Does COVID-19 cause or worsen LUT dysfunction, what are the mechanisms and possible treatments? ICI-RS 2023.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and produced a worldwide pandemic in 2020. There have been 770,875,433 confirmed cases and 6,959,316 attributed deaths worldwide until September 19, 2023. The virus can also affect the lower urinary tract (LUT) leading to bladder inflammation and producing lower urinary tract symptoms (LUTS) in both the acute and chronic phases of disease. METHODS: At the 2023 meeting of the International Consultation on Incontinence-Research Society (ICI-RS), the literature relating to COVID-19 and bladder dysfunction was reviewed. The LUTS reported, as well as the pathophysiology of these bladder symptoms, were the subject of considerable discussion. A number of different topics were discussed including lower LUTS reported in COVID-19, how SARS-CoV-2 may infect and affect the urinary tract, and proposed mechanisms for how viral infection result in new, worsened, and in some persisting LUTS. CONCLUSIONS: The workshop discussed the interaction between the virus and the immune system, covering current evidence supporting theories underlying the causes of acute and chronic LUTS related to COVID-19 infection. Research questions for further investigation were suggested and identified.

Propolis as an adjunctive therapy for treatment of uncomplicated cystitis in women: A randomized double-blind placebo-controlled trial.

The current research is designed to investigate the effect of propolis supplementation on the clinical manifestations in women suffering from uncomplicated cystitis. In this randomized double-blind, placebo-controlled trial, 120 women with uncomplicated cystitis were selected and randomly assigned into two groups to receive two 500 mg capsules of propolis or placebo daily for 7 days along with ciprofloxacin (250 mg). Clinical symptoms including hematuria, urinary frequency, dysuria, suprapubic pain, and urgency, as well as bacteriuria, were assessed before and after the intervention. After supplementation, participants in the intervention group had significantly fewer days of urinary frequency (p < 0.001), dysuria (p = 0.005), and urgency (p = 0.03). However, there was no significant difference between the two groups regarding hematuria and suprapubic pain (p > 0.05). Furthermore, the severity of bacteriuria decreased significantly in both groups. In conclusion, it seems that propolis supplementation in women with uncomplicated cystitis could improve urinary frequency, dysuria, and urgency. However, further clinical trials should be conducted to fully understand the effects of propolis in women suffering from uncomplicated cystitis.

Beneficial effects of saw palmetto (Serenoa repens) fruit extract on the urinary symptoms of healthy Japanese adults with possible lower urinary tract symptoms: A randomized, double-blind, placebo-controlled study.

Saw palmetto extract (SPE) is the most commonly used supplement for the treatment of lower urinary tract symptoms (LUTS), but most evidence is for those with LUTS, and little data is verifying its effectiveness for those who do not have the disease but are troubled by symptoms. The purpose of this study was to examine the effect of SPE on the improvement of urinary frequency problems that present stress due to urinary urgency in daily life, among healthy Japanese adults aged ≥50 years who are not diagnosed with benign prostatic hyperplasia or overactive bladder. They were randomly assigned to the SPE group or placebo group (34 participants per group) using a computerized random number generator. Each participant was instructed to take one capsule containing SPE (320 mg) or placebo every day for 12 weeks. Subjective symptoms were assessed using the overactive bladder questionnaire, and the score of symptom bother by frequent urination during the daytime hours was set as the primary outcome. The other outcomes were subjective urinary symptoms and urinary frequencies. The final efficacy analysis dataset was per protocol set, and 33 participants in each group were analyzed. After SPE intervention for 12 weeks, the score of symptom bother by frequent urination during the daytime hours was significantly improved and the daytime frequency of urination assessed using the urinary log was significantly decreased. The consumption of SPE improved urinary frequency-related quality of life such as bother of urinary symptoms in healthy Japanese adults (UMIN000045334).

Effects of preoperative intravaginal estrogen on pelvic floor disorder symptoms in postmenopausal women with pelvic organ prolapse.

BACKGROUND: Menopause and the decline in systemic estrogen are associated with the development of pelvic floor disorders, such as prolapse, urinary incontinence, overactive bladder, and vulvovaginal atrophy symptoms. Past evidence suggests that postmenopausal women with symptomatic prolapse gain benefit from the preoperative application of intravaginal estrogen, but it is unknown whether they would experience improvement in other pelvic floor symptoms when treated with intravaginal estrogen. OBJECTIVE: This study aimed to determine the effects of intravaginal estrogen (compared with placebo) on stress and urgency urinary incontinence, urinary frequency, sexual function and dyspareunia, and vaginal atrophy symptoms and signs in postmenopausal women with symptomatic prolapse. STUDY DESIGN: This was a planned ancillary analysis of a randomized, double-blind trial, "Investigation to Minimize Prolapse Recurrence Of the Vagina using Estrogen," which included participants with ≥stage 2 apical and/or anterior prolapse scheduled for transvaginal native tissue apical repair at 3 US sites. The intervention was 1 g conjugated estrogen intravaginal cream (0.625 mg/g) or identical placebo (1:1), inserted nightly for 2 weeks and then twice weekly for ≥5 weeks total before surgery and continued twice weekly for 1 year postoperatively. For this analysis, question responses were compared from participants' baseline and preoperative visits: lower urinary tract symptoms (Urogenital Distress Inventory-6 Questionnaire); sexual health questions, including dyspareunia (Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-IUGA-Revised); and atrophy-related symptoms (dryness, soreness, dyspareunia, discharge, and itching; each scored 1-4, 4 being quite a bit bothersome). Masked examiners assessed vaginal color, dryness, and petechiae (each scored 1-3, total range 3-9, with 9 being the most estrogenized appearing). Data were analyzed by intent to treat and "per protocol" (ie, those adherent with ≥50% of expected intravaginal cream use, per objective tube before and after weights). RESULTS: Of 199 participants randomized (mean age of 65 years) and contributing baseline data, 191 had preoperative data. The characteristics were similar between groups. Total Urogenital Distress Inventory-6 Questionnaire scores showed minimal change during this median time of 7 weeks between baseline and preoperative visits, but for those with at least moderately bothersome baseline stress urinary incontinence (32 in the estrogen group and 21 in the placebo group), 16 (50%) in the estrogen group and 9 (43%) in the placebo group showed improvement (P=.78). In addition, 43% of participants in the estrogen group and 31% of participants in the placebo group showed improvement in urgency urinary incontinence (P=.41), and 41% of participants in the estrogen group and 26% of participants in the placebo group showed improvement in urinary frequency (P=.18). There was minimal change in the Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-IUGA-Revised scores among sexually active women; dyspareunia rates did not differ between intravaginal estrogen and placebo at the preoperative assessment: 42% and 48%, respectively (P=.49). The maximum score for most bothersome atrophy symptom (among those with baseline symptoms and adherent to study cream) improved slightly more with intravaginal estrogen (adjusted mean difference, -0.33 points; 95% confidence interval, -0.98 to 0.31), but this was not statistically significant (P=.19). However, on examination, among adherent participants, objective signs of atrophy were more improved with intravaginal estrogen treatment (+1.54 vs +0.69; mean difference, 0.85; 95% confidence interval, 0.05-1.65; P=.01). CONCLUSION: Despite objective changes in the vaginal epithelium consistent with increased estrogenization among drug-adherent participants, the results were inconclusive regarding whether 7 weeks of preoperative intravaginal estrogen cream in postmenopausal women with symptomatic pelvic organ prolapse was associated with improved urinary function, sexual function, dyspareunia symptoms, and other symptoms commonly attributed to atrophy. Additional study is needed.

Healthy bladder storage and emptying functions in community-dwelling women measured by a 2-day bladder health diary.

INTRODUCTION: The prevalence of healthy bladder storage and emptying function in community-dwelling women is not well established. METHODS: A planned secondary analysis of a US cross-sectional study designed to validate a bladder health instrument was conducted in women aged ≥18 years. A subset was invited to complete the novel 2-day bladder health diary capturing bladder storage and emptying experiences. Overall healthy bladder function was defined as ≤8 waking/daytime voids and ≤1 void during sleeping/nighttime; along with the absence of leakage, urgency, emptying difficulties (initiation, flow, efficacy, relief of urge sensation) and pain. Descriptive statistics of healthy bladder functions and regression models of factors associated with healthy function are reported. RESULTS: Of the 383 invited, 237 (62%) eligible women returned complete dairies. Of these, 12% (29/237) met criteria for overall healthy bladder function. Most (96%) denied pain, 74% had healthy daytime and 83% had healthy nighttime voiding frequency, 64% were continent, 36% reported healthy emptying and 30% denied any urgency episodes. Middle income (odds ratio [OR]:95% confidence interval [CI] = 11.4:1.9-67.4 for $75k-$99 999 vs. $25 000-$49 999), Graduate education (4.8:1.4-17) and previously seeking treatment for bladder problems (OR:95%CI = 0.1; 0-0.9) were associated with overall healthy function. CONCLUSION: The prevalence of overall healthy bladder function was very low based on our strict definition of health as measured on a 2-day diary. However, most women had healthy voiding frequency and denied pain or urinary leakage. Postvoid dribbling and urgency most commonly contributed to an overall unhealthy bladder. Further investigation is needed to determine whether these diary derived measures are meaningful for patient-oriented bladder health research.

Reduced versus standard intradetrusor OnabotulinumtoxinA injections for treatment of overactive bladder.

BACKGROUND: Intradetrusor onabotulinumtoxinA injection is an effective advanced treatment for overactive bladder. While the effective dosages have been well studied, very little data exist on treatment efficacy using differing injection techniques. The objective of this study was to determine whether the efficacy of a reduced injection technique of 5 injection sites was noninferior to the standard technique of 20 injection sites of intradetrusor onabotulinumtoxinA for treatment of overactive bladder. METHODS: In this randomized noninferiority trial, men and women seeking treatment of overactive bladder with intradetrusor onabotulinumtoxinA injections were randomized to receive 100 units administered via either a reduced injection technique of 5 injection sites or a standard injection technique of 20 injection sites. Subjects completed a series of standardized questionnaires at baseline and at 4-12 weeks postprocedure to determine symptom severity and treatment efficacy. The primary outcome was treatment efficacy as determined by Overactive Bladder Questionnaire-Short Form with a noninferiority margin of 15 points. Secondary outcomes were incidence of urinary tract infection and urinary retention requiring catheterization. RESULTS: Data from 77 subjects were available for analysis with 39 in the control arm (20 injections) and 38 in the study arm (5 injections). There was a significant improvement in both arms from baseline to follow-up in Overactive Bladder Questionnaire-Short Form and International Consultation on Incontinence Questionnaire scores (p < 0.001). Overall treatment success was 68% with no statistically significant difference between arms. A significant difference between arms was found on the Overactive Bladder Questionnaire-Short Form quality of life survey favoring the control arm (confidence interval [CI]: 0.36-20.5, p = 0.04). However, there were no significant differences between arms in the remaining validated questionnaires. The study arm did not demonstrate noninferiority to the control arm. Subjects in the study arm were significantly more likely to express a willingness to undergo the procedure again (odds ratio = 3.8, 95% CI: 1.42-10.67, p = 0.004). Adverse events did not differ between arms. CONCLUSIONS: A reduced injection technique for administration of intradetrusor onabotulinumtoxinA demonstrates similar efficacy to the standard injection technique but did not demonstrate noninferiority. Subjects preferred the reduced injection technique over the standard technique. A reduced injection technique is a safe and effective alternative to the standard technique.

Initial experience using the Axonics sacral neuromodulation system in patients with multiple sclerosis.

INTRODUCTION: Sacral neuromodulation (SNM) is third-line therapy approved for urge urinary incontinence (UUI) and urgency, and nonobstructive urinary retention. Multiple sclerosis (MS) patients often suffer from neurogenic lower urinary tract dysfunction (NLUTD). The utility of SNM in the MS population is limited by magnetic resonance imaging (MRI) incompatibility as routine MRIs to evaluate for disease progression are required. The Axonics System is the first Food and Drug Administration-approved SNM device that is 1.5/3 T full-body MRI-conditionally safe. This study seeks to investigate the symptomatic improvement in MS patients after implantation of the Axonics System. METHODS: All MS patients who elected for Axonics SNM from December 2019 to January 2021 were included. Demographics and scores were queried for urogenital distress inventory (UDI-6), incontinence impact questionnaire (IIQ-7), and global response assessment (GRA). RESULTS: Fifteen MS patients with UUI were included. The time to follow-up averaged 121 days. On UDI-6, 12 patients reported improvement, 1 worsening, and 2 no change. Average UDI-6 scores before and after implantation were 56.6 and 25.2 (p < 0.0001). Improvements were significant for all questions under stress urinary incontinence, UUI, and voiding difficulty subcategories. On IIQ-7, 14 patients reported improvement and 1 reported worsening. Average IIQ-7 scores before and after implantation were 59.0 and 22.2 (p < 0.001). Improvements were significant for travel, social, and emotional subcategories, but not for physical activity. The average GRA score was 6 ("moderately improved"). CONCLUSION: The majority of MS patients reported significant initial improvement in UUI and associated quality of life measures on validated questionnaires after implantation of the Axonics System. Future studies are needed to determine the long-term outcomes and durability of this MRI full-body conditionally-safe system.

Laparoscopic resection rectopexy significantly affects preexisting urinary symptoms in female patients.

PURPOSE: It has previously been noted that following rectopexy, some patients report changes in urinary function. So far, not much is known about the extent of such changes. This study assesses the effects of laparoscopic rectopexy on urinary symptoms. METHODS: Prospective observational study with 100 consecutive female patients indicated for laparoscopic resection rectopexy. Stated urinary symptoms, pre- and postoperative "International Consultation on Incontinence Questionnaire" (ICIQ), supplemented by a "quality of life " (QoL) visual analogue scale, and residual urine measurements (RUM) were compared and correlated. RESULTS: Postoperative QoL was significantly improved, irrespective of preexisting urinary symptoms. Twenty-four (24%) patients noticed improved urinary function. This corresponded with 42% of 45 patients who had positive preoperative ICIQ scores indicating preexisting urinary symptoms. Conversely, 14 (14%) patients noticed a postoperative increase of urinary complaints. The stated symptom change was only in part reflected by changes of the ICIQ scoring. Comparing ICIQ, 19 (19%) patients scored "better" postoperatively against 8% scoring worse; 5 of the 8 patients experienced "de novo" symptoms. The improved postoperative ICIQ scoring was highly significant. RUM did not sufficiently correlate to symptoms/ICIQ for any meaningful conclusion. CONCLUSIONS: Laparoscopic resection rectopexy had predominantly beneficial and to a lesser extent detrimental effects on urinary symptoms. Effects were highly significant; they were mainly noted in patients with preexisting urinary complaints. So far, it is not possible to predict such effects on an individual basis. It appears likely that similar effects may be found for most of the alternative operative procedures for the treatment of rectal prolapse. Without more factual knowledge and awareness about the extent of potential "collateral" effects of pelvic floor repair procedures, expert guidance of patients appears limited.

Pelvic organ prolapse surgery and overactive bladder symptoms-a population-based cohort (FINPOP).

INTRODUCTION AND HYPOTHESIS: It is unclear how compartment of pelvic organ prolapse (POP) impacts overactive bladder (OAB) symptom severity or improvement after POP surgery. We hypothesized that anterior and apical prolapse are more strongly associated with OAB symptoms than posterior compartment prolapse. METHODS: A total of 2933 POP surgeries from a prospective population-based cohort were divided into two groups: (1) anterior and/or apical compartment surgery (± posterior repair), N = 2091; (2) posterior repair only, N = 478. Urinary frequency and urgency urinary incontinence (UUI) were evaluated using PFDI-20 (bothersome symptom: score 3-4) at baseline, 6, and 24 months. Association between degree of POP in specific compartments and symptoms at baseline was estimated with generalized linear models and between compartment of surgery and symptom improvement with generalized estimating equations. RESULTS: At least one bothersome symptom was reported by 40% at baseline, 14% at 6, and 19% at 24 months. At baseline, urinary frequency was associated with degree of anterior and apical and UUI with anterior compartment prolapse. Women undergoing surgery for anterior/apical compartment started with worse symptoms and experienced greater improvement than women undergoing posterior compartment surgery. Bothersome frequency resolved in 82% after anterior/apical and in 63% after posterior compartment surgery. Bothersome UUI resolved in 75% after anterior/apical and in 61% after posterior compartment surgery. After surgery, symptom severity was comparable between groups. Bothersome de novo symptoms occurred in 1-3%. CONCLUSIONS: OAB symptoms are more strongly related to anterior and apical than to posterior compartment prolapse, but improvement is seen after surgery for any vaginal compartment.

Normative noninvasive bladder function measurements in healthy women: A systematic review and meta-analysis.

AIM: To conduct an evidence synthesis of normative reference values for bladder function parameters in women. METHODS: We conducted a systematic review and meta-analysis of studies reporting bladder function parameters obtained from noninvasive tests in healthy women. Seven databases were searched for relevant studies from inception through December 2018, with manual searching of reference lists. We included English language articles that provided quantitative data on urination frequency, voided and postvoid residual volumes, and uroflowmetry results in women without lower urinary tract symptoms. Study selection, data extraction, and quality assessment were undertaken by at least two independent reviewers. Random-effects meta-analytic models were used to derive study-level pooled mean estimates and 95% confidence intervals. RESULTS: A total of 24 studies (N = 3090 women, age range, 18-91 years) met eligibility criteria. Pooled mean estimates of bladder function parameters were: 6.6 daytime voids (95% confidence interval (95% CI), 6.2, 7.0), 0.4 nighttime voids (95% CI, 0.0, 0.8), 1577 mL for 24-hour voided volume (95% CI 1428,1725); 12 mL for postvoid residual volume (95% CI, 4, 20); and 28 mL/sec for maximum flow rate (95% CI, 27,30). Between-study heterogeneity was high for all outcomes (I2 = 61.1-99.6%), but insufficient data were available to explore reasons for this high heterogeneity (eg, differences by age). CONCLUSION: Although summary mean estimates of bladder function parameters were calculated, the wide heterogeneity across studies precludes generalization of these estimates to all healthy women. Further research is needed to determine normative reference values within specific groups, such as those defined by age.

Enduring impact of childhood adversity on lower urinary tract symptoms in adult women.

AIMS: To determine whether childhood adversity is associated with self-reported lower urinary tract symptoms (LUTS) among older adult women. METHODS: A convenience sample of women (≥55 years old) who presented to an academic urology practice or who had participated in a previous bladder health prevention study completed questionnaires including the LUTS Tool (on frequency and bother of LUTS), the Adverse Childhood Experiences (ACEs) Questionnaire, the Spielberger State-Trait Anxiety Inventory, and the Center for Epidemiologic Studies Depression Scale. RESULTS: The average age (SD) of participants (N = 151) was 64.7 (6.9) years. The total number of ACEs predicted the total number of LUTS, ß = .39 (95% confidence interval [CI] = 0.14, 0.64), P = .003, as well as LUTS frequency, ß = .09 (95% CI = 0.04, 0.13), P < .001. ACEs predicted bother for nocturia, ß = 0.12 (95% CI = 0.03, 0.22), P = .008. Negative affect symptoms did not mediate the relationship between the total number of ACEs and the total number of LUTS. Rather, ACEs predicted LUTS and negative affect symptoms through (at least partially) independent pathways. Analyses controlled for tobacco use, number of vaginal deliveries, hypertension, overactive bladder medication use, body mass index, income, and race because these variables were significantly associated with the total number of ACEs or total number of LUTS. CONCLUSIONS: Childhood adversity has an enduring impact on risk for LUTS in adulthood even when controlling for potential confounds and this relationship cannot be explained by negative affect symptoms.

Effects of non-ablative vaginal erbium:YAG laser treatment for interstitial cystitis/bladder pain syndrome: a case series (UNICORN-2 study).

Purpose: There are no established treatments for treating interstitial cystitis/bladder pain syndrome (IC/BPS). We conducted a study to verify the effectiveness of non-ablative vaginal erbium:YAG laser (VEL) treatment for patients with IC/BPS who were resistant to conventional treatments.Methods: A total of 12 patients without improvement after several treatments before 2016 underwent VEL treatment once a month for 12 months as per their convenience. The numeric rating scale-11 (NRS-11), O'Leary-Sant interstitial cystitis symptom and problem indexes (ICSI and ICPI), functional bladder capacity, and daily urinary frequency were obtained.Results: In total, nine patients responded to the treatment and three did not. The NRS-11 scores and ICSI and ICPI improved in all responders. The bladder capacity and urinary frequency also normalized. The residual effect lasted for 18 months from the first treatment without long-term side-effects.Conclusions: VEL treatment is a safe and effective treatment in patients with IC/BPS.

How can we improve the diagnosis and management of bladder pain syndrome? Part 1: ICI-RS 2018.

BACKGROUND: This paper summarizes the discussion in a think tank at the ICI-RS 2018 about the diagnosis of bladder pain syndrome (BPS). AIMS: To review the guidelines, investigations and subtypes of BPS. MATERIALS AND METHODS: Review of literature in the light of the think tank discussion. RESULTS: All guidelines recommend completing history, physical examination, urine analysis, urine culture, and urine cytology to define the BPS phenotype but there are differences on further investigations. In those guidelines which recommend cystoscopy, the identification of Hunner's lesions (HLs) is recommended as this changes the treatment plan and outcome. CONCLUSION: We propose that the differentiation of Hunner's ulcers is an important step in the assessment of these patients. Further suggestions for research are suggested.

Randomized, open-label, tolterodine-controlled, comparative study of the novel antimuscarinic agent imidafenacin in patients with overactive bladder.

BACKGROUND: The role of the selective antimuscarinic imidafenacin in Caucasian patients with overactive bladder (OAB) has not been previously assessed. OBJECTIVE: To evaluate the safety and efficacy of imidafenacin 0.2 mg vs tolterodine 4 mg per day in patients with OAB. DESIGN SETTING AND PARTICIPANTS: This study was a randomized, open-label, tolterodine-controlled, comparative multicenter trial of 300 randomized patients with OAB symptoms for 12 weeks with full analysis of 289 patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Based on 5-day bladder diaries, the primary efficacy endpoint was the change in the mean number of micturitions per day. The secondary endpoints were the change in the mean incontinence episodes, voiding frequency, the OAB Awareness Tool score, and the European Quality of Life Questionnaire (EQ-5D) score. The superiority of tolterodine over imidafenacin in the mean number of micturitions/24 hours was the null hypothesis. RESULTS AND LIMITATION: The median age was 46.6 years, and 82% of patients were female. After treatment, the change in the mean number of incontinence episodes was -2.1 ± 2.2 in the imidafenacin group and -1.9 ± 1.8 in the tolterodine group (P = .001). The change in the mean number of daytime incontinence episodes was -1.7 ± 1.7 and -1.5 ± 1.4 ( P = .01). The OAB Awareness Tool score decreased by 14.2 ± 8.5 and 14.5 ± 8.0, respectively ( P = 0.5). Most adverse events were mild and resolved without treatment. CONCLUSIONS: The clinical efficacy and safety of imidafenacin are not inferior to those of tolterodine for the treatment of Caucasian patients with OAB. PATIENT SUMMARY: Imidafenacin is as effective as tolterodine for the treatment of OAB.

The combination of loratadine with famotidine to relieve the symptoms of urinary frequency in female patients with bladder function disorders：First report of three cases.

WHAT IS KNOWN AND OBJECTIVES: Urinary frequency is a common presentation of bladder function disorders in female patients. Few medicines are effective in all patients. The use of loratadine combined with famotidine had not been previously reported for this indication. CASE DESCRIPTION: Three female patients complaining of urinary frequency had been given loratadine at 10 mg QD combined with famotidine 20 mg BID for about 5 months. They all achieved symptom improvement. WHAT IS NEW AND CONCLUSION: The combination of loratadine with famotidine was used to treat urinary frequency. It was safe, effective, and convenient, and may be an option for oral medical therapy in female patients with bladder function disorders.

Tadalafil improves bladder dysfunction and object recognition in rats with pelvic venous congestion.

OBJECTIVES: To examine the effects of tadalafil on bladder function and object recognition ability in rats with alterations in urinary frequency and locomotor activity as a result of pelvic venous congestion. METHODS: A total of 48 female rats were divided into three groups (sham, pelvic venous congestion and pelvic venous congestion/tadalafil groups). In the pelvic venous congestion and pelvic venous congestion/tadalafil groups, the bilateral common iliac veins and uterine veins were ligated under anesthesia. Rats in the pelvic venous congestion/tadalafil group received a diet containing tadalafil, and the other rats were fed a normal diet. After 4 weeks, rats underwent analysis of voiding behavior, locomotor activity, a novel object recognition test, continuous cystometry, measurement of plasma monoamines, and measurement of plasma and urinary nitric oxide metabolites. Expression of nitric oxide synthase messenger ribonucleic acid in the bladder wall was also assessed, along with histological examination of the bladder. RESULTS: Rats with pelvic venous congestion showed a higher urinary frequency, lower locomotor activity, and lower plasma and urinary nitric oxide levels than sham rats. The bladder wall endothelial nitric oxide synthase messenger ribonucleic acid level was low and object recognition was impaired. Pelvic venous congestion/tadalafil rats showed improvement in locomotor activity, bladder function and object recognition compared with pelvic venous congestion rats, as well as elevation of plasma and urinary nitric oxide, plasma monoamines, and bladder neuronal nitric oxide synthase messenger ribonucleic acid expression. Bladder wall vascularity was greater in pelvic venous congestion/tadalafil rats compared with sham rats. CONCLUSIONS: In rats with pelvic venous congestion, tadalafil might improve bladder function and the general condition by increasing blood flow to the bladder and brain, and by increasing dopamine levels.

Intravesical ATP instillation induces urinary frequency because of activation of bladder afferent nerves without inflammatory changes in mice: A promising model for overactive bladder.

ATP in the suburothelial layer is released from the bladder urothelium by mechanical stimuli. ATP directly activates purinergic receptors that are expressed on primary bladder afferent neurons and induces the micturition reflex. Although ATP is also released to the bladder lumen from the bladder urothelium, the role of ATP in the bladder lumen is unknown. Recently, clinical studies have reported that urinary ATP levels are much higher in patients with an overactive bladder than healthy controls. These results suggest that ATP in the bladder lumen is also involved in the micturition reflex. In this study, we performed intravesical ATP instillation in the mouse bladder. We evaluated urinary function with novel reliable methods using improved cystometry and ultrasonography, which we previously established. We found that intravesical ATP instillation induced urinary frequency because of activation of bladder afferent nerves without inflammatory changes in the bladder or an increase in post-void residual urine. These results suggest that not only ATP in the suburothelial layer, but also ATP in the bladder lumen, are involved in enhancement of the micturition reflex.

Pretransplant defunctionalized bladder-overrated condition?

AIMS: The objective of this study was to evaluate the expression of bladder receptors in patients with defunctionalized bladder (DB) and to assess voiding behavior after refunctionalization. METHODS: A total of 68 pretransplant patients were divided in two groups: DB (diuresis <300 mL/24 h; n = 33) and NDB (non-DB; diuresis ≥300 mL/24 h; n = 35). A sample of mucosa and detrusor at the site of the future ureteral implantation was collected. The following receptors were assessed by real-time polymerase chain reaction (qRT-PCR): M2 , M3 , α1D , ß3 , P2X2 , P2X3 , TRPV1, TRPV4, TRPA1, and TRPM8. At 3, 6, and 12 months after transplant patients answered IPSS and ICIQ-OAB questionnaires and filled a 3-day 24 h frequency/volume chart (FVC) at 6 and 12 months. RESULTS: The expression of all receptors in the mucosa and in the detrusor was similar in both groups, except from α1D , which was overexpressed in the detrusor of DB relatively to NDB group. ICIQ-OAB symptom score was similar between the groups at 3, 6, and 12 months. There was a reduction of this score in both groups with time. The same pattern was found for IPSS score. Bother scores were similar between groups. No difference was observed for all FVC parameters between DB and NDB patients. CONCLUSION: Gene expression of bladder receptors involved in micturition control was similar in patients with or without DB. Bladder behavior had a similar pattern independently of pretransplant residual diuresis. These findings question the relevance of the term DB in pretransplant patients.

Patterns of medical management of overactive bladder (OAB) and benign prostatic hyperplasia (BPH) in the United States.

AIMS: Overactive bladder (OAB) and benign prostatic hyperplasia (BPH) are highly prevalent conditions that place a large burden on the United States (US) health care system. We sought to analyze patterns of prescription medication usage for incident OAB in men and women, and for incident BPH in men using US health insurance claims data. MATERIALS AND METHODS: This study used Truven Health MarketScan® Commercial and Medicare Supplemental Research databases. The data were pooled from diverse points of care. BPH subjects included men age 18+ with the first and last two diagnoses of BPH ≥30 days apart and no BPH diagnosis for 1 year prior. OAB subjects included men and women age 18+, who were diagnosed similarly with incident OAB. The type of medication, medication continuation (persistence), and switching to a different medication were analyzed through September 30, 2013. RESULTS: Medication persistence was much higher overall for BPH than OAB (56% vs 34%, respectively, P < 0.0001), and was highest among men with BPH age 65+ (62%). Patients age 18-64 were less likely to continue medication than older adults (age 65+) for both BPH and OAB. A 9.4% of patients in the OAB cohort and 6.9% of men with BPH switched from one medication to another. CONCLUSIONS: Persistence was higher with BPH than OAB medications overall, whereas switching rates were higher in the OAB group. The lower persistence of OAB medication may be due to less efficacy or tolerability. The possibility of under treatment of OAB also warrants future investigations.

Troubleshooting Interstim Sacral Neuromodulation Generators to Recover Function.

PURPOSE OF REVIEW: Sacral neuromodulation (SNM) is being used to treat lower urinary tract symptoms (LUTS) with growing popularity among clinicians in multiple specialties. As this therapy becomes more common in the USA and Europe, urologists will encounter more patients implanted with SNM generators. RECENT FINDINGS: Over time, it has recently been understood that up to 53% will develop pain at the implant site as reported by Groen et al. (J Urol 186:954, 2011) and 3-38% will lose effective stimulation as reported by Al-zahrani et al. (J Urol 185:981, 2011) and White et al. (Urology 73:731, 2009). There is a paucity of troubleshooting methodology in the literature, apart from revision surgery, to salvage the SNM generator. In fact, it has been suggested that one contemporary series' failure rate is lower than some historic series because of the ability to reprogram devices as reported by Siegel et al. (J Urol 199:229, 2018). Standard algorithms for such reprogramming efforts are lacking in the literature and may salvage some patients otherwise destined for surgical revision or addition of multimodal therapy to achieve acceptable symptom control. It is possible to troubleshoot and thereby salvage many SNM generators, saving patients from surgical revision in many cases and increasing the number of patients with persistent benefit from SNM. The algorithms presented in this manuscript represent a systematic strategy for reprogramming and troubleshooting SNM generators.