Nomogram predicting early urinary incontinence after radical prostatectomy.

PURPOSE: One of the most frequent side effects of radical prostatectomy (RP) is urinary incontinence. The primary cause of urine incontinence is usually thought to be impaired urethral sphincter function; nevertheless, the pathophysiology and recovery process of urine incontinence remains unclear. This study aimed to identify potential risk variables, build a risk prediction tool that considers preoperative urodynamic findings, and direct doctors to take necessary action to reduce the likelihood of developing early urinary incontinence. METHODS: We retrospectively screened patients who underwent radical prostatectomy between January 1, 2020 and December 31, 2023 at the First People 's Hospital of Nantong, China. According to nomogram results, patients who developed incontinence within three months were classified as having early incontinence. The training group's general characteristics were first screened using univariate logistic analysis, and the LASSO method was applied for the best prediction. Multivariate logistic regression analysis was carried out to determine independent risk factors for early postoperative urine incontinence in the training group and to create nomograms that predict the likelihood of developing early urinary incontinence. The model was internally validated by computing the performance of the validation cohort. The nomogram discrimination, correction, and clinical usefulness were assessed using the c-index, receiver operating characteristic curve, correction plot, and clinical decision curve. RESULTS: The study involved 142 patients in all. Multivariate logistic regression analysis following RP found seven independent risk variables for early urinary incontinence. A nomogram was constructed based on these independent risk factors. The training and validation groups' c-indices showed that the model had high accuracy and stability. The calibration curve demonstrates that the corrective effect of the training and verification groups is perfect, and the area under the receiver operating characteristic curve indicates great identification capacity. Using a nomogram, the clinical net benefit was maximised within a probability threshold of 0.01-1, according to decision curve analysis (DCA). CONCLUSION: The nomogram model created in this study can offer a clear, personalised analysis of the risk of early urine incontinence following RP. It is highly discriminatory and accurate, and it can help create efficient preventative measures and identify high-risk populations.

Single-dose Tadalafil Reduces Opening Urethral Pressure: A Randomized, Double-blind, Placebo-controlled, Crossover Trial in Healthy Women.

INTRODUCTION AND HYPOTHESIS: Phosphodiesterase enzymes are widely distributed in female urogenital tissues. Yet, the understanding of their physiological roles and the impact of phosphodiesterase inhibitors on lower urinary tract symptoms in women remains limited. Current hypotheses are conflicting: one suggests that vasodilation might expand the periurethral vascular plexus, leading to increased urethral pressure, whereas the other proposes a relaxation of urethral musculature, resulting in decreased pressure. To further clarify this, we investigated the effect of tadalafil on the opening urethral pressure and voiding function in healthy women. METHODS: We conducted a randomized, double-blind, placebo-controlled crossover trial involving 24 healthy women. Participants were randomly assigned to receive a single dose of tadalafil (40 mg) or placebo during their initial visit and then switched to the alternative treatment during their second visit. Opening urethral pressure was measured with urethral pressure reflectometry during both resting and squeezing conditions of the pelvic floor. Subsequently, voiding parameters were recorded. RESULTS: Compared with placebo, a single dose of tadalafil significantly reduced opening urethral pressure during both resting (-6.8 cmH20; 95% confidence interval [CI], -11.8 to -1.9; p = 0.009) and squeezing conditions (-8.8 cmH20; 95% CI, -14.6 to -3.1; p = 0.005). Voiding parameters did not show significant differences (average flow rate: -0.8 ml/s [95% CI, -2.0 to 0.4; p = 0.2]; maximum flow rate: -1.7 ml/s [95% CI, -4.8 to 1.5; p = 0.3]). CONCLUSIONS: A single dose of 40 mg tadalafil moderately reduced urethral pressure in healthy women, without affecting voiding parameters. The clinical implications of this are yet to be determined.

Botulinum toxin A injection to the external urethral sphincter for voiding dysfunction in females: A tertiary center experience.

AIM: The aim of this study is to examine the functional outcomes of ona-botulinum toxin A (BTX-A) injection into the external urethral sphincter (EUS) for female patients with nonneurogenic nonrelaxing sphincter as the underlying cause of voiding dysfunction (VD). METHOD: A retrospective analysis was performed for all the patients with the urodynamic findings of higher than expected maximum urethral closure pressure (MUCP) who received their first injection during the study period. All patients were evaluated with preoperative videourodynamic study and urethral pressure profilometry and received 100 U of EUS BTX-A. Patients aged less than 18 years and those with neurogenic bladder were excluded. All patients were followed up with the free flow, postvoid residuals (PVR), and patient global impression of improvement (PGI-I) scale at 6 weeks and then at 3 monthly intervals. RESULT: We identified 35 female patients with a mean age of 37.5 ± 15 years (range 18-72 years) with a mean follow-up of 20 months. More than 50% of patients had a history of prior surgical intervention and 28 (80%) patients were catheter dependent, a suprapubic catheterization, or clean intermittent self-catheterization. Mean MUCP was 97.1 ± 22 cm of water. After treatment with BTX-A, 21 (60%) patients were able to void per urethral (p = 0.02). The mean maximum flow rate (Qmax) improved from 8.8 to 11 mls/s and the mean PVR decreased from 200 to 149 mls (p < 0.05). On multivariate analysis, we identified high preoperative PVR, high preoperative actual MUCP, and previous surgical intervention (urethral dilatation, sacral neuromodulation, and pelvic surgery) as predictors of successful voiding restoration. The mean duration of response was 4.7 months, 46% of patients requested repeat injection, and 29% were established on maintenance injections. On the 5-point PGI-I score, 13 (37%), 12 (34%), and 10 (29%) patients reported good, some, and no improvement, respectively. Quality of life was also improved in 60% of patients. Two patients had transient stress urinary incontinence (for <6 weeks) and there were no significant long-lasting adverse events. CONCLUSION: EUS BTX-A is a valid treatment option for VD considering therapeutic options are limited. The patient must be made aware of the need for repeat treatments.

Effect of single doses of citalopram and reboxetine on urethral pressure: A randomized, double-blind, placebo- and active-controlled three-period crossover study in healthy women.

AIMS: Urethral closure function is essential for urinary continence in women and decreased urethral pressure is associated with stress urinary incontinence (SUI). For decades, the effects of serotonergic drugs on central neural control of urethral closure have been investigated and discussed. Epidemiological studies suggest that the use of selective serotonin reuptake inhibitors (SSRIs), such as citalopram, is associated with SUI. However, the literature findings are conflicting. This study aimed to evaluate citalopram's effect on opening urethral pressure (OUP) in healthy women. METHODS: We conducted a randomized, double-blind, placebo- and active-controlled crossover study in 24 healthy women. On three study days, which were separated by 8 days of washout, the subjects received single doses of either 40 mg citalopram (and placeboreboxetine ), 8 mg reboxetine (and placebocitalopram ), or two placebos. Study drugs were administered at a 1-h interval due to a difference in estimated time to peak plasma concentration (tmax ). We measured OUP with urethral pressure reflectometry under both resting and squeezing conditions of the pelvic floor at estimated tmax for both study drugs (one timepoint). RESULTS: Compared to placebo, citalopram increased OUP by 6.6 cmH2 0 (95% confidence interval [CI] 0.04-13.1, p = 0.048) in resting condition. In squeezing condition, OUP increased by 7.1 cmH2 0 (95% CI: 1.3-12.9, p = 0.01). Reboxetine increased OUP by 30.0 cmH2 0 in resting condition compared to placebo (95% CI: 23.5-36.5, p < 0.001), and 27.0 cmH2 0 (95% CI: 21.2-32.8, p < 0.001) in squeezing condition. CONCLUSION: Citalopram increased OUP slightly compared to placebo suggesting that SSRI treatment does not induce or aggravate SUI.

Urethral pressure profile before radical prostatectomy as a predictor of early postoperative continence.

OBJECTIVE: Urinary incontinence (UI) is one of the most common complications of radical prostatectomy (RP). Impaired urethral sphincter function is generally considered to be the most important contributing factor for UI; however, the mechanism of onset and recovery of urinary continence has not been fully elucidated. The objective of this research was to evaluate preoperative functional urethral length (FUL) and maximum urethral closure pressure (MUCP) as early continence recovery predictors after open retropubic RP (ORRP). METHODS: The research was conducted on a group of 43 patients with localized prostate cancer (PCa) in the period from July 2019 to May 2021. The urodynamic method of urethral pressure profile (UPP) was used to assess FUL and MUCP, and correlate with the postprostatectomy continence recovery. The severity of UI and bothersome were assessed using fully validated International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-UI SF) and number of pads used in 24 h. Patients were interviewed about the use of urinary pads and asked to fill out the ICIQ-UI SF before and 2, 8, 16 and 24 weeks after ORRP. RESULTS: The median value of FUL (mm) and MUCP (cmH2O) was 69 (28-94) and 76 (16-223), respectively. Correlation and linear regression showed a statistically significant negative correlation between preoperative values of FUL and MUCP with ICIQ symptom score and the number of pads used per day at the four observed time intervals (p < 0.05). Such a result showed that patients with higher preoperative FUL and MUCP values were more likely to recover urinary continence earlier. A value of 65 mm for FUL and 80 cmH2 O for MUCP proved to be the cut-off values for continence recovery in 24 weeks after ORRP. CONCLUSION: Preoperatively evaluated FUL and MUCP seem to be valuable prognostic factors for early continence recovery after ORRP. Further investigation on a larger patient cohort is needed to evaluate the role of UPP in the preoperative management of patients with PCa.

Stress urinary incontinence is caused predominantly by urethral support failure.

Whales are mammals that can dive to depths of > 1000 m without the high water pressure pushing open their mouth or anus. The same is true for the female urethra. The meatus externus and internus are seals that cannot be pushed open by high water pressures. Recent evidence suggests that the female meatus internus is pushed open when the bladder pressure exceeds the urethral pressure. For a relaxed detrusor, this opening is not possible for at least three reasons: the law of elastic collision, Pascal's law of hydrostatics and the Hagen-Poiseuille law. The three laws do not support that urethral function failure is the predominant cause of stress urinary incontinence (SUI); however, they do support that urethral support failure is. Influential urogynecologists claim the opposite. TVT surgery, according to the integral theory of SUI (IT), has high failure rates because it does not principally prevent the urethra from hanging on a less mobile bladder neck. In the case of a long urethra, the tape is set too distally, and in hypomobile SUI, the use of a tension-free suburethral tape is unwarranted/ineffective, because the proximal urethra is not elevated above its resting position. A successful operation corrects urethral support failure and not urethral function failure.

Urodynamic evaluation before and after to RARP to identify pre and intraoperative factors affecting postoperative continence.

AIMS: To investigate factors contributing to pre and postoperative urethral function in male patients who underwent robot-assisted radical prostatectomy (RARP) using the urethral pressure profile (UPP). METHODS: Study A A total of 313 patients who underwent RARP between April 2013 and March 2015 were prospectively investigated. UPP was performed preoperatively in all patients. Correlation and multiple regression analyses were performed to investigate predictive factors for low preoperative maximum urethral closure pressure (MUCP). Study B To validate the predictive factors for low preoperative MUCP obtained in Study A, 755 patients who underwent RARP between May 2010 and October 2017 were retrospectively examined. Relationships between the time to pad-free status and the following factors were investigated: number of predictive factors, nerve-sparing surgery, and vesicourethral anastomosis (VUA) methods (barbed vs. nonbarbed suture). RESULTS: Study A A total of 187 patients were enrolled. Multivariate analysis revealed that older age, large prostate volume, low erectile function domain scores in International Index Erectile Function 15, and use of calcium channel blockers were significantly associated with low preoperative MUCP. Study B A total of 515 patients were included. Cox proportional hazard regression showed that the number of predictive factors and VUA method were significantly associated with the time to pad-free status. CONCLUSIONS: Our study demonstrated that older age, larger prostate volume, poor erectile function, and calcium channel blocker use could be predictive markers for recovery from postprostatectomy urinary incontinence.

Exploratory analysis of the effect of mirabegron on urodynamic sensation parameters and urethral pressure variations.

INTRODUCTION AND HYPOTHESIS: Urethral instability (URI) has in the past been defined by the International Continence Society (ICS), but was excluded from ICS terminology and definitions shortly after because of a lack of consensus about the clinical importance of this phenomenon. Recently, interest in URI and its possible role in overactive bladder (OAB) increased again. In the last decade, a beta 3 adrenoreceptor agonist (mirabegron) was approved for the treatment of OAB. The effect of mirabegron on urethral pressure during filling cystometry is unknown. The aim of this study was to assess the influence of mirabegron on urethral pressure variations during urodynamic investigation and the association of symptoms and voiding diary data before and during treatment. METHODS: This prospective study included 51 consecutive adult female patients, referred with OAB. Patients were evaluated using a voiding diary, two validated questionnaires and two urodynamic investigations, one before and one after 6 weeks of treatment with mirabegron. URI was defined as an urethral pressure drop exceeding 30 cmH2O during filling cystometry. RESULTS: The prevalence of URI was 31% at initial urodynamic investigation, and 19% at second investigation. URI is more common than DO with 18% prevalence at initial evaluation. Treatment with mirabegron resulted in significant changes in symptoms and urodynamic sensory markers in patients with URI. CONCLUSION: Urethral pressure variations are significantly reduced by treatment with mirabegron in patients with URI. URI seems to have a predictive value in treatment choices for OAB. Future research should elucidate this.

TAS-303 effects on urethral sphincter function in women with stress urinary incontinence: phase I study.

INTRODUCTION AND HYPOTHESIS: TAS-303, which selectively inhibits noradrenaline reuptake, was developed for treating stress urinary incontinence (SUI). The proximal urethra mainly comprises smooth muscle fibers in which α1 adrenergic receptors are abundant. This study was conducted to evaluate the effect of TAS-303 on urethral function and its safety profile in female patients with SUI. METHODS: In total, 16 women (age, 20-64 years) with SUI and > 5.0 g of leakage in the 1-h pad test at screening were randomized and administered the assigned treatment in a double-blind manner. The primary end point was change in the maximal urethral closure pressure (MUCP) at 6 h post-dose. The secondary end point was change in the urethral closure pressure of the entire urethra and each urethral region (proximal, middle, and distal) at 6 h post-dose. The results were analyzed using a t-test. RESULTS: The mean change ± standard deviation in MUCP at 6 h post-dose was 3.473 ± 12.154 cmH2O for TAS-303 and 2.615 ± 9.794 cmH2O for placebo (between-group difference: 0.858 cmH2O, P = 0.8047). The mean changes ± standard deviation in urethral closure pressure of the proximal urethra at 6 h after the administration of TAS-303 18 mg and placebo were 3.863 ± 10.941 and 1.634 ± 12.093, respectively (between-group difference: 2.229 cmH2O, P = 0.5976). CONCLUSIONS: No significant difference in MUCP and urethral closure pressure was found between TAS-303 and placebo. However, the change in the proximal urethral closure pressure with TAS-303 was larger than that with placebo. This suggests that TAS-303 has pharmacological effects on urethral sphincteric function.

[Application of urethral pressure profilometry in artificial urinary sphincter implantation].

Objective: To investigate the changes of maximum urethral pressure (MUP) and maximum urethral closure pressure (MUCP) after artificial urethral sphincter (AUS) implantation and their prognostic value. Methods: The clinical data of patients who had undergone AUS implantation in multiple medical centers between March and July 2019 were retrospectively analyzed. Data of urethral pressure profilometry, pad usage, related scores and complications related to surgery were collected and compared. The primary endpoint was social continence (defined as 0-1 pad/d) 1 month after activation of the pump. Results: A total of five male patients were included in this study. Two underwent transurethral resection of the prostate for benign prostatic hyperplasia, two underwent radical prostatectomy for prostate cancer, and one underwent urethral reunion, urethral stricture dilatation and cystostomy due to trauma from traffic accident. All patients had different degrees of urinary incontinence. The results of preoperative urethral profilometry test showed that the MUP of five patients were 52, 53, 88, 32, and 66 cmH(2)O(1 cmH(2)O=0.098 kPa), respectively, and the MUCP were 17, 52, 62, 27, and 40 cmH(2)O, respectively. AUS implantation was performed. The intraoperative urethral pressure profilometry showed that the MUP were 53, 113, 50, 77, and 89 cmH(2)O in the inactivated state, and the MUCP were 50, 97, 31, 71, and 51 cmH(2)O, respectively. In the activated state, the MUP were 112, 174, 193, 121, and 120 cmH(2)O, and the MUCP were 109, 160, 175, 114, and 92 cmH(2)O, respectively. All patients met the social continence (0-1 pad/d) criterion. No complications were reported during the follow-up. Conclusions: The relationship between the range of intraoperative urethral pressure and the effect of urinary control can be gained by measuring the specific values of MUP and MUCP during AUS implantation and the post-operative effects, which provides as a data basis for standardizing AUS implantation.

Analysis of continence reflexes by dynamic urethral pressure recordings in a rat stress urinary incontinence model induced by multiple simulated birth traumas.

The present study evaluated real-time changes in urethral pressure during the storage phase using a rat model with stress urinary incontinence (SUI) induced by simulated multiple birth traumas and investigated the relationship between urethral continence function and dynamic parameters associated with the changes in urethral pressure. Sprague-Dawley rats were divided into the following two groups: the sham group, which underwent three catheterizations of the vagina without distension at 2-wk intervals, and the vaginal distension (VD) group, which underwent three VDs at 2-wk intervals. After transection of the T8-T9 spinal cord, simultaneous bladder and urethral pressure recordings were performed during intravesical pressure elevation. Urodynamic parameters such as leak point pressure (LPP), urethral baseline pressure (UBP), maximum urethral pressure (MUP), the MUP-UBP differential (dUP) during intravesical pressure elevation, the bladder pressure when urethral contraction begins (Puc), and the bladder pressure at bladder neck opening (Pno) were then measured and compared. Compared with the sham group, LPP, UBP, dUP, MUP, Puc, and Pno were significantly decreased in the VD group. Pressure differences between LPP and Pno and between LPP and UBP (LPP-UBP) were also significantly different in the two groups. However, difference values of LPP and MUP or Pno and UBP were not altered after VD. Our new methods of simultaneous recordings of dynamic changes in bladder and urethral pressures are useful to fully evaluate the functional alterations in urethral continence function in the SUI model induced by multiple VDs. Moreover, LPP-UBP values, which correspond to the difference between Valsalva LPP and maximum urethral closure pressure in clinical urodynamics, would be useful to evaluate the impaired urethral continence function after simulated birth traumas in animal models.

Effect of ASP2205 fumarate, a novel 5-HT2C receptor agonist, on urethral closure function in rats.

The pharmacological profile of ASP2205 fumarate (ASP2205), a novel 5-HT2C receptor agonist, was evaluated in vitro and in vivo. ASP2205 showed potent and selective agonistic activity for the human 5-HT2C receptor, with an EC50 of 0.85 nM in the intracellular Ca2+ mobilization assay. Rat 5-HT2C receptor was also activated by ASP2205 with an EC50 of 2.5 nM. Intraduodenal administration (i.d.) of ASP2205 (0.1-1 mg/kg) significantly elevated the leak point pressure (LPP) in anesthetized rats in a dose-dependent manner. This ASP2205 (0.3 mg/kg i.d.)-induced LPP elevation was inhibited by SB242084 (0.3 mg/kg i.v.), a selective 5-HT2C receptor antagonist. Urethral closure responses induced by intravesical pressure loading in rats were enhanced by ASP2205 (0.3 mg/kg i.v.), which was abolished by pretreatment with SB242084 (0.3 mg/kg i.v.) and bilateral transection of the pudendal nerve. In contrast, ASP2205 (0.3 mg/kg i.v.) did not change the resting urethral pressure in rats. These results indicate that ASP2205 can enhance the pudendal nerve-mediated urethral closure reflex via the 5-HT2C receptor, resulting in the prevention of involuntary urine loss.

Additional value of triple-sensor urethral catheter in demonstrating urethral pressure variations during filling cystometry.

AIMS: During filling cystometry, urethral pressure variations (UPV) can be observed. The clinical relevance and a clear definition of this phenomenon are still a matter of debate. For further research and definition of UPV, it is important to determine how this condition can best be demonstrated. The purpose of this study is to compare continuous urethral pressure measurements with a single urethral-sensor catheter and a triple urethral-sensor catheter in demonstrating UPV. METHODS: Seventy-five adult female patients requiring urodynamic investigation enrolled in this prospective study. All patients underwent two series of filling and voiding cystometry. One series was performed with a dual-air balloon sensor urodynamic catheter, the other series with a triple urethral-sensor catheter. UPV were defined as urethral pressure drop exceeding 30 cmH2O. RESULTS: The prevalence of UPV was 37.3% (28 out of 75 patients), more common than detrusor overactivity. The triple urethral-sensor catheter was more sensitive than the single urethral-sensor catheter: In eight patients UPV were demonstrated with both catheters and in 18 patients only in the measurement with the triple urethral-sensor catheter. This difference in detection was significant (P < .001). CONCLUSION: There is an additional value in measurement with the triple urethral-sensor catheter for demonstration of UPV during filling cystometry. Currently, continuous measurement of urethral pressure during filling cystometry and UPV is not defined within International Continence Society terminology. The single urethral-sensor catheter is useful for a start, however, it demonstrates less than half of all UPV.

Effect of a 5-HT2c receptor agonist on urethral closure mechanism in healthy women.

AIMS: To evaluate the effect of ASP2205, a selective serotonin 5-HT2c receptor agonist, and Duloxetine on the urethral pressure in healthy female subjects. METHODS: Healthy females aged 18 to 55 years were recruited for this phase 1, single site, placebo-controlled, randomized, four-period, cross-over study. The interventions were single oral doses of 10 and 60 mg ASP2205, 80 mg duloxetine, and placebo. As a pharmacodynamics endpoint, opening urethral pressure (OUP), corrected for placebo, was measured using urethral pressure reflectometry under both resting and squeezing condition of the pelvic floor at predose and 3, 6, 12, and 24 hours after dosing. Safety and tolerability of ASP2205 were also compared with duloxetine and placebo. RESULTS: Eighteen healthy women signed informed consent, however, one dropped out before dosing and one dropped out after the first period, therefore, 16 subjects completed the study. Duloxetine significantly increased the OUP during both resting and squeezing condition (maximal increase 18.1 and 16.8 cmH2 O, respectively). Both doses of ASP2205 did not increase OUP at any time point. During squeezing OUP decreased significantly in the ASP2205 60 mg group from 6 to 24 hours after dosing. All subjects experienced predominantly central nervous system-related side effects (eg, dizziness and nausea) during ASP2205 treatment, which was most pronounced at 60 mg. CONCLUSIONS: ASP2205, a serotonin 5-HT2c receptor agonist, does not increase the urethral pressure and it is therefore unlikely that 5-HT 2c receptor agonists can be used as a treatment for stress urinary incontinence. ASP2205 was less well tolerated than the high dose of duloxetine.

Prolapse reduction deteriorates the urethral closure mechanism.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) reduction is often performed in the preoperative assessment of women before POP surgery. Using urethral pressure reflectometry (UPR), we sought to investigate how POP reduction affects the urethral closure mechanism. METHODS: Women with anterior or posterior vaginal wall prolapse stage ≥II with and without POP reduction were examined with a speculum. We performed prolapse staging according to the Pelvic Organ Prolapse Quantification system, UPR measurements at rest and during squeezing, and standardized stress tests with 300 ml saline. All examinations were repeated after insertion of a speculum. RESULTS: We included 38 women: 22 with anterior and 16 with posterior vaginal wall prolapse POP-Q stage ≥II. During POP reduction, resting and squeezing urethral pressures decreased by 2.5 cmH2O (p = 0.007) and 5.1 cmH2O (p < 0.0001), respectively, in all women. During POP reduction, the number of positive stress tests increased from four (18%) to eight (36%) in women with anterior vaginal wall prolapse and from one (6%) to nine (56%) in women with posterior vaginal wall prolapse. CONCLUSIONS: POP reduction decreases urethral pressure, especially during squeezing, and consequently increases the number of positive stress tests. The test itself artificially deteriorates the urethral closure mechanism.

Acute urinary retention in two adolescent girls with imperforate hymen.

Acute urinary retention is rare symptom in young adolescent girls. Imperforate hymen can be a cause of acute urinary retention possibly due to the pressure effect of the distended vagina (hematocolpos) on the lower urinary tract. However, the mechanism of progression to urinary retention is unknown. We report on two cases of adolescent girls with imperforate hymen who presented with acute urinary retention. A series of volume tolerance tests of the urinary bladder and urodynamic studies before operation revealed highly elevated urethral resistance, which was induced by interaction of large amount of urinary volume in the bladder and the large size of hematocolpos. After operation, urinary retention could not be observed and the urethral pressure returned to normal.

The effect of single oral doses of duloxetine, reboxetine, and midodrine on the urethral pressure in healthy female subjects, using urethral pressure reflectometry.

AIMS: To evaluate the effect on urethral pressure of reference drugs known to reduce stress urinary incontinence symptoms by different effect size and mechanisms of action on urethral musculature under four test conditions in healthy female subjects using urethral pressure reflectometry. METHODS: Healthy females aged 18-55 years were recruited by advertising for this phase 1, single site, placebo-controlled, randomized, four-period, crossover study. The interventions were single oral doses of 10 mg Midodrine, 80 mg Duloxetine, 12 mg Reboxetine, and placebo. The endpoints were the opening urethral pressure measured in each period at four time points (predose and 2, 5.5, and 9 h after dosing). RESULTS: Twenty-nine females were enrolled; 25 randomized and 24 completed the study. The opening urethral pressure was higher in all measurements with filled bladder compared with empty bladder, and during squeezing compared to the resting condition. All three drugs increased the opening urethral pressure during all four conditions with a ranking of their effect on urethral pressure matching their reported clinical effect (difference vs. placebo at their reported time of peak plasma concentrations [Tmax ] during resting with filled bladder: Midodrine 9.3 cmH2 O [95%CI 3.0, 15.5], Duloxetine 24.2 cmH2 O [95%CI 17.9, 30.5], and Reboxetine 44.9 cmH2 O [95% CI 40.2, 52.8] cmH2 O). CONCLUSIONS: Urethral pressure reflectometry is capable of detecting drug-induced changes in urethral tone in various conditions. The magnitude of drug-induced changes by the test drugs seems to match their clinical profile and differences in mode of action.

Does the appearance of the urethral pressure profile trace correlate with the sphincter EMG findings in women with voiding dysfunction?

AIMS: Women with functional voiding dysfunction often experience a "catching" sensation when catheterising and are in general investigated with both urethral pressure profilometry (UPP) and sphincter electromyography (EMG). It is unknown whether the pattern of the UPP trace correlates with this sensation of "catching" or with sphincter EMG findings. METHODS: We reviewed the database of all women with voiding dysfunction who had undergone both sphincter EMG and UPP to assess for any relationship between pattern of UPP trace and "catching" on catheterization and/or sphincter EMG findings. UPP traces were classified as smooth or pulsatile and the EMG was classified as normal or abnormal. Statistical analysis was by Chi squared test for pulsatile UPP trace as a predictor of abnormal EMG. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a pulsatile UPP trace for predicting abnormal EMG were also determined. These patients were asked to complete a telephone interview assessing discomfort on catheterization, particularly on catheter removal ("catching"). RESULTS: A total of 107 women of mean age 35.8 years underwent both sphincter EMG and UPP between 2011 and 2015. There was no significant association between "catching" on catheterization and pattern of UPP. There was a significant association between the presence of a pulsatile UPP and the finding of an abnormal EMG (P < 0.0001) The PPV of pulsatile UPP for abnormal EMG was 0.82 and the NPV of pulsatile UPP for abnormal EMG was 0.74. CONCLUSIONS: A pulsatile UPP trace is a sensitive predictor for abnormal EMG in patients with voiding dysfunction. There is no obvious correlation between a pulsatile UPP trace and a reported "catching" sensation on catheterization.

Does assessing urethral function allow the selection of the optimal therapy for recurrent SUI? Report from the ICI-RS 2017.

AIMS: The management of recurrent stress urinary incontinence following failed previous continence surgery remains challenging. Whilst the role of urodynamic investigations has been questioned in the management of primary stress incontinence there is a widely held view that women with recurrent symptoms require further investigation although there is no agreement regarding which tests are required. We sought to understand what testing is recommended prior to managing this difficult cohort of patients. METHOD: This research proposal was presented at the International Consultation on Incontinence Research Society (ICI-RS) in order to clarify our current knowledge regarding the assessment of urethral function and to set research priorities for the future. RESULTS: Whilst the majority of clinicians would advocate urodynamic evaluation of women with recurrent stress incontinence following previous surgery there is no consensus of opinion as to which tests should be performed, on whom or where. The available evidence to date suggests that urethral function tests do have a role with regard to prognosis following surgery and also in planning the most appropriate surgical intervention. CONCLUSION: The ICI-RS developed a list of research questions which may be able to assist in improving the investigation and management of women with recurrent SUI. Questions included whether patients felt the information gained via urethral function tests had an important role in their counseling regarding outcome of repeat SUI surgery.

Posterior colporrhaphy does not affect the urethral closure mechanism.

INTRODUCTION AND HYPOTHESIS: Studies have suggested that a posterior vaginal wall prolapse might compress the urethra and mask stress urinary incontinence (SUI), much like an anterior vaginal wall prolapse. A recent study with urethral pressure reflectometry (UPR) has shown that the urethral closure mechanism deteriorates after anterior colporrhaphy; this could explain the occurrence of postoperative de novo SUI. We hypothesized that urethral pressure would also decrease after posterior colporrhaphy. METHODS: This was a prospective, observational study where women with posterior vaginal wall prolapse ≥stage II were examined before and after posterior colporrhaphy. We performed prolapse staging according to the Pelvic Organ Prolapse Quantification system, UPR measurements at rest, during squeezing and straining, and standardized stress tests with 300 ml saline. The women filled out International Consultation on Incontinence-Urinary incontinence (ICIQ-UI) short forms. The sample size was 18, with a power of 99.9% and a level of significance of 5%. Parameters were compared using paired t tests or Fisher's exact test, where appropriate; p values <0.05 were considered statistically significant. RESULTS: Eighteen women with posterior vaginal wall prolapse ≥stage II were recruited. One woman did not undergo surgery. There were no changes in urethral pressure at rest (p = 0.4), during squeezing (p = 0.2) or straining (p = 0.2), before and after surgery. The results of the stress tests and ICIQ-UI short forms were the same after surgery. CONCLUSIONS: The urethral closure mechanism is not affected by posterior colporrhaphy. Our study does not support the theory that the posterior vaginal wall prolapse compresses the urethra and masks SUI.