with migraine (87%). This corresponds to the data on the extremely frequent occurrence of IBS (70% of patients) and other gastrointestinal pathology obtained from the patient history. CONCLUSION: In our work, the microbiota of the oropharynx in patients with migraine was studied for the first time using a new MSMM method. Disturbance of the oropharyngeal microbiome compared to the norm was detected in 100% of people with migraine. The changes characteristic of most patients included a significant decrease in the content of normal flora, an increase in the concentration of conditionally pathogenic microorganisms and the appearance of pathogenic microflora characteristic of chronic diseases of the upper respiratory tract and gastrointestinal tract, which may indicate their role in the pathogenesis of migraine.

OnabotulinumtoxinA in elderly patients with chronic migraine: insights from a real-life European multicenter study.

INTRODUCTION: Although migraine prevalence decreases with aging, some older patients still suffer from chronic migraine (CM). This study aimed to investigate the outcome of OnabotulinumtoxinA (OBT-A) as preventative therapy in elderly CM patients. METHODS: This is a post hoc analysis of real-life prospectively collected data at 16 European headache centers on CM patients treated with OBT-A over the first three treatment cycles (i.e., Cy1-3). We defined: OLD patients aged ≥ 65 years and nonOLD those < 65-year-old. The primary endpoint was the changes in monthly headache days (MHDs) from baseline to Cy 1-3 in OLD compared with nonOLD participants. The secondary endpoints were the responder rate (RR) ≥ 50%, conversion to episodic migraine (EM) and the changes in days with acute medication use (DAMs). RESULTS: In a cohort of 2831 CM patients, 235 were OLD (8.3%, 73.2% females, 69.6 years SD 4.7). MHDs decreased from baseline (24.8 SD 6.2) to Cy-1 (17.5 SD 9.1, p < 0.000001), from Cy-1 to Cy-2 (14.8 SD 9.2, p < 0.0001), and from Cy-2 to Cy-3 (11.9 SD 7.9, p = 0.001). DAMs progressively reduced from baseline (19.2 SD 9.8) to Cy-1 (11.9 SD 8.8, p < 0.00001), to Cy-2 (10.9 SD 8.6, p = 0.012), to Cy-3 (9.6 SD 7.4, p = 0.049). The 50%RR increased from 30.7% (Cy-1) to 34.5% (Cy-2), to 38.7% (Cy-3). The above outcome measures did not differ in OLD compared with nonOLD patients. CONCLUSION: In a population of elderly CM patients with a long history of migraine OBT-A provided a significant benefit, over the first three treatment cycles, as good as in non-old patients.

An Algorithm for the Selection of Probes for Specific Detection of Human Disease Pathogens Using the DNA Microarray Technology.

The aim of the study was to develop an algorithm for the selection of discriminating probes to identify a wide range of causative agents of human infectious diseases. Materials and Methods: The algorithm for selecting the probes was implemented in the form of the disprose (DIScrimination PRObe SElection) computer program written in the R language. Additionally, third-party software was used: the BLAST+ and ViennaRNA Package programs. The developed algorithm was tested by selecting specific probes for detecting Chlamydophila (Chlamydia) pneumoniae - an atypical bacterial pathogen causing community-acquired pneumonia (CAP). Nucleotide sequences for analysis were downloaded from the NCBI databank. Results: An algorithm for the selection of specific probes capable of detecting human infectious pathogens has been developed. The algorithm is implemented in the form of the disprose modular program, which allows for performing all stages of the probe selection process: loading the nucleotide sequences and their metadata from available databanks, creating local databases, forming a pool of probes, calculating their physicochemical parameters, aligning the probes and sequences contained in local databases, processing and evaluating the alignment results. The algorithm was successfully tested and its performance was confirmed by selecting a set of probes for the specific detection of Chlamydophila pneumoniae. The specificity of the selected probes calculated in silico indicated a low risk of their nonspecific binding and a high potential of using them as molecular genetic diagnostic tools (DNA microarrays, PCR). Conclusion: An algorithm for the selection of specific probes detecting a wide range of human pathogens in clinical biomaterial has been developed and implemented in the form of the disprose modular program. The probes selected using this program can serve as the functional basis of DNA-oriented microarrays able to identify causative agents of polyetiological diseases, such as CAP. Due to the flexibility and openness of the program, the scope of its application can be expanded.

The fluorescent immunocytochemical diagnostics of precancerous diseases and cancer of the oral mucosa.

Purpose of the study improving the diagnosis of precancerous diseases and cancer of the oral mucosa using fluorescent immunocytochemical studies by direct immunofluorescence. A clinical laboratory examination of 111 patients was carried out: 46 patients with squamous cell carcinoma of the oral mucosa, 35 people with precancerous lesions (17 leukoplakia, 18 - oral lichen planus) and 30 healthy people. All patients underwent a traditional cytological examination and an additional immunocytochemical examination by direct immunofluorescence, the expression levels of tumor markers P53, P16 and Ki67 were determined. The data were compared with the results of histological analysis. As a result of the study, it was revealed that in patients with cancer, the expression of oncomarker P53 was four times higher than in patients with precancerous pathology. In 6.52% of cases, co-expression of markers Ki67 and P16 was found. Thus, the advantages of fluorescent immunocytochemical diagnostics were the absence of invasive traumatic intake of the biomaterial in the patient, reduction in the timing of obtaining the result, high sensitivity, and the possibility of remote evaluation of the results. Therefore, that increases the accessibility of the method, and the possibility of using this method for a screening study of population.

Cytokine Profile of CCR6+ T-Helpers Isolated from the Blood of Patients with Peptic Ulcer Associated with Helicobacter pylori Infection.

We previously found that the number of CCR6+ T-helpers with the phenotype of effector/effector memory T cells increases in the blood of patients with H. pylori-associated peptic ulcer. The mature phenotype and the expression of the chemokine receptor CCR6, which is involved in migration of lymphocytes to the inflamed mucous membrane of the gastrointestinal tract, suggests that these cells are involved in the immune response observed in this clinical condition. To better understand the pathogenetic role of these cells, it is necessary to study their functional activity, specifically, the production of pro-inflammatory cytokines involved in the pathogenesis of the disease. The aim of the study was to evaluate changes in the blood level of pro-inflammatory types of mature CCR6+ T-helpers in H. pylori-associated peptic ulcer disease. MATERIALS AND METHODS: CCR6+ T-helpers were isolated from the blood by using immuno-magnetic separation adapted to this study. The number of T-helpers of types 1 and 17 (Th1 and Th17) and cells with mixed properties of Th1 and Th17 (Th1/Th17) was determined by intracellular cytokine assay. RESULTS: Initially, we planned to activate unseparated peripheral blood mononuclear cells ex vivo and evaluate the number of cytokine producers among mature CCR6+ T-helper cells by gating them during the flow cytometry. However, dramatic changes in the phenotype of T-helpers upon activation did not allow us to reliably identify the cells of interest. Subsequently, we used a two-stage immunomagnetic separation procedure to obtain functionally active mature CCR6+ T-helpers with a purity of >90%. The quantitative yield of these cells from the blood of patients with gastric and duodenal peptic ulcer associated with H. pylori was 9 times higher than that from the blood of healthy donors. Activation of CCR6+ T-helpers purified from blood of ulcer patients revealed an increased content of Th1, Th17, and Th1/Th17. One ml of the patient's blood yielded 18.1 times more CCR6+ Th1, 19.4 times more CCR6+ Th17, and 21.1 times more CCR6+ Th1/Th17 compared with the blood of healthy subjects. CONCLUSION: The content of mature CCR6+ T-helper cells with pro-inflammatory activity significantly increases in the blood of patients with peptic ulcer associated with H. pylori infection.

[Method of onabotulinumtoxin type A injection in chronic migraine: the PREEMPT protocol in clinical practice]. / Metodika in"ektsii onabotulotoksina tipa A (Botoks) pri khronicheskoi migreni ­ protokol PREEMPT v real'noi praktike.

Chronic migraine (CM), a condition where patients experience over 15 days of headache per month, was identified as a separate disease in the International Classification of Headache Disorders 3-beta version. Onabotulinumtoxin type A was approved for the treatment of CM in 2010 after the completion of the extensive PREEMPT (Phase III Research Evaluating Migraine Prophylaxis Therapy) clinical program. The efficacy of onabotulinumtoxin type A was demonstrated in numerous studies in CM and medication-overuse headache. The paper focuses on the PREEMPT injection paradigm and provides guidance for successful and safe treatment of CM.

[Efficacy of combined use of glycosaminoglycan peptide complex for intramuscular administration and oral diacerein in osteoarthritis: evaluation according to an observational multicenter clinical trial].

BACKGROUND: The combined use of intramuscular injection glycosaminoglycan peptide complex (GPC) and oral diacerein can increase the effectiveness of treatment of osteoarthritis (OA). AIM: Compare the effectiveness of combination GPC + diacerein and GPC monotherapy in the treatment of OA in clinical practice. MATERIALS AND METHODS: A retrospective evaluation of the results of a 12-week multicenter observational non-interventional study of the effectiveness of GPC (Rumalon, a course of intramuscular injections 3 times a week, №25) in patients with moderate/severe OA (n=2955) requiring regular administration of nonsteroidal anti-inflammatory drugs (NSAIDs). The analysis identified a group of patients (n=414) who received GPC in combination with diacerein 100 mg/day (Diaflex Rompharm). The therapeutic effect was compared in the groups of GPC monotherapy (n=2541) and the combination of GPC with diacerein. These groups did not differ in average age (61.411.8 and 61.911.3 years), both were dominated by women (76.3 and 70.3%), there was approximately equal intensity of pain during movement and impaired joint function: 6.11.8/6.01.6 and 4.92.1/5.11.8 (according to the numerical rating scale 010). The dynamics of pain intensity, the need for NSAIDs, and the frequency of adverse events (AE) were compared 12 weeks after the start of treatment. RESULTS AND DISCUSSION: In the majority of patients with OA both on the background of GPC monotherapy and combined use of GPC and diacerein, there was a significant improvement. The number of patients with pain reduction 50% was 54.3 and 62.8% (p0.001), NSAID administration was completely stopped in 66.7 and 77.5% (p0.001), respectively. The effectiveness of the combination of GPC and diacerein was significantly higher than that of GPC monotherapy in OA of the knee joint, hip joint, and generalized OA. AE from the gastrointestinal tract was observed in 7.8 and 8.9%, arterial hypertension in 6.3 and 4.6%, allergic reactions in 0.3 and 0.5% of patients (not significant). CONCLUSION: The application of the code of civil procedure is an effective treatment for OA. The combination of GPC and diacerein provides a more significant improvement than GPC monotherapy. GPC and diacerein (including in combination) are well tolerated and rarely cause AE.

[Control of pain in the early post-traumatic period in the outpatient practice. Results of the multi-center observational study RAPTOR (Rational Analgesia PostTraumatic: an Observational Research)].

AIM: Evaluate the frequency, nature and course of PTP, as well as the effectiveness and safety of NSAIDs in PTP in real clinical practice. MATERIALS AND METHODS: The assessment of the condition and need for NSAIDs (original meloxicam) in 1115 outpatient patients who suffered a fracture of the radius (32.2%), injury to the knee (35.2%) or ligaments of the ankle (32.6%); women/men 51.5 and 48.5%, average age 46.915.5 years. We evaluated the dynamics of pain intensity (on a numerical rating scale NRS 010) at rest and during movement, the preservation of moderate and severe pain, as well as the development of adverse drugs reactions (ADR) to NSAIDs 48 weeks after injury. RESULTS: The average intensity of pain during movement decreased from 7.031.66 to 2.211.38 (p0.001), at rest from 4.462.07 to 0.710.989 (p0.001). The number of people with pain severity 4 in the NRS in 48 weeks after the radius fracture, injury of the knee and ligaments of ankle was 21.0, 16.9 and 11.9%, with moderate or severe impairment of the injured limb 40.4, 26.2 and 16.3%, respectively. The need for taking NSAIDs up to 7 days was noted in 43.3%, 714 days-in 41.8%, more than 2 weeks or constantly in 14.9% of patients. Weak or moderate ADR were observed in 20.8% of patients, mainly dyspepsia and hypertension. Discontinuation of NSAIDs due to ADR was required in only 2.6% of patients. Pain retention 4 in NRS was associated with initially expressed pain (7 in NRS) OR 2.75 (95% CI 0.834.13; p0.001) and the presence of osteoarthritis of knee and/or hip OR 1.56 (95% CI 1.032.34; p=0.039). CONCLUSION: PTP decreases rapidly in most patients after a radius fracture, injury of the knee, and ankle ligament injury while taking the original meloxicam. However, in a significant part of patients, moderate or severe PTP persists after 48 weeks, which requires prolonged analgesic therapy and active rehabilitation.

[Migraine burden and clinical inertia: what can we do?] / Migren' i klinicheskaia inertsiia: chto my mozhem sdelat'?

AIM: To study the compliance of neurologists and headache specialists to chronic headache and chronic migraine (CM) diagnosis and treatment guidelines. MATERIAL AND METHODS: The survey included 634 neurologists from all regions of the Russian Federation. Mean age of respondents was 40.7±8.5 years, mean years of experience 14.2±7.8 years. RESULTS: Most doctors work in outpatient or hospital settings (49% and 24%, respectively), 7% were headache specialists. Tension-type headache (TTH) was diagnosed in 30% and CM in 17% of patients while 44% of patients were presumed to have a mixed headache disorder (TTH+CM). Only 10% of physicians do not use instrumental diagnostic methods in chronic headache. This study has shown sufficient attention to comorbid conditions and frequent prescription of headache preventative treatment. Botox prescription data is equivocal: 35% of physicians recommend such treatment, 27% do not, while other doctors prescribe it for off-label indications. CONCLUSION: To overcome clinical inertia, further education in chronic headaches and their optimal treatment is warranted.

[Memory and attention deficit in migraine: overlooked symptoms]. / Narusheniia pamiati i vnimaniia u patsientov s migren'iu: nedootsenennye simptomy.

AIM: To evaluate the prevalence of objective cognitive impairment (CI) in patients with episodic migraine (EM) during the interictal period and in the chronic migraine (CM) population. MATERIAL AND METHODS: Sixty-four patients with CM and 42 patients with low-frequency EM (less than 4 headache days a month), aged 18-59, were enrolled. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS). Cognitive functions were evaluated with the Montreal Cognitive Assessment scale (MoCA), Digit Symbol Substitution Test (DSST) and the Rey Auditory Verbal Learning Test (RAVLT). RESULTS: In the CM group DSST and MoCA performance as well as the RAVLT total learning index were significantly decreased compared to EM; 38% of CM patients scored lower than 26 points of the MoCA scale. Negative correlations between headache frequency and DSST and MoCA results were observed. There was no correlation between cognitive test performance and anxiety/depression levels. CONCLUSION: Patients with EM and CM present with objective CI. The prevalence and severity of cognitive deficits rise with increasing headache frequency.

[Temporomandibular disorder and cervicalgia: pathophysiology underlying the comorbidity with chronic migraine]. / Disfunktsiia visochno-nizhnecheliustnogo sustava i tservikalgiia: patofiziologicheskie mekhanizmy i komorbidnaia sviaz' s khronicheskoi migren'iu.

AIM: To analyze the prevalence of various clinical forms of temporomandibular disorder (TMD) and cervicalgia in episodic (EM) and chronic migraine (CM). MATERIAL AND METHODS: Ninety patients with CM and 42 patients with EM as defined by the International Classification of Headache Disorders (ICHD)-3 beta were recruited. TMD and sleep bruxism were diagnosed according to the DC/TMD criteria and the International Classification of Sleep Disorders (ICSD-R), respectively. RESULTS: Myofascial pain was the most prevalent form of TMD in both EM and CM. The prevalence of TMD was higher in CM as compared to EM (60% vs. 21.4%, respectively, p=0.0001). The prevalence of bruxism was comparable across EM and CM (14.3% vs. 28.8%, respectively, p=0.08) and significantly lower than that of TMD in the CM population (28.8% vs. 60%, respectively, p=0.0001). Frequent cervicalgia (≥15 days per month) was reported by 65.5% and 21.4% of CM and EM patients, respectively (p=0.0001); 44.4% of CM patients reported neck pain immediately before or during migraine attacks only, 14.4% during the headache and interictal phases. CONCLUSION: The higher prevalence of pain-related TMD and cervicalgia in CM population compared to EM and the general population was shown. In CM, myofascial pain and tenderness in the masticatory and neck muscles may be caused by central sensitization (CS) with no link to temporomandibular joint or spinal pathology. Myofascial TMD and neck muscle dysfunction are an integral part of CM pathophysiology underlying headache chronification.