Uninhibited Detrusor Contractions Research Articles

Nabiximols oromucosal spray in patients with multiple sclerosis-related bladder dysfunction: A prospective study.

Spasticity and urinary disturbances can profoundly impact the daily lives of persons with multiple sclerosis (pwMS). Cannabis has been associated with improvement in sphincteric disturbances. To our knowledge, few studies have evaluated the effect of nabiximols oromucosal spray (Sativex®) on urinary disturbances by instrumental methods. This longitudinal study was conducted to assess the effect of nabiximols oromucosal spray on urinary disturbances by clinical and urodynamic evaluation in pwMS. Neurological, spasticity, and quality of life (QoL) assessments were performed before (T0), and at one (T1) and six (T6) months after the start of nabiximols treatment. At these same time points, patients were assessed for urinary disturbances by the International Prostatic Symptoms Score (IPSS) and a urodynamic test evaluating maximum detrusor pressure (Pdet), bladder filling capacity (CCmax), uninhibited detrusor contractions (UDC), bladder volume at first desire (BVFD), post-void residual volume (PVR) and voluntary abdominal pressure (PA). Of 31 pwMS enrolled in the study, 25 reached T1 and 18 reached T6. Mean IPSS total score, its subscores, and IPSS QoL decreased significantly from T0 to T6 (p=0.000), with no differences according to sex, age, MS type, disease duration and disability at baseline. Pdet improved significantly from T0 to T6 (p=0.0171), and CCmax changed only marginally (p=0.0494); results were similar in patient subgroups naïve to or previously exposed to urological treatment. All patients with overactive bladder showed improvement in their urodynamic assessment based on significant reduction of Pdet (p=0.0138). In patients with mainly hypotonic bladder, mean Pdet decreased from T0 to T6 without reaching statistical significance; most urodynamic parameters showed a trend to improve. Mean numerical scale scores for MS spasticity, and for spasms, pain and tremors, decreased significantly from T0 to T6. The mean 'physical health composite' score of the MS Quality of Life-54 questionnaire increased significantly from T0 to T6 (p=0.0126). Our data suggest that nabiximols has an appreciable effect on ameliorating subjective perception of urinary disturbances and appears to have a positive effect on objective urodynamic parameters, particularly in patients with hyperactive bladder.

Treating Lower Urinary Tract Symptoms in Older Adults: Intravesical Options.

This article provides an overview of the diagnosis and the treatment of lower urinary tract symptoms in older adults complicated by the neurodegenerative changes in the micturition reflex and further confounded by age-related decline in hepatic and renal clearance raising the propensity of adverse drug reactions. The first-line drug treatment for lower urinary tract symptoms, orally administered antimuscarinics, fails to reach the equilibrium dissociation constant of muscarinic receptors even at their maximum plasma concentration and tends to evoke a half-maximal response at a muscarinic receptor occupancy of just 0.206% in the bladder with a minimal difference from exocrine glands, which raises the adverse drug reaction risk. On the contrary, intravesical antimuscarinics are instilled at concentrations 1000-fold higher than the oral maximum plasma concentration and the equilibrium dissociation constant erects a downhill concentration gradient that drives passive diffusion and achieves a mucosal concentration around ten-fold lower than the instilled concentration for a long-lasting occupation of muscarinic receptors in mucosa and sensory nerves. A high local concentration of antimuscarinics in the bladder triggers alternative mechanisms of action and is supposed to engage retrograde transport to nerve cell bodies for neuroplastic changes that underlie a long-lasting therapeutic effect, while an intrinsically lower systemic uptake of the intravesical route lowers the muscarinic receptor occupancy of exocrine glands to lower the adverse drug reaction relative to the oral route. Thus, the traditional pharmacokinetics and pharmacodynamics of oral treatment are upended by intravesical antimuscarinics to generate a dramatic improvement (~ 76%) noted in a meta-analysis of studies enrolling children with neurogenic lower urinary tract symptoms on the primary endpoint of maximum cystometric bladder capacity as well as the secondary endpoints of filling compliance and uninhibited detrusor contractions. The therapeutic success of intravesical multidose oxybutynin solution or oxybutynin entrapped in the polymer for sustained release in the pediatric populationbodes well for patients with lower urinary tract symptoms at the other extreme of the age spectrum. Though generally used to predict oral drug absorption, Lipinski's rule of five can also explain the ten-fold lower systemic uptake from the bladder of positively charged trospium over oxybutynin, a tertiary amine. Chemodenervation by an intradetrusor injection of onabotulinumtoxinA is merited for patients with idiopathic overactive bladder discontinuing oral treatment because of a lack of efficacy. However, age-related peripheral neurodegeneration potentiates the adverse drug reaction risk of urinary retention that motivates the quest of liquid instillation, delivering larger fraction of onabotulinumtoxinA to the mucosa as opposed to muscle by an intradetrusor injection can also probe the neurogenic and myogenic predominance of idiopathic overactive bladder. Overall, the treatment paradigm of lower urinary tract symptoms in older adults should be tailored to individual's overall health status and the risk tolerance for adverse drug reactions.

Influence of urodynamic conditions on bladder sensations and detrusor activity in patients with multiple sclerosis.

The study aimed to assess the impact of bladder filling rate and fluid temperature during urodynamics on bladder sensations and volume of apparition of detrusor overactivity in patients with multiple sclerosis (PwMS). Consecutive PwMS assessed with a standardized urodynamic test including three consecutive cystometries (20 ml/min, 100 ml/min, and 100 ml/min with 4°C fluid (Ice water test [IWT]) between June 2020 and March 2022 were included in this retrospective study. Data collected were bladder sensation with first desire to void (FDV) and strong desire to void (SDV). The presence of detrusor overactivity (DO) and the volume of the first uninhibited detrusor contraction were recorded. One hundred and fifty-seven patients (mean age 47.4 ± 11.8 years, median EDSS 3 IQR[2-5], 73.9% of women) were included. Increased filling rate induced delayed bladder sensations (FDV 219 ± 109 ml vs. 194 ± 100 ml; SDV 349 ± 113 ml vs. 322 ± 124 ml for 100 ml/min and 20 ml/min filling rate, respectively, p < 0.001). Ice water increased bladder sensations with earlier reports of needs to void (FDV 163 ± 99 ml vs. 218 ± 117 ml; SDV 263 ± 104 ml vs. 351 ± 112 ml respectively; p < 0.001). Thirty-four patients had DO during both 20 ml/min and 100 ml/min fillings, without difference in the volume of apparition (p = 0.78). Forty-four patients had DO during both 100 ml/min and IWT. Detrusor overactivity appeared for a reduced volume during IWT compared with room temperature fluid perfusion (-68 ml [-95 to -41]; p < 0.001). Filling rate and fluid temperature impact bladder sensations during cystometry in PwMS. Ice water decreased the volume of the first uninhibited detrusor contraction.

Assessment of Correction of Female Stress Urinary Incontinence with Trans Obturator Tape; Traditional versus Tailored

Abstract Background: Female genuine stress urinary incontinence (SUI) affects a great number of females, with important social and economic consequences. SUI is more frequent after several deliveries, after menopause as a result of changes in the urethral support or the sphincter mechanism. Aim of Study: To compare traditional tension free trans-obturator tape (TOT) and surgeon tailored mesh (STM) in treatment of female stress urinary incontinence as regard of safety, efficacy, side effects, cost, and follow-up. Patients and Method: Prospective randomized study was done on sixty three female patients were suffered SUI with determining of eligibility of the study as shown in COSORT flow chart Fig. (1) at Al Zahraa University Hospital, Al Azhar University from December 2016 to April 2019. All patients subjected to full history, general, and local examination (cases of cystocele, rectocele, or previous vaginal surgeries were excluded). Cystometrogram (CMG) was done for exclusion of uninhibited detrusor contractions, small bladder capacity ( 100 CC) assessed by ultrasonography were excluded from this study. All patients requested surgical treatment and provided informed written consent, and the study was approved by the ethical committee. With follow-up for six month post-operatively. Results: Depending on subjective criteria obtained from the Patric questionnaire, and objective criteria from physical examination.As regards traditional tape group, 13 patients (43.33%) were cured; two patients (6.67%) improved with no failed cases and STM group 14 patients (46.67%) were cured; one patient (3.33 %) improved with no failed cases (p-value 0.542, Pearson Chi-Square test). Conclusions: TOT (outside in technique) using both STM and traditional tape are minimally invasive techniques and are equally effective and safe in treatment of pure female SUI, with short hospital stay which reduces the cost of surgery. Both techniques could be used in treatment of pure SUI with good outcome. This technique is more economical due to the cheap ordinary polypropylene mesh. So, it should be considered as a low-cost alternative to the available commercial kits in the treatment of female SUI, mainly for public health systems with few financial resources.

Cluster analysis of men undergoing surgery for BPH/LUTS reveals prominent roles of both bladder outlet obstruction and diminished bladder contractility.

Lower urinary tract symptoms (LUTS) in aging men are commonly attributed to bladder outlet obstruction from benign prostatic hyperplasia (BPH) but BPH/LUTS often reflects a confluence of many factors. We performed a hierarchical cluster analysis using four objective patient characteristics (age, HTN, DM, and BMI), and five pre-operative urodynamic variables (volume at first uninhibited detrusor contraction, number of uninhibited contractions, Bladder Outlet Obstruction Index (BOOI), Bladder Contractility Index (BCI) and Bladder Power at Qmax) to identify meaningful subgroups within a cohort of 94 men undergoing surgery for BPH/LUTS. Two meaningful subgroups (clusters) were identified. Significant differences between the two clusters included Prostate Volume (95 vs 53 cc; p-value = 0.001), BOOI (mean 70 vs 49; p-value = 0.001), BCI (mean 129 vs 83; p-value <0.001), Power (689 vs 236; p-value <0.001), Qmax (8.3 vs 4.9 cc/sec; p-value <0.001) and post-void residual (106 vs 250 cc; p-value = 0.001). One cluster is distinguished by larger prostate volume, greater outlet resistance and better bladder contractility. The other is distinguished by smaller prostate volume, lower outlet resistance and worse bladder contractility. Remarkably, the second cluster exhibited greater impairment of urine flow and bladder emptying. Surgery improved flow and emptying for patients in both clusters. These findings reveal important roles for both outlet obstruction and diminished detrusor function in development of diminished urine flow and impaired bladder emptying in patients with BPH/LUTS.

Clinical urologic and urodynamic outcomes in patients with anorectal malformation and absent vagina after vaginal replacement

Introduction and objectivesAnorectal malformations (ARMs) represent a complex spectrum of anorectal and genitourinary anomalies and a paucity of evidence is available on long-term urologic outcomes in all ARM subtypes. It was our subjective bias from being a referral center for ARM patients that the subtype of rectovestibular fistula and absent vagina had higher risk of renal and bladder abnormalities than typical rectovestibular fistula patients. Therefore, to confirm or refute our clinical suspicions, the purpose of this study was to review this specific cohort of ARM patients and describe both the clinical urological and urodynamic outcomes. MethodsA retrospective cohort study was performed for 120 patients who were treated for ARM and vaginal replacement at our institution between 1991 and 2017. Fifteen patients with rectovestibular fistula and absent vagina were included in our review. Demographic and clinical data were abstracted from their medical records, including urodynamic findings, need for clean intermittent catheterization (CIC), urinary continence, and renal function. ResultsVaginal replacement surgery was undertaken concomitantly with ARM repair in 10 of the 15 patients (67%). One patient was lost to follow up, and mean follow up postoperatively was 39 months. In all but one patient, rectum or colon was used as the substrate for vaginal replacement. Of the 15 patients, 13 had continence data available. A total of 10 patients (77%) were able to achieve social continence. Overall six patients used CIC to manage their bladder and 40% of continent patients used CIC. Urinary continence outcomes in patients who had partial vaginal replacement compared to those with total vaginal replacement did not reveal a clinically significant difference. Continence was achieved in 3/4 patients (75%) with a history of tethered cord compared to 7/9 patients (78%) without a history of tethered cord release. Urodynamics were performed postoperatively in 7 of the 157 patients (47%). Uninhibited detrusor contractions (UDCs) were present in 3 out of 7 patients, and a cystometric capacity greater than expected was noted in 4 patients. Additionally, 2 patients had end filling detrusor pressure greater than 40 cm H2O. GFR data were available for 13 of the 15 patients and (85%) were classified as chronic kidney disease (CKD) stage I or not having any significant loss of renal function. ConclusionsIn this cohort of rectovestibular fistula and absent vagina, 77% reported achieving urinary continence. However CIC was employed in 40% of the patients which is higher than prior published noncloaca female ARM patient population. Urodynamic abnormalities were noted when performed and led to change in bladder management. Renal function measured with GFR was normal in 85%. Patients with rectovestibular fistula and absent vagina benefit from urologic screening given higher rates of lower urinary tract dysfunction that can require CIC to protect the upper urinary tract and achieve urinary continence. Type of studyCase series. Level of evidenceLevel IV.

Objective impacts of tadalafil on storage and voiding function in male patients with benign prostatic hyperplasia: 1-year outcomes from a prospective urodynamic study.

To investigate the 1-year effects of tadalafil on storage and voiding function in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (LUTS/BPH) based on a urodynamic study. In a one-armed, prospective study, 105 untreated outpatients with LUTS/BPH received 5mg tadalafil every day for 12months. Subjective symptoms and objective findings on voiding and storage functions, obtained through urodynamic studies that included cystometry and pressure flow study, were evaluated before, at 3months, and at 12months of treatment. The analysis included 94 patients with a mean age of 70.7years and a mean prostate volume of 44.5mL. Subjective symptom parameters of LUTS were significantly ameliorated after 3months, and progressively improved until study conclusion. Similarly, monitoring of storage and voiding functions revealed significant improvements after 3months that continued to improve until 12months. In 49 patients who revealed detrusor overactivity during cystometry at the baseline assessment, uninhibited detrusor contractions disappeared in 15 (30.6%) patients after 3months (p = 0.02), and in 22 (44.9%) after 12months (p < 0.001). Mean maximum flow rate significantly increased by 2.9mL/s during the 12-month treatment (p < 0.001), whereas mean bladder outlet obstruction index significantly decreased from 59.5 at baseline to 45.7 at 3months (p = 0.001), and to 42.9 at 12months (p < 0.001). Tadalafil significantly improved storage and voiding functions, along with LUTS, in patients with LUTS/BPH during a 1-year treatment.

Switch to Abobotulinum toxin A may be useful in the treatment of neurogenic detrusor overactivity when intradetrusor injections of Onabotulinum toxin A failed.

To assess the outcomes of switching to a different brand of botulinum toxin A (BTA, from Botox® to Dysport®) in case of failure of intradetrusor injections (IDI) of Botox® in the treatment of neurogenic detrusor overactivity (NDO). The charts of all patients who underwent a switch to IDI of Dysport® after failure of an IDI of Botox® at six departments of neurourology were retrospectively reviewed. The main outcomes of interest were the bladder diary data and four urodynamic parameters: maximum cystometric capacity (MCC), maximum detrusor pressure (PDET max), and volume at first uninhibited detrusor contraction (UDC). Fifty-seven patients were included. After the first injection of Dysport®, no adverse events were reported. A significant decrease in number of urinary incontinence episodes per day was observed in 52.63% of patients (P < 0.001) and all patients experienced a reduction in PDET Max (-8.1 cmH20 on average; P = 0.003). MCC significantly increased by a mean of 41.2 (P = 0.02). The proportion of patients with no UDC increased significantly at week 6 after ATA injections (from 15.79% to 43.9%; P = 0.0002). Hence, 32 patients draw clinical and/or urodynamic benefits from the botulinum toxin switch from (56.14%). After a median follow up of 21 months, 87% of responders to BTA switch were still treated successfully with BTA. Most patients refractory to Botox® (56.14%) draw benefits from the switch to Dysport®.

Does sacral pulsed electromagnetic field therapy have a better effect than transcutaneous electrical nerve stimulation in patients with neurogenic overactive bladder?

ObjectiveTo compare the effectiveness of pulsed electromagnetic field therapy (PEMFT) and transcutaneous electrical nerve stimulation (TENS) on neurogenic overactive bladder dysfunction (OAB) in patients with spinal cord injury (SCI). Patients and methodsIn all, 80 patients [50men and 30 women, with a mean (SD) age of 40.15 (8.76)years] with neurogenic OAB secondary to suprasacral SCI were included. They underwent urodynamic studies (UDS) before and after treatment. Patients were divided into two equal groups: Group A, comprised 40 patients who received 20min of TENS (10Hz with a 700s generated pulse), three times per week for 20 sessions; Group B, comprised 40 patients who received PEMFT (15Hz with 50% intensity output for 5s/min for 20min), three times per week for 20 sessions. ResultsIn Group B, there was a significant increase in the maximum cystometric capacity (P<0.001), volume at first uninhibited detrusor contraction (P<0.002), and maximum urinary flow rate (P<0.02). ConclusionThe UDS showed that the effects of PEMFT in patients with neurogenic OAB secondary to suprasacral SCI was better than TENS for inducing an inhibitory effect on neurogenic detrusor overactivity.

Comparison of spinal cord contusion and transection: functional and histological changes in the rat urinary bladder

To compare the effect of complete transection (tSCI) and contusion spinal cord injury (cSCI) on bladder function and bladder wall structure in rats. A total of 30 female Sprague-Dawley rats were randomly divided into three equal groups: an uninjured control, a cSCI and a tSCI group. The cSCI group underwent spinal cord contusion, while the tSCI group underwent complete spinal cord transection. At 6 weeks post-injury, 24-h metabolic cage measurement and conscious cystometry were performed. Conscious cystometry analysis showed that the cSCI and tSCI groups had significantly larger bladder capacities than the control group. The cSCI group had significantly more non-voiding detrusor contractions than the tSCI group. Both injury groups had more non-voiding contractions compared with the control group. The mean threshold pressure was significantly higher in the tSCI group than in the control and cSCI groups. The number of voids in the tSCI group was lower compared with the control group. Metabolic cage analysis showed that the tSCI group had larger maximum voiding volume as compared with the control and cSCI groups. Vesicular acetylcholine transporter/smooth muscle immunoreactivity was higher in the control than in the cSCI or tSCI rats. The area of calcitonin gene-related peptide staining was smaller in the tSCI group than in the control or cSCI groups. Spinal cord transection and contusion produce different bladder phenotypes in rat models of SCI. Functional data suggest that the tSCI group has an obstructive high-pressure voiding pattern, while the cSCI group has more uninhibited detrusor contractions.

Prospective Evaluation of Sacral Neuromodulation in Children: Outcomes and Urodynamic Predictors of Success

Sacral neuromodulation has been demonstrated to improve refractory bowel bladder dysfunction in children. The purpose of the current study was to determine whether results are durable in children after longer followup, whether children with a lower body mass index are at risk for device failure and whether pretreatment urodynamic evaluation can predict posttreatment outcome. Pediatric patients with refractory bowel bladder dysfunction were enrolled following informed consent and followed prospectively. All patients underwent preoperative videourodynamic evaluation and a 2-stage implantation procedure. Validated questionnaires were used to assess symptom severity and quality of life. Complications were analyzed with regard to treatment required and patient body mass index. During 45 months 30 patients were enrolled. Median age was 8.3 years at enrollment. Median followup was 14.8 months. Patients had significant improvement in quality of life and symptom scores, which persisted at the most recent followup. Patients who had uninhibited detrusor contractions on preoperative urodynamic assessment had significantly greater improvement in symptoms. Of the patients 23% had a complication requiring reoperation, most commonly neurostimulator lead breakage in those with a significantly lower body mass index. Sacral neuromodulation significantly improves quality of life and symptom severity in children with refractory bowel bladder dysfunction. Children gain greater benefit if they show uninhibited bladder contractions on preoperative urodynamic evaluation. Children have a high rate of lead breakage requiring operative revision, which was seen after minor trauma in those with a lower body mass index.

266 Objective efficacy of mirabegron on storage and voiding function in patients with over-active bladder that are unresponsive to antimuscarinic treatment, based on a urodynamic study

INTRODUCTION AND OBJECTIVES: Oral anti-muscarinic agents are currently the mainstay pharmacotherapy for the treatment of overactive bladder (OAB). However, some patients experience insufficient improvement or adverse events such as dry mouth and constipation. Such patients either persist with the unsatisfactory treatment or discontinue therapy. Mirabegron is a novel, first-in-class selective b3-adrenoceptor agonist. The results of the phase III clinical trials performed in the US, Europe, and Japan using this agent have reported to relieve subjective symptoms associated with OAB. However, the evidence proving that, this drug is effective for OAB that is unresponsive to antimuscarinic treatment is absent. We investigated the objective effectiveness of mirabegron for patients with OAB that cannot be managed with antimuscarinics METHODS: In this prospective study, 50 OAB female patients already treated with antimuscarinic agents having poor therapeutic effects (OAB symptom scores (OABSS) of 3 and 1 urgency episodes a week). The patients stop taking antimuscarinics and after 2weeks wash out, received 50 mg mirabegron once a day for 12 weeks. The OABSS was conducted before and after mirabegron administration to evaluate subjective symptom severity. In this UDS, we assessed the first desire to void (FDV), maximum cystometric capacity (MCC), and occurrence of uninhibited detrusor contraction as parameters of storage function. Maximum flow rate and detrusor pressure at Qmax were assessed as parameters of voiding function. RESULTS: The patients0 mean age was 71.3 years. Between preand post-administration, the mean OABSS score decreased from 8.3 to 4.9 points (p < 0.001), indicating significant improvement of subjective symptoms. From the UDS results, we observed a statistically significant improvement in the storage function parameters, with mean FDV and MCC. Although uninhibited detrusor contraction was observed in 32 patients (64%) before administration, no contraction was observed in 15 of these 32 patients (46.9%) after administration (p 1⁄4 0.01). On voiding function, mirabegron does not inhibit voiding function. Treatment was discontinued in only 1 patient (2.5%) because of the adverse reaction. CONCLUSIONS: Mirabegron was shown to be effective in women with OAB that is unresponsive to antimuscarinic treatment in terms of both subjective symptoms and bladder storage function. In addition,the incidence of side effects is low. Mirabegron may be a new therapeutic alternative for treating OAB.

MP75-02 EARLY EFFICACY OF ANTICHOLINERGIC TREATMENT FOR THE WOMEN WITH OVERACTIVE BLADDER FOLLOWING LUMBAR SPINE OPERATIONS

INTRODUCTION AND OBJECTIVES: Oral anti-muscarinic agents are currently the mainstay pharmacotherapy for the treatment of overactive bladder (OAB). However, some patients experience insufficient improvement or adverse events such as dry mouth and constipation. Such patients either persist with the unsatisfactory treatment or discontinue therapy. Mirabegron is a novel, first-in-class selective b3-adrenoceptor agonist. The results of the phase III clinical trials performed in the US, Europe, and Japan using this agent have reported to relieve subjective symptoms associated with OAB. However, the evidence proving that, this drug is effective for OAB that is unresponsive to antimuscarinic treatment is absent. We investigated the objective effectiveness of mirabegron for patients with OAB that cannot be managed with antimuscarinics METHODS: In this prospective study, 50 OAB female patients already treated with antimuscarinic agents having poor therapeutic effects (OAB symptom scores (OABSS) of 3 and 1 urgency episodes a week). The patients stop taking antimuscarinics and after 2weeks wash out, received 50 mg mirabegron once a day for 12 weeks. The OABSS was conducted before and after mirabegron administration to evaluate subjective symptom severity. In this UDS, we assessed the first desire to void (FDV), maximum cystometric capacity (MCC), and occurrence of uninhibited detrusor contraction as parameters of storage function. Maximum flow rate and detrusor pressure at Qmax were assessed as parameters of voiding function. RESULTS: The patients0 mean age was 71.3 years. Between preand post-administration, the mean OABSS score decreased from 8.3 to 4.9 points (p < 0.001), indicating significant improvement of subjective symptoms. From the UDS results, we observed a statistically significant improvement in the storage function parameters, with mean FDV and MCC. Although uninhibited detrusor contraction was observed in 32 patients (64%) before administration, no contraction was observed in 15 of these 32 patients (46.9%) after administration (p 1⁄4 0.01). On voiding function, mirabegron does not inhibit voiding function. Treatment was discontinued in only 1 patient (2.5%) because of the adverse reaction. CONCLUSIONS: Mirabegron was shown to be effective in women with OAB that is unresponsive to antimuscarinic treatment in terms of both subjective symptoms and bladder storage function. In addition,the incidence of side effects is low. Mirabegron may be a new therapeutic alternative for treating OAB.

MP75-01 OBJECTIVE EFFICACY OF MIRABEGRON ON STORAGE AND VOIDING FUNCTION IN PATIENTS WITH OVERACTIVE BLADDER THAT IS UNRESPONSIVE TO ANTIMUSCARINIC TREATMENT, BASED ON A URODYNAMIC STUDY

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Female Urology II1 Apr 2014MP75-01 OBJECTIVE EFFICACY OF MIRABEGRON ON STORAGE AND VOIDING FUNCTION IN PATIENTS WITH OVERACTIVE BLADDER THAT IS UNRESPONSIVE TO ANTIMUSCARINIC TREATMENT, BASED ON A URODYNAMIC STUDY Yoshihisa Matsukawa, Shun Takai, Katsuhisa Tsuruta, Masashi Kato, Tokunori Yamamoto, and Momokazu Gotoh Yoshihisa MatsukawaYoshihisa Matsukawa More articles by this author , Shun TakaiShun Takai More articles by this author , Katsuhisa TsurutaKatsuhisa Tsuruta More articles by this author , Masashi KatoMasashi Kato More articles by this author , Tokunori YamamotoTokunori Yamamoto More articles by this author , and Momokazu GotohMomokazu Gotoh More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2374AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Oral anti-muscarinic agents are currently the mainstay pharmacotherapy for the treatment of overactive bladder (OAB). However, some patients experience insufficient improvement or adverse events such as dry mouth and constipation. Such patients either persist with the unsatisfactory treatment or discontinue therapy. Mirabegron is a novel, first-in-class selective β3-adrenoceptor agonist. The results of the phase III clinical trials performed in the US, Europe, and Japan using this agent have reported to relieve subjective symptoms associated with OAB. However, the evidence proving that, this drug is effective for OAB that is unresponsive to antimuscarinic treatment is absent. We investigated the objective effectiveness of mirabegron for patients with OAB that cannot be managed with antimuscarinics METHODS In this prospective study, 50 OAB female patients already treated with antimuscarinic agents having poor therapeutic effects (OAB symptom scores (OABSS) of ≥3 and ≥1 urgency episodes a week). The patients stop taking antimuscarinics and after 2weeks wash out, received 50 mg mirabegron once a day for 12 weeks. The OABSS was conducted before and after mirabegron administration to evaluate subjective symptom severity. In this UDS, we assessed the first desire to void (FDV), maximum cystometric capacity (MCC), and occurrence of uninhibited detrusor contraction as parameters of storage function. Maximum flow rate and detrusor pressure at Qmax were assessed as parameters of voiding function. RESULTS The patients′ mean age was 71.3 years. Between pre- and post-administration, the mean OABSS score decreased from 8.3 to 4.9 points (p < 0.001), indicating significant improvement of subjective symptoms. From the UDS results, we observed a statistically significant improvement in the storage function parameters, with mean FDV and MCC. Although uninhibited detrusor contraction was observed in 32 patients (64%) before administration, no contraction was observed in 15 of these 32 patients (46.9%) after administration (p = 0.01). On voiding function, mirabegron does not inhibit voiding function. Treatment was discontinued in only 1 patient (2.5%) because of the adverse reaction. CONCLUSIONS Mirabegron was shown to be effective in women with OAB that is unresponsive to antimuscarinic treatment in terms of both subjective symptoms and bladder storage function. In addition,the incidence of side effects is low. Mirabegron may be a new therapeutic alternative for treating OAB. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e873 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Yoshihisa Matsukawa More articles by this author Shun Takai More articles by this author Katsuhisa Tsuruta More articles by this author Masashi Kato More articles by this author Tokunori Yamamoto More articles by this author Momokazu Gotoh More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Onabotulinumtoxin-A intradetrusorial injections modulate bladder expression of NGF, TrkA, p75 and TRPV1 in patients with detrusor overactivity

How onabotulinumtoxinA (onab/A) injected in the detrusor muscle improves detrusor overactivity (DO) is still a matter of debate. Nerve growth factor (NGF) seems to play a role in determining urgency and DO. Recent studies showed that NGF decreases in patients with DO who respond to onab/A treatment. We investigated onab/A-induced changes on gene expression of NGF, TRPV1, TrkA and p75 in bladder wall tissue of patients affected by neurogenic and idiopathic DO. Twenty-five patients (18 with neurogenic DO and 7 with idiopathic DO) received onab/A injections into the detrusor muscle. Urodynamic studies and cystoscopies with sampling of the bladder wall were performed before and 1 month after onab/A injections. Onab/A-induced changes in urodynamic variables (first volume and maximum pressure of uninhibited detrusor contractions and maximum cystometric capacity) and NGF, TRPV1, TRKA, p75 gene expression by means of quantitative Real Time-Polymerase Chain Reaction. NGF protein levels were assessed in tissue homogenates by enzyme-linked immunosorbent assay. Onab/A significantly improved urodynamic findings (as shown by the increase in maximum cystometric capacity), decreased the bladder tissue levels of NGF protein and significantly increased NGF, TrkA, p75 and TRPV1 gene expression independently from the etiology of DO. No significant correlation has been found between NGF down-regulation and the increase in MCC. Correlations between NGF gene expression and NGF receptors’ gene expression were influenced by onab/A dosages. In the short time follow-up, onab/A decreases NGF protein levels and increases NGF and associated receptors’ gene expression possibly by inhibiting NGF release. Further studies with longer follow-up will clarify time course of onab/A-induced modifications in NGF expression.

Efficacy of Silodosin for Relieving Benign Prostatic Obstruction: Prospective Pressure Flow Study

We investigated the effect of the new sympathetic α1A-adrenoceptor antagonist silodosin for relieving benign prostatic obstruction by pressure flow study. In this open, nonblinded, prospective study we administered 8 mg silodosin daily for 4 weeks in 60 patients with lower urinary tract symptoms associated with benign prostatic enlargement. As a primary outcome measure, we assessed changes in bladder function and benign prostatic obstruction using pressure flow study. As secondary outcome measures, changes in subjective symptoms and quality of life were assessed by the International Prostate Symptom Score. Objective changes in urination status were also assessed by free uroflowmetry in terms of maximum flow rate and post-void residual urine volume. A total of 57 patients were enrolled for analysis. In the storage phase of the pressure flow study bladder capacity at first desire to void increased significantly with no significant change in maximum cystometric capacity. Of 24 patients 14 (58.3%) with uninhibited detrusor contractions before administration showed apparent improvement in detrusor overactivity after administration, including 6 in whom uninhibited contractions disappeared. In the voiding phase mean detrusor pressure at maximum flow significantly decreased from 72.5 to 51.4 cm H(2)O. The mean bladder outlet obstruction index decreased significantly from 60.6 to 33.8. Obstruction grade assessed by the Schaefer nomogram improved in all except 1 patient. Total symptom and quality of life scores, maximum flow rate and post-void residual urine volume on free uroflowmetry significantly improved. Silodosin improved lower urinary tract symptoms by improving bladder storage function and relieving benign prostatic obstruction.

Troubles mictionnels de l’enfant : de la symptomatologie au diagnostic

The new definitions of voiding disorders in children should be used in clinical practice. Two major kinds of voiding disorders are identified: 1) isolated primary enuresis as a disorder occurring exclusively during sleep with no daytime leakage; 2) urinary dysfunctions that include uninhibited detrusor contraction, sphincter hypertonicity, and urethral instability. These dysfunctions may be primary or secondary. Constipation as an underlying cause is frequent and usually underestimated. The diagnostic process requires one (or more) long consultations. After ruling out a urine leak without a voiding disorder and secondary causes (constipation, inadequate hydration, poor voiding hygiene, crystalluria, etc.), the aim is to distinguish isolated sleep-time disorders (primary enuresis) from daytime ± sleep-time symptoms (primary urinary dysfunctions). Anamnesis, long and accurate, can be sensitized by a questionnaire completed at home. The physical examination focuses on the exclusion of anatomic abnormalities and local inflammation (vulvitis, balanitis, etc.). Diagnostic tests are rarely required at the beginning. Urodynamic exploration may be indicated, never at the first consultation, in case of primary urinary dysfunction. This diagnostic approach provides an appropriate therapeutic decision.

Clinical symptoms and videourodynamic findings of detrusor overactivity in women

ObjectiveDetrusor overactivity (DO) is a urodynamic term for uninhibited detrusor contractions, which occur in the bladder-filling phase. Women with urodynamic DO might have different clinical presentations and pathophysiology involving the bladder, urethra, and pelvic floor. This retrospective study used videourodynamic study (VUDS) to analyze the correlation between clinical symptoms and DO subtypes in women. Materials and MethodsThe records of 526 consecutive women with urodynamic DO who underwent VUDS for lower urinary tract symptoms (LUTS) from 1996 to 2009 were included. LUTS were classified as storage, emptying, pain, and postmicturition symptoms. A final diagnosis was made based on VUDS findings. Patients were stratified into the categories idiopathic DO only, DO with inadequate contractility (DHIC), and DO with bladder outlet obstruction (BOO). The main symptoms and associated symptoms were used to analyze the correlation with DO subgroups. A group of 272 women with LUTS who were urodynamically normal served as the symptomatic controls. ResultsAmong women with DO, 308 (58.6%) had idiopathic DO only, 69 (13.1%) had DHIC, and 149 (28.3%) had BOO. All of the women in the DO subgroups had storage symptoms as the main or associated symptoms. A combination of storage and emptying symptoms were more common in patients with DHIC [49 (71%)] and BOO [77 (51.7%)]. According to the reported storage symptoms in all women, urodynamic DO was detected in 504 (65.5%) of 770 with frequency symptoms, 467 (73.3%) of 637 with urgency symptoms, and 293 (87.5%) of 335 with urgency urinary incontinence. ConclusionStorage and emptying symptoms are common in women with different DO subtypes. Differential diagnosis of the DO subtype in women should not be based on LUTS alone.

Urodynamic assessment of children treated with botulinum toxin A injections for urge incontinence: a pilot study

This study aimed to investigate changes in urodynamic findings and symptoms after detrusor injections of botulinum toxin A (BTX-A) in children with idiopathic detrusor overactivity (IDO) and urge incontinence. Eight girls and five boys, aged 7-19 years, who had urge incontinence refractory to scheduled voiding and anticholinergics, were included this prospective study. Urodynamic studies showed postoperative IDO in 12 patients. A dose of 50-100 IU (1.3 -- 4.8 IU/kg) BTX-A was primarily administered at 15-20 detrusor sites. A control urodynamic study was performed within 3 months after the injections. Seven patients had a repeated procedure 16 (range 6-24) months on the average after the first one. Eleven of the 13 patients had daily incontinence and two had incontinence a couple of times a week in association with urge symptoms. Postoperatively, no patient had urinary retention, but one girl had a urinary tract infection 4 months after the therapy. Five patients had a full response, seven partial responses and one no response 1-3 months after the first treatment. After 1 year, three of nine patients still have full response. Maximum cystometric capacity increased after the first treatment from a median of 227 ml to 379 ml (p = 0.005) and the number of patients with uninhibited detrusor contractions more than 30 cmH₂O during the filling phase decreased from eight to two out of 13 (p = 0.041). Intradetrusor BTX-A injections effectively reduce day-time wetting, significantly increase bladder volume and decrease detrusor overactivity in children with urge incontinence refractory to scheduled voidings and anticholinergics.

1002 EARLY EFFICACY OF SILODOSIN ON STORAGE AND VOIDING FUNCTION IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA, BASED ON PRESSURE-FLOW STUDY

RESULTS: Mean age of the patients and mean prostate volume were 67.8 years and 43.9 mL, respectively. Mean I-PSS and QOL scores dropped from 17.8 to 9.8 points (p <0.001) and from 5.1 to 3.2 points (p < 0.001), respectively, indicating a significant improvement of subjective symptoms and QOL. On free uroflowmetry, mean Qmax significantly increased from 7.5 to 11.3 mL/sec (p = 0.005), while the residual urine volume significantly decreased from 69.8 to 32.1 mL (p = 0.002), showing an improvement in the voiding function. Although not statistically significant, improvement was observed in the parameters of the storage function on PFS, with mean FDV rising from 127 to 159 mL (p = 0.168), MCC from 262 to 298 mL (p = 0.135). While uninhibited detrusor contraction was observed in 21 patients before silodosin administration, it disappeared in 14 patients after administration. Qmax significantly improved from 5.8 to 9.7 mL/sec (p = 0.01). Mean Pdet Qmax declined significantly from 73.9 to 52.4 cmH 2 0 (p <0.001), demonstrating that silodosin relieved bladder outlet obstruction CONCLUSIONS: Silodosin may be considered improving not only subjective symptoms but also voiding function and bladder outlet obstruction in BPH patients with lower urinary tract symptoms. Q2: Week 0.5 −0.5 (1.08) −0.3 (0.96) 0.0002 Last observation −0.9 (1.34) −0.5 (1.16) <0.0001 Q4: Week 0.5 −0.4 (1.21) −0.3 (1.14) 0.0075 Last observation −0.8 (1.36) −0.4 (1.27) <0.0001 Q7: Week 0.5 −0.4 (1.06) −0.3 (1.03) 0.0968 Last observation −0.6 (1.14) −0.4 (1.15) 0.0037 Obstructive symptoms Q1: Week 0.5 −0.6 (1.14) −0.3 (0.97) <0.0001 Last observation −0.9 (1.42) −0.6 (1.22) <0.0001 Q3: Week 0.5 −0.7 (1.19) −0.4 (1.10) 0.0002 Last observation −1.1 (1.41) −0.6 (1.33) <0.0001 Q5: Week 0.5 −0.8 (1.29) −0.4 (1.03) <0.0001 Last observation −1.1 (1.41) −0.5 (1.21) <0.0001 Q6: Week 0.5 −0.7 (1.16) −0.3 (1.21) <0.0001 Last observation −0.9 (1.32) −0.5 (1.24) <0.0001