[The effect of a medicinal plant preparation on the frequency of episodes of exacerbation of recurrent cystitis and metabolic parameters in patients with type 2 diabetes mellitus taking glyphlosins].

BACKGROUND: The problem of recurrent urinary tract infections (UTI) in patients with type 2 diabetes mellitus (DM 2) is relevant, especially when there is a combination of predisposing factors, such as female gender, history of UTI episodes, and therapy with sodium glucose cotransporter type 2 (SGLT-2) inhibitors, and the choice of effective and safe means could cause some difficulties, including ina terms of the burden of antibiotic resistance. AIM: To evaluate the effectiveness and safety of the phytoproduct Canephron® N for the prevention of exacerbations of recurrent cystitis and the effect on metabolic parameters in patients with type 2 diabetes taking SGLT-2 inhibitors. MATERIALS AND METHODS: Prospective, randomized, open, parallel group study in 60 women. The main group took the drug Canephron® N for 3 months. The main parameters for evaluating were the frequency of recurrence of cystitis, level of albuminuria and LDL-cholesterol peroxidation product - malondialdehyde. RESULTS: Within 3 months of taking Canephron® N, exacerbations of chronic cystitis were diagnosed 2 times less often, a decrease in albuminuria was found in the form of an increase in the proportion of patients with an optimal level of albuminuria by 20%, a 50% reduction in the frequency of the initial increase in albuminuria, and the absence of moderate albuminuria in all patients at the end of course of therapy. A decrease in the level of MDA by 1.4 times was noted (p=0.019). CONCLUSION: Thus, the herbal drug Canephron® N can be used for accompanying therapy and prophylactic treatment in patients with recurrent cystitis on the background of DM 2, taking SGLT-2 inhibitors. The course of therapy should last at least 3 months.

[Modern algorithm of diagnosis and treatment of acute gestational pyelonephritis in a large industrial city].

THE PURPOSE OF THE STUDY: to develop a modern algorithm for the diagnosis and treatment of acute gestational pyelonephritis in a large industrial city and to study the possibilities of phytotherapy as an integral part of this algorithm. MATERIALS AND METHODS: The study consisted of two stages and included 629 patients treated over 12 years (2010-2021) in Perm city with a population of 1.1 million people. At the first stage, the developed algorithm for the diagnosis and treatment of acute gestational pyelonephritis in 440 pregnant women was tested. A city emergency center for patients with gestational pyelonephritis was created with 3 urologists and related specialists on duty around the clock, what accelerated hospitalization timelines by 2.1 times. The patients underwent a level 1 examination, which included ultrasound examination, urine bacteriology and other methods. Patients in serve condition underwent, a level 2 examination, which included magnetic resonance imaging (MRI), ultrasound Dopplerography (USDG) and extended laboratory tests. RESULTS: During an urgent examination, acute purulent pyelonephritis was diagnosed in 27 (6.1%) patients who underwent 13 open surgeries (11 organ-preserving, 2 nephroectomies) and 14 minimally invasive (percutaneous nephrostomy, puncture of a kidney abscess) within 2-5 hours from the moment of hospitalization. Serve obstructive pyelonephritis was diagnosed in 286 patients, the passage of urine was restored by the installation of a stent or catheterization of the ureter. Conservative antibacterial therapy was performed in 127 patients with serous non-obstructive pyelonephritis. Positive results of treatment were observed in 439 (99.8%) patients: recovery in 95%, significant improvement in 4.8%, with a mortality rate of 0.2%. Bed-day decreased by 30.4%. At the second stage, a comparative randomized study was conducted during 4 years with 189 pregnant women with acute serous pyelonephritis enrolled. In the group 1 (n=94) patients received standard therapy according to the implemented algorithm, in the group 2 (n=95) patients had 60-day use of Canephron N. In the group 2, treatment results were better: recovery was achieved in 96.8% of patients, improvement in 3.2%, the number of pregnant women with leukocyturia and bacteriuria decreased 4.1 times, which prevented the occurrence of repeated attacks of acute pyelonephritis. Compared with standard therapy, Canephron N increased glomerular filtration by 12,3%, diuresis by 14.2%, increased urea excretion function of the kidneys, sanitized the urinary tract at an earlier timelines, reduced the number of premature births and the birth of dead and premature babies. CONCLUSION: As a result of the development and implementation of an algorithm for the diagnosis and treatment of acute gestational pyelonephritis and creation of the treatment center for such patients, it was possible to reduce significantly the time of hospitalization and inpatient treatment and achieve good treatment results in 99.8% of patients. The inclusion of long-term phytotherapy with Canephron N in the treatment regimen increased the effectiveness of treatment, improved kidney function in patients, significantly reduced the number of pregnant women with leukocyturia and bacteriuria, and reduced the risk of a repeated attack of pyelonephritis.

[The efficiency of combined regimens for the treatment of urinary tract infections in women using the herbal drug Canephron N].

INTRODUCTION: Currently, empiric antibiotic therapy is considered the standard for acute cystitis. However, additional treatment may be required to alleviate the patient's condition and shorten the time to subjective recovery. AIM: To evaluate the efficiency of the combined administration of fosfomycin trometamol and herbal drug Canephron N in comparison with a single oral dose of fosfomycin trometamol in women with uncomplicated bacterial cystitis. MATERIALS AND METHODS: A randomized, comparative, open-label study was carried put between January 2018 and June 2019. The study included 112 women with symptoms of acute uncomplicated cystitis, who were randomized between two groups in a 1:1 ratio. In the main group, patients received a single oral dose of fosfomycin in combination with Canephron N (2 tablets t.i.d. for 2 weeks), while in the control group patients received only a single dose of fosfomycin (3 g). Symptoms were assessed using the Russian version of the Acute Cystitis Symptom Score (ACSS), completed daily for a week. Also, all patients underwent urine analysis on the 1st, 3rd, 5th and 7th days of therapy. The mean time to complete recovery based on the ACSS questionnaire and the time to resolution of pyuria were compared using the Mann-Whitney U test. Comparison of the proportion of patients with complete cure, according to the questionnaire, or with the elimination of pyuria was carried out using the chi-square test. RESULTS: The final analysis included 46 patients who received fosfomycin in combination with Canephron and 47 patients who received fosfomycin as monotherapy. In the group of combination therapy, patient-reported complete recovery (assessed by the ACSS questionnaire) was seen on average after 1 day, while in patients treated with monotherapy, the median time to subjective recovery was 3 days (p=0.00012). A significant difference between the groups in the proportion of patients with complete resolution of symptoms of acute cystitis was observed on days 1, 2, and 3 (p<0.05). The therapy was well tolerated in both groups. The most frequent adverse events were dyspepsia (8.7% in the combination group compared to 6.4% in the control group) and headache (in 4.3% and 6.4% of patients, respectively). CONCLUSION: the combined use of fosfomycin trometamol and the herbal drug Canephron N allows to reduce the duration of symptoms in patients with acute cystitis, thereby accelerating return to their usual lifestyle patterns.

Acute Cystitis Symptom Score questionnaire for measuring patient-reported outcomes in women with acute uncomplicated cystitis: Clinical validation as part of a phase III trial comparing antibiotic and nonantibiotic therapy.

PURPOSE: The Acute Cystitis Symptom Score (ACSS) used in a clinical trial comparing the phytodrug Canephron®N (BNO 1045) with an antibacterial agent (fosfomycin trometamol [FT]) in the treatment of acute uncomplicated cystitis (AC) in women was evaluated as a patient-reported outcome measure in a post hoc analysis. MATERIALS AND METHODS: This double-blind, randomized, multicenter, phase III noninferiority trial was performed in 51 centers in Europe. The ACSS questionnaire was used to assess severity and course of symptoms. RESULTS: The post hoc analysis included 325 patients treated with BNO 1045 and 332 patients treated with FT (total of 657 patients). The mean sum-scores of the ACSS-typical domain were comparable between groups on day 1 (BNO 1045: 10.2; FT: 10.1), and then decreased on day 4 (BNO 1045: 5.1; FT: 4.5), at end of treatment on day 8 (BNO 1045: 2.1; FT: 2.1), and at late follow-up on day 38 (BNO 1045: 0.8; FT: 0.9). Predefined thresholds using the scoring system of the ACSS could be established and validated to define "clinical cure." CONCLUSIONS: Evaluating not only antibacterial but also nonantibacterial agents indicated for the treatment of AC in women, clinical criteria for diagnostics, and measures of patient-reported outcomes are more important as main objectives than microbiological criteria. In this post hoc evaluation, we showed that the ACSS questionnaire, validated in several languages, has the potential to be used as a suitable instrument for diagnostics and patient-reported outcomes in well-designed, international, clinical studies investigating different treatment modalities of uncomplicated urinary tract infections.

[Treatment of acute uncomplicated cystitis in women with antibiotic allergy or intolerance].

AIM: A comparative evaluation of the efficacy and safety of Canephron N and Cystone as monotherapy in women with acute uncomplicated cystitis and antibiotic allergy or intolerance was performed. MATERIALS AND METHODS: A prospective, randomized, controlled study of drug Canephron N as monotherapy for acute uncomplicated cystitis in 51 women with a history of antibiotic allergy or intolerance was carried out in 3 urological centers in Perm from 2016 to 2019. In the main group, patients received Canephron N for 30 days, while in comparison group, Cystone was prescribed. The Acute Cystitis Symptom Score (ACSS), microscopic study of urine sediment, urine culture and other methods were used. Results were evaluated 3, 6, 30 days and 1 year after the start of treatment. RESULTS: In the main group, monotherapy with Canephron N for 30 days resulted in a decrease in the total ACSS score from the baseline 12.9 to 0.3 points, while in Cyston group, changes of ACSS score were less pronounced, from baseline 12.8 to 1.4 points (p<0.01). Clinical cure rate in the main and comparison group was 88.5% and 68%, respectively. In another 3.8% and 1% of patients in the main and comparison group, an improvement was seen. The number of patients with leukocyturia in the Canephron N group decreased to 11.5% compared to 28% in Cyston group (p>0.05). Bacteriuria rate in the main group was 7.7%, which was less than in the comparison group (20%, p>0.05). Number of sick days in the main group was 4.9+/-0.4, compared to 7.4+/-0.6 days in Cyston group. In the Canephron N group, 1-year recurrence rate was only 7.7%, while in the Cyston group the recurrence was seen in 16% of patients. CONCLUSION: According to the results, Canephron N is an effective and safe drug as monotherapy for acute uncomplicated cystitis, and can be considered as drug of choice for the treatment of women with antibiotic allergy or intolerance.

[Comparative effectivenesss of standard antibiotic therapy and Canephron N asymptomatic bacteriuria in pregnant women].

Current international and Russian clinical guidelines recommend treating asymptomatic bacteriuria in pregnancy to prevent acute gestational pyelonephritis. At the same time, the growing resistance of uropathogens and the risks associated with antibiotic therapy in pregnancy dictate the need to limit the use of antibiotics and seek alternative approaches to antibacterial therapy. MATERIALS AND METHODS: A retrospective analysis was performed on 60 pregnant women who received either a standard antibiotic regimen (n=32) or the herbal preparation Canephron N (n=28). The primary outcomes were the incidence of symptomatic infections (cystitis or pyelonephritis), premature birth and low birth weight delivery, and incidence of persistent/recurrent bacteriuria. RESULTS: In the group of antibiotic therapy, one patient developed cystitis and three had pyelonephritis; in the Canephron N group, cystitis occurred in one patient, no pyelonephritis cases were observed. Among the whole study cohort (n=60), the incidence of symptomatic infections and pyelonephritis was 8.3 and 5.0%, respectively. The incidence of symptomatic infections (cystitis, pyelonephritis) did not differ statistically significantly between the study groups (p=0.2157). There were three and one premature births in the group of antibiotic therapy and the Canephron N group, respectively (p=0,373), and two low birth weight deliveries in each group (p=0.891). Recurrent bacteriuria was registered in 17 patients from the group of antibiotic therapy and in three in the Canephron N group (p=0.0006). CONCLUSIONS: The management of asymptomatic bacteriuria in pregnancy using Canephron N is not inferior to standard antibiotic therapy regarding the incidence of symptomatic infection, premature birth, and low birth weight delivery. Persistent/recurrent bacteriuria was more common in women receiving the antibiotic therapy.

[Comparative assessment of Canephron N and ciprofloxacin as monotherapy of acute uncomplicated cystitis in women].

The study aimed to compare the efficacy and safety of Canephron N and ciprofloxacin as monotherapy in the management of mild forms of acute uncomplicated cystitis in women of working age. MATERIALS AND METHODS: A prospective, randomized study of Canephron N and ciprofloxacin for treating mild forms of acute uncomplicated cystitis (ACSS score less or equal 10) comprising 160 women aged 18-55 years was conducted from 2015 to 2017. Group I consisted of 80 women, who received oral Canephron N 2 tablets 3 times daily for 30 days. Group II included 80 women who took oral ciprofloxacin 0.5 g twice daily for 3 days. The results were assessed using the ACSS scale, urinalysis by microscopy, bacteriological examination of urine, etc. The outcomes were evaluated at 3, 6 and 30 days, and one year after the treatment initiation. RESULTS: In group I, monotherapy with Canephron NH resulted in a marked improvement in symptoms, a decrease in the ACSS scores from 7.9 at baseline to 0.1 at day 30. The indicator of clinical efficacy (recovery) was 93.75%, bacteriological efficiency was 91.3%, relapse of cystitis within one year was observed in 5% of patients; no side effects were registered. In group II, the symptoms and bacteriuria decreased more rapidly in the early periods, but after 30 days the results of clinical and bacteriological efficacy did not differ from the group I (93.75 and 91.3%, respectively). Side effects and cystitis relapses were noted in 18.8% and 12.5% of patients, respectively. CONCLUSION: The findings of the study show that Canephron N is an effective and safe alternative to treating mild forms (ACSS score less or equal 10) of acute uncomplicated cystitis in women, allowing the use of antibiotics to be reduced. In our opinion, patients with more severe forms of acute uncomplicated cystitis should be treated with traditional antibiotic therapy.

[Diagnosis and treatment of cystitis: more questions than answers?]

INTRODUCTION: Despite the prevalence of acute cystitis, there are still many unsolved problems of diagnosis and treatment of this disease. MATERIAL AND METHODS: To determine the nosological structure of dysuria, 126 female patients who sought medical attention for frequent painful urination were examined. To determine the incidence of outpatient visits to an urologist for patients with cystitis, medical records of 6753 patients of municipal outpatient clinic were analyzed. The results of treating cystitis in 85 patients also were evaluated. RESULTS: Among 126 patients with dysuria, 31 (24.6%), 42 (33.3%) and 47 (37.3%) patients had acute uncomplicated cystitis, recurrent (chronic) cystitis without the complicating factors and recurrent (chronic) cystitis with complicating factors, respectively. Three (2.4%), 2 (1.6%) and 1 (0.8%) patients had trichomoniasis, urogenital herpes and tuberculosis, respectively. As a result of 6753 visits to the urologist, inflammatory diseases of the genitourinary system were detected in 3194 (47.3%) patients, of which 64.7%, 19.6%, 5.3% and 2.7% had chronic pyelonephritis, chronic cystitis, chronic prostatitis and acute cystitis, respectively. Selecting the optimal drugs increases the treatment effectiveness of acute uncomplicated and chronic cystitis by 6% and 17%, respectively. CONCLUSIONS: Most of clinical guidelines and scientific publications aimed at acute uncomplicated cystitis, while the proportion of the disease does not exceed 26% among the patients presenting with dysuria, and comprise only 2.7% among outpatient urologist visits for infectious and inflammatory diseases of the urogenital tract. Selecting the optimal drugs increases the treatment effectiveness of acute uncomplicated and chronic cystitis by 6% and 17%, respectively.

Efficacy and safety of the phytotherapeutic drug Canephron® N in prevention and treatment of urogenital and gestational disease: review of clinical experience in Eastern Europe and Central Asia.

This review evaluates 17 clinical studies from 18 selected publications concerning the safety, tolerability, and additional effects of the phytotherapeutic drug, Canephron® N (CAN, containing the medicinal plants, Centaurium erythraea, Levisticum officinale, and Rosmarinus officinalis) as standard therapy in various clinical settings. Its role in the prophylaxis and treatment of urinary tract infections in adults and in children, therapy and prophylaxis in adult patients with renal stones, treatment and prevention of urinary tract infections and other gestational diseases in pregnancy, and also its safety and tolerability. The dosage was as recommended and over a varying duration. Overall, CAN was shown to be effective in the treatment and prophylaxis of UTI compared with standard therapy, both in adults and children, and there was a reduced number of relapses. Children undergoing surgical correction of vesicoureteral reflux benefited from a prophylactic course of CAN. Ten-day add on therapy increased the rate of spontaneous elimination of kidney stones compared with standard therapy alone and may also have had a positive effect on stone prevention. Pregnant women showed earlier relief of symptoms and normalization of pyuria on additional treatment with the herbal combination. Only one adverse effect was reported (skin rash) in the 3115 patients included in this review. No teratogenic, embryotoxic, or fetotoxic effects, or negative interference with the psychological development or health of children born of mothers treated with the drug were reported. Because some of the studies were not well designed, their statistical significance remains unclear.