Urinary and sexual function after treatment with temporary implantable nitinol device (iTind) in men with LUTS: 6-month interim results of the MT-06-study.

PURPOSE: To evaluate the functional outcomes as they relate to the preservation of urinary continence and sexual function after treatment with the temporarily implanted nitinol device (iTind; Medi-Tate Ltd, Israel); a novel minimally invasive treatment for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). METHODS: Men with symptomatic BPH (IPSS ≥ 10, Qmax < 12 ml/s, and prostate volume (PV) < 120 ml) were invited to participate in this single-arm, prospective multicenter study (MT06). Patients were not washed out of BPH medications before the procedure. The iTind was implanted through a 22F rigid cystoscope under intravenous sedation and was removed 5-7 days later through a 22F Foley catheter under local anesthesia. Post-operative VAS and complications (Clavien Dindo-Grading System) were recorded. Preservation of urinary continence and erectile and ejaculatory function were assessed according to ISI, MSHQ-EjD and SHIM questionnaires. Post-operative IPSS, QoL, Qmax and PVR were also assessed at 1, 3, and 6 months post-operatively. RESULTS: This interim report includes data out to 6 months on the first 70 patients enrolled in the study. The median age was 62.31 years, and the mean prostate volume was 37.68 ml (15-80 ml). Baseline and follow-up data are reported in Table 1. No intraoperative complications were observed, the average post-operative VAS score was 3.24 ± 2.56. On average patients returned to daily life after 4.3 days following the retrieval procedure. Sexual function and urinary continence were preserved in all subjects according to the ISI, SHIM and MSHQ-EjD questionnaires and significant improvements (p < 0.0001) from baseline levels were recorded in IPSS, QoL and peak flow. CONCLUSION: iTind is a well-tolerated, minimally invasive treatment for BPH-related LUTS which preserves sexual function and urinary continence, offers a rapid recovery and return to daily life, and a significant improvement of symptoms and urinary flow at 6-month follow-up.

The efficacy and safety of Vibegron in treating overactive bladder: A systematic review and pooled analysis of randomized controlled trials.

OBJECTIVE: Vibegron is a new kind of ß3-adrenergic receptor agonist. We performed a systematic review and pooled analysis to assess the efficacy, safety, and tolerability of Vibegron for treating overactive bladder (OAB). METHODS: MEDLINE, the Cochrane Controlled Trial Register and EMBASE were used to pick out randomized controlled trials (RCTs) of Vibegron in treating OAB. The reference lists of the retrieved articles were also studied. We used RevMan version 5.3.0. to analyze the data. RESULTS: Three high-quality RCTs involving a total of 2120 OAB patients were adopted in the systematic review and pooled analysis. The mean number of micturitions episodes/d (mean difference [MD] = -0.77; 95% confidence interval [CI] = -1.0 to -0.55; P < .00001); the mean number of urgency episodes/d (MD = -0.77; 95% CI = -1.03 to -0.52; P < .00001); mean number of urgency incontinence episodes/d (MD = -0.50; 95% CI = -0.64 to -0.35; P < .00001); mean number of incontinence episodes/d (MD = -0.45; 95% CI = -0.66 to -0.25; P < .0001); and mean volume voided/micturition (MD = 22.22; 95% CI = 17.36 to 27.07, P < .00001) showed that Vibegron was more efficacy in treating OAB than placebo. Dry mouth, drug-related treatment-emergent adverse event (TEAE), serious adverse event (SAE), and discontinuations due to adverse event (AE) suggested that Vibegron was well tolerated. CONCLUSIONS: Our systematic review and pooled analysis demonstrate that Vibegron 75 mg or 100 mg/d statistically significant improved OAB symptoms. The treatment was well-tolerated, with a favorable safety profile.

The clinical characteristics of situational syncope in children and adults undergoing head-up tilt testing.

OBJECTIVE: Situational syncope is a subtype of neurally mediated syncope and associated with specific circumstances. This paper is to assess the clinical characteristics and underlying causes of situational syncope. METHODS: This is a retrospective study of patients who underwent head-up tilt testing (HUTT). Medical records including age at HUTT, gender, number of syncopal episodes, family history of syncope, triggers before the syncopal episode, position during the syncopal episode and the responses to HUTT were reviewed. RESULTS: Among 3140 patients, 354 patients (mean age 28.3 ± 16.6 years old, with 184 males and 170 females) were diagnosed with situational syncope. The causes of situational syncope included micturition (50.85%), defecation (15.82%), bathing (10.45%), swallowing (6.50%), cough (4.80%), post-dinner (3.95%), singing (3.11%), teeth brushing (2.26%), and hair grooming (2.26%). Patients with syncope triggered by micturition, cough, post-dinner were more likely to be men, while those caused by bathing, swallowing, singing, teeth brushing and hair grooming were more likely to be women. 34.75% of patients with situational syncope were between the ages of 10-19 years old, and 20.34% were between the ages of 40-49 years old. 74.01% of situational syncopal events occurred in an upright position. 47.74% of patients had positive responses to HUTT. CONCLUSIONS: These findings show that micturition was the most common cause of situational syncope in both children and adults. There were significant gender and age differences among situational syncope triggered by different causes. Most of situational syncope occurred in the upright position and nearly half of the patients had positive responses to HUTT.

Efficacy and Safety of Tolterodine and Pilocarpine in Patients with Overactive Bladder.

PURPOSE: We evaluated the efficacy and safety of a combination of 2 mg tolterodine and 9 mg pilocarpine, vs tolterodine monotherapy in patients with overactive bladder. MATERIALS AND METHODS: We enrolled patients with overactive bladder symptoms in a multicenter, randomized, double-blind, parallel, active control study. Patients were randomized to the combination or 2 mg tolterodine twice daily for 12 weeks. After the double-blind period finished all patients were started on the combination for 12 weeks. Study co-primary end points were the change from baseline in the mean number of daily micturitions and cumulative incidence of dry mouth at the end of 12 weeks. Secondary end points were other overactive bladder symptoms, the total xerostomia inventory score and results of a visual analogue scale for dry mouth at the end of 12 and 24 weeks. RESULTS: The mean change in the number of daily micturitions from baseline to 12 weeks was -1.49 and -1.74 in the combination and tolterodine monotherapy groups, respectively. The mean difference was -0.26 (95% CI -0.79-0.27), confirming noninferiority. At 12 weeks the incidence of dry mouth was lower in the combination group than in the tolterodine monotherapy group (30.0% vs 42.9%, p = 0.009). All secondary and other efficacy outcomes related to overactive bladder symptoms improved in each group with no significant differences between the groups at 12 weeks. Changes from baseline in the total xerostomia inventory score and the visual analogue scale for dry mouth were significantly lower in the combination group than in the tolterodine monotherapy group. CONCLUSIONS: Tolterodine and pilocarpine alleviated dry mouth in patients with overactive bladder while maintaining anticholinergic efficacy similar to that of tolterodine.

Impact of Dry Mouth on Fluid Intake and Overactive Bladder Symptoms in Women taking Fesoterodine.

PURPOSE: We investigated the long-term relationships between dry mouth, fluid intake and overactive bladder symptoms in women undergoing treatment with fesoterodine. We hypothesized that women who experienced dry mouth would increase their fluid intake and worsen their urinary symptoms. MATERIALS AND METHODS: We conducted a prospective ancillary study to a 9-month open-label trial of fesoterodine for women with urgency urinary incontinence. Fluid intake was measured and compared according to reported dry mouth. Multivariable analysis was used to study the interaction between dry mouth, fluid intake and urinary symptoms. RESULTS: During the study 407 women without dry mouth significantly reduced their fluid intake (mean decrease 172.1 ml, median 118.3 ml, p = 0.02), while 91 women with dry mouth did not (mean decrease 95.8 ml, median 118.3 ml, p = 0.54). On univariable analysis a greater proportion of women who experienced dry mouth reported improvement in their urinary symptoms compared to women without dry mouth (60.5% vs 47.2%, p = 0.03). On multivariable analysis black women were less likely to report dry mouth (OR 0.4, 95% CI 0.2-0.9, p = 0.03) and older women were less likely to report improvement in urinary symptoms (OR 0.98, 95% CI 0.96-0.99, p = 0.003). Factors not associated with improvement in urinary symptoms on multiple regression were dry mouth, baseline fluid intake volume, change in fluid intake volume and caffeine intake volume. CONCLUSIONS: In women with overactive bladder receiving fesoterodine dry mouth may prevent restriction of fluid intake but does not diminish treatment efficacy.

Clinical Efficacy and Tolerability of the Nicotinic Channel Modulator Dexmecamylamine in Subjects with Overactive Bladder.

PURPOSE: We evaluated the efficacy and tolerability of the nicotinic channel modulator dexmecamylamine for overactive bladder. MATERIALS AND METHODS: This was a randomized, double-blind, placebo controlled trial in 768 randomized subjects. Those with at least a 6-month history of overactive bladder were randomized to 0.5, 1 or 2 mg dexmecamylamine or placebo in a ratio of 1:1:1:2, respectively. Subjects completed a 3-day diary before each visit associated with the 12-week treatment period. They were required to have 8 or more micturitions per day and 3 or more urinary urge incontinent episodes per day if overactive bladder wet at the end of a placebo run-in period. Co-primary end points for the study included a change from baseline 1) in micturition frequency per 24 hours at week 12 and 2) in urge urinary incontinence episodes per 24 hours at week 12. Secondary end points were voided volume, nocturia episodes, OABq (Overactive Bladder Questionnaire) and urgency questionnaire. RESULTS: Dexmecamylamine (2 mg) produced a statistically significant decrease in micturition frequency (p = 0.03) but did not produce a statistically significant decrease in urge incontinence (wet) episodes (p = 0.38). Secondary end points, including volume voided in the 1 mg group only, CGI-I (Clinical Global Impression of Improvement), visual analog scale urgency impact, intensity and severity, were statistically significant at week 12 for the 2 mg dose. Dexmecamylamine was well tolerated in this subject population with a low incidence of discontinuations due to adverse effects. Constipation, dry mouth and urinary tract infection showed a dose dependent increase in frequency. CONCLUSIONS: Dexmecamylamine does not appear to offer an enhanced therapeutic profile for the treatment of overactive bladder relative to current therapies.

Rat animal model for preclinical testing of microparticle urethral bulking agents.

OBJECTIVES: To develop an economic, practical and readily available animal model for preclinical testing of urethral bulking therapies, as well as to establish feasible experimental methods that allow for complete analysis of hard microparticle bulking agents. METHODS: Alumina ceramic beads suspended in hyaluronic acid were injected into the proximal urethra of 15 female rats under an operating microscope. We assessed overall lower urinary tract function, bulking material intraurethral integrity and local host tissue response over time. Microphotographs were taken during injection and again 6 months postoperatively, before urethral harvest. Urinary flow rate and voiding frequency were assessed before and after injection. At 6 months, the urethra was removed and embedded in resin. Hard tissue sections were cut using a sawing microtome, and processed for histological analysis using scanning electron microscopy, light microscopy and immunohistochemistry. RESULTS: Microphotographs of the urethra showed complete volume retention of the bulking agent at 6 months. There was no significant difference between average urinary frequency and mean urinary flow rate at 1 and 3 months postinjection as compared with baseline. Scanning electron microscopy proved suitable for evaluation of microparticle size and integrity, as well as local tissue remodeling. Light microscopy and immunohistochemistry allowed for evaluation of an inflammatory host tissue reaction to the bulking agent. CONCLUSIONS: The microsurgical injection technique, in vivo physiology and novel hard tissue processing for histology, described in the present study, will allow for future comprehensive preclinical testing of urethral bulking therapy agents containing microparticles made of a hard material.

Reporting combined outcomes with Trifecta and survival, continence, and potency (SCP) classification in 337 patients with prostate cancer treated with image-guided hypofractionated radiotherapy.

OBJECTIVE: To report the image-guided hypofractionated radiotherapy (hypo-IGRT) outcome for patients with localised prostate cancer according to the new outcome models Trifecta (cancer control, urinary continence, and sexual potency) and SCP (failure-free survival, continence and potency). PATIENTS AND METHODS: Between August 2006 and January 2011, 337 patients with cT1-T2N0M0 prostate cancer (median age 73 years) were eligible for a prospective longitudinal study on hypo-IGRT (70.2 Gy/26 fractions) in our Department. Patients completed four questionnaires before treatment, and during follow-up: the International Index of Erectile Function-5 (IIEF-5), the International Prostate Symptom Score (IPSS), and the European Organization for Research and Treatment of Cancer prostate-cancer-specific Quality of Life Questionnaires (QLQ) QLQ-PR25 and QLQ-C30. Baseline and follow-up patient data were analysed according to the Trifecta and SCP outcome models. Cancer control, continence and potency were defined respectively as no evidence of disease, score 1 or 2 for item 36 of the QLQ-PR25 questionnaire, and total score of >16 on the IIEF-5 questionnaire. Patients receiving androgen-deprivation therapy (ADT) at any time were excluded. RESULTS: Trifecta criteria at baseline were met in 72 patients (42% of all ADT-free patients with completed questionnaires). Both at 12 and 24 months after hypo-IGRT, 57% of the Trifecta patients at baseline were still meeting the Trifecta criteria (both oncological and functional success according to the SCP model). The main reason for failing the Trifecta criteria during follow-up was erectile dysfunction: in 18 patients after 6 months follow-up, in 12 patients after 12 months follow-up, and in eight patients after 24 months. Actuarial 2-year Trifecta failure-free survival rate was 44% (95% confidence interval 27-60%). In multivariate analysis no predictors of Trifecta failure were identified. Missing questionnaires was the main limitation of the study. CONCLUSION: The Trifecta and SCP classifications can be used as tools to report RT outcome.

Painful micturition in a small child: an unusual clinical picture of paroxysmal extreme pain disorder.

BACKGROUND: Paroxysmal extreme pain disorder (PEPD) is a rare autosomal dominant pain disorder linked to a mutation in the SCN9A gene, which encodes voltage-gated sodium channel Nav1.7. Abnormal pain sensitivity occurs because of changes in the properties of voltage-gated sodium channels. Different mutations in SCN9A and a spectrum of clinical expressions have been described. CASE-DIAGNOSIS/TREATMENT: Here we describe a 3-year-old child with a rare clinical picture of PEPD. Extremely painful voiding had been present since the child's birth. The diagnosis was confirmed by the detection of a heterozygous pathogenic mutation in the SCN9A gene, c.554G>A (p.Arg185His) inherited paternally. The same mutation was also found in the girl's father, who has occasionally had some pain in his jaw while yawning since childhood. Significant reduction of the pain was achieved with carbamazepine. CONCLUSIONS: The case is interesting because the same mutation as that found in the girl and her father has been found in patients with small fiber sensory neuropathy. These data do not correlate with the clinical picture of our case and her father, but intra- and interfamily phenotypic diversity in symptoms associated with a gain-of-function variant of Na(V)1.7 are also described and may explain our case.

The efficacy and tolerability of the ß3-adrenoceptor agonist mirabegron for the treatment of symptoms of overactive bladder in older patients.

INTRODUCTION: mirabegron is a ß3-adrenoceptor agonist developed for the treatment of symptoms of overactive bladder (OAB). As the prevalence of OAB increases with age, a prospective subanalysis of individual and pooled efficacy and tolerability data from three 12-week, randomised, Phase III trials, and of tolerability data from a 1-year safety trial were conducted in order to evaluate the efficacy and tolerability of mirabegron in subgroups of patients aged ≥65 and ≥75 years. METHODS: primary efficacy outcomes were change from baseline to final visit in the mean number of incontinence episodes/24 h and the mean number of micturitions/24 h. Tolerability was assessed by the incidence of treatment-emergent adverse events (TEAEs). RESULTS: over 12 weeks mirabegron 25 mg and 50 mg once-daily reduced the mean numbers of incontinence episodes and micturitions/24 h from baseline to final visit in patients aged ≥65 and ≥75 years. Mirabegron was well tolerated: in both age groups, hypertension and urinary tract infection were among the most common TEAEs over 12 weeks and 1 year. The incidence of dry mouth, a typical anticholinergic TEAE, was up to sixfold higher among the older patients randomised to tolterodine than any dose of mirabegron. CONCLUSIONS: these analyses have demonstrated the efficacy of mirabegron over 12 weeks and the tolerability of mirabegron over 12 weeks and 1 year in OAB patients aged ≥65 and ≥75 years, supporting mirabegron as a therapeutic option in older patients with OAB.

A randomised, prospective double-blind, propiverine-controlled trial of imidafenacin in patients with overactive bladder.

AIM: To assess the efficacy and safety of imidafenacin compared with propiverine for treatment of overactive bladder (OAB) in Korean patients. MATERIALS AND METHODS: Patients with OAB symptoms were randomised to double-blind treatment with 0.1 mg of imidafenacin twice daily (group A) or propiverine 20 mg once daily (group B) for 12-week regimen, and assessed for efficacy and safety. The primary efficacy outcome was per cent change of weekly urgency urinary incontinence (UUI) episodes at week 12. The secondary efficacy outcomes were changes in the micturitions per day, urine volume voided per micturition, urgency episodes per day, complete disappearance of incontinence episodes and severity of urgency from baseline to week 12. Quality of life and safety profiles were also compared. RESULTS: Of 162 patients randomised, 140 completed the study protocol. The per cent change of weekly UUI episodes at week 12 was -69.1% in group A and -70.4% in group B (both p < 0.0001). The lower limit of 95% one-sided confidence interval of the difference between the groups was above the non-inferiority margin (-19.42%). Other voiding parameters and quality of life significantly improved at week 12 in both the groups. The discontinuation rates caused by adverse events were low in both the groups. While dry mouth was the most common adverse event (group A: 28.4% vs. B: 30.4%, p = 0.783), the severity of dry mouth was significantly less in the group A than B (p = 0.042) There were no significant differences in other safety profiles. CONCLUSIONS: After the 12-week treatment of imidafenacin 0.1 mg twice daily, all OAB symptoms and quality of life improved. Imidafenacin was not inferior to propiverine for the reduction of UUI episodes, and was better tolerated than propiverine in the safety profile. Our results indicate that imidafenacin is a safe and effective drug in Korean patients with OAB.

Orthodontic widening of the palate may provide a cure for selected children with therapy-resistant enuresis.

AIM: According to a number of small case series, orthodontic treatment may have anti-enuretic effects. Thus, we evaluated whether widening of the palate can alleviate enuresis and whether prognostic information can be gained from examining children's nocturnal respiration and nasal airway dimensions. METHODS: Children with therapy-resistant enuresis underwent polysomnography, focusing on nocturnal respiration, and had their nasal airways examined. Rapid maxillary expansion was performed, widening the maxilla by approximately 0.5 cm. The dental appliance was removed after 6 months. Enuresis frequency was evaluated four times: at baseline, with the orthodontic apparatus in situ, after completed maxillary expansion and 1 year post-treatment. RESULTS: Of the 34 children recruited, one dropped out due to oral discomfort. The numbers of wet nights per week on the four assessment occasions were 5.48 ± 1.48, 5.12 ± 1.73, 3.09 ± 2.49 and 2.63 ± 2.81; p < 0.001. The proportions of responders, intermediate responders and non-responders during treatment were 21.2%, 27.3% and 51.5%, respectively. Responders were found to have a lower enuresis frequency at baseline (p = 0.001) and to have larger nasal airway dimensions (p = 0.01). CONCLUSION: Orthodontic widening of the palate may be curative in a subgroup of children with therapy-resistant enuresis.

Chronic urinary retention could decrease the number of suburothelial myofibroblasts in the rat bladder.

AIMS: To demonstrate changes in the number of suburothelial myofibroblasts in the rat bladder due to chronic urinary retention (CUR). METHODS: Bladder specimens were obtained from 12-week-old Wistar female rats that were divided into two groups: a CUR group and a sham-operated group. In the CUR rats, the urethra was intubated with a polyethylene catheter, and a double 4-0 silk ligature was placed around the proximal urethra, after which the catheter was removed. After 8 weeks, the cystometric findings and immunohistochemical staining of the suburothelial myofibroblasts were compared between the groups. RESULTS: The bladder weight of the control rats was 0.20 ± 0.01 g and that of CUR rats 1.6 ± 0.4 g. The bladder capacity of the control rats was 0.5 ± 0.3 ml and that of the CUR rats 12.9 ± 3.1 ml. The number of suburothelial myofibroblasts of the control rats was 417 ± 123 and that of the CUR rats 44 ± 42. The number of suburothelial myofibroblasts in the CUR rats was significantly less than that observed in the sham-operated rats (p < 0.01). CONCLUSIONS: In this study, we demonstrated that mechanical stress over a long period on the bladder wall can decrease the number of suburothelial myofibroblasts. The reduced expression of suburothelial myofibroblasts may be related to prolongation of the micturition interval by CUR.

Efficacy and safety of once-daily oxybutynin patch versus placebo and propiverine in Japanese patients with overactive bladder: A randomized double-blind trial.

OBJECTIVES: To evaluate the efficacy and safety of once-daily oxybutynin patch therapy for overactive bladder. METHODS: A randomized double-blind trial was carried out in patients with overactive bladder syndrome, who received an oxybutynin patch, propiverine (20 mg) or placebo once daily for 12 weeks. The primary efficacy end-point was the change of the mean daily number of micturitions in week 12. RESULTS: A total of 1530 patients were randomized to receive the oxybutynin patch (573), propiverine (576) or placebo (381). The change of the mean daily frequency of micturition from baseline in the full analysis set was -1.89 ± 2.04 with the oxybutynin patch, which was significantly higher than with placebo (-1.44 ± 2.23) (P = 0.0015). The difference of the mean change in the mean daily number of micturitions between the oxybutynin patch and propiverine groups showed a 95% confidence interval of -0.28 to 0.21, and the upper limit of this interval was below the predefined non-inferiority margin of 0.37, showing non-inferiority of the oxybutynin patch to propiverine. The incidence of dry mouth and constipation was higher with propiverine than with the oxybutynin patch or placebo. Application site dermatitis was more frequent with the oxybutynin patch (31.8%) than with propiverine (5.9%) or placebo (5.2%), but the dermatitis was generally mild. CONCLUSION: This trial shows the efficacy of the new once-daily oxybutynin patch for overactive bladder. Despite a higher rate of dermatitis with the oxybutynin patch, dry mouth and constipation occurs less often than during treatment with propiverine.

Mirabegron 50 mg once-daily for the treatment of symptoms of overactive bladder: an overview of efficacy and tolerability over 12 weeks and 1 year.

The aim of the present review article was to summarize the efficacy and tolerability for mirabegron 50 mg over 12 weeks and 1 year versus placebo (SCORPIO) or tolterodine ER 4 mg (SCORPIO and TAURUS). After a 2-week placebo run-in, adults with overactive bladder symptoms for ≥3 months were randomized if, during a 3-day micturition diary period before baseline, they had an average of ≥8 micturitions/24 h and ≥3 urgency episodes. Efficacy end-points were change from baseline to each study visit and final visit in incontinence, micturitions, volume voided/micturition, urgency incontinence, urgency (grades 3 or 4), level of urgency and nocturia. Additional secondary efficacy variables included patient-reported outcomes. Safety variables included changes in treatment-emergent adverse events and vital signs. For SCORPIO, statistically significant improvements from baseline in efficacy variables and patient-reported outcomes were seen with mirabegron versus placebo from week 4, and were maintained over time. For TAURUS, numerical improvements in efficacy were evident from month 1, and were maintained throughout 12 months. Treatment-emergent adverse events incidence was similar between groups, except for dry mouth, which was reported by fourfold (SCORPIO) and threefold (TAURUS) more patients taking tolterodine than mirabegron. Mirabegron 50 mg for 12 weeks was associated with statistically significant improvements in objective measures of efficacy and patient-reported outcomes. At final visit, improvements with mirabegron 50 mg were statistically greater versus placebo. The efficacy profile of mirabegron 50 mg appears to be maintained over 12 months.

Severity of overactive bladder symptoms and response to dose escalation in a randomized, double-blind trial of solifenacin (SUNRISE).

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Antimuscarinics are effective and well tolerated for treatment of OAB. Studies have found that a flexible dosing strategy can be effective in improving OAB symptoms with minimal impact on tolerability. This study confirms these findings with two doses of solifenacin, and shows that improved outcomes can be achieved by increasing solifenacin dose (from 5 to 10 mg) in patients with more severe symptoms. OBJECTIVE: To determine the relationship between severity of baseline overactive bladder (OAB) symptoms and requests for solifenacin dose increases, and the efficacy of 5 and 10 mg solifenacin doses in relieving OAB symptoms in patients who requested a dose increase. PATIENTS AND METHODS: In a 16-week clinical study, patients with OAB were randomized to double-blind treatment with solifenacin or placebo once daily. At week 8, all patients could request a dose increase; these patients entered a second phase of 8 weeks in which those in the solifenacin group were randomized to either 5 or 10 mg doses. The primary efficacy variable was mean change in the number of urgency episodes with or without incontinence per 24 h, measured using the Patient Perception of Intensity of Urgency Scale (PPIUS; grades 3 and 4). RESULTS: Of 591 patients receiving solifenacin at 8 weeks, 275 (46.5%) requested a dose increase to 10 mg, and were further randomized to receive 10 mg (n = 140) or to remain on 5 mg (n = 135). Patients who requested a dose increase at week 8 generally had more severe OAB symptoms at baseline and a smaller response at week 8 to the initial solifenacin 5 mg dosage than those who did not. Greater reductions in the mean number of severe urgency episodes (PPIUS grades 3 and 4) were observed from week 8 to the end of treatment for patients requesting a dose increase and randomized to 10 mg solifenacin compared with those randomized to remain on 5 mg (mean reductions -0.9 vs -0.4, respectively), although these did not reach statistical significance. Statistically significant reductions were observed in mean total urgency score (TUS; -2.7 vs -0.6; P = 0.010), mean maximum PPIUS urgency rating (-0.3 vs -0.1; P = 0.034) and mean micturition frequency (-0.8 vs -0.1; P = 0.037). For all other OAB variables, greater changes were observed in the solifenacin 10 mg group but these did not reach statistical significance. Of those who requested a dose increase, eight (5.7%) patients randomized to receive 10 mg and one (0.7%) patient randomized to remain on 5 mg reported new or worsening cases of dry mouth. CONCLUSIONS: Increasing the solifenacin dose to 10 mg further improved OAB symptoms in patients who requested a dose increase after 8 weeks' treatment with 5 mg solifenacin. The present study supports the view that patients with severe OAB symptoms benefit from a higher antimuscarinic dose.

[Transurethral injection of polyacrylamide hydrogel (Bulkamid®) for the treatment of female stress urinary incontinence and changes in the cure rate over time]. / Transuretrální aplikace polyacrylamid hydrogelu (Bulkamidu®) pri lécbe zenské stresové inkontinence mocia zmeny lécebného efektu v závislosti na case od operace.

OBJECTIVE: The objective of this study was to evaluate short term and long term efficacy of a transurethral injection (TUI) using bulking agent Bulkamid® for female stress (SUI) and mixed urinary incontinence by women with ISD or where anti-incontinence surgery has failed. DESIGN: Retrospective clinical study. SETTINGS: Gynecological and Obstetric Dpt. 1st Medical Faculty UK and VFN, Prague. MATERIALS AND METHODS: A retrospective study was performed on 52 women with urinary incontinence (stress, 43; mixed 9). One patient died during study. Forty patients had previously undergone anti-incontinence surgery. The efficacy of TUI was evaluated 3 months (± 1 week) and an average of 22 months after surgery. Subjective assessment of the leakage of urine was based on the International Consultation on Incontinence Questionnaire - Short form (ICIQ-UI SF) filled in before, three and - on average - 22 months after the surgery (minimum time after surgery was 6 months). Improvement in urinary incontinence was defined as a drop in the score of more than 50%. Objective assessment of leakage of urine was assessed by cough test. The cure effect was evaluated by VAS (Visual Analogue Scale) score and by using the five-point Likert score. Ethical committee approval was obtained, and all subjects gave written informed consent to participate in the study. RESULTS: Mean age of patients was 70 years, mean body mass index (BMI) 28.65, and mean parity was 1.76. The cough test showed that 19/51 (37.3%) of patients had negative results for this test 3 months and 10/51 (19.6%) 22 months after the operation. The ICIQ-UI SF questionnaire showed that 16/51 (31.4%) of our patients were completely dry 3 months after the operation and 8/51 (15.7 %) 22 months after the operation. 41/51 (80.4%) of patients were dry or improved 3 months after the operation and 23/51 (45.13%) 22 months after the operation. The mean cure effect evaluated by VAS score 3 months after the operation was 72 and 22 months after the operation it was 51.3. The Likert score was 4 or 5 (cured or improved) three and 22 months after operation by 78.4% / 54.9% patients. CONCLUSIONS: The cure effect of Bulkamid® operation decreases in correlation with the time that elapses after the operation, although this procedure is minimally invasive and is an option in cases where anti-incontinence surgery has failed.

A novel animal model of underactive bladder: analysis of lower urinary tract function in a rat lumbar canal stenosis model.

AIMS: An animal model of neurogenic underactive bladder (UAB) has not been established. It was reported that a rat lumbar spinal canal stenosis (LCS) model created by cauda equina compression manifested intermittent claudication and allodynia. In this study, we examined the lower urinary tract function of the rat LCS model. METHODS: One small hole was drilled at the fifth lumbar vertebral arch (sham), and a rectangular piece of silicone rubber was inserted into the L5-L6 epidural space (LCS). Before and after surgery, a metabolic cage study was performed. After surgery, awake cystometry (CMG) and an in vitro muscle strip study were performed. Bladder morphology was evaluated by hematoxylin and eosin staining. RESULTS: The LCS rats showed a significant decrease in voided volume and a significant increase in postvoid residual volume and residual urine rate compared with Sham rats. CMG showed that the postvoid residual urine volume and numbers of non-voiding contractions significantly increased, while the voided volume, threshold pressure, and maximum intravesical pressure during voiding significantly decreased. There were no significant differences between sham and LCS rats in response to carbachol. In contrast, there was a significant increase in response to field stimulation, especially at lower frequencies, in LCS rats. LCS rats showed no obvious difference in detrusor morphology. CONCLUSIONS: This rat model requires a relatively simple surgical procedure and has characteristics of neurogenic UAB. It seems to be useful in the pathophysiological elucidation of UAB and might have potential for assessment of pharmacotherapy of UAB.

Intravesical immune suppression by liposomal tacrolimus in cyclophosphamide-induced inflammatory cystitis.

AIMS: Potent immunosuppressive effect of tacrolimus has encouraged its topical application for achieving local anti-inflammatory effect. However, its poor aqueous solubility presents challenges in formulating biocompatible instillations to justify the investigation of liposomes as vehicle for tacrolimus. METHODS: Adult female Sprague-Dawley rats (N=52) divided into 4 groups were injected with cyclophosphamide (CYP) (200 mg/kg, ip) except for sham (saline injection, ip). Other three groups were instilled with either saline (1 cc, retained for 1 hr), liposome (LP- 1 cc) or liposomal encapsulated tacrolimus (LFK- 0.2 mg tacrolimus/1 ml LP). Baseline cystometrogram was performed on day 1 and day 3 prior to bladder harvest for histological staining (N=24) in all groups except sham. In addition, 4-hr baseline urine on day 1 and day 3 was collected from all groups for urine PGE2 assay and bladder harvested for PGE2 and IL2 assay on day 3 (N=28). RESULTS: Rats treated with LFK demonstrated suppression of CYP induced inflammatory reaction with reduced EP4 staining and bladder overactivity (intercontraction interval 61.0% decrease in untreated animals) as well as normalized the several fold elevation of IL 2 and PGE2 levels in tissue and urine. CYP induced effects were not suppressed in rats left untreated with tacrolimus. CONCLUSIONS: This is the first report of immunosuppression in bladder by intravesical delivery of tacrolimus using liposomes. LFK significantly inhibited CYP induced inflammatory cystitis through the modulation of IL2, PGE2, and EP4 function. These findings support investigation of local tacrolimus in cases of inflammatory cystitis refractory to conventional therapy.

A short biodegradable helical spiral ureteric stent provides better antireflux and drainage properties than a double-J stent.

OBJECTIVE: The use of ureteric stents is a standard treatment for the relief of ureter blockages for benign or malignant reasons. The most common stent design in clinical use is a double-J stent with coiled ends to avoid stent displacement. However, there are a number of complications associated with stent use. A double-J stent design bypasses the ureterovesical junction, enables bladder pressure reflection to the renal pelvis and causes vesicoureteral reflux (VUR). This may result in scarring and renal failure. MATERIAL AND METHODS: An animal model was used to investigate whether VUR can be avoided in stented ureters using a short biodegradable partial helical spiral stent design that leaves the ureterovesical junction intact. MATERIALS AND METHODS: Eight female pigs were used. Ureters on the left side were stented using a short helical spiral SR-PLGA stent (group A) and ureters on the right side using double-J stents (group B). Simulated voiding cystoureterography and standard intravenous urography examinations were performed on all eight animals at 4 weeks and on the remaining four animals at 8 weeks. RESULTS: An SR-PLGA single coiled partial stent demonstrated superior drainage properties to a double-J stent at 4 weeks (p = 0.020). A marked but not statistically significant difference in favour of a SR-PLGA stent was also observed at 8 weeks (p = 0.102). A statistically significant difference was observed in VCUG findings in favour of group A at immediate postoperative control as well as in the 4 and 8 week follow-up studies (p = 0.011, p = 0.010, p = 0.046, respectively). CONCLUSION: A self-expandable, SR-PLGA partial ureteric stent presented with superior drainage and antireflux properties compared to a double-J stent. The reflux commonly related to double-J stent use can be minimized by using a partial ureteric stent design.