Outcomes of sequential third-line therapies in patients with refractory overactive bladder.

INTRODUCTION: Sacral neuromodulation (SNM) and onabotulinumtoxinA (BoNTA) injection are third-line therapies for overactive bladder (OAB). Although the efficacy of each third-line treatment has been well established in clinical trials, there is far less information about performing one third-line therapy after the other. Our aim is thus to investigate the outcomes of post-SNM BoNTA and post-BoNTA SNM as "second" third-line treatments. METHODS: We retrospectively reviewed all OAB patients who had both SNM and BoNTA between 2013 and 2022. The primary endpoint was the response rates (>50% improvements) of the second third-line treatments. Secondary endpoints were the proportion of the patients who achieved total dry, the duration of treatments of patients who had significant responses, and risk factors that are associated with treatment response or duration of treatments. RESULTS: A total of 172 patients had two third-line therapies. There were 104 patients who had post-SNM BoNTA and 68 patients who had post-BoNTA SNM. In the post-SNM BoNTA group, 62.5% (65/104) had significant responses after BoNTA treatment. In the post-BoNTA SNM group, 61.8% (44/68) had significant responses after SNM treatment. The proportions of patients who became dry were 21.2% and 23.5%, respectively. In the post-SNM BoNTA group, spinal pathology is associated with a lower probability of a significant response (48.9% vs. 73.7%, p-value = 0.0105). CONCLUSIONS: BoNTA or SNM remains a viable option for refractory OAB after patients fail from one another. Spinal pathology is associated with a poorer response of post-SNM BoNTA.

Overactive bladder negatively affects erectile function and promotes premature ejaculation: findings from large representative population-level study.

PURPOSE: The effect of overactive bladder (OAB) on sexual health has been evaluated extensively for women but much less for men. Therefore, the aim of this study was to evaluate the relationship between OAB and men's sexual activity and the effect of OAB on erectile dysfunction (ED) and premature ejaculation (PE) in a large representative cohort of men at the population level. METHODS: This study was based on computer-assisted web interviews that used validated questionnaires. The most recent census and the sample size estimation calculations were employed to produce a population-representative pool. RESULTS: The study included 3001 men, representative of the population in terms of age and place of residence. The frequency of sexual intercourse was higher for respondents without OAB symptoms compared with persons who had OAB (p = 0.001), but there was no association between OAB symptoms and number of sexual partners (p = 0.754). Regression models did not confirm the effect of OAB on sexual activity (odds ratio 0.993, CI 0.974-1.013, p = 0.511). Both ED and PE were more prevalent in respondents with OAB symptoms compared with persons who lacked those symptoms (p < 0.001). Importantly, the effect of OAB on ED or PE was independent of age, comorbidities, and lifestyle habits (regression coefficients of 0.13 and 0.158 for ED and PE, respectively). CONCLUSION: Overactive bladder did not significantly affect men's sexual activity, but it significantly correlated with ED and PE. Our results suggest a need in daily clinical practice to screen for OAB symptoms for persons who report ED or PE.

First in Human Subjects Testing of the UroMonitor: A Catheter-free Wireless Ambulatory Bladder Pressure Monitor.

PURPOSE: Urodynamics is the standard method of diagnosing bladder dysfunction, but involves catheters and retrograde bladder filling. With these artificial conditions, urodynamics cannot always reproduce patient complaints. We have developed a wireless, catheter-free intravesical pressure sensor, the UroMonitor, which enables catheter-free telemetric ambulatory bladder monitoring. The purpose of this study was twofold: to evaluate accuracy of UroMonitor pressure data, and assess safety and feasibility of use in humans. MATERIALS AND METHODS: Eleven adult female patients undergoing urodynamics for overactive bladder symptoms were enrolled. After baseline urodynamics, the UroMonitor was transurethrally inserted into the bladder and position was confirmed cystoscopically. A second urodynamics was then performed with the UroMonitor simultaneously transmitting bladder pressure. Following removal of urodynamics catheters, the UroMonitor transmitted bladder pressure during ambulation and voiding in private. Visual analogue pain scales (0-5) were used to assess patient discomfort. RESULTS: The UroMonitor did not significantly alter capacity, sensation, or flow during urodynamics. The UroMonitor was also easily inserted and removed in all subjects. The UroMonitor reproduced bladder pressure, capturing 98% (85/87) of voiding and nonvoiding urodynamic events. All subjects voided with only the UroMonitor in place with low post-void residual volume. Median ambulatory pain score with the UroMonitor was rated 0 (0-2). There were no post-procedural infections or changes to voiding behavior. CONCLUSIONS: The UroMonitor is the first device to enable catheter-free telemetric ambulatory bladder pressure monitoring in humans. The UroMonitor appears safe and well tolerated, does not impede lower urinary tract function, and can reliably identify bladder events compared to urodynamics.

Removal of Sacral Neuromodulation Devices Is an Office Procedure.

OBJECTIVE: To present our experience removing sacral neuromodulation (SNM) components under local in the office. In some instances, SNM devices need to be removed. Traditionally, permanent lead and/or implantable pulse generator (IPG) removals are done in the operating room under sedation. However, it is our practice to perform this procedure in the office using only local anesthesia. MATERIALS AND METHODS: We performed a retrospective chart review from 2017 to 2022 of SNM lead and IPG removals performed under local anesthesia in the office by a single surgeon. Patient characteristics, outcomes, and complications were reported. RESULTS: From 2017 to 2022, 41 SNM leads with and without IPGs were removed in the office using local anesthesia. 88% were female, mean age 66 ± 15.8years, and mean body mass index 28.6 (19.1-49.4). The most common indications for SNM treatment were urgency incontinence (56%) and nonobstructive urinary retention (24%). 44% (18/41) of SNM device removals were leads removed after failed stage I and 56% (23/41) were leads with IPGs removed most commonly for decreased efficacy (52%). In the latter group, median time to removal was 3.1 (0.3-12.3) years, and 52% (12/23) required a separate medial incision for lead retrieval. 9% (2/23) required fluoroscopy, of which, one was planned secondary to body mass index 49.4, and the other needed secondary to excessive scar tissue. No stage I failures required fluoroscopy. 7% (3/41) of leads required cutdown to the sacrum for removal with leads in place between 3.1 and 3.9years. All leads were removed completely intact and there were no complications. CONCLUSION: Removal of SNM devices in the office using local anesthesia is effective, well-tolerated, and safe.

Urinalysis Exhibits Excellent Predictive Capacity for the Absence of Urinary Tract Infection.

OBJECTIVE: To assess predictive value of urinalysis for negative urine culture and absence of urinary tract infection, re-evaluate the microbial growth threshold for positive urine culture result, and describe antimicrobial resistance features. Urine culture is associated with 27% of U.S. hospitalizations, and unnecessary antibiotic prescription is a main antibiotic resistance contributor. METHODS: Urinalyses with urine culture from women ages 18-49 from 2013 to 2020 were studied. Clinically diagnosed urinary tract infection (CUTI) was defined as (1) uropathogen growth, (2) documented diagnosis of urinary tract infection, and (3) antibiotic prescription. Sensitivity, specificity, and diagnostic predictive values were used to assess urinalysis performance in predicting isolation of a uropathogen by culture and in detection of CUTI. RESULTS: Total 12,252 urinalyses were included. Forty-one percent of urinalyses were associated with positive urine culture and 1287 (10.5%) with CUTI. Negative urinalysis exhibited high predictive accuracy for negative urine culture (specificity 90.3%, PPV 87.3%) and absence of CUTI (specificity 92.2%, PPV 97.4%). Twenty-four percent of patients not meeting the CUTI definition were still prescribed antibiotics. Twenty-two percent of cultures associated with CUTI exhibited growth less than 100,000 CFU/mL. Escherichia coli was implemented as causing 70% of CUTIs, and 4.2% of these produced an extended spectrum beta-lactamase. CONCLUSION: Negative urinalysis exhibits high predictive accuracy for absence of CUTI. A reporting threshold of 10,000 CFU/mL is more clinically appropriate than a 100,000 CFU/mL cutpoint. Reflex culture based on urinalysis results could complement clinical judgement and improve laboratory and antibiotic stewardship in premenopausal women.

Effect of pulse width variations on sacral neuromodulation for overactive bladder symptoms: A prospective randomized crossover feasibility study.

INTRODUCTION/BACKGROUND: The pulse width (PW) parameter in sacral neuromodulation (SNM) is understudied, with no evidence-based guidance available on optimal PW for urinary indications. The aim of this prospective, randomized, single-blinded, 3 × 3 cross over design study was to estimate the effect of two PW settings (60 µs, 420 µs) compared to the industry standard (210 µs) on SNM efficacy, quality of life, and device parameters in patients who were stable and satisfied with their SNM treatment. METHODS/MATERIALS: Eligible patients were previously implanted and had urge incontinence or urgency-frequency with satisfaction on SNM at time of enrollment. Patients completed a 3-day voiding diary, validated questionnaires, and device interrogations with sensory threshold assessment at baseline and after a 4-week period on each of the three PW settings, to which they were randomized. Eighteen participants completed the study, as called for by power analysis. RESULTS: Eighteen patients were enrolled in the study. Mean age was 68 years and implant duration at the time of participation was 4.4 years. While PW variations did not produce significant differences in overall objective outcomes, device parameters, including sensory threshold amplitude and battery life differed significantly. Shortened PW necessitated higher amplitude while conserving battery life. Stimulus sensation location, quality, and intensity did not differ between PW. Standard PW was chosen by 11 patients after the study, 5 chose extended, and 2 chose shortened. Those who chose alternative PW achieved significant reductions in urinary frequency from enrollment -2.23 voids/day (p = 0.015). Upon sub-analysis, patients reporting "much better" or "very much better" on extended PW achieved significant reductions in urinary frequency and nocturia at 5.6 and 0.4, compared to 8.5 and 2.16 at baseline (p = 0.005, p = <0.001). Whereas those reporting "much better" or "very much better" on shortened PW achieved significant reductions in urinary frequency at 5.15 compared to 7.35 (p = 0.026). There were no adverse events or complications. CONCLUSIONS: Overall SNM effectiveness was unchanged with alternative PW; however, 39% of patients preferred alternative to standard PW and achieved significant improvements in urinary symptoms with such. Shorter PW can also provide savings in estimated battery life without sacrificing therapeutic efficacy.

Biofilms on Indwelling Artificial Urinary Sphincter Devices Harbor Complex Microbe-Metabolite Interaction Networks and Reconstitute Differentially In Vitro by Material Type.

The artificial urinary sphincter (AUS) is an effective treatment option for incontinence due to intrinsic sphincteric deficiency in the context of neurogenic lower urinary tract dysfunction, or stress urinary incontinence following radical prostatectomy. A subset of AUS devices develops infection and requires explant. We sought to characterize biofilm composition of the AUS device to inform prevention and treatment strategies. Indwelling AUS devices were swabbed for biofilm at surgical removal or revision. Samples and controls were subjected to next-generation sequencing and metabolomics. Biofilm formation of microbial strains isolated from AUS devices was reconstituted in a bioreactor mimicking subcutaneous tissue with a medical device present. Mean patient age was 73 (SD 10.2). All eighteen artificial urinary sphincter devices harbored microbial biofilms. Central genera in the overall microbe−metabolite interaction network were Staphylococcus (2620 metabolites), Escherichia/Shigella (2101), and Methylobacterium-Methylorubrum (674). An rpoB mutation associated with rifampin resistance was detected in 8 of 15 (53%) biofilms. Staphylococcus warneri formed greater biofilm on polyurethane than on any other material type (p < 0.01). The results of this investigation, wherein we comprehensively characterized the composition of AUS device biofilms, provide the framework for future identification and rational development of inhibitors and preventive strategies against device-associated infection.

Cognitive impairment does not impact sacral neuromodulation implant rates for overactive bladder.

OBJECTIVE: To evaluate the impact of cognitive impairment (CI) diagnoses on sacral neuromodulation (SNM) outcomes in older patients. MATERIALS AND METHODS: We completed a retrospective review of all patients aged ≥55 years who underwent test-phase SNM (peripheral nerve evaluation (PNE) or stage 1) for overactive bladder (OAB) between 2014 and 2021 within a large multi-regional health system. Patient demographics, relevant comorbidities, CI diagnoses (dementia or mild CI), and SNM procedures were recorded. Logistic regression modeling was performed to evaluate the impact of CI on SNM implantation rates. RESULTS: Five-hundred and ten patients underwent SNM test phase (161 PNE, 349 Stage 1) during the study period. The mean age was 71.0(8.5) years, and most (80.6%) were female. Overall, 52(10.1%) patients had a CI diagnosis at the time of SNM, and 30 (5.8%) were diagnosed at a median of 18.5 [9.25, 39.5] months after SNM. Patients with CI diagnoses were older, with more comorbidities, and were more likely to undergo PNE. Univariable comparison found no difference in implantation rate based on pre-SNM CI (85.4% vs. 76.9%, p = 0.16). Multivariable analysis identified PNE (OR 0.43, 95% CI 0.26-0.71), age (OR 0.96, 95%CI 0.93-0.98), and prior beta-3 agonist use (OR 0.60, 95% CI 0.37-0.99) but not CI or dementia as independent negative predictors of implantation. Implanted patients had a median follow-up of 25 [12.0, 55.0] months. Explant and revision rates did not differ according to CI. CONCLUSION: Patients with OAB and CI diagnoses proceed to SNM implant at rates similar to patients without CI diagnoses. A diagnosis of CI should not necessarily exclude patients from SNM therapy for refractory OAB.

Neural networks outperform expert humans in predicting patient impressions of symptomatic improvement following overactive bladder treatment.

INTRODUCTION AND HYPOTHESIS: The objective was to accurately predict patient-centered subjective outcomes following the overactive bladder (OAB) treatments OnabotulinumtoxinA (OBTX-A) injection and sacral neuromodulation (SNM) using a neural network-based machine-learning approach. In the context of treatments designed to improve quality of life, a patient's perception of improvement should be the gold standard outcome measure. METHODS: Cutting-edge neural network-based algorithms using reproducing kernel techniques were trained to predict patient-reported improvements in urinary leakage and bladder function as assessed by Patient Global Impression of Improvement score using the ROSETTA trial datasets. Blinded expert urologists provided with the same variables also predicted outcomes. Receiver operating characteristic curves and areas under the curve were generated for algorithm and human expert predictions in an out-of-sample holdout dataset. RESULTS: Algorithms demonstrated excellent accuracy in predicting patient subjective improvement in urinary leakage (OBTX-A: AUC 0.75; SNM: 0.80). Similarly, algorithms accurately predicted patient subjective improvement in bladder function (OBTX-A: AUC 0.86; SNM: 0.96). The top-performing algorithms outcompeted human experts across outcome measures. CONCLUSIONS: Novel neural network-based machine-learning algorithms accurately predicted OBTX-A and SNM patient subjective outcomes, and generally outcompeted expert humans. Subtle aspects of the physician-patient interaction remain uncomputable, and thus the machine-learning approach may serve as an aid, rather than as an alternative, to human interaction and clinical judgment.

Patient perceived improvement and medication resumption rates after intradetrusor onabotulinumtoxina for idiopathic urgency urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Intradetrusor onabotulinumtoxinA (BTX-A) is a third-line therapy for overactive bladder (OAB), however several gaps exist in periprocedural care. Prior studies have demonstrated BTX-A efficacy at 2-3 weeks, but there are limited data documenting when patients should begin to note symptom improvement. The primary aim of this study was to evaluate patient-reported temporal improvement in symptoms, with secondary aim to evaluate medication resumption rates, following initial BTX-A injection. METHODS: A prospective, single-arm cohort study of patients with non-neurogenic urgency incontinence undergoing initial BTX-A injection was performed. Intradetrusor 100 units BTX-A was administered in standard 20-site template. Patients discontinued OAB medication(s) at BTX-A injection and completed a daily Patient Global Impression of Improvement (PGI-I) diary for 3 weeks. Data were collected at 1 month, including final satisfaction score, medication resumption rates, and adverse outcomes. RESULTS: Fifty-one patients were included, with 25 patients (49%) actively taking an OAB medication. Median time to first improvement was 3 days, at least "much better" (PGI-I <2) was 5 days, and maximal improvement was 7 days. Twenty of 25 patients (80%) opted to remain off OAB medications at 1 month based on symptomatic improvement following injection. Adverse outcomes included urinary tract infection in three patients (6%) and symptomatic incomplete emptying requiring temporary intermittent catheterization in two patients (4%). CONCLUSIONS: Median time to first and maximal improvement was 3 and 7 days, respectively, following initial 100 units BTX-A. Eighty percent of patients on medications opted to remain off at 1 month. These data may help further counsel patient expectations following initial BTX-A therapy.

Successfully treated urethral condyloma acuminatum utilizing intraurethral self-application of 5-fluorouracil via Q-tip.

Condyloma acuminatum is a benign genital lesion associated with low-risk human papillomavirus subtypes. Approximately 20% of HPV-associated genital warts occur in the urethra. Topical treatment of urethral condyloma in women can be challenging to treat due to difficulty applying the medication such that it maintains contact with the urethra long enough to be effective. We present a case of a successfully cleared urethral condyloma acuminatum treated via self-application using a Q-tip.

SUFU white paper on overactive bladder anticholinergic medications and dementia risk.

AIMS: Anticholinergic medications are widely used in the treatment of overactive bladder (OAB), as well as for short-term treatment of bladder symptoms following a variety of urologic surgeries. Mounting evidence points to an association between anticholinergic medications and the increased risk of incident dementia. The Society for Urodynamics, Female Pelvic Medicine, and Urogenital Reconstruction (SUFU) thus convened a committee of subject experts to contextualize the current understanding of the cognitive risks of anticholinergic medications in the urologic patient population and to provide practical clinical guidance on this subject. METHODS: Statements are based on an expert literature review and the committee's opinion. The document has been reviewed and approved by the SUFU board. RESULTS: Chronic use (>3 months) of OAB anticholinergic medications is likely associated with an increased risk of new-onset dementia. Short-term (<4 weeks) use of most OAB anticholinergic medications is likely safe in most individuals. Clinicians should consider potential cognitive risks in all patient populations when prescribing OAB anticholinergics for chronic use. Consideration should be given to progressing to advanced therapy (botulinum toxin or neuromodulation) earlier in the OAB treatment paradigm CONCLUSIONS: The current body of literature supports a likely small but significant increased risk of dementia with chronic exposure to OAB anticholinergic medications. Potential harms should be balanced against potential quality of life improvement with treatment.

Randomised Controlled Trials Assessing the Clinical Value of Urodynamic Studies: A Systematic Review and Meta-analysis.

Context: The role of urodynamic studies (UDSs) in the diagnosis of lower urinary tract symptoms (LUTS) is crucial. Although expert statements and guidelines underline their value for clinical decision-making in various clinical settings, the academic debate as to their impact on patient outcomes continues. Objective: To summarise the evidence from all randomised controlled trials assessing the clinical usefulness of UDS in the management of LUTS. Evidence acquisition: For this systematic review, searches were performed without language restrictions in three electronic databases until November 18, 2020. The inclusion criteria were randomised controlled study design and allocation to receive UDS or not prior to any clinical management. Quality assessment was performed by two reviewers independently, using the Cochrane Collaboration's tool for assessing the risk of bias. A random-effect meta-analysis was performed on the uniformly reported outcome parameters. Evidence synthesis: Eight trials were included, and all but two focused on women with pure or predominant stress urinary incontinence (SUI). A meta-analysis of six studies including 942 female patients was possible for treatment success, as defined by the authors (relative risk 1.00, 95% confidence interval: 0.93-1.07), indicating no difference in efficacy when managing women with UDS. Conclusions: Although UDSs are not replaceable in diagnostics, since there is no other equivalent method to find out exactly what the lower urinary tract problem is, there are little data supporting its impact on outcomes. Randomised controlled trials have focussed on a small group of women with uncomplicated SUI and showed no added value, but these findings cannot be extrapolated to the overall patient population with LUTS, warranting further well-designed trials. Patient summary: Despite urodynamics being the gold standard to assess lower urinary tract symptoms (LUTS), as it is the only method that can specify lower urinary tract dysfunction, more studies assessing the clinical usefulness of urodynamic studies (UDSs) in the management of LUTS are needed. UDS investigation is not increasing the probability of success in the treatment of stress urinary incontinence.

Impact of Duration of Antibiotic Prophylaxis on Incidence of UTI after OnabotulinumtoxinA Injection.

OBJECTIVE: To assess the impact of duration of antibiotic prophylaxis on incidence of urinary tract infection (UTI) after intravesical OnabotulinumtoxinA (BTX) injection. METHODS: A retrospective cohort study of patients with overactive bladder who underwent office BTX injections from 2014 to 2020. UTI incidence within 30 days of BTX was compared between 3 durations of antibiotic prophylaxis: no antibiotic, single day, or multiple day course. Association of UTI with units of BTX, body mass index, history of diabetes, immunosuppression, neurogenic overactive bladder, chronic catheter, or recurrent UTI were investigated. RESULTS: Two hundred ninety patients and 896 cycles of BTX injections were included: 877 injections (97.7%) were women, with mean age 61.4 years (range 20-96; SD 13.3). No antibiotic prophylaxis was given to 112 (12.5%) patients, 595 (66%) received a single day, and 189 (21%) received a multiple day regimen (3-7 days). Overall incidence of UTI within 30 days was 11.4%. On multivariable logistic regression, use of any antibiotic prophylaxis was associated with a lower incidence of UTI (single odds ratio [OR] 0.34; 95% confidence interval [CI] 0.19-0.61; P < .001; multiple OR 0.47; 95% CI 0.24-0.92; P = .029), with no difference between single and multiple day regimens (OR 1.38; 95% CI 0.80-2.38; P = .249). History of recurrent UTI (OR 3.77; 95% CI 2.23-6.39; P < .001) and chronic suprapubic catheter (OR 2.88; 95% CI 1.04-7.95; P = .041) were additional predictors. CONCLUSION: A multiple day regimen of antibiotic prophylaxis was not more effective than a single day in preventing UTI for intravesical BTX injection. Use of any antibiotic prophylaxis was associated with a significantly lower incidence of UTI compared to no antibiotic.

Is sacral neuromodulation effective in patients with Parkinson's disease? A retrospective review.

INTRODUCTION AND OBJECTIVE: Parkinson's disease (PD) is the second-most common degenerative neurologic disease worldwide. Overactive bladder (OAB) is prevalent in this population but can be challenging to treat. Sacral neuromodulation (SNM) is an attractive option but remains understudied. We have utilized SNM in PD patients and herein describe our outcomes. METHODS: We performed a retrospective chart review of PD patients who underwent peripheral nerve evaluation (PNE) or Stage 1 SNM from 2000 to 2020. The primary outcome was progression to a permanent implant. The impact of PD stage and preprocedural urodynamic (UDS) parameters on test-phase outcome were investigated. Long-term efficacy was assessed using Wilcoxon matched-pairs test looking at a change in urinary symptoms (frequency, nocturia, incontinence episodes, and pad use) documented at follow-up visits and further need for treatment. RESULTS: Thirty-four patients underwent test phase SNM (7 PNE and 27 Stage 1). Median follow-up was 11 (interquartile range 5.8-29.8) months. Indications included refractory OAB (30/34) and nonobstructive urinary retention (4/34). Overall, 82% (28/34) of patients proceeded to a permanent implant. 71% (5/7) of PNEs were successful. Test-phase success did not differ based on PD disease severity or UDS parameters. In patients with OAB/urgency incontinence who progressed to the permanent implant, there was a statistically significant improvement in their urinary symptoms from baseline. Most (68%) patients were able to discontinue OAB medications post-implant. The overall lead revision rate was 14% (4/28) and 3 devices required removal. CONCLUSIONS: SNM is an efficacious treatment option for PD patients with a high percentage of patients having improvement in their urinary symptoms.