The Analysis of the Effects of Executive Functions, Working Memory and Other Factors on Medication Adherence in Elderly Men with Benign Prostatic Hyperplasia and Overactive Bladder Symptoms.

AIM: Evaluation of the executive function and working memory influence, as well as the general state of memory, on adherence to Benign Prostatic Hyperplasia (BPH) and overactive bladder symptoms treatment in elderly men. BACKGROUND: The influence of the executive function and working memory on treatment adherence in older men with BPH has not been studied enough. OBJECTIVE: To determine the level of influence of various factors on the treatment adherence in older men with BPH. METHODS: The executive function and working memory evaluation, as well as a general memory assessment, were carried out using the Wisconsin Test, the Wechsler Memory Scale, and the California Verbal Test. Hierarchical and simultaneous regressions were calculated to study the effect of executive function and working memory. RESULTS: After the end of the study, the symptoms of hyperactive bladder significantly decreased, the symptoms of evacuation did not change significantly, and the cognitive status of the patients remained unchanged. The predictor variables significantly influencing adherence of elderly men to BPH and overactive bladder (OAB) treatment are executive function and working memory composite (ß = .33, p < .05), severe symptoms of lower urinary tract (-.34, p < .05), and age (-.27, p < .05). CONCLUSION: The status of executive function and working memory, as well as the age and severity of the pathological symptoms of the lower urinary tract, should be taken into account when predicting the risks of rejecting BPH and OAB treatment in elderly patients.

Effectiveness of a new tool for self-evaluation of adherence to antimuscarinic drug treatment in older patients of both sexes with urge incontinence.

AIM: The present study was a comparison of the validity of the Medication Adherence Self-Report Inventory (MASRI) questionnaire with other methods of assessing adherence to antimuscarinic drugs treatment in older patients with urge incontinence. METHODS: The experiment involved 733 men and women aged >65 years who had noted no less than one urge incontinence episode per day. At the beginning of the experiment, and after 4, 8 and 12 weeks, their adherence to treatment was monitored using the MASRI. RESULTS: The construct validity of the tool was confirmed by data on the correlation of the percentage of non-adherent patients according to the MASRI and the percentage of patients having a belief barrier on the Brief Medication Questionnaire screen (r = 0.89, P ≤ 0.01; r = 0.91, P ≤ 0.01; and r = 0.91, P ≤ 0.05 at the 4th, 8th and 12th week of the follow up). The hypothesis of competitive validity was supported by comparing the percentage of non-adherent patients according to the MASRI and the number of missed doses on the Brief Medication Questionnaire screen (r = 0.94, P ≤ 0.01; r = 0.85, P ≤ 0.05; and r = 0.7, P ≤ 0.05), and according to a visual count of pills. The area under the curve at the 4th, 8th , and 12th week was 0.95 ± 0.04, 0.92 ± 0.03 and 0.94 ± 0.04, respectively. CONCLUSION: The MASRI questionnaire has high validity, and is effective for evaluating adherence to treatment among older patients with urge incontinence taking antimuscarinic drugs. Using the MASRI would imply lower costs and greater availability of diagnostics, and it is the tool of choice in clinical practice. Geriatr Gerontol Int 2018; 18: 115-122.

Caffeine as a Probable Factor for Increased Risk of OAB Development in Elderly People.

OBJECTIVE: This study was conducted to compare overactive bladder (OAB) prevalence among people greater than 60 years of age who intake various doses of caffeine, as well as those who abstain from caffeine. PATIENTS AND METHODS: A randomized observational study was carried out in Vladivostok Gerontological Hospital. A total of 1,098 retired people greater than 60 years of age (659 women and 439 men, average age 67.1 years) took part in the study. They were admitted to the in-patient department with the purpose of annual physical examination performed in accordance with the order of the Ministry of Public Health of the Russian Federation. People over age 60, who at the moment of examination were in satisfactory health condition, were included into the study. People in which OAB had been detected or who used to take antimuscarinic were excluded from the study. Assessment tools for examining the patients' lower urinary tract condition were as follows: OAB-q SF, urination diaries, and uroflowmetry. RESULTS: In the course of the experiment conducted, we found that 1/3 of people, both men and women greater than 60 years of age, who did not previously seek medical advice due to urination troubles, had symptoms of detrusor overactivity. These symptoms were moderate and did not bother patients too much in most cases (63.4%). It was also found that most patients consumed no more than 300mg caffeine with beverages per day, with 30% and 10% of patients suffering from OAB or severe detrusor overactivity, respectively. At the same time, almost 50% of patients taking more than 300 mg of caffeine per day suffer from OAB. CONCLUSION: 48.1% of people over 60 years of age suffering from overactive detrusor symptoms consume greater than 300 mg caffeine daily, which is significantly higher than that of their peers who do not intake excessive amounts of caffeine.

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.

The efficacy of different doses of solifenacin in elderly patients after treating a urinary tract infection.

OBJECTIVE: To determine the efficacy and safety of solifenacin for correcting the residual symptoms of an overactive bladder (OAB) in patients who were treated for a urinary tract infection (UTI). PATIENTS AND METHODS: Using random sampling, 524 patients aged >60 years were selected (347 women, 66.2%, and 177 men, 33.8%). They denied the presence of any symptoms of detrusor overactivity in their medical history, but had a diagnosis of a UTI. At least 1 month after the end of treatment and a laboratory confirmation of the absence of infection, each patient completed an OAB-Awareness Tool questionnaire (OAB signs, total score 8 points), and a noninvasive examination of urinary function (uroflowmetry). Each day patients in group A took solifenacin 10 mg and those in group B took 5 mg, with patients in group C being given a placebo. RESULTS: During the study 58.8% of patients had symptoms of an OAB at 1 month after the end of the treatment for a UTI, and normal laboratory markers. During treatment with the standard and higher dose of solifenacin, within 8 weeks most variables of the condition of the lower urinary tract reached a normal state or improved. CONCLUSION: Patients aged >60 years who had been treated for a UTI have a high risk of developing symptoms of an OAB. Solifenacin in standard doses is an efficient and safe means of managing overactive detrusor symptoms after a UTI.

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.

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.

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.

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.

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.

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

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.

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.

Maintenance of the therapeutic effect of two high-dosage antimuscarinics in the management of overactive bladder in elderly women.

PURPOSE: To improve the long-term efficiency of the pharmacologic management of overactive bladder (OAB) in elderly women. METHODS: The study comprised 229 women (mean age, 66.3 years; range, 65-77 years) with urodynamically and clinically confirmed OAB. All patients received the most effective treatment regimen based on the data obtained in the initial part of the study (trospium 60 mg/day + solifenacin 40 mg/day, for 6 weeks), and positive results similar to those in the first phase were obtained. They were then divided into four groups, based on the maintenance therapy: group A (59 women), trospium (60 mg/day) + solifenacin (40 mg/day) for 1 month; group B (51 women), electrical stimulation of the detrusor muscle for 1 month; group C (63 women), laser puncture for 1 month; group D (56 women), placebo. Maintenance therapy was administered 2.5 months after completion of primary treatment. The patients' condition was monitored through the OAB questionnaire for 1 year and by urodynamic examination at months 6 and 7 from the start of the study. RESULTS: In group A, the clinical and urodynamic results achieved after the initial + main treatment phase (two high-dosage antimuscarinics of different generations, trospium and solifenacin, for a total of 2.5 months) were maintained for at least 7 months. Electrical stimulation of the urinary bladder as a method of maintenance therapy proved to be less effective. In groups C and D, deterioration in results was observed at 6-8 months, which led us to conclude that laser puncture was an inefficient method of maintenance therapy in elderly women with OAB. CONCLUSIONS: Maintenance treatment of OAB in elderly women with a combination of high-dosage antimuscarinics is an effective method for reducing the risk of recurrence of the disease.

Detection of glycosylase, endonuclease and methyltransferase enzyme activities using immobilized oligonucleotides.

A novel rapid assay for detection of DNA glycosylase, restriction endonuclease, and DNA methyltransferase enzyme activities is presented. The assay is based on enzyme-dependent label release (in case of glycosylase and endonuclease), or non-release (in case of methyltransferase) into solution from end-labeled DNA immobilized on solid support (CPG or Tenta Gel S-NH2). The assay has been validated for monitoring activity of repair enzyme uracil-DNA glycosylase, restriction endonucleases SsoII, MvaI and EcoRII and (cytosine-5)-DNA methyltransferase SsoII. Two types of labels have been tested and found compatible with the assay: radioactive (32P) and fluorescent (rhodamine B and fluorescein). The enzyme activity is estimated as a ratio of the label released into solution to the total amount of the label. Use of fluorescent labeling facilitates detection while use of solid phase-immobilized substrates facilitates product separation, improved assay sensitivity, and increases throughput of assay. Proposed technique provides an estimate of enzyme activity but not its specific activity. Thus, the assay will most valuable in the applications where rapid estimation of enzyme activity is necessary.