Pathogenetic approach to the treatment of functional disorders of the gastrointestinal tract and their intersection: results of the Russian observation retrospective program COMFORT.

BACKGROUND: The aim of this study was to investigate the efficacy and safety of the novel complex drug, consisting of released-active form of antibodies to S-100 protein, tumor necrosis factor-α and histamine, (Kolofort) under outpatient conditions in patients with functional dyspepsia (FD), irritable bowel syndrome (IBS), and FD-IBS overlap. METHODS: The subjects of the observational noninterventional retrospective program were the data of 14,362 outpatient records of patients with diagnosed FD, IBS, and/or overlap, who were observed by gastroenterologists from November 01, 2017, through March 30, 2018, who received the drug Kolofort in monotherapy for 12 weeks, 2 tablets twice a day. To assess the presence and severity of symptoms of functional gastrointestinal disorders (FGID), the "7*7" questionnaire developed by a working group from the Russian Gastroenterological Association was used. The evaluated parameters included the proportion of patients: who had a 50% or more reduction in the total score; who have switched to the less severe category of the condition; who have switched to the "healthy" or "borderline ill" severity categories; and the change in the score in domains 1-7. RESULTS: The final efficacy analysis included data from 9254 patients. A decrease in the total score by 50% or more was observed in 80.45% of patients with FD, 79.02% of patients with IBS, and in 83% of patients with both IBS and FD. Switch to a lower severity category of the condition at the end of therapy was noted in 93.35% of patients with FD, in 93.80% of cases in patients with IBS, and in 96.17% of cases in patients with a combination of IBS and FD. A total of 94 adverse events (AEs) were reported in 80 patients (0.65%). CONCLUSION: The COMFORT program has demonstrated the positive effect of treatment in the majority of patients with IBS and FD and their combination in real clinical practice.

The level of natural autoantibodies to IFN-gamma in varicella infection treated with antiviral drug Anaferon for children: A pilot study.

Natural circulating antibodies (NAbs) to endogenous regulators have shown to be potential biomarkers in medicine. Due to the lack of reliable assays, only few of them have been well studied. To employ NAbs as biomarkers, an evaluation of changes over the course of a treatment is required. This paper describes our work to analyze the dynamics of NAbs titer to interferon-gamma (IFN-γ) among healthy children of different age and in patients with varicella infection receiving an antiviral drug Anaferon for children (AC, the API are highly diluted antibodies to IFN-γ) in comparison with placebo, and to correlate the findings with the treatment results. IFN-γ plays an essential role during varicella infection, and this fact causes the consequent increase of NAbs to IFN-γ level. The mean anti-IFN-γ NAbs level in the healthy volunteer group was 101 × 103 U/ml (age: 0-15 years), which was significantly lower than the mean pre-treatment value in patients with varicella infection 167 × 103 U/ml (age: 3-17 years). In the AC group, the NAbs level observed on days 5 and 10 decreased significantly to a level of 154 × 103 U/ml, whereas in the placebo group it continued to rise in a time-dependent manner reaching 229 × 103 U/ml on day 10. Our findings suggest that treatment with AC is characterized by "normalization" of the anti-IFN-γ NAbs levels in patients with varicella infection.

Distribution and antibiotic resistance profile of key Gram-negative bacteria that cause community-onset urinary tract infections in the Russian Federation: RESOURCE multicentre surveillance 2017 study.

BACKGROUND: Urinary tract infections (UTIs) are among the most common bacterial infections in clinical practice. This RESOURCE (pathogen distribution and antibiotic RESistance prOfile of key Gram-negative bacteria caUsing community-onsEt URinary traCt) study aimed to determine the antimicrobial resistance profile of Gram-negative bacteria isolated from outpatient urine samples collected across the Russian Federation. METHODS: A total of 96 781 urine samples were collected from 520 cities in the Russian Federation between 01 January 1 and 31 December 2017. Antibiotic susceptibility was performed using semi-automated analysers. The mean age of the study population was 40.9 years; 80.2% were female and 19.8% were male. RESULTS: Of the uropathogens that were isolated, 64.2% were Gram-negative bacteria. Among these, Escherichia coli (E. coli) was the most common (49.1%) followed by Klebsiella pneumoniae (9.5%), Proteus mirabilis (2.9%), Pseudomonas aeruginosa (1.7%), and Enterobacter spp. (1.0%). Of the antibiotics that were tested, 50% of the isolated E. coli strains were resistant to ampicillin, 30.3% to co-trimoxazole, 26.2% to aztreonam, 28.8% to levofloxacin, and 21% to cefuroxime. Conversely, E. coli was highly susceptible to imipenem (0.7% resistant strains isolated), amikacin (0.9%), nitrofurantoin (4.5%), and fosfomycin (1.2%). The most active antimicrobials against Klebsiella pneumoniae were imipenem (6.8% resistant strains) and colistin (0.5%), while piperacillin/tazobactam (4.2%), cefoperazone/sulbactam (3.1%) and imipenem (0%) were the most active agents against Proteus mirabilis. The antimicrobials showing the highest activity against Pseudomonas aeruginosa were colistin (10.7% resistant strains) and aztreonam (0%), while piperacillin/tazobactam (7.1%) and cefoperazone/sulbactam (2.3%) showed the highest activity against Enterobacter spp. CONCLUSION: The prevalence of fluoroquinolone and cephalosporin resistance among common UTI-causing Gram-negative bacteria highlights the growing challenge of successfully treating community-onset UTIs.

Efficacy and safety of Subetta add-on therapy in type 1 diabetes mellitus: The results of a multicenter, double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: To examine efficacy of Subetta as an add-on to insulin therapy in patients with type 1 diabetes mellitus (T1DM) a multicenter, double-blind, placebo-controlled, randomized clinical trial was performed. Derived by technological treatment of antibodies to insulin receptor ß-subunit and endothelial NO synthase Subetta was previously proved to activate insulin signaling pathway. METHODS: A total of 144 randomized patients with poor glycemic control in basal-bolus insulin regime were included in intention-to-treat analysis in Subetta add-on therapy or placebo (n = 72 in both groups). Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), basal and prandial insulin doses, number of hypoglycemia episodes confirmed by self-monitoring of blood glucose were recorded for 36 weeks. RESULTS: The baseline characteristics of subjects did not differ between the two groups. HbA1c mean (±standard deviation) change was -0.59 ±â€¯0.99% (95% CI -0.84 to -0.37) after 36 weeks in Subetta (vs. -0.20 ±â€¯1.14%; 95% CI -0.44 to 0.11 in placebo; p = 0.028). The rate of overall hypoglycemia events was 7.9 per patient year (95% CI 7.1-8.6) in Subetta group and 7.6 (95% CI 6.9-8.4) in Placebo group (p = 0.63). The basal and total insulin doses did not change at the end of 36 weeks in both groups. CONCLUSIONS: Subetta add-on therapy boosting insulin activity and improving glycemic control in patients with T1DM is proved to be beneficial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01868594.

Efficacy and safety of Afalaza in men with symptomatic benign prostatic hyperplasia at risk of progression: a multicenter, double-blind, placebo-controlled, randomized clinical trial.

INTRODUCTION: In order to investigate the efficacy and safety of Afalaza in men with benign prostatic hyperplasia (BPH) at risk of progression, this multicenter, double-blind, placebo-controlled, randomized clinical trial was performed. Derived by technological treatment of antibodies to prostate-specific antigen (PSA) and endothelial nitric oxide synthase (eNOs), Afalaza was previously proved to modulate its molecular targets. The mechanism of action of the drug is associated with the modulating effect of the antibiodies (RA-Abs) on the molecular targets (PSA and eNOS) by way of conformational changes. MATERIAL AND METHODS: A total of 49 patients aged 45-60 years with BPH and moderate lower urinary tract symptoms (LUTS), total prostate volume (TPV) ≥30 cm3, Qmax 10-15 ml/s, and serum PSA<4 ng/ml were randomly assigned to receive either Afalaza (n = 125) or placebo (n = 124) for 12 months. Changes in BPH/LUTS symptoms (according to the International Prostate Symptom Score), Qmax, TPV, PSA, BPH clinical progression, occurrence of acure urinary retention (AUR) events or BPH-related surgery were estimated as the study endpoints. RESULTS: IPSS mean change was -3.7 ±3.0 (95% CI -4.3 to -3.2) after 12 months of Afalaza (vs. -2.9 ±2.4; 95% CI -3.3 to -2.4 in placebo; р = 0.02). Qmax growth was 2.5 ±4.3 ml/s (vs. 1.4 ±3.3 in placebo; p = 0.049), TPV reduced by 11.8 ±16.0% (vs. 6.5 ±14.7%; p = 0.01, and PSA remained unchanged. Afalaza therapy resulted in a significant decrease in the total sum of BPH progression symptoms (p = 0.01). The maximum effect of Afalaza was registered after 12 months without a tendency to form a 'plateau'. During the study, no patients experienced AUR or BPH-related surgery. CONCLUSIONS: A 12-month course of Afalaza therapy is effective and safe for patients with BPH. The results of end points measurements revealed asignificant advantage of Afalaza compared to placebo in the overall symptoms benefit and a decline in the risk of BPH progression.ClinicalTrials.gov: NCT01716104.

Efficacy and safety of Ergoferon versus oseltamivir in adult outpatients with seasonal influenza virus infection: a multicenter, open-label, randomized trial.

OBJECTIVES: Ergoferon is an antiviral complex drug containing released-active forms of antibodies to interferon gamma, CD4, and histamine. Its efficacy and safety in the treatment of acute respiratory viral infections has been reported previously. The aim of this study was to compare Ergoferon with oseltamivir. METHODS: A multicenter, open-label, randomized controlled trial of patients aged 18 to 65 years, who had tested positive for influenza A or B antigens, was performed. A total of 156 patients were enrolled as the intention-to-treat population; these patients were assigned randomly to receive either Ergoferon or oseltamivir (n=78 in each group). RESULTS: The percentage of patients achieving a normal body temperature (≤37.0°Ð¡) following 5 days of treatment did not differ significantly between the groups. The mean duration of fever in the Ergoferon and oseltamivir groups was 2.1±1.5 days and 2.3±1.6 days, respectively (p=0.01). The average time to the resolution of influenza symptoms was approximately 3 days, with no significant between-group difference. Total quality of life scores were similar in the two groups following 5 days of drug administration. The incidence of adverse events did not differ significantly between the groups, nor were there any serious adverse events. CONCLUSIONS: Ergoferon and oseltamivir were equally effective and safe in adult outpatients with seasonal influenza A or B virus infection. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifierNCT01804946.