Vaginal Laser Therapy for Female Stress Urinary Incontinence: New Solutions for a Well-Known Issue-A Concise Review.

Background and Objectives: Insufficient connective urethra and bladder support related to childbirth and menopausal estrogen decrease leads to stress urinary incontinence (SUI). The aim of this review is to narratively report the efficacy and safety of new mini-invasive solutions for SUI treatment as laser energy devices, in particular, the microablative fractional carbon dioxide laser and the non-ablative Erbium-YAG laser. Materials and Methods: For this narrative review, a search of literature from PubMed and EMBASE was performed to evaluate the relevant studies and was limited to English language articles, published from January 2015 to February 2022. Results: A significant subjective improvement, assessed by the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI-SF) was reported at the 6-month follow up, with a cure rate ranged from 21% to 38%. A reduction of effect was evidenced between 6 and 24-36 months. Additionally, the 1-h pad weight test evidence a significant objective improvement at the 2-6-month follow up. Conclusions: SUI after vaginal laser therapy resulted statistically improved in almost all studies at short-term follow up, resulting a safe and feasible option in mild SUI. However, cure rates were low, longer-term data actually lacks and the high heterogeneity of methods limits the general recommendations. Larger RCTs evaluating long-term effects are required.

The Learning Curve of Urodynamics for the Evaluation of Lower Urinary Tract Symptoms.

Background and Objectives: Urodynamics is considered the gold standard for lower urinary tract functional assessment. However, it requires very specific skills and training, which are currently difficult to master due to its reduced use. Moreover, no studies or data are available to define the workload and the learning curve of this diagnostic tool. As a consequence, we aimed to evaluate the learning curve of residents with no previous experience to correctly perform and interpret urodynamics, and properly address and manage patients with pelvic floor disorders based on urodynamics findings. Materials and Methods: This prospective study analyzed a series of proficiency parameters in residents performing urodynamics under consultant supervision, including the following: duration of procedure, perceived difficulty, need for consultant intervention, accuracy of interpretation, and therapeutic proposal. The number of procedures performed was then divided into groups of five to evaluate the progressive grade of autonomy (technical and full management autonomy) reached by each resident. Results: In total, 69 patients underwent urodynamics performed by three residents, with every resident performing at least 20 exams. Duration of procedure, perceived difficulty, need for consultant intervention, accuracy of interpretation, and the appropriateness of the hypothetical proposal of management/treatment based on their interpretation of clinical data and urodynamic findings was shown to be directly related to the number of exams performed. Technical autonomy in the execution of uroflowmetry was reached in the group performing 6-10 procedures, while technical autonomy in the execution of cystomanometry with pressure/flow study was obtained in the group of 16-20 procedures. The latter corresponded also to the gain of full autonomy which also included an optimal therapeutic proposal. Conclusion: We found that there is a tangible learning curve for urodynamics in terms of several proficiency parameters. A workload of 5 uroflowmetries and 15 cystomanometries with pressure/flow studies may be adequate to complete the learning curve.

Impact of Sport Activity and Physical Exercise on Obstetrical and Perineal Outcomes at Delivery: A Prospective Study.

OBJECTIVE: This study was aimed to investigate the effects of physical activity on perineal outcomes at delivery according to the different levels and types of maternal physical activity before and during pregnancy. STUDY DESIGN: We prospectively evaluated the obstetrical and perineal outcomes of all consecutive women who delivered at the Del Ponte Hospital, in the period between July 2014 and September 2014. Women were divided into three groups according to the features of physical activity performed before pregnancy: group 1: "very sporty women," group 2: "moderately sporty women," and group 3: "inactive women." A subanalysis of our data was performed based on the specific type of sport activity, on the degree of involvement of perineal muscles during physical activity, and on the continuation/discontinuation of this activity during pregnancy. RESULTS: A total of 135, 84, and 85 women were included in group 1, group 2, and group 3, respectively. The demographic characteristics were comparable among all the groups. Sport activity during pregnancy was more frequent in groups 1 and 2 (59.3 and 53.6%, respectively, vs. 29.4% in group 3; p = 0.003). No differences among groups were detected in terms of perineal outcomes. A lower rate of episiotomy/lacerations ≥ 2nd degree was found among women who practiced sports that specifically involved the perineal muscles and who continued this practice during pregnancy. CONCLUSION: Perineal outcomes are not influenced by the intensity of sport activity performed before/during pregnancy. Continuous sports during pregnancy that specifically train the perineal muscles are associated with a lower rate of episiotomy and perineal lacerations ≥ 2nd degree.

Tension-free vaginal tape for treatment of pure urodynamic stress urinary incontinence: efficacy and adverse effects at 17-year follow-up.

OBJECTIVE: To assess the efficacy and safety of retropubic tension-free vaginal tape (TVT) 17 years after implantation for the treatment of female pure stress urinary incontinence (SUI). PATIENTS AND METHODS: A prospective study was conducted in two urogynaecological units in two countries. All consecutive women with urodynamically proven pure SUI treated by TVT were included. Patients with mixed incontinence and/or anatomical evidence of pelvic organ prolapse were excluded. Data regarding subjective outcomes (International Consultation on Incontinence Questionnaire-Short Form, Patient Global Impression of Improvement, and patient satisfaction scores), objective cure (stress test) rates, and adverse events were collected during follow-up. Univariable analysis was performed to investigate outcomes. RESULTS: A total of 52 women underwent TVT implantation. At 17-year follow-up, 46 women (88.4%) were available for the evaluation. We did not find any significant change in surgical outcomes during this time. At 17 years after surgery, 41 of 46 women (89.1%) declared themselves cured (P = 0.98). Similarly, at 17-year evaluation, 42 of 46 women (91.4%) were objectively cured. No significant deterioration in objective cure rates was observed over time (P for trend 0.50). The univariate analysis did not find any risk factor statistically associated with the recurrence of SUI. Of the 46 women, 15 (32.6%) reported the onset of de novo overactive bladder at 17-year follow-up. No other late complications were reported. CONCLUSIONS: The 17-year results of this study showed that TVT is a highly effective and safe option for the treatment of SUI.

Vaginal cystocele repair and hysteropexy in women with anterior and central compartment prolapse: efficacy and safety after 30 months of follow-up.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess the safety and efficacy of vaginal native tissue repair and uterine suspension after a follow-up of at least 1 year. METHODS: We included all consecutive women with an anterior vaginal prolapse of stage II or higher and a concomitant uterine prolapse of stage II who underwent this surgical procedure. We considered women with a descensus with maximum point of less than -1 in any compartment as objectively cured. Overall success was defined as no prolapse symptoms, together with a Patient Global Impression of Improvement (PGI-I) score of 2 or less, prolapse of stage lower than II, and no need for other surgery. RESULTS: A total of 102 patients underwent this surgical procedure during the study period and met all the inclusion criteria for statistical analysis. The mean follow-up was 31 ± 8.2 months; no patient was lost to follow-up. Five patients (4.9%) showed postoperative complications. In terms of subjective outcomes, at the last available follow-up, failure of this surgical procedure was seen in 2% of patients. The objective cure rate and the overall cure rate were the 95.1%. No significant deterioration in objective cure rates was observed over time (p = 0.6). CONCLUSIONS: Vaginal repair and hysteropexy appear to be an effective and safe option for women with advanced uterovaginal prolapse.

TVT for the treatment of urodynamic stress incontinence: Efficacy and adverse effects at 13-year follow-up.

AIM: To assess long-term subjective, objective, and urodynamic outcomes of retropubic mid-urethral slings at 13-year follow-up. METHODS: This was a prospective observational study. Consecutive women with proven urodynamic stress incontinence were treated with standard retropubic tension free vaginal tape (TVT). Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded. All the included patients underwent preoperative clinical and urodynamic evaluations. During follow-up examinations, women were assessed for subjective satisfaction and objective cure rates. The Cox model was used in order to investigate factors predicting the risk of recurrent stress urinary incontinence (SUI), over the study period. RESULTS: Overall, 55 patients were suitable for the analysis. At 13-year follow-up, 47 out of 55 (85.5%) patients declared themselves cured (p-for-trend 0.02) and 48 out of 58 (87.2%) were at least improved (p-for-trend 0.07). No significant deterioration of objective cure rates was observed over time (P = 0.29). At the time of the last evaluation, 50 out of 55 (90.9%) women were objectively cured; urodynamic evaluation confirmed this finding in 49 (89.1%) patients. Considering factors predictive of SUI recurrence, we observed that, via multivariate analysis, obesity (HR 7.2; P = 0.01) and maximum detrusor pressure during the voiding phase ≤29 cmH2 O (HR 8.0; P = 0.01) were the only independent predictors of recurrent SUI. CONCLUSION: Our data confirmed that TVT is a highly effective and safe procedure also at 13-year follow-up. Interestingly, we observed a significant decrease of subjective satisfaction over time. Neurourol. Urodynam. 36:192-197, 2017. © 2015 Wiley Periodicals, Inc.

Is mirabegron equally as effective when used as first- or second-line therapy in women with overactive bladder?

INTRODUCTION AND HYPOTHESIS: No previous studies have investigated the efficacy of mirabegron 50 mg as the first-line therapy in OAB patients. Hence, the primary objective of this study was to evaluate the efficacy of mirabegron in treatment-naive patients in comparison with those who had discontinued antimuscarinic therapy because of insufficient efficacy. METHODS: All consecutive women who had pure OAB symptoms (including urgency with or without urgency incontinence and frequency) for at least 3 months were considered for this study. Women were divided into two groups: women without any previous pharmacological treatment for OAB (group 1) and women with a previous history of failed antimuscarinics therapy (group 2). RESULTS: At 3-month follow-up, the objective results on the basis of the frequency-volume chart showed a significant improvement in both groups. Furthermore, a significant reduction in the Overactive Bladder Questionnaire Short Form (OABq-SF) score and in the Indevus Urgency Severity Scale (IUSS) questionnaire were reported in both groups. However, the improvement in objective and subjective outcomes was superior in group 1 to that in group 2. CONCLUSIONS: Mirabegron is efficacious in improving OAB symptoms in both naïve patients and those who discontinued primary antimuscarinic therapy; however, its efficacy is superior when prescribed as first-line therapy.

Position in the second stage of labour and de novo onset of post-partum urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate the role of the maternal position at the time of delivery on the onset of de novo symptoms of urinary incontinence (UI) in the post-partum period. METHODS: This prospective study evaluated the data of consecutive women undergoing labour and delivery, between January 2014 and July 2014. We included only women with a singleton pregnancy undergoing vaginal delivery. During the study period, patients chose to deliver in the position that they considered the most comfortable. The onset of UI was evaluated according to the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-sf). RESULTS: Overall, 716 primiparous women were included in the study. Sixty women refused the 12-week post-partum interview (8.4%). Women were divided in two groups: 296 women (45.1%) who chose an upright position during delivery (group 1) and 360 women (54.9%) who chose a supine position (group 2). Group 1 had a significantly lower episiotomy rate, but a higher rate of greater than second degree perineal tears. In group 1 we found a significantly lower rate of de novo UI (40.5% vs 48.9%, p = 0.03) and in particular of stress urinary incontinence. Via multivariate analysis, birth position was the only factor correlating with the occurrence of urinary incontinence in the post-partum period (OR: 1.52; 95%CI: 1.06, 2.18; p = 0.02). CONCLUSIONS: Upright positions at delivery are related to a lower episiotomy rate and a higher rate of greater than second degree perineal tears. Supine positions are an independent risk factor for the onset of de novo UI.

Urethral bulking agents versus other surgical procedures for the treatment of female stress urinary incontinence: a systematic review and meta-analysis.

Bulking agents provide an alternative option in the management of women with stress urinary incontinence and they seem to have an important role in the management flow chart of SUI. However, evidence on this issue is scanty. The most important aspect is to understand whether bulking agents are comparable with the other first-line anti-incontinence surgical procedure (MUS, Burch colposuspension and pubovaginal slings). Hence, the primary aim of the current review was to assess the objective and subjective outcomes of bulking agents in comparison with the other surgical procedures for the treatment of SUI. PubMed and Medline were systematically searched and we included studies evaluating the use of bulking agents in comparison with other surgical approaches for either primary or recurrent treatment of female SUI. Three studies meeting the inclusion criteria were identified. Two of these studies were RCTs evaluating the use of bulking agents versus other surgical procedures for the treatment of primary female SUI; the remnant article was a retrospective cohort study that compared the effectiveness and safety of repeat midurethral sling with urethral bulking after failed midurethral sling. The combined results of all analyses showed that the objective recurrence rate of peri- or trans-urethral injections is significantly higher in comparison with the other surgical procedures. Similar findings were observed when considering separately the treatment for primary or recurrent SUI. Furthermore, lower subjective recurrence rate was observed among patients undergoing other surgical treatment in comparison with those undergoing bulking agents; however, this trend was not statistically significant. Moreover, patients undergoing injection of bulking agents experienced a lower rate of voiding dysfunctions in comparison to the control group. According to current evidence, bulking agents should not be proposed as first-line treatment in those women seeking permanent cure for both primary and recurrent SUI. However, the effectiveness of a procedure should be balanced with its invasiveness and patients' expectations. Bulking agents are a minimally invasive approach to treat SUI and their use should be considered as an alternative strategy particularly in special conditions: patients who are fragile, in those who do not wish to have surgery, or in whom surgical options are restricted (postoperatively, after irradiation).

Iliococcygeus fixation for the treatment of apical vaginal prolapse: efficacy and safety at 5 years of follow-up.

INTRODUCTION AND HYPOTHESIS: Sacrocolpopexy is considered the gold standard treatment for vaginal vault prolapse. However, the vaginal approach is very common, with 80-90 % of procedures being performed via this route. The aim of this study was to evaluate the safety and efficacy of iliococcygeus (ICG) fixation in the treatment of vaginal vault prolapse, with a minimum follow-up of 5 years. METHODS: We prospectively enrolled women with symptomatic vaginal vault prolapse (Pelvic Organ Prolapse Quantification [POP-Q] stage ≥2) who were treated with ICG fixation. Subjective success was defined in the case of Patient Global Impression of Improvement ≤ 2 and an absence of bulging symptoms. Objective success was defined as stage of prolapse < 2 in all compartments. Overall success rate was defined as women without prolapse symptoms, PGI-I ≤ 2, stage of prolapse < 2, and no need for other surgery. All women filled in the Prolapse Quality of Life (P-QOL) questionnaire both at the preoperative visit and at every follow-up visit. Multiple logistic regression was performed to identify factors involved in the risk of recurrent POP. RESULTS: After a median (range) follow-up of 68.8 (60-92) months the subjective, objective, and overall cure rates were 88.6 % (39 out of 44), 84.1 % (37 out of 44), and 84.1 % (37 out of 44) respectively. Only preoperative stage IV vault descensus independently predicted POP recurrence after iliococcygeus fixation (OR: 8.78 [95 % CI: 1.31-9.42]; p < 0.001). CONCLUSIONS: Iliococcygeus fixation is a safe and effective surgical technique for the treatment of vaginal vault prolapse with long-lasting effectiveness.

Is there a learning curve for the TVT-O procedure? A prospective single-surgeon study of 372 consecutive cases.

OBJECTIVES: To evaluate for the first time in the literature the learning curve of Inside-out transobturator tape (TVT-O™). STUDY DESIGN: A prospective observational study was conducted in a tertiary reference center. Consecutive women treated by TVT-O™ performed by one surgeon were included. Data regarding subjective, objective cure rates, and adverse events were collected. Trends, over the number of procedures, were estimated using assay analyses. Number of procedures and variables were interpolating in standard curves using linear lines. RESULTS: Three hundred and seventy two procedures were included. Postoperative pain levels decreased with the increase in the level of expertise (pain levels: 1-day: from 6.6 (±3.3) to 4.3 (±3.1); 95%CI: -0.01603 to 0.001235, p=0.04; 2-day: from 5.6 (±4.1) to 3.6 (±3.7); 95%CI: -0.02092 to -0.002497, p=0.01; 12-month: from 0.1 (±0.7) to 0 (±0); 95%CI: -0.001814 to 0.05019, p=0.07). Overall, objective cure rate was achieved in 93.5% of patients. Additionally, 88.2% and 88.7% patients reported "much better" feeling at PGI-I scale and 80% reduction in UDI score, respectively. We observed, that delta ICIQ-sf (from 12 (±8.7) to 14 (±6.0); p=0.04) and delta-UDI (from 91% to 97%; p=0.04) improved over the time. CONCLUSIONS: TVT-O procedure offers excellent outcomes with high objective and subjective cure rates and low complications rate, even at the beginning of the surgeon's learning curve. However, a high experience of the surgeon could significantly improve the subjective cure rate and could reduce postoperative the groin pain.

Benefit of pelvic floor muscle therapy in improving sexual function in women with stress urinary incontinence: a pretest-posttest intervention study.

Very few data are available on the effect of pelvic floor muscle training on sexual function in incontinent women. The authors used the Female Sexual Function Index to assess the effect of pelvic floor muscle training on female sexual function. Participants included women with stress urinary incontinence, without overactive bladder symptoms, who completed a 3-month pelvic floor muscle training. All patients completed the Female Sexual Function Index and the International Consultation on Incontinence Questionnaire-Short Form at baseline and at the 3-month follow-up. Thirty-four patients completed all of the questionnaires; 64.7% patients were referred with stress urinary incontinence without sexual disorders, while 35.3% complained of stress urinary incontinence and sexual symptoms. The International Consultation on Incontinence Questionnaire-Short Form score significantly decreased after 3 months of pelvic floor muscle training (p =.01). The Female Sexual Function Index score significantly improved after pelvic floor muscle training even in women with sexual disorders (12.5 ± 9.5 vs. 29.7 ± 3.7; p <.001). This study showed that pelvic floor muscle training may improve female sexual function in women with pure stress urinary incontinence.

Medication adherence and persistence in the treatment of rheumatoid arthritis with adalimumab and etanercept. Six years of analysis.

OBJECTIVE: The aim of this study was to evaluate medication adherence and persistence of patients treated with Etanercept and Adalimumab for Rheumatoid Arthritis, also giving economic evaluations on therapy costs for Received Daily Dose (RDD). MATERIALS AND METHODS: This retrospective study took into account 6 years from January 1, 2007 to December 31, 2012. Medication adherence was quantified utilizing the ratio between RDD and Prescribed Daily Dose (PDD). Persistence has been reckoned taking into account the actual days of therapy comparing posology with supplied dose. The persistence has been graphed according to Kaplan-Meier method. The cost per RDD was reckoned starting from the expense incurred by Pescara General Hospital. RESULTS: Medication adherence gave results in values between 0.88-0.97 for Etanercept and 0.83-0.90 for Adalimumab. The value of persistence was 100% for Etanercept and 90% for Adalimumab for the first year, and 70% for Etanercept and 80% for Adalimumab for the second year. In the 3rd year the persistence for Etanercept was 50% while for Adalimumab it was 60%. In the fourth year the persistence for Etanercept was 21% while for Adalimumab it was 27%. The statistical analysis was conducted using the Log rank test. The average cost per RDD was €32.97 for Etanercept and for Adalimumab it was €32.00 as an average of 6 years. CONCLUSION: The medication adherence was good for both Etanercept and Adalimumab. The rate of persistence decreased strictly in the fourth year of treatment. This data suggests the need for continuous monitoring of patients in treatment with TNF blockers.

Robot-assisted sacrocolpopexy for pelvic organ prolapse: a systematic review and meta-analysis of comparative studies.

CONTEXT: Surgery represents the mainstay of treatment for pelvic organ prolapse (POP). Among different surgical procedures, abdominal sacrocolpopexy (SC) is the gold standard for apical or multicompartmental POP. Research has recently focused on the role of robot-assisted sacrocolpopexy (RASC). OBJECTIVE: To conduct a systematic review on the outcomes of RASC. EVIDENCE ACQUISITION: PubMed, Scopus, and Web of Science databases as well as ClinicalTrials.gov were searched for English-language literature on RASC. A total of 509 articles were screened; 50 (10%) were selected, and 27 (5%) were included. Studies were evaluated per the Grading of Recommendations, Assessment, Development, and Evaluation system and the European Association of Urology guidelines. EVIDENCE SYNTHESIS: Overall, data on 1488 RASCs were collected from 27 studies, published from 2006 to 2013. Objective and subjective cures ranged from 84% to 100% and from 92% to 95%, respectively. Conversion rate to open surgery was <1% (range: 0-5%). Intraoperative, severe postoperative complications, and mesh erosion rates were 3% (range: 0-19%), 2% (range: 0-8%), and 2% (range: 0-8%), respectively. Surgical-related outcomes have improved with increased experience, with an estimated learning curve of about 10-20 procedures. Laparoscopic SC is less costly than RASC, although the latter has lower costs than abdominal SC. CONCLUSIONS: RASC is a safe and feasible procedure for POP; it allows the execution of complex surgical steps via minimally invasive surgery without medium- and long-term anatomic detriments. Further prospective studies are needed to confirm these findings. PATIENT SUMMARY: We looked at the outcomes of robotic sacrocolpopexy for prolapse. We found that the use of robotic technology is safe and effective for the treatment of prolapse in women.

Solifenacin in women with de novo overactive bladder after tension-free obturator vaginal tape--is it effective?

PURPOSE: To our knowledge no group has evaluated antimuscarinic efficacy in patients with de novo overactive bladder after mid urethral sling placement. We assessed solifenacin efficacy in women with de novo overactive bladder after obturator tension-free vaginal tape placement compared to a control group. MATERIALS AND METHODS: We prospectively considered all women with de novo overactive bladder symptoms at a 3-month followup visit after placement of obturator tension-free vaginal tape. Patients with overactive bladder preoperatively and those with obstructive symptoms or signs were excluded from analysis. Women who satisfied inclusion and exclusion criteria (group 1) were compared with a series of consecutive naïve patients with overactive bladder symptoms without a previous surgical procedure for stress urinary incontinence (group 2). We prescribed 12-week antimuscarinic therapy with oral solifenacin 5 mg once daily. Objective outcomes included changes from baseline in 3-day voiding diary data. Subjective efficacy was evaluated using the Overactive Bladder Questionnaire Short Form, Urgency Severity Scale and Patient Global Impression of Improvement questionnaires. RESULTS: A total of 110 patients with de novo overactive bladder after obturator tension-free vaginal tape placement completed solifenacin treatment and were included in group 1. They were compared with 120 consecutive naïve women with overactive bladder (group 2). Group 1 presented at the 3-month followup visit with significantly less benefit in the mean decrease in urgency and urgency urinary incontinence episodes daily (-1.1 vs -2.3 and -0.2 vs -1.1, respectively, each p <0.0001). In group 1 we also found a lower subjective solifenacin effect. Previous obturator tension-free vaginal tape placement was an independent predictor of failed solifenacin treatment. CONCLUSIONS: Antimuscarinic treatment with solifenacin had significantly lower efficacy in women with de novo overactive bladder after mid urethral sling placement than in controls.

Risk factors for the failure of antimuscarinic treatment with solifenacin in women with overactive bladder.

OBJECTIVE: To evaluate the outcomes of women treated with Solifenacin 5 mg once a day for overactive bladder (OAB) to identify the factors associated with the risk of treatment failure. METHODS: Women with OAB symptoms for at least 3 months were considered for this study. At visit 0, patients received a 3-day voiding diary. Eligibility was determined at visit 1, 2 weeks later, on the basis of the results recorded in the 3-day voiding diary. To be included, patients had to have experienced at least 3 episodes of urgency during the 3-day voiding diary period. Eligible women received a 12-week antimuscarinic therapy with oral Solifenacin 5 mg once a day. At the follow-up examination, objective outcomes included changes from baseline in the 3-day voiding diary data. Subjective efficacy was evaluated using the Overactive Bladder Questionnaire Short Form (OABq-SF), the Indevus urgency severity scale (USS) questionnaire, and the Patient Global Impression of Improvement. RESULTS: A total of 675 (69.3%) women met the inclusion criteria and were directed to Solifenacin therapy. After a 12-week treatment, 632 (93.6%) women were assessed for office evaluation, and 101 (16%) patients were considered as nonresponders. The antimuscarinics were effective both in terms of improvement of questionnaires scores and in terms of reduction of episodes of urgency/24 hour (P <.0001). In multivariable analysis, the number of episodes of urgency/24 hour, baseline OABq-SF symptom severity score, and baseline USS were independent predictors of Solifenacin failure. CONCLUSION: Some markers of OAB severity, such as the higher number of episodes of urgency/24 hour and the higher OABq-SF symptom severity score and USS at baseline, were associated with a lower therapeutic efficacy of Solifenacin.