Preliminary evidence for therapeutic impact of intravesical glucosamine on protamine sulfate and potassium chloride-induced bladder overactivity in rat model.

PURPOSE: To investigate the protective effect of intravesical glucosamine in treating overactive bladder (OAB). METHODS: Ninety-two female Sprague-Dawley (SD) rats were divided into 4 groups i.e. protamine sulfate (PS), N-acetylcysteine (NAC), and glucosamine-treated PS (GPS), and normal saline control (NC) were used. We induced hyperactivity in rats via intravesical infusion of PS and potassium chloride (KCl), whereas the NC group underwent a sustained intravesical saline infusion for 1 h. N-acetylcysteine (NAC), a potential antioxidant as well as anti-inflammatory agent was employed as positive control. Cystometrography (CMG) was then conducted to determine urodynamic parameters, i.e., leak point pressure (LPP, n = 48) and inter-contractile interval, the duration between two voids (ICI, n = 32). RESULTS: LPP was significantly elevated in the GPS group (mean ± SD: 110.9 ± 6.2 mmHg) compared to the NC (81.0 ± 32.5 mmHg), PS (40.3 ± 10.9 mmHg), and NAC group (70.3 ± 19.4 mmHg). The cystometrogram data also reveals a prolonged ICI in the GPS group (241.3 ± 40.2 s) compared to the NC group (216.0 ± 41.7 s), PS group (128.8 ± 23.6 s), and NAC group (193.8 ± 28.3 s). CONCLUSION: This preliminary study implies the ameliorative impact of GPS treatment on OAB in terms of improved urodynamic parameters, including LPP and ICI.

An observational, patient-reported outcome study of sleep quality and depression among individuals with overactive bladder syndrome.

INTRODUCTION: Overactive bladder (OAB) can adversely affect health-related quality-of-life (HRQoL) and adherence to treatments; however, the extent of their association is unknown. This study sought to characterize Sleep Disturbance, Depression, Fatigue, and patient-reported medication adherence among adults with OAB in the United States. MATERIALS AND METHODS: In this descriptive, observational study, patients completed patient-reported outcome (PRO) measures of urinary symptoms, anxiety, depression, fatigue, sleep quality, and medication adherence. PRO scores were compared across age, sex, body mass index, and sleep and antidepressant medication-taking subgroups. Exploratory analyses compared PRO scores between groups and estimated the effect size of differences. RESULTS: Of 1013 patients contacted, 159 completed the assessments (female: 67.3%; ≥65 years of age: 53.5%; most severe OAB symptom: nocturia). Scale scores for Sleep Disturbance, Fatigue, and Depression were consistent with US population norms. No correlations of moderate or greater magnitude were observed between the severity of lower urinary tract symptoms and Sleep Disturbance, Fatigue, or Depression. When comparing individuals receiving antidepressants with those who were not, almost all outcomes including urinary symptoms, anxiety, and depression were significantly worse. Patients taking antidepressants also had poorer adherence to their OAB medications. CONCLUSION: In this cohort of individuals with OAB, Sleep Disturbance, Fatigue, and Depression scores were in line with general population reference values; however, among the subgroups analyzed, patients on antidepressants had worse HRQoL and more substantial impacts on medication adherence, highlighting the importance of the assessment and management of depression in this population.

The brain, gut, and bladder health nexus: A conceptual model linking stress and mental health disorders to overactive bladder in women.

OBJECTIVE: A small, but growing literature links stressors and mental health disorders (MHDs) across the life course to overactive bladder (OAB) and urinary incontinence symptoms. Mechanisms by which stressors and MHDs may impact bladder health are not fully understood, limiting novel prevention and treatment efforts. Moreover, potential biopsychosocial mechanisms involving the brain and gut have not been considered in an integrated, comprehensive fashion. METHODS: Members of the prevention of lower urinary tract symptoms Research Consortium developed conceptual models to inform research on biopsychosocial mechanisms through which stress and MDHs may impact bladder health among girls and women, focusing on brain and gut physiology. RESULTS: Two conceptual models were developed-one to explain central (brain-based) and peripheral (gut-based) mechanisms linking stressors and MHDs to OAB and bladder health, and one to highlight bidirectional communication between the brain, gut, and bladder. Traumatic events, chronic stressors, and MHDs may lead to a maladaptive stress response, including dysregulated communication and signaling between the brain, gut, and bladder. Gut bacteria produce molecules and metabolites that alter production of neurotransmitters, amino acids, short-chain fatty acids, and inflammatory immune response molecules that mediate communication between the gut and brain. Microbiota signal neurogenesis, microglia maturation, and synaptic pruning; they also calibrate brain-gut-bladder axis communication through neurotransmission and synaptogenesis, potentially influencing bladder symptom development. Life course trajectories of risk may be prevented or interrupted by central and peripheral resources for neuropsychological resilience. CONCLUSIONS: Depicted pathways, including brain-gut-bladder communication, have implications for research and development of novel prevention and treatment approaches.

The cost of lifelong LUTS-A systematic literature review.

BACKGROUND: Lower urinary tract symptoms (LUTS) are highly prevalent and very bothersome. To support the best possible allocation of health care resources and to avoid unnecessary expenditures, it is important to understand and quantify the wide-ranging health care costs affecting people suffering from LUTS. We aimed at creating a foundation for exploring the cost of LUTS. METHOD: In this systematic literature review, we explored the costs of illness of the LUTS umbrella. We used the online literature review tool Silvi.ai for transparent decision-making and literature management. RESULTS: A total of 1821 original articles were screened. Forty had explored the cost of illness of a LUTS disease since 2013. The studies were conducted in 18 countries. A number of different study designs were applied, including both retrospective and prospective studies. In total, seven LUTS indications were explored. None of them focused on lifelong LUTS. None of them were conducted in infants or children. Eighty-two percent were conducted in adults and 18% in frail elderly. Most cost of illness studies focused on the cost of hospitalization and use of medicine. CONCLUSION: We have created the groundwork for understanding the cost of LUTS illness. To fully understand the cost of illness of lifelong LUTS, the main gap in research is to investigate the cost of LUTS in infants and children.

APP-based treatment of urgency and mixed urinary incontinence in women: factors associated with long-term satisfaction.

PURPOSE: App-based treatment of urgency (UUI) and mixed (MUI) urinary incontinence has proved to be effective. To further improve treatment, it will be beneficial to analyze baseline and treatment-related factors that are associated with satisfaction. METHODS: A secondary analysis was conducted of data from a randomized controlled trial (RCT) assessing an app for UUI or MUI treatment, encompassing 98 women for whom there was long-term treatment satisfaction data. All participants completed a short-term (15 weeks) and a long-term (15 months) follow-up questionnaire after being given access to treatment. The outcome was a 3-item question on current treatment satisfaction at the long-term follow-up. Factors potentially associated with the outcome were analyzed using the chi-square test, Student's t test or logistic regression. RESULTS: At the long-term follow-up, 58% of the women were satisfied with the treatment. The most important baseline variable associated with satisfaction was incontinence-related quality of life (International Consultation on Incontinence Questionnaire (ICIQ) - Lower Urinary Tract Symptoms Quality of Life Module) (OR 0.91, 95% CI 0.58-0.97). Short-term follow-up variables associated with long-term treatment satisfaction were improvement in the ability to endure urgency (OR 4.33, 95% CI 1.43-13.12), and confidence in pelvic floor contraction ability (OR 2.67, 95% CI 1.04-6.82). CONCLUSION: App-based treatment for UUI and MUI may be an alternative first-line treatment that is satisfactory to many women over the long-term. Furthermore, short-term treatment that focuses on improving the ability to endure urgency, and confidence in pelvic floor contraction ability, can also be recommended for long-term satisfaction.

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.

Prevalence and impact on daily life of lower urinary tract symptoms in Japan: Results of the 2023 Japan Community Health Survey (JaCS 2023).

OBJECTIVES: A large-scale nationwide epidemiological survey of lower urinary tract symptoms (LUTS) was conducted via the Internet in 2023 to clarify the current prevalence of LUTS and evaluate its impact on daily life in Japan. METHODS: The survey was conducted among individuals aged 20-99 years old who had anonymously registered with a Japanese online research company. The survey consisted of 48 questions related to LUTS and daily life. RESULTS: A total of 6210 participants (3088 females and 3122 males), who were selected by probability sampling based on the composition of the Japanese population (age range: 20-99), were recruited. The overall prevalence of LUTS was 77.9% among the subjects aged ≥20 and 82.5% among those aged ≥40. The prevalence of LUTS differed between the sexes and trends toward significant increases in prevalence with age were seen for almost all LUTS. Furthermore, the prevalence of overactive bladder (OAB) was 11.9% among the subjects aged ≥20 and 13.8% among those aged ≥40. This study also showed that LUTS negatively affected daily life. However, the percentage of subjects who visited a physician to receive treatment for LUTS was low, including for participants with a history of treatment for LUTS, although this increased with age. CONCLUSION: The prevalence of LUTS, including OAB, increased with age and negatively affected daily life. However, since the percentage of patients who visit a physician to receive treatment for LUTS remains low, further educational activities regarding LUTS are necessary.

What Is in the Pipeline on Investigational Neuromodulation Techniques for Lower Urinary Tract Dysfunction: A Narrative Review.

OBJECTIVES: Overactive bladder (OAB) affects millions of patients worldwide. Its treatment is challenging but improves the patient's quality of life. Besides standard techniques for neuromodulation (sacral and pudendal neuromodulation and posterior tibial nerve stimulation), several new techniques have been investigated to treat symptoms of refractory OAB. The purpose of the present review is to outline the state of the art of new neuromodulation techniques for lower urinary tract dysfunction (LUTD). MATERIALS AND METHODS: In March 2023, a comprehensive MEDLINE, EMBASE, and Scopus search was carried out (keywords: LUTD, new technologies, neuromodulation, LUTS, OAB, painful bladder syndromes, etc). Articles were included according to inclusion (randomized controlled trials, prospective trials, large retrospective studies) and exclusion (case reports, outcomes not clearly expressed in full text, animal studies) criteria. The reference lists of the included studies also were scanned. Both adult and pediatric populations were included, in addition to both neurogenic and nonneurogenic OAB. A narrative review was then performed. RESULTS: Peroneal neuromodulation, transcutaneous electrical nerve stimulation, magnetic nerve stimulation, and parasacral transcutaneous neuromodulation are the most studied investigative techniques and were shown to yield promising results in treating OAB symptoms. Most studies showed promising results even in the complex scenarios of patients with OAB refractory to standard treatments. Comparing investigational techniques with standard of care and their respective clinical outcomes and safety profiles, and confronting their pros and cons, we reasonably believe that once such treatment modalities are further developed, they could play a role in the OAB treatment algorithm. CONCLUSIONS: Although the described neuromodulation techniques are being intensely studied, the available results are not yet sufficient for any guidelines to recommend their use.

Ligand-Receptor Interactions and Structure-Function Relationships in Off-Target Binding of the ß3-Adrenergic Agonist Mirabegron to α1A-Adrenergic Receptors.

The ß3-adrenoceptor agonist mirabegron is available for the treatment of storage symptoms of overactive bladder, including frequency, urgency, and incontinence. The off-target effects of mirabegron include binding to α1-adrenoceptors, which are central in the treatment of voiding symptoms. Here, we examined the structure-function relationships in the binding of mirabegron to a cryo-electron microscopy structure of α1A. The binding was simulated by docking mirabegron to a 3D structure of a human α1A-adrenoceptor (7YMH) using Autodock Vina. The simulations identified two binding states: slope orientation involving 10 positions and horizontal binding to the receptor surface involving 4 positions. No interactions occurred with positions constituting the α1A binding pocket, including Asp-106, Ser-188, or Phe-312, despite the positioning of the phenylethanolamine moiety in transmembrane regions close to the binding pocket by contact with Phe-288, -289, and Val-107. Contact with the unique positions of α1A included the transmembrane Met-292 during slope binding and exosite Phe-86 during horizontal binding. Exosite binding in slope orientation involved contact of the anilino part, rather than the aminothiazol end, to Ile-178, Ala-103, and Asn-179. In conclusion, contact with Met-292 and Phe-86, which are unique positions of α1A, accounts for mirabegron binding to α1A. Because of its lack of interactions with the binding pocket, mirabegron has lower affinity compared to α1A-blockers and no effects on voiding symptoms.

Does treatment of lichen sclerosus improve overactive bladder symptoms?

INTRODUCTION AND HYPOTHESIS: Lichen sclerosus (LS) is a chronic disease which mainly affects the vulvar area in women. A few studies have shown a possible relationship between LS and overactive bladder (OAB) symptoms, but no studies have investigated whether OAB symptoms improve after initiating treatment of LS. The aim of this study was to investigate whether the treatment of LS also improves OAB symptoms in women newly diagnosed with LS. METHODS: This was a prospective cohort pilot study based on questionnaires from women newly diagnosed with LS and with symptoms of OAB. Women above the age of 18 who were newly diagnosed with LS were included. The women completed two questionnaires on OAB at inclusion and after 3 months. The questionnaires consisted of the validated questionnaires OAB-q (33 questions, maximum score 198) and ICIQ-OAB (8 questions, maximum score 56). All women initiated treatment with local steroid by the time of the LS diagnosis. RESULTS: A total of 40 women were included, and 13 women dropped out during the data collection time. Comparing month 0 to month 3 for the remaining 27 women, a mean difference at 28.8 points was observed for OAB-q and a mean difference of 5.7 points was observed for ICIQ-OAB. Both results showed a statistically significant difference after 3 months (p < 0.05). A total of 92.6% (25/27) of the women improved their symptoms. CONCLUSION: Treatment with local steroid might improve OAB symptoms in women newly diagnosed with LS.

How I Do It: Transcutaneous tibial nerve stimulation TENSI+ system.

Overactive bladder (OAB) is a common condition that significantly impacts the quality of life (QoL), well-being and daily functioning for both men and women. Among various treatments, peripheral tibial nerve stimulation (PTNS) emerges as an effective third-line treatment for OAB symptoms, with options for either a percutaneous approach (P-PTNS) or by transcutaneous delivery (T-PTNS). Recent studies have shown negligible differences between P-PTNS and T-PTNS efficacy in alleviating urinary urgency and frequency and QoL improvement and, overall no difference in efficacy over antimuscarinic regimens. The TENSI+ system offers a cutting-edge transcutaneous approach, allowing patients to self-administer treatment conveniently at home with electrical stimulation delivery through surface electrodes. It stands out for its ease of preparation, tolerability, and high levels of patient satisfaction. Prospective multicentric data highlights TENSI+ to be an effective and safe treatment for lower urinary tract symptoms with high treatment adherence at 3 months. This paper aims to familiarize readers with the TENSI+ system, current studies, device assembly, operation, and treatment recommendations.

Predictive factors of de novo overactive bladder in clinically localized prostate cancer patients after robot-assisted radical prostatectomy.

OBJECTIVES: To assess the postoperative status of clinically localized prostate cancer patients who underwent robot-assisted radical prostatectomy (RARP) with a focus on de novo overactive bladder (OAB). METHODS: The present study included 156 patients who did not have preoperative OAB and underwent RARP between December 2015 and April 2020 at our institution. Patients were divided into the de novo OAB group and non-OAB group based on the findings of overactive bladder symptoms score (OABSS) 6 months after RARP, and comparative assessments were performed between the two groups. RESULTS: Six months after RARP, de novo OAB was detected in 38 (24.4%) out of 156 patients. Body mass index (BMI) and the proportion of patients with hypertension were significantly higher in the de novo OAB group than in the non-OAB group. No significant differences were observed in the other characteristics examined. Furthermore, the preoperative findings of uroflowmetry and a urodynamic study did not significantly differ between the two groups. Despite the lack of significant differences in preoperative OABSS, total international prostate symptom score, the voiding symptom score, storage symptom score, and quality of life score between the two groups, all of these findings 6 months after RARP were significantly worse in the de novo OAB group than in the non-OAB group. Among the several factors examined, only BMI was independently associated with the development of de novo OAB 6 months after RARP. CONCLUSIONS: Patients with a high BMI may develop de novo OAB after RARP, resulting in the significant deterioration of lower urinary tract symptoms.

[Impact of the SARS-CV-2 virus on the urinary bladder].

INTRODUCTION: There are publications about the impact of a new coronavirus infection (COVID) on the lower urinary tract, including the development of overactive bladder (OAB) or COVID-associated cystitis. The cause of dysuria in patients with COVID is not fully understood. MATERIAL AND METHODS: A total of 14 consecutive patients after COVID with complaints of frequent urination with urgency were included in the study. The main inclusion criterion was the development or worsening of OAB symptoms after resolution of COVID, confirmed by the eradication of SARS-CoV-2 by a polymerase chain reaction. The severity of OAB was assessed using the International Scale of Symptoms (Overactive Bladder Symptom Score, OABSS). RESULTS: Three (21.4%) out of fourteen patients had OAB symptoms prior to COVID, while in 11 (78.6%) patients OAB symptoms developed in post-COVID period. In 4 patients (28.6% of the entire cohort and 36.4% of patients in de novo group) urge urinary incontinence and urgency developed. The average score on the OABSS scale in patients with baseline OAB was 6.7+/-0.8, which corresponded to the moderate severity. In this group, one patient developed urge urinary incontinence and urgency, which were not present prior to COVID. In a retrospective evaluation of symptoms before the COVID, their average score on the OABSS scale was 5.2 +/- 0.7, i.e., past COVID led to an increase in OAB symptoms by 1.5 points. In patients with OAB de novo, the symptoms were less pronounced, with a score of 5.1+/-0.6 points, that is between mild and moderate OAB. At the same time, urinalysis in 9 patients did not have signs of inflammation: in 5 cases, 5-7 white blood cells per field of view was seen only once. A follow-up urine test was normal, suggesting contamination. None of the cases revealed bacteriuria over 102 CFU/ml. All patients were prescribed trospium chloride at a dose of 30 mg per day. The choice of the drug was due to the absence of a negative effect on the central nervous system, which is very important both during COVID and in post-COVID period, since the neurotoxicity of SARS-CoV-2 has been proven. CONCLUSION: A past history of COVID led to an increase in OAB symptoms by 1.5 points in patients who had OAB prior to infection. In 11 patients, after the treatment of COVID, the moderate symptoms of OAB developed de novo. Our small study showed the importance of focusing the attention of internists and infectious disease doctors on urination disorders in patients with COVID and timely referral to a urologist. For the treatment of post-COVID OAB, trospium chloride is the drug of choice, as it does not aggravate the potential neurotoxicity of SARS-CoV-2.

Overactive bladder (OAB): a failed concept needing revision to accommodate an external anatomical control system.

THESIS AND AIMS: In 45 years, the definitions and practice of the urodynamically based overactive bladder (OAB)/detrusor overactivity (DO) system have failed to adequately address pathogenesis and cure of urinary urge incontinence, frequency and nocturia. METHODS: We analysed the OAB syndrome with reference to the Integral Theory paradigm's (ITS) binary feedback system, where OAB in the female is viewed as a prematurely activated, but otherwise normal micturition caused mainly, but not entirely, by ligament damage/laxity. The ITS Clinical Assessment Pathway which details the relationships between structural damage (prolapse), ligaments and dysfunction (symptoms) is introduced. RESULTS: The ITS was able to "better explain" OAB pathophysiology in anatomical terms with reference to the binary model. The phasic patterns diagnostic of "detrusor overactivity" are explained as a struggle for control by the closure and micturition reflexes. The exponentially determined relationship between urethral diameter and flow explains why obstructive patterns occur, why they do not and why urine may leak with no recorded pressure. Mechanically supporting ligaments ("simulated operations") during urodynamic testing can improve low urethral pressure, negative pressure during coughing with SUI and diminish urge sensation or even DO patterns, transforming urodynamics from non-predictive test to accurate predictor of continence surgery results. High cure rates for OAB by daycare repair of damaged ligaments is a definitive test of the binary system's validity. CONCLUSION: Conceptual progression of OAB to the Integral Theory paradigms's prematurely activated micturition validates OAB component symptoms as a syndrome, explains pathogenesis, and unlocks a new way of understanding, diagnosing, treating and researching OAB.

Changes in brain response to urgency before and after treatment of urgency urinary incontinence with onabotulinumtoxin A.

INTRODUCTION: To better understand the role of the brain in urgency urinary incontinence (UUI), we used onabotulinumtoxin A (BoNTA) as a probe to evaluate changes in the brain's response to urgency in successful and unsuccessful treatment. Because BoNTA acts peripherally, brain changes observed should represent a reaction to changes in bladder function caused by BoNTA, or changes in the brain's compensatory mechanisms, rather than a direct effect of BoNTA on the brain. METHODS: We recruited 20 women aged over 60 years with nonneurogenic UUI who were to undergo treatment with onabotulinum A toxin injected intravesically. We performed a baseline evaluation which included a 3-day bladder diary and functional magnetic resonance imaging with an urgency provocation task; we repeated this evaluation 6 weeks posttreatment. We performed an analysis of variance on a priori selected regions of interest and post hoc voxel-wise analysis on responders and nonresponders to treatment. RESULTS: We found a significant interaction in the right insula [F(1,18) = 5.5, p = 0.031]; activity was different during urgency provocation in responders and non-responders to therapy, before and after therapy. The supramarginal gyrus (SMG) and inferior frontal gyrus (IFG) also displayed significant interactions (p < 0.005). Activity in the periaqueductal gray and prefrontal cortex was correlated with number of leakage episodes (p < 0.05). CONCLUSION: The changes seen in the brain control mechanism after therapy likely reflect reduced bladder sensation caused by BoNTA's peripheral action. We ascribe the SMG and IFG changes to a coping mechanism for urgency which is reduced in those who respond well to treatment.

Patient-tailored healthcare and tibial nerve neuromodulation in the treatment of patients with overactive bladder symptoms.

PURPOSE: The aim of this study was to demonstrate features predictive of treatment response for patient-tailored overactive bladder (OAB) intervention with an implantable tibial neurostimulator using patient and technical prediction factors. MATERIALS AND METHODS: This study was designed as a follow-up study based on parameter settings and patients' preferences during the pilot and extended study of the implantable tibial nerve stimulator (RENOVA™ iStim system). For this study, we compared all treatment parameters (stimulation amplitude, frequency, and pulse width) and usage data (duration of treatment) during the different follow-up visits. RESULTS: We obtained usage data from a total of 32 patients who were implanted with the system between February and September 2015. Age, sex, body mass index (BMI) and previous experience with percutaneous tibial nerve stimulation (PTNS) treatment were considered as possible prediction factors for treatment success. However, only BMI was considered a statistically significant prediction factor (p = 0.042). A statistically significant increase in mean treatment level was seen in the responder group during the 3 month follow-up visit (mean: 6.7 mA, SD 0.416) as compared with the initial system activation visit (mean: 5.8 mA, SD 0.400) (p = 0.049). No other visits demonstrated statistically significant changes in both groups (responders and nonresponders) during the defined timepoints. CONCLUSION: This data underscores the need to use patient-tailored OAB treatment. BMI was found to be a negative predictive factor for treatment success. However, it was not possible to develop a specific responder model. A model predicting response to treatment could be useful for implementing shared decision making.

Defining urge as an uncontrolled micturition explains pathogenesis, informs cure and helps solve the burgeoning OAB crisis.

BACKGROUND: Parallel with the demographic ageing crisis, is a disabling overactive bladder (OAB) crisis (urgency/frequency/nocturia), 30% prevalence in older women, pathogenesis stated as unknown and, according to some learned societies, incurable. HYPOTHESIS/AIMS: To review International Continence Society and Integral System paradigms to test our thesis that OAB per se is not a pathological condition, rather, a prematurely activated uncontrolled micturition; pathogenesis being anatomical damage in a nonlinear feedback control system comprising cortical and peripheral (muscle/ligament) components. METHODS: We examined studies from basic science, anatomy, urodynamics, ultrasonic and video xrays, ligament repairs, from which we created a nonlinear binary model of bladder function. We applied a Chaos Theory feedback equation, Xnext = Xc(1 - X) to test our hypothesis against existing concepts and hypotheses for OAB pathogenesis. RESULTS: The bladder has ONLY two modes, EITHER closed OR open (micturition). Closure is reflexly controlled cortically and peripherally: muscles contracting against ligaments stretch the vagina to suppress afferent signals to micturate from urothelial stretch receptors. "OAB" can be caused by anatomical damage anywhere in the model, by childbirth or age-weakened ligaments, which can be repaired to cure all three OAB symptoms. Urodynamic "DO" graphs are interpreted anatomically and by the feedback equation. CONCLUSION: OAB is in crisis. Our thesis of OAB as an uncontrolled micturition from anatomical defects in the bladder control system provides fresh directions for further development of new treatments, nonsurgical and surgical, to help break the crisis and bring hope and cure to 600 million women sufferers.

An anatomical pathogenesis of lower urinary tract definitions from the 2002 ICS report symptoms, conditions, syndromes, urodynamics.

AIM: To present an anatomical pathogenesis parallel with the 2002 International Continence Society Lower Urinary Tract (LUTS) definitions standardization Report 2002. METHODS: Each LUTS section is discussed using the same numbers as the Report. RESULTS: Normal function Bladder control is binary, with two reflexes alternating, either closure (dominant) or open (micturition), with the same cortical and peripheral components: three directional muscle forces contracting against pubourethral (PUL) and uterosacral (USL) ligaments for closure, two against uterosacral ligaments for micturition. Dysfunction OAB symptoms reflect a prematurely activated micturition; PUL/USL weakness prevents muscle forces from controlling afferent urothelial emptying signals. Stress urinary incontinence is a consequence of weak PULs allowing posterior muscle forces to open the urethra during effort. Lax USLs weaken contractile force of the posterior urethral opening vectors, so detrusor has to contract against an unopened urethra. This is experienced as "obstructive micturition." CONCLUSIONS: Anatomical analysis indicates the ICS definitions are fundamentally sound, except for "OAB" which implies detrusor causation. Minor changes, OAB to "overactivated" bladder allow causation outside of bladder. This construct supports OAB and its component symptoms as a syndrome, as intuited by the Committee, (albeit as a prematurely activated micturition), retains the acronym, explains OAB cure by ligament repair, and incontinence pathogenesis from two post-2002 syndromes which need an addition to the definitions, Posterior Fornix Syndrome (of which OAB is a component) and Tethered Vagina Syndrome, which is the basis for skin-grafting cure of the 30%-50% of women who continue leaking urine massively after successful obstetric fistula closure.

An analysis of factors that influence patient preference of third-line therapy for overactive bladder.

OBJECTIVE: Patients with overactive bladder (OAB) refractory to first- and second-line therapy may pursue third-line therapies, including intradetrusor onabotulinum toxin-A (BTX), peripheral tibial nerve stimulation (PTNS), and sacral neuromodulation (SNM). The factors that influence patient preference for each treatment modality have not yet been explored. This study sought to investigate the specific parameters that patients consider in choosing a third-line therapy for OAB. METHODS: Patients refractory to first- and second-line therapies for OAB were identified in our outpatient clinic and asked to watch an educational video providing information on the risks and benefits of each third-line treatment option. They were then given a questionnaire to rank their preference of therapy and select reasons for why they found each therapy favorable and unfavorable. Patients under age 18 years, non-English speakers, those with a developmental disability, and those with a diagnosis of neurogenic bladder were excluded. RESULTS: Of the 98 patients included in the study, 40 participants (40.8%) chose intradetrusor BTX injections, 34 (34.7%) chose PTNS, and 16 (16.3%) chose SNM as their first choice. Seven patients (7.1%) chose none of the offered therapies, and one patient (1.0%) chose all three therapies with equal preference. BTX was found most attractive for its long efficacy (47%); its least attractive feature was the potential need for self-catheterization due to urinary retention (54%). PTNS was found most attractive for being a nonsurgical option (32%) and having no reported significant complications (39%); its least attractive feature was need for frequent office visits (61%). SNM was found most attractive for its potential for long-term relief without frequent office visits (53%); its least attractive feature was need for an implanted device (33%). Patients opting for SNM had higher scores on Urinary Distress Inventory-6 and Incontinence Impact Questionnaire-7 questionnaires when compared to patients opting for BTX injections or PTNS (p < 0.05). 47.4% of patients eventually pursued a third-line therapy. Of those, there was a 67.6% concordance rate between the therapy patients ranked first and the therapy they eventually underwent. CONCLUSIONS: Patients with more severe OAB symptoms opt for more invasive and less time-consuming therapy with the potential for long-term relief, namely SNM. Despite thorough counseling, many patients do not progress to advanced OAB therapies. Understanding factors that influence patients' affinity toward a specific type of treatment can aid with individualized counseling on third-line OAB therapies.

Interplay between bladder microbiota and overactive bladder symptom severity: a cross-sectional study.

BACKGROUND: It is widely accepted that there exist microbiota communities in urinary tract of healthy individuals. Imbalance in the urinary microbiome plays important roles in the development of various benign urological conditions including lower urinary track symptoms (LUTS) and overactive bladder (OAB). However, whether alteration in urinary microbiome exerts influence on the severity of OAB symptom has yet to be elucidated. The purpose of this study is to examine the correlation between urinary microbiome and the severity of OAB. METHODS: A total of 70 OAB patients were recruited to finish overactive bladder symptom score (OABSS) questionnaires. Catheterized urine samples were obtained for 16S rRNA gene sequencing. The species richness and evenness were evaluated by α diversity, and the difference in urinary microbiome between patients with mild or moderate/severe severity was evaluated by ß diversity. The relationship between urinary microbiome and the severity of OAB symptom was evaluated using Pearson's correlation analysis. RESULTS: Mild patients (OABSS ≤ 5, n = 17) had lower bacterial diversity (Simpson index, P = 0.024) and richness (Chao1, P = 0.023) than those with moderate/severe symptom (OABSS > 5, n = 53). Beta-diversity of urinary microbiome between two groups were significantly different. Furthermore, the score of OABSS was positively correlated with the richness index (Chao1, P = 0.002) and diversity index (Shannon index, P = 0.044) of urinary microbiome. Certain bacterial genera (e.g., Porphyromona and Prevotella) were significantly correlated with severity of OAB sub-symptoms. CONCLUSION: This study demonstrated that urinary microbiome was intimately correlated with the severity of OAB symptom and the increase of the diversity and richness of urinary microbiome was accompanied by more severe OAB symptoms, indicating that urinary dysbiosis may play pivotal roles in the deterioration of functional bladder diseases.