Kirill Kosilov

A randomized, controlled trial of effectiveness and safety of management of OAB symptoms in elderly men and women with standard-dosed combination of solifenacin and mirabegron

OBJECTIVES Comparison of effectiveness and safety of solifenacin and mirabegron, as well as their combination, for managing heavy symptoms of overactive bladder. MATERIALS AND METHODS All patients who participated in the examination (average age: 71.2) were split into 4 groups. Patients included in Group А (n=63) were treated with mirabegron 50mg/day/6 weeks, in Group B (n=52)-with solifenacin 10mg/day/6 weeks, in Group С (n=65)-with the same doses of both drugs simultaneously/6 weeks, and in Group D (n=59)-with placebo. Monitoring was carried out using OAB-questionnaires, bladder diaries and urodynamic examination. RESULTS In elderly patients with initial frequency of episodes of incontinence (EI)≥3/day standard doses of mirabegron (50mg/day) and solifenacin 10mg/day administered during 6 weeks result with the decrease in frequency of EI with high correlation (r=0,74, p≤0.05); final results in both groups are significantly different from initial value of p≤0.05. In the group, where patients were taking both drugs simultaneously, final results significantly differ from both initial values of the parameters in these groups (EI: 5.1→1.6 per day, p≤0.01; urination: 9.1→5.3 per day, p≤0.01; post-void residual 19.4→29.9, p≤0.01) and final values in Groups A and B (p≤0.05). The percentage of side effects in this group does not significantly differ from that in the groups, where patients were receiving monotherapy. CONCLUSION Combined treatment for severe symptoms of OAB in elderly men and women with standard doses of solifenacin and mirabegron provides satisfactory therapeutic effect within short period of time without increasing the risk of side effects, which undoubtedly improves quality of life and self-esteem of patients. At the same time, taking any of these drugs separately for the treatment of severe malfunction of lover urinary tracts in elderly people may turn out to be insufficient for effective symptom management.

Effectiveness of combined high–dosed trospium and solifenacin depending on severity of OAB symptoms in elderly men and women under cyclic therapy

Material and methods 313 patients, 196 women and 117 men over 65 (average age 68.6) were included in this study. All patients underwent urodynamic examination before enrollment and after the study was completed. For clinical evaluation of LUT state ICIQ-SF questionnaires and bladder diaries were used. Patients with moderate (А, n = 155) and severe (В, n = 158) symptoms of OAB. Each group was divided into subgroups in which patients received Trospium 60 mg/day and Solifenacin 20 mg/day during two cycles – 1.5 and 1 month with one month interval (А1 and В1); subgroups in which second cycle was substituted with placebo (А2, В2), and control groups (А3, В3). Results In groups with moderate symptoms of OAB ratio of patients demonstrated decrease of frequency of EI ≥1.5 a day remained at the level of 45-60% during all observation period. In subgroups with severe symptoms of OAB percentage of such patients was 55.3% for the subgroup which received two cycle therapy, and decreased to 26% in the subgroup which underwent 1 cycle therapy. Urodynamic indices for state of LUT correlated with clinical indicators (r =0.57-0.71 at p≤ 0.05). Conclusions Short single cycle of high-dosed Solifenacin and Trospium in elderly patients with moderate symptoms of OAB enables to maintain long therapeutic effect with acceptable level of side effects. This treatment algorithm applied in two cycle course is an effective and safe method for management of severe symptoms of OAB in elderly patients without increased risk of side effects.

Effectiveness of Solifenacin and Trospium for Managing of Severe Symptoms of Overactive Bladder in Patients With Benign Prostatic Hyperplasia.

This research is aimed to study the possibility of management of severe symptoms of overactive bladder (OAB) with solifenacin and trospium in patients who receive treatment with tamsulosin due to benign prostatic hyperplasia (BPH). The 338 men more than 50 years old (average age 58.4 years) diagnosed with BPH and severe symptoms of OAB were enrolled in the study. Over three episodes of urinary incontinence per day (registration according to bladder diaries), International Prostate Symptom Score over 19, OAB-V8 questionnaire score over 32, and urodynamic disorders diagnosed using cystometry and uroflowmetry were taken as a criterion of severe symptoms of OAB. Patients of the main group during 2 months received treatment with daily combination of solifenacin 5 mg and trospium 5 mg simultaneously with tamsulosin 0.4 mg. Patients of the control group were treated only with tamsulosin. First endpoint is a quantitative assessment of patients with BPH having severe symptoms of OAB. Second endpoint is a state of the patients’ lower urinary tract after the treatment. In the main group, most of urodynamic indices normalized significantly. Number of episodes of incontinence reduced from middle level 3.4 (0.8) per day to 0.9 (0.7) per day. In the control group changes of urodynamic indices were not significant. Quantity of side effects did not exceed the level which is common for antimuscarinic monotherapy. Therefore, percentage of patients with severe symptoms of OAB is not less than 44% of all cases of prostatic hyperplasia accompanied by OAB symptoms. Combination of trospium and solifenacin in standard doses is an efficient and safe method of management of severe symptoms of OAB in the course of the treatment of with tamsulosin in patients more than 50 years of age.

Additional correction of OAB symptoms by two anti-muscarinics for men over 50 years old with residual symptoms of moderate prostatic obstruction after treatment with Tamsulosin.

Abstract Objectives: To study the effectiveness and safety of combined standard-dosed Solifenacin and Trospium for management of symptoms of overactive bladder (OAB) in elderly patients after the treatment with Tamsulosin. Patients and methods: A total of 417 men over 50 years of age (average age 57.9 (8.3)) with diagnosed prostatic obstruction (score 8–19 according to I-PSS), who had not taken Tamsulosin before, were enrolled in the study. I-PSS questionnaire (from 8 to 19 – moderate) and Awareness Tool questionnaire for evaluating OAB symptoms (total score for OAB symptoms over 8) were used at the beginning and at the end of the observation. Also, urodynamic parameters were examined. Result: Percentage of patients with prevalent symptoms of obstruction of urethra decreases after the treatment with Tamsulosin and then rises again (36.2%), but absolute number of patients remains smaller than initial data. Percentage of patients with relative prevalence of symptoms of overactive bladder slightly increases against administration of Tamsulosin and reaches initial values at the time of administration of anti-muscarinic drugs with absolute decrease in number of such patients. Conclusion: Combination of Trospium and Solifenacin is an effective way to manage residual symptoms of hyperactive bladder during treatment of early obstruction of urinary bladder.

Comparative effectiveness of combined low- and standard-dose trospium and solifenacin for moderate overactive bladder symptoms in elderly men and women.

Objective: To increase the safety and effectiveness of treatments for overactive bladder (OAB) with moderate symptoms in elderly patients. Patients and Methods: Patients were examined at the Urodynamic Department of the Regional Diagnostic Center (Vladivostok, Russian Federation) from September 1, 2012 to December 31, 2012. The assignment of patients [n = 177, average age 69. 4 years, 98 women (55.4%) and 79 men (44.6%)] was random and blind in this placebo-controlled study. Patients were distributed into subgroups according to the method of treatment as follows: group А1: n = 57, trospium 30 mg/day + solifenacin 10 mg/day; group А2: n = 61, trospium 15 mg/day + solifenacin 5 mg/day; group А3: n = 59, placebo. All patients underwent a urodynamic examination in accordance with international standards before and 2 months after treatment. ICIQ-SF questionnaires recommended by the International Continence Society (ICS) and bladder diaries were used to evaluate the clinical results. The clinical severity of the OAB symptoms and the effectiveness of the treatment were evaluated based on the frequency of episodes of incontinence (EI) per day. Three or fewer EI per day were considered moderate dysfunction of the lower urinary tract. Results: Groups of elderly patients with moderate symptoms of OAB who were treated with standard- and low-dose trospium and solifenacin demonstrated a significant increase in the median values of reflex volume, bladder capacity, and detrusor compliance and a decrease in the frequency of urination and urinary urgencies. The frequency of EI in both of the main groups decreased by almost 2-fold in comparison to the initial data and reached the following values: group А1: 1.27 (-1.08), p ≤ 0.05; group A2: 1.49 (-1.18), p ≤ 0.05. The correlation with the decrease in the frequency of EI in these groups was r = 0.85 (p ≤ 0.01). The percentage of patients with a significant decrease (EI ≥1.0) among those treated with standard- and low-dose trospium and solifenacin increased synchronously, prompting us to suppose the absence of a direct correlation between medicine dose and therapeutic effect for moderate OAB symptoms. Conclusion: The combination of low-dose trospium and solifenacin provides good clinical and urodynamic effects in elderly patients with moderate symptoms of OAB. Combination of these drugs in standard doses for such patients is excessive.

Randomized controlled trial of cyclic and continuous therapy with trospium and solifenacin combination for severe overactive bladder in elderly patients with regard to patient compliance

Objectives: The aim of the study was to increase the efficiency of treatment for severe symptoms of overactive bladder (OAB) with antimuscarinic drugs in elderly men and women. Methods: A total of 341 patients over 65 years of age (average age 69.9; 186 women and 155 men) with severe symptoms of OAB (frequency of incontinence episodes [IEs] ≥ 3/day) underwent examination. Patients were distributed into three main groups: A (n = 58; trospium 60 mg/day + solifenacin 20): three cycles, each cycle 8 weeks, with an 8-week interval; B (n = 55; trospium 30 mg/day + solifenacin 10), regimen was the same as in group A; C (n = 62; trospium 30 mg/day + solifenacin 10) daily during 1 year. Results: The most successful treatment for the clinical and urodynamic symptoms of OAB was observed in group A, without an increase in the quantity or intensity of side effects (IEs = 4.8 (0.9) → 1.4 (0.8); p ≤ 0.01). Groups B and C also demonstrated positive effects for most of the markers for lower urinary tract state with statistical significance p ≤ 0.01. Nonparametric correlation between decrease in IEs and relative number of patients who accurately fulfilled prescriptions was in group A, r = 0.53, p ≤ 0.05; in group B, r = 0.61; p ≤ 0.05; in group C, r = 0.55, p ≤ 0.05. Conclusions: Cyclic therapy with two different spectrum antimuscarinics appears to be effective for controlling severe OAB in elderly patients. One-year cyclic therapy with a trospium and solifenacin combination provides a high compliance level (76–84%). However, continuous therapy with standard doses of trospium and solifenacin results in low adherence and high rates of treatment withdrawals (≥ 66%) despite satisfactory clinical and urodynamic results.

Social, Economic, and Medical Factors Associated With Solifenacin Therapy Compliance Among Workers Who Suffer From Lower Urinary Tract Symptoms

Purpose The prevalence of hyperactive-type lower urinary tract symptoms is 45.2%, with shares of overactive bladder (OAB) and urge incontinence (UI) symptoms of 10.7% and 8.2%, respectively. We investigated the possible impact of a wide range of social, economic, and medical factors on compliance with solifenacin treatment in the working population. Methods Social, economic, and medical factors as well as the Overactive Bladder questionnaire – the OAB-q Short Form (OAB-q SF), bladder diaries, and uroflowmetry of 1,038 people who were administered solifenacin for a year were gathered from employer documentation. Results Among the subjects, 32% maintained their compliance with solifenacin treatment throughout the year. Only 65% of the patients had compliance exceeding 80%, and 17% of patients had compliance of ≥50%, yet less than 80% were still taking solifenacin 12 months after the beginning of this experiment. Working people whose compliance level was, at least, 80% had reliably higher (P≤0.01) average age, annual salary, and treatment efficacy, and a greater treatment satisfaction level, as well as a lack of satisfaction with other antimuscarinic treatments and higher rate of urge UI diagnosis. The same cohort also featured a lower level (P≤0.01) of caffeine abuse and lower share of salary spent purchasing solifenacin. Conclusions This study has shown that compliance with solifenacin treatment is associated with a number of significant medical, social, and economic factors. The medical factors included the type of urination disorder, severity of incontinence symptoms, presence of side effects, treatment efficacy and patients’ satisfaction with it, and experience using other antimuscarinic treatments. Among the social and economic factors, those with the strongest correlation to compliance were patient age, employment in medicine and education, annual income level, percentage of solifenacin purchase expenditures, and caffeine abuse. Factors with a weaker, but still significant, association were gender, employment in the transportation industry, and monthly income level.

Night diuresis stimulation increases efficiency of alarm intervention.

INTRODUCTION The prevalence of primary monosymptomatic nocturnal enuresis (PMNE) varies from 1.6% to 15%. Although treatment with enuretic alarms has been used for a long period of time, there are many disadvantages, including the necessity for long-term use and the high percentage of children who are resistant to such therapy. We hypothesized that more intense use of the alarm system would accelerate the process of forming the conditioned response to awakening, caused by the desire to urinate and, probably, increase the percentage of patients with positive results. Increased fluid intake will cause more frequent awakenings, so the use of alarm system will be more intense (Figure). OBJECTIVE To study the effect of increased fluid intake, prior to going to bed, on the efficacy of alarm therapy. STUDY DESIGN The treatment group consisted of 294 children (178 boys) average age: 11.3 (9.1-11.9) years. All participants completed an overactive bladder questionnaire (OAB-q) and a bladder diary, and underwent uroflowmetry, blood and urine testing. Group A (n = 141, mean age 10.9 (9.1-11.6) years), used the alarm system traditionally (Wet Stop/BYE-WET, USA). Group В (n = 153, mean age 11.5 (9.3-11.9) years) drank either water or any other transparent non-colored fluid (any table mineral water with mineralization of less than 1 g per dm³) once immediately prior to sleep at a volume of 4-5 ml/kg of body weight. The effectiveness of therapy was assessed by the change in frequency of urination episodes during sleep per week, episodes of spontaneous awakenings, caused by the desire to urinate per week. Data were analyzed using JMP SAS Statistical Discovery 8.0.2. Wilcoxon criterion was used for comparison of results between groups; correlation of changes in groups was analyzed using the Spearman coefficient. RESULTS Complete resolution of NE, 2 weeks after the end of alarm therapy, was found in 34 patients (24%) in Group A and 59 (39%) in Group B. This difference was statistically significant with a confidence level of 95%. DISCUSSION Having searched the publication databases, including PubMed and Scopus, we failed to find any publication presenting evidence or recommendations on the ideal management of fluid intake in patients with PMNE. Although a limitation of fluid intake is commonly recommended, there is no evidence showing an increase in dry night frequency when such fluid restriction is used as monotherapy. In contrast, our study has shown an improvement in outcome when an increased fluid intake is used in combination with enuretic alarm therapy. CONCLUSION We were able to prove that increased fluid intake improved the efficiency of alarm therapy intervention during the treatment of PMNE in children.

Decrease of risk of developing symptoms of OAB in elderly men and women treated with loop diuretic for hypertensive disease using solifenacin.

OBJECTIVES MATERIALS AND METHODS Randomized double blind longitudinal study was performed from December 1, 2012 to June 15, 2013 in urological ward of gerontological hospital (Vladivostok city, Russian Federation). 378 men and women over 65 (average age: 69.8 (7.2)), who suffered from stage 1 (initial) hypertension, had participated in this study. During the treatment all patients, except for those who were assigned to the control group, received Loop Diuretic Furosemide dosed at 20-30 mg per day and Solifenacin dosed at 5 mg per day (First comparison group) and 10 mg per day (Second comparison group). Functional performance of lower urinary tract (LUT) at enrollment and at the end of the treatment was evaluated using ICIQ-SF questionnaires. During the whole period of treatment patients were keeping bladder diaries where records on frequency and volume of daily urinations, episodes of urgency (EU), episodes of incontinence (EI) and other symptoms were kept. RESULT Comparison of data obtained from control group (7.2%), group of the patients treated with Furosemide and standard- dosed (11.1%) and low-dosed (16.2%) Solifenacin allows to draw conclusion on the absence of significant differences in number of patients with symptoms of OAB between these groups (p ≥ 0.05). At the same time percentage of patients with symptoms of OAB in the group treated only with Furosemide was significantly different from three other groups (p ≤ 0.05) and reached 46.1%. CONCLUSION Risk of developing symptoms of OAB in elderly patients, whose hypertensive disease has been treated with loop diuretic for a long period of time, decreases significantly, provided antimuscarinic drug Solifencin is administered at the same time. Administration of low dosed Solifenacin is sufficient for significant decrease in risk of developing symptoms of overactive bladder.

Health-related quality of life's dependence on socio-economic status and demographic characteristics among men with benign prostatic hyperplasia

This study investigated the effect of socio‐economic status (SES) on health‐related quality of life (HRQoL) among persons with benign prostatic hyperplasia (BPH). The data were collected by way of surveying persons with BPH aged from 35 to 85 (937) and selected via random sample. The diagnosis was confirmed with the use of I‐PSS questionnaires (8–19 points), OABq‐AT (≥8 points) and daily urinations. A study on HRQoL was conducted using the SF‐36 questionnaire. SES was evaluated using the patients’ ambulance cards (F112U) and tax inspection documents with their written permission. Verification of the viability of the differences in the HRQoL level of patients with different SES was conducted in each age cohort using ANOVA. The goal of the multifactor regressive analysis using least weighted squares was identified as featuring the strongest relationships between SES and HRQoL. In comparing the average regression squares with average error squares, selection of the entry variables was conducted. Among persons with a BPH, the strongest relationship was discovered between profession, level of education, place of residence and HRQoL. A weaker relationship was identified between income and HRQoL, and there was no relationship between marital status and HRQoL. HRQoL among persons with a different level of SES figures aged 65+ proved homogeneous. We can expect HRQoL improvement among persons with BPH while increasing informedness on the possibilities for treating and improving help for workers of industrial and rural production residing in rural areas.