Examining the safety of mirabegron: an analysis of real-world pharmacovigilance data from the US FDA adverse event reporting system (FAERS) database.

Background: Mirabegron, the first ß-3 adrenergic receptor agonist, received approval from the Food and Drug Administration (FDA) in 2012 for the treatment of overactive bladder (OAB). This pharmacovigilance study investigated the safety profile of mirabegron treatment using the US FDA Adverse Event Reporting System (FAERS) database. Methods: This study employed disproportionality analyses, including the reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) algorithm, to quantify signals of adverse events associated with mirabegron. Results: From the first quarter of 2012 to the third quarter of 2023, a comprehensive total of 14,356,234 adverse event (AE) reports were submitted to the FDA Adverse Event Reporting System database. Within this dataset, encompassing 18,763 reports specifically associated with mirabegron, healthcare professionals notably contributed 2,902 of these reports. A total of 80 preferred terms (PTs) of interest were identified using both the ROR and information component algorithms. The most common AEs included blood pressure increased, urinary retention, atrial fibrillation, dry mouth, and tachycardia, which were consistent with the product instructions. Unexpected significant AEs, such as arrhythmia, palpitations, dementia, transient ischemic attack, Parkinson's disease, anti-neutrophil cytoplasmic antibody positive vasculitis, lip swelling, and swollen tongue, were also identified. The study findings indicated that the majority of onset time occurred within 30 days (n = 358, 55.68%). However, AEs were still possible after 1 year of mirabegron treatment. Conclusion: This study provided valuable evidence for the real-world safety of mirabegron, helping clinical professionals enhance their understanding of mirabegron's safety in clinical practice. It also contributed valuable evidence for further safety studies on mirabegron.

Association of socioeconomic status and overactive bladder in US adults: a cross-sectional analysis of nationally representative data.

Background: Socioeconomic status inequality is an important variable in the emergence of urological diseases in humans. This study set out to investigate the association between the prevalence of overactive bladder (OAB) and the poverty income ratio (PIR) that served as a more influential indicator of socioeconomic status compared to education and occupation. Method: Data from the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2020 were used in this cross-sectional study. The association between the PIR and OAB was examined using weighted multivariate logistic regression and weighted restricted cubic splines (RCS). Additionally, interaction analysis was used for investigation to the connections between PIR and OAB in various covariate groups in order to confirm the stability of the results. Results: We observed a noteworthy inverse association between PIR and OAB after adjusting for potential confounding variables (OR = 0.87, 95% CI, 0.84-0.90, p < 0.0001). PIR was transformed into categorical variables, and the association held steady after that (1.0 < PIR <4.0 vs. PIR ≤ 1.0, OR = 0.70, 95% CI =0.63-0.77, p < 0.0001; PIR ≥ 4.0 vs. PIR ≤ 1.0, OR = 0.56, 95% CI =0.48-0.65, p < 0.0001). Additionally, RCS analysis showed that PIR and OAB had a negative nonlinear response relationship. Subgroup analyses showed that the inverse association between PIR and prevalence of OAB was stronger in obese than in nonobese individuals (P for interaction < 0.05). Conclusion: In our study, we observed a significant negative association between the PIR and the prevalence of OAB. In the future, PIR could be used as a reference standard to develop strategies to prevent and treat OAB.

Fragility of overactive bladder medication clinical trials: A systematic review.

PURPOSE: Overactive bladder (OAB) syndrome significantly impairs quality of life, often necessitating pharmacological interventions with associated risks. The fragility of OAB trial outcomes, as measured by the fragility index (FI: smallest number of event changes to reverse statistical significance) and quotient (FQ: FI divided by total sample size expressed as a percentage), is critical yet unstudied. MATERIALS AND METHODS: We conducted a systematic search for randomized controlled trials on OAB medications published between January 2000 and August 2023. Inclusion criteria were trials with two parallel arms reporting binary outcomes related to OAB medications. We extracted trial details, outcomes, and statistical tests employed. We calculated FI and FQ, analyzing associations with trial characteristics through linear regression. RESULTS: We included 57 trials with a median sample size of 211 participants and a 12% median lost to follow-up. Most studies investigated anticholinergics (37/57, 65%). The median FI/FQ was 5/3.5%. Larger trials were less fragile (median FI 8; FQ 1.0%) compared to medium (FI: 4; FQ 2.5%) and small trials (FI: 4; FQ 8.3%). Double-blinded studies exhibited higher FQs (median 2.9%) than unblinded trials (6.7%). Primary and secondary outcomes had higher FIs (median 5 and 6, respectively) than adverse events (FI: 4). Each increase in 10 participants was associated with a +0.19 increase in FI (p < 0.001). CONCLUSIONS: A change in outcome for a median of five participants, or 3.5% of the total sample size, could reverse the direction of statistical significance in OAB trials. Studies with larger sample sizes and efficacy outcomes from blinded trials were less fragile.

Sacral neuromodulation in nursing home residents: Predictors of success and complications in a national cohort of older adults.

AIMS: There is limited evidence to support the efficacy of sacral neuromodulation (SNM) for older adults with overactive bladder (OAB). This study aims to report outcomes following SNM among nursing home (NH) residents, a vulnerable population with high rates of frailty and comorbidity. METHODS: This is a retrospective cohort study of long-stay NH residents who underwent a trial of percutaneous nerve evaluation (PNE) or Stage 1 permanent lead placement (Stage 1) between 2014 and 2016. Residents were identified using the Minimum Data Set linked to Medicare claims. The primary outcome of this study was successful progression from trial to implant. Rates of 1-year device explant/revisions were also investigated. RESULTS: Trial of SNM was observed in 1089 residents (mean age: 77.9 years). PNE was performed in 66.9% of residents and 33.2% underwent Stage 1. Of Stage 1 procedures, 23.8% were performed with simultaneous device implant (single-stage). Overall, 53.1% of PNEs and 72.4% of Stage 1 progressed to device implant, which was associated with Stage 1 procedure versus PNE (adjusted relative risk [aRR]: 1.34; 95% confidence interval [95% CI]: 1.21-1.49) and female versus male sex (aRR: 1.26; 95% CI: 1.09-1.46). One-year explant/revision was observed in 9.3% of residents (6.3% for PNE, 10.5% for Stage 1, 20.3% single-stage). Single stage procedure versus PNE was significantly associated with device explant/revision (aRR: 3.4; 95% CI: 1.9-6.2). CONCLUSIONS: In this large cohort of NH residents, outcomes following SNM were similar to previous reports of younger healthier cohorts. Surgeons managing older patients with OAB should use caution when selecting patients for single stage SNM procedures.

The association between wet overactive bladder and consumption of tea, coffee, and caffeine: Results from 2005-2018 National Health and Nutrition Examination Survey.

BACKGROUND & AIMS: Previous studies have reported an inconsistent relationship between overactive bladder (OAB) and the consumption of tea, coffee, and caffeine. Our study aims to determine these associations in a large and nationally representative adult sample. METHODS: This cross-sectional study included 15,379 participants from the 2005-2018 US National Health and Nutrition Examination Survey (NHANES) database. The outcome was the risk of wet OAB that was diagnosed when the OAB symptom score was ≥3 with urgent urinary incontinence and excluded other diseases affecting diagnosis. The exposures were the consumption of tea, coffee, and caffeine. Weighted logistic regression models were established to explore these associations by calculating odds ratios (OR) and 95% confidence intervals (CI), as did restricted cubic splines (RCS) used to analyze the nonlinear associations. RESULT: Of all the participants (n = 15,379), 2207 had wet OAB. Mean [SE] consumption of tea, total coffee, caffeinated coffee, decaffeinated coffee, and caffeine was 233.6 [15.7] g/day, 364.3 [15.5] g/day, 301.6 [14.9] g/day, 62.7 [7.9] g/day, 175.5 [6.6] mg/day in participants with wet OAB, respectively. In the fully adjusted model, compared to those without tea consumption, the high consumption of tea (>481 g/day) was associated with an increased risk of wet OAB (OR: 1.29; 95%CI: 1.01-1.64). Low decaffeinated coffee (0.001-177.6 g/day) had a negative association with the risk (OR: 0.66; 95%CI: 0.49-0.90). In the RCS analysis, tea consumption showed a positive linear association with the risk of wet OAB, and decaffeinated coffee showed a nonlinear relationship with the risk and had a turning point of 78 g/day in the U-shaped curve between 0 and 285 g/day. Besides, total coffee, caffeinated coffee, and caffeine consumption had no significant association with the risk. Interestingly, in the high tea consumption, participants with high total coffee consumption [>527.35 g/day, OR and 95%CI: 2.14(1.16-3.94)] and low caffeine consumption [0.1-74.0 mg/day, OR and 95%CI: 1.50(1.03-2.17)] were positively associated with the risk of wet OAB. CONCLUSION: High tea consumption was associated with the increased risk of wet OAB, especially intake together with high total coffee and low caffeine consumption, but no significant association with the single consumption of total coffee and caffeine. Low decaffeinated coffee was associated with a decreased risk of wet OAB. It is necessary to control tea intake when managing the liquid intake of wet OAB patients.

Promising therapeutic targets for the treatment of urine storage dysfunction: what's the status?

INTRODUCTION: Opinions differ on what drugs have both a rationale and a development potential for the treatment of bladder storage dysfunction. AREAS COVERED: In the present review, the focus is given to small molecule blockers of TRP channels (TRPV1, TRPV4, TRPA1, and TRPM8), P2 × 3receptor antagonists, drugs against oxidative stress, antifibrosis agents, cyclic nucleotide - dependent pathways, and MaxiK±channel - gene therapy. EXPERT OPINION: TRPV1 channel blockers produce hypothermia which seems to be a problem even with the most efficacious second-generation TRPV1 antagonists. This has so far precluded their application to urine storage disorders. Other TRP channel blockers with promising rationale have yet to be tested on the human lower urinary tract. The P2 × 3receptor antagonist, eliapixant, was tested in a randomized controlled clinical trial, was well tolerated but did not meet clinical efficacy endpoints. Antifibrosis agent still await application to the human lower urinary tract. New drug principles for oxidative stress, purine nucleoside phosphorylase inhibition, and NOX inhibition are still at an experimental stage, and so are soluble guanylate cyclase stimulators. Gene therapy with MaxiK±channels is still an interesting approach but no new trials seem to be in pipeline.

Evolving types of pudendal neuromodulation for lower urinary tract dysfunction.

Introduction: Sacral neuromodulation and posterior tibial nerve stimulation for lower urinary tract dysfunction (LUTD) and overactive bladder yield good and reliable results. However, neuromodulation research is continuously evolving because there is still need for more patient-friendly treatment options in the therapeutic management of LUTD. Pudendal neuromodulation (PNM) has been emerging as a promising alternative treatment option for the last few decades. The aim of this study is to review the current state of the art of PNM. Material and methods: A wide literature search was conducted in the field of PNM using Medline through the PubMed database and Elsevier using the Scopus database; a critical review of the results was then carried out. PNM has been studied in its various possible aspects: percutaneous PNM, transrectal/transvaginal PNM, and both percutaneous and transcutaneous dorsal genital nerve stimulation. Results: Each technique was found to result in promising improvements in different clinical outcomes, with some trials reporting even better results than sacral neuromodulation. Conclusions: As a result of a comparison between the various PNM techniques with both sacral neuromodulation and posterior tibial nerve stimulation, we think that PNM should be seen as seriously promising, and we believe it will expand the treatment options for overactive bladder. Even though several studies accordingly showed PNM to be safe and effective, a systematic review and meta-analysis were not feasible. PNM in its various techniques is a promising treatment for LUTD. Nevertheless, further research is needed to include it in treatment algorithms.

The use of Botulinum toxin in various urological conditions.

OBJECTIVE: Aim: The objective of this review paper is to comprehensively analyze and summarize the current understanding and clinical applications of Botulinum toxin in the field of urology. PATIENTS AND METHODS: Materials and Methods: The materials and methods for this review paper involved an extensive literature search on the use of Botulinum toxin in urology. Multiple online databases such as PubMed, Web of Science, and Google Scholar were utilized to gather peer-reviewed articles, clinical trials, and relevant books published within the last decades. A few articles used in the review come from before 21 century because the information is essential to fully describe the topic. Studies were selected based on their relevance to the topic, with a focus on those that reported on the clinical applications of Botulinum toxin in urology - we use information from other review papers, clinical trials and research papers. To expand the database, we have looked through the literature not only in English but also other languages. Thanks to this method we were able to compare the results from different countries and scientific groups all over the world. Data extracted from these sources were then analyzed and synthesized to provide a comprehensive overview of the subject matter. CONCLUSION: Conclusions: In conclusion, Botulinum toxin has shown significant promise and utility in the field of urology. Its ability to effectively relax muscles has led to its application in a variety of urological conditions, including NDO, OAB, BPS/IC, DSD, BPH, CPP, and PE. The effectiveness and safety of Botulinum toxin have been demonstrated in numerous studies, providing a robust evidence base for its clinical use. However, further research is needed to optimize the administration methods, dosage, and treatment protocols. Additionally, more randomized controlled trials are required to establish the long-term safety and efficacy of Botulinum toxin, especially for conditions for which the current data is limited. Overall, Botulinum toxin represents a valuable tool in the urologist's armamentarium and is likely to continue to be an area of active research and development in the future.

Sleep and Overactive Bladder in Parkinson's Disease.

Patients with Parkinson's disease (PD) have disturbances in their bladder and sleep physiology that lead to nocturia and overactive bladder (OAB). These symptoms can be extremely bothersome and impact not only their quality of life (QoL) but also the QoL of their caretakers. We aim to highlight the changes in bladder and sleep physiology in PD and explore OAB/nocturia treatment strategies in this population.

Association between overactive bladder and depression in American adults: A cross-sectional study from NHANES 2005-2018.

BACKGROUND AND AIM: Overactive bladder (OAB) and depression are both common disorders and there is research suggesting an association between the two, but there is a lack of studies with large samples. The aim of this study is to investigate the association between OAB and depressive symptoms. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) database for the period 2005 to 2018. OAB was characterized by the Overactive Bladder Symptom Score (OABSS, score > 3) and depression was diagnosed by the Patient Health Questionnaire (PHQ-9, score ≥ 10). There were three models employed in our analysis: (1) Crude model was unadjusted; (2) Model 1 was adjusted for age, sex, race/ethnicity, educational level, and marital status; (3) Model 2 was adjusted for factors in Model 1 plus the remained potential covariates. We used survey-weighted logistic regression models to assess the association between OAB and depression. Subsequently, subgroup analyses and smoothed curve analyses were used to evaluate the reliability of the findings. RESULTS: Finally, a total of 6612 participants were included in our study, consisting of 1005 participants with diagnosis of OAB and 5607 participants without diagnosis of OAB. After adjusting for all covariates, there was a significant positive association between OAB and depression (OR: 2.89, 95 % CI: 1.91, 4.37). The severity of OAB was also positively associated with depression. Compared to participants without OAB, the fully adjusted ORs for depression were 2.76 (95 % CI: 1.64, 4.65) for those with mild OAB, 3.79 (95 % CI: 1.68, 8.55) for those with moderate OAB, and 5.21 (95 % CI: 1.39, 19.53) for those with severe OAB. CONCLUSIONS: This study revealed a strong association between OAB and depression and a progressive increase in the risk of depression as the severity of OAB (mild, moderate, and severe) increased. Therefore, it is important for clinicians to recognize the assessment of OAB symptoms in patients who are at risk for or have developed depressive symptoms, as well as the mental health of patients with OAB.

Urine biomarker could be a useful tool for differential diagnosis of a lower urinary tract dysfunction.

A precision diagnosis of lower urinary tract dysfunctions (LUTD) such as bladder outlet obstruction, detrusor overactivity (DO), interstitial cystitis/bladder pain syndrome (IC/BPS), dysfunctional voiding (DV), or detrusor underactivity (DU) needs invasive videourodynamic study. Exploring non-invasive tools to help screening LUTD is necessary for clinicians in their daily practice. This article reviews recently clinical studies of using urinary inflammatory proteins and oxidative stress biomarkers in the identification of specific LUTD among men and women with lower urinary tract symptoms (LUTS). Some important findings have been reported: (1) Using urine chemokines CXCL-1 and interleukin-8 (IL-8), we may discriminate overactive bladder (OAB) symptoms in women between DO and urinary tract infection. (2) Urinary levels of oxidative stress biomarkers such as 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane have a potential being used as a tool to identify women with mixed DO and stress urinary incontinence. (3) Urine levels of total antioxidant capacity (TAC), and prostaglandin E2 (PGE2) are positively correlated with voiding detrusor pressure in patients with DU. (4) Urine levels of brain-derived neurotrophic factor (BDNF) and PGE2 were significantly higher in the DU patients with detrusor function recovery. (5) Women with DV had higher urinary levels of tumor necrosis factor-alpha (TNF-α) and 8-OHdG, and urinary IL-2 level was significantly lower. (6) Urine level of 8-isoprostane was higher in the patients with idiopathic DO and neurogenic DO. (7) Higher urine cytokine levels of monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted (RANTES), CXCL-10, IL-7, and eotaxin-1 in patients with IC/BPS than controls. (8) The urine levels of IL-8, CXCL-10, BDNF, IL-6, and RANTES were significantly higher in patients with Hunner's IC than non-Hunner's IC. (9) Male patients with IC/BPS had a significantly higher level of eotaxin, MCP-1, TNF-α, 8-OHdG, and TAC. Combining a higher eotaxin and a higher TNF-α can provide a satisfactory diagnostic value in discriminating IC/BPS from other LUTD in men. These studies provide evidence that measurement of cluster of urine biomarkers could be used as a diagnostic tool to differentiate different LUTD in patients with similar LUTS.

Efficacy and safety of pelvic floor magnetic stimulation combined with mirabegron in female patients with refractory overactive bladder: a prospective study.

Objective: To observe the efficacy and safety of pelvic floor magnetic stimulation (PFMS) combined with mirabegron in female patients with refractory overactive bladder (OAB) symptoms. Patients and methods: A total of 160 female patients with refractory OAB symptoms were prospectively randomized into two groups. Eighty cases in the combination group accepted PFMS and mirabegron therapy and 80 cases as control only accepted mirabegron therapy (The clinical trial registry number: ChiCTR2200070171). The lower urinary tract symptoms, OAB questionnaire (OAB-q) health-related quality of life (HRQol), symptom bother score and OABSS between two groups were compared at the 1st, 2nd and 4th week ends. Results: All of 160 patients were randomly assigned to two groups, of which 80 patients were included in the combination group and 80 in the mirabegron group. The incidences of LUTS, including urgency, frequent urination, and incontinence episodes, in the 2nd week and the 4th week after combination treatment were significantly lower than those in the mirabegron group (p < 0.05). The incidence of drug-related adverse events between two groups was similar, and there was no statistically significant difference (p > 0.05). With respect to secondary variables, the OAB-q HRQol score in the combination group was statistically superior in comparison with that in the mirabegron group between the 2nd week and the 4th week (p < 0.05). This was consistent with the primary outcome. Meanwhile, from the second to fourth week, the OAB-q symptom bother score and OABSS in the combination group were both lower than in the mirabegron group (p < 0.05). Conclusion: Combination therapy of PFMS and mirabegron demonstrated significant improvements over mirabegron monotherapy in reducing refractory OAB symptoms for female patients, and providing a higher quality of life without increasing bothersome adverse effects. Clinical Trial Registration: https://www.chictr.org.cn/, ChiCTR-INR-22013524.

[Urinary tract infection and overactive bladder. Is there an association?]

A discussion of key research findings dedicated to the relationship between urinary tract infection (UTI) and overactive bladder (OAB) is presented in the article. The results of the publications support the concept that UTI may be an underappreciated contributor to the development of OAB in some patients and vice versa. This information raises a number of questions regarding the treatment and diagnosis of OAB and UTI. The main question is the potential use of antibiotics, anti-inflammatory drugs, and other drugs in the treatment of patients with OAB, as well as the rationale for the use of therapy that normalize lower urinary tract (LUT) function in the presence of chronic recurrent UTI.

Novel pharmacotherapeutic avenues for bladder storage dysfunction in men.

INTRODUCTION: Bladder storage dysfunction is associated with low quality of life in men and remains a challenging field in pharmacotherapy because of low persistence followed by patient-perceived lack of efficacy and adverse effects. The persistent desire for the development of novel pharmacotherapy is evident, leading to numerous research efforts based on its pathophysiology. AREAS COVERED: This review describes the pathophysiology, current pharmacotherapeutic strategies, and emerging novel drugs for male bladder storage dysfunction. The section on emerging pharmacotherapy provides an overview of current research, focusing on high-potential target molecules, particularly those being evaluated in ongoing clinical trials. EXPERT OPINION: As pharmacotherapies targeting alpha-adrenergic, beta-adrenergic, and muscarinic receptors - the current primary targets for treating male bladder storage dysfunction - have demonstrated insufficient efficacy and side effects, researchers are exploring various alternative molecular targets. Numerous targets have been identified as central to regulating bladder afferent nerve activity, and their pharmacological effects and potential have been evaluated in animal-based experiments. However, there is a limited number of clinical trials for these new pharmacotherapies, and they have not demonstrated clear superiority over current treatments. Further research is needed to develop new effective pharmacotherapies for bladder storage dysfunction in men.

A prospective study to assess the effectiveness and safety of the BlueWind System in the treatment of patients diagnosed with urgency urinary incontinence.

BACKGROUND: Overactive bladder (OAB) affects one in six adults in Europe and the United States and impairs the quality of life of millions of individuals worldwide. When conservative management fails, third-line treatments including tibial neuromodulation (TNM) is often pursued. TNM has traditionally been accomplished percutaneously in clinic. OBJECTIVE: A minimally invasive implantable device activated by a battery-operated external wearable unit has been developed for the treatment of urgency urinary incontinence (UUI), mitigating the burden of frequent clinic visits and more invasive therapies that are currently commercially available. METHODS: A prospective, multicenter, single-arm, open-label, pivotal study evaluated the safety and effectiveness of the device in adult females with UUI (i.e., wet OAB) (BlueWind Implantable Tibial Neuromodulation [iTNM] system; IDE number #G200013; NCT03596671). Results with the device were previously published under the name RENOVA iStim, which has been since renamed as the Revi™ System. Approximately 1-month post-implantation of the device, participants delivered therapy at their convenience and completed a 7-day voiding diary before visits 6- and 12-months post-treatment initiation. The primary efficacy and safety endpoints were the proportion of responders to therapy ( ≥ 50% improvement on average number of urgency-related incontinence episodes) and incidence of adverse events from implantation to 12-month post-activation. RESULTS: A total of 151 participants, mean age 58.8 (SD: 12.5), were implanted; 144 and 140 completed the 6- and 12-month visits, respectively. The participants demonstrated mean baseline of 4.8 UUI/day (SD 2.9) and 10 voids/day (SD 3.3). Six and 12-months post-activation, 76.4% and 78.4% of participants, respectively, were responders to therapy in an intent-to-treat analysis. Of the 139 participants with completed 12-month diaries, 82% were responders, 50% were classified as "dry" (on at least 3 consecutive diary days), and 93.5% of participants reported that their symptoms improved. No implanted participant experienced an SAE related to the procedure or device. CONCLUSIONS: iTNM, delivered and powered by a patient-controlled external wearable communicating with an implant, demonstrated clinically meaningful and statistically significant improvement in UUI symptoms and a high safety profile. This therapy highlights the value of patient-centric therapy for the treatment of UUI.

Percutaneous tibial neuromodulation initial therapy compliance and subsequent third-line treatment patterns.

PURPOSE: Percutaneous Tibial Neuromodulation (PTNM) is used to treat Overactive Bladder (OAB). This analysis summarizes patient adherence to PTNM treatment and examines trends of other third-line therapy use during and after PTNM. METHODS: Optum's deidentified Clinformatics® Data Mart Database (CDM) and CMS Research Identifiable Files were queried for adults with OAB symptoms and who underwent PTNM treatment (2019-2020). We evaluated the proportion of patients who completed 12 visits within 1 year, and defined patients as treatment compliant if 12 PTNM visits were completed within 12 weeks. We then identified the proportion of patients who used other third-line therapies after PTNM and stratified these patients based on their PTNM therapy compliance status. RESULTS: 2302 patients met selection criteria from CDM and 16,473 patients from CMS. The proportion of patients completing a full PTNM treatment course increased over time; from 16% at week 12% to 42% by week 52 (CDM) and 24% to 38% (CMS). Other third-line therapy use increased over time and was higher for PTNM noncompliant versus compliant patients at 52 weeks: onabotulinumtoxinA was 6.5% versus 5.7% for noncompliant versus compliant (CMS, p = 0.0661) and 6.4% versus 4.9% (CDM, p = 0.035), SNM trial procedure was 6.5% versus 2.5% (CDM, p = 0.002) and 4.2% versus 2.0% (CMS, p = 0.010). CONCLUSIONS: Most patients are noncompliant with recommended PTNM treatment regimen. Albeit low, third-line therapy was pursued more frequently by noncompliant patients. Given low compliance, the effectiveness of PTNM may be compromised. Alternative implantable technologies may be needed to assure effectiveness of neuromodulation.

Urodynamic insights: exploring the relationship between detrusor overactivity and pelvic organ prolapse in women with urge incontinence.

PURPOSE: Pelvic organ prolapse (POP) and overactive bladder (OAB) commonly affect the aging female population. We aimed to investigate the possible relationship between the two, as reflected by urodynamic studies. METHODS: A retrospective analysis was conducted on women who underwent urodynamic studies at a university-affiliated tertiary medical center from January 2018 to January 2021. Women presenting with urge incontinence and diagnosed with detrusor overactivity (DO) were included in the study. Based on the presence or absence of a modified POP-Q ≥ grade 2, these women were categorized into two groups. Data on general demographics, clinical symptoms, and urodynamic findings were extracted and compared using SPSS. RESULTS: During the study period, 949 urodynamic evaluations were performed. Of these, 303 (31.92%) reported urge incontinence. Out of this subset, 151 (49.83%) were diagnosed with DO. Within this group, 18 (11.9%) had POP, while 134 (88.1%) did not. The POP group had a notably higher incidence of prior vaginal hysterectomy and anterior colporrhaphy (p = 0.02 and p = 0.01, respectively). While most urodynamic parameters were similar between groups, there was a significant increase in hesitancy in the POP group (13 s vs 8 s, p = 0.03). There was a trend indicating a reduced median Q max (12 ml/s vs. 18 ml/s, p = 0.06) and an increased flow time (55 s vs 40 s, p = 0.08) in the POP group. CONCLUSION: The urodynamic profile of the POP group suggests an obstructive voiding pattern. Further longitudinal research is essential to fully understand the relationship between POP and OAB.

The role of botulinum toxin in the management of nonneurogenic overactive bladder in children: Highlights for clinical practice. A systematic review.

Overactive bladder (OAB) is the most common voiding dysfunction in children; however, nonneurogenic or idiopathic OAB remains poorly studied. First-line treatment includes conservative measures; however, as many patients are refractory, have adverse effects, or are contraindicated for anticholinergics, new options must be explored. This review covers the use of intravesical botulinum toxin (BoNT) for idiopathic OAB treatment in children, emphasizing its efficacy, safety, differences between toxins, doses, and injection techniques. Clinical results were promising, with all 8 studies reporting good results. All authors used BoNT type A (BoNT-A), either onabotulinum or abobotulinum toxin A. Response rates were variable, with full-response percentages of 32%-60%. As proven by the full-response rates of 50%, repeated injections are as safe and effective as first injections. Only a few cases of urinary tract infection, transient urinary retention, and hematuria have been reported, with no major local or systemic adverse effects. Despite these limitations, evidence encourages and supports BoNT-A use as a safe and effective treatment modality for refractory idiopathic OAB in pediatric settings, regardless of dosage and target toxin. To the best of our knowledge, this is the first systematic review of the use of intravesical BoNT-A for idiopathic OAB treatment in children.

Medicinal plants and natural products for treating overactive bladder.

BACKGROUND: Overactive bladder (OAB) presents a high prevalence of 16-18% worldwide. The pathophysiology of OAB is still poorly understood while effective therapy or countermeasure are very limited. On the other hand, medicinal plants and herbal remedies have been utilized for treating lower urinary tract symptoms (LUTS) in both Eastern and Western cultures since ancient times. In recent years, accumulating progress has also been made in OAB treatment research by using medicinal plants. METHODS: Relevant literature on the studies of medicinal plants and herbs used to treat OAB was reviewed. The medicinal plants were summarized and categorized into two groups, single-herb medications and herbal formulations. RESULTS: The present review has summarized current understanding of OAB's pathophysiology, its available treatments and new drug targets. Medicinal plants and natural products which have been used or have shown potential for OAB treatment were updated and comprehensively categorized. Studies on a wide variety of medicinal plants showed promising results, although only a few phytochemicals have been isolated and identified. Until now, none of these herbal compounds have been further developed into clinical therapeutics for OAB. CONCLUSIONS: This review provides the basis for discovering and designing new phytopharmaceutical candidates with effective and well-tolerated properties to treat OAB. Increasing evidences indicate new strategies with alternative herbal treatment for OAB have high efficacy and safety, showing great promise for their clinical use. Future studies in a rigorously designed controlled manner will be beneficial to further support the eligibility of herbal treatment as OAB therapeutics.

Real-Life Treatment Outcome of Botulinum Toxin A Injection on Overactive Bladder and Voiding Dysfunction in Patients with Central Nervous System Lesions.

PURPOSE: Neurogenic lower urinary tract dysfunction (NLUTD) is common in patients with neurological lesions in the central nervous system (CNS). Medical treatment usually cannot adequately relieve NLUTD. This study reported the real-life treatment outcome of botulinum toxin A (BoNT-A) for overactive bladders (OAB) and voiding dysfunction in patients with CNS lesions. METHODS: We retrospectively analyzed the first-time treatment outcome of 74 patients who received detrusor 100 U BoNT-A for OAB and 45 patients who received a urethral sphincter 100 U BoNT-A injection for voiding dysfunction. The treatment outcome, therapeutic duration, and adverse events (AE) after BoNT-A were compared among different CNS lesions and among patients with different urodynamic characteristics. RESULTS: The study included 74 patients receiving detrusor injections for OAB (36 with cerebrovascular accidents, 13 with Parkinson's disease, and 25 with dementia) and 45 patients receiving a urethral sphincter injection for voiding dysfunction (26 with cerebrovascular accidents, 7 with Parkinson's disease, and 12 with dementia). After detrusor BoNT-A treatment, urinary continence was achieved in 28.4% of patients with neurogenic OAB, postoperative difficult urination in 59.5%, acute urinary retention (AUR) in 9.5%, and urinary tract infection (UTI) in 14.9%, with a therapeutic duration of 6.43 months. There were no differences among subgroups or between patients with detrusor overactivity (DO) and DO with detrusor underactivity (DU) in terms of treatment outcomes and AEs. The improvement rate of urethral sphincter BoNT-A injections was 75.6% without any difference among subgroups. After treatment, 24.4% of the patients had exacerbated urinary incontinence, 33.3% had persistent difficult urination, and 15.6% had UTI. Patients with dementia had higher rates of difficult urination and UTI, higher postvoid residual volume, and a shorter therapeutic duration. Patients with DU and those without urethral sphincter dyssynergia had less favorable outcomes after their urethral sphincter BoNT-A injection. CONCLUSIONS: The therapeutic efficacy of detrusor BoNT-A injection for OAB due to CNS lesions is limited, with high rates of difficult urination, AUR, and UTI. Although urethral sphincter BoNT-A injection is effective in treating voiding dysfunction; however, exacerbated urinary incontinence and persistent difficult urination remain a problem, particularly in patients with dementia.