OAB Patients Research Articles

215 - Anticholinergic burden in treatment naïve OAB patients: how much is too much?

215 - Anticholinergic burden in treatment naïve OAB patients: how much is too much?

Increased prevalence of metabolic syndrome in female patients with overactive bladder: A population-based study.

To assess the association between overactive bladder syndrome (OAB) and the metabolic syndrome (MetS). A population-based study was conducted to compare OAB patients with age-, sex- and ethnicity-matched control subjects regarding the prevalence of the parameters of the MetS, with respect to obesity, hyperlipidemia, hypertension and diabetes mellitus. The characteristics of the OAB population were assessed. Adjusted odds ratios (OR) were calculated by logistic regression. 110 024 OAB patients and 220 455 controls. were identified. OAB was associated with a higher prevalence of MetS (35.4% vs. 27.5%, p < 0.001). The fully adjusted OR for MetS in patients with OAB compared to controls was 1.44; 95% confidence interval (CI) 1.42-1.46; p < 0.001. Among metabolic parameters, obesity was found to be the strongest factor associated with OAB (OR 1.55, 95% CI 1.53-1.58, p < 0.001), and higher high-density lipoprotein cholesterolelevels (>50) had a protective effect on the risk of OAB (OR 0.75, 95% CI 0.73-0.76, p < 0.001). Data from this cohort suggest that OAB is positively associated with MetS. Clinicians approaching patients with OAB should be aware of this association. A multimodal treatment focusing on the MetS may be considered in these patients.

Microstructural white matter abnormalities in overactive bladder syndrome evaluation with diffusion kurtosis imaging tract-based spatial statistics analysis.

This prospective study aimed to explore the microstructural alterations of the white matter in overactive bladder syndrome (OAB) using the Tract-based Spatial Statistics (TBSS) method of diffusion kurtosis imaging (DKI). A total of 30 patients were enrolled and compared with 30 controls. White matter (WM) status was assessed using tract-based spatial statistics for DKI. The differences in DKI-derived parameters, including kurtosis fractional anisotropy (KFA), fractional anisotropy (FA), mean kurtosis (MK), mean diffusivity (MD), radial kurtosis (RK), axial kurtosis (AK), axial diffusivity (AD), and radial diffusivity (RD), were compared between the two groups using the TBSS method. The correlation between the altered DKI-derived parameters and the (OABSS) scores was analyzed. A receiver operating characteristic curve (ROC) was used to evaluate the diagnostic performance of different white matter parameters. As a result, compared with the HC group, the KFA, and FA values decreased significantly in the OAB group. Compared with the HC group, the MK and MD values increased significantly in the OAB group. The KFA values of the genu of corpus callosum (GCC) were significantly correlated with the OABSS scores (r = -0.509; p = 0.004). The FA values of anterior corona radiata (ACR) were significantly correlated with OABSS scores (r = -0.447; p = 0.013). The area under the ROC curve (AUC) for the genu of corpus callosum KFA values was higher than FA for the diagnosis of OAB patients. DKI is a promising approach to the investigation of the pathophysiology of OAB and a potential biomarker for clinical diagnosis of OAB.

Overactive bladder ‘symptoms’ or ‘complaints’ in young and elderly patients or healthy volunteers?

Objective:The overactive bladder symptom complex is multifactorial and heterogeneously influenced by genetic and environmental factors. The role of ageing is not exactly known. Our objective is to evaluate age-related differences in bladder sensations in healthy volunteers and overactive bladder patients. Methods:68 patients with an overactive bladder, diagnosed by their urologist using the International Continence Society criteria, and 66 healthy volunteers were included: 41 patients and 20 volunteers were ≥60 years old. Subjects filled out sensation-related bladder diaries, for 2 periods of 3 days. Results:To obtain the following results, 6160 voids were assessed. Both young and older healthy volunteers experienced storage symptoms. However, older volunteers experienced more symptoms than younger ones. The healthy aged experienced more nocturia and voided 34% more often over 6 days, compared to the young people. They experienced more urge at a lower mean voided volume too. Younger OAB patients perceived their bladder to be ∼25% fuller at 100 ml compared to younger volunteers, older patients experienced a similar mean bladder fullness sensation to their healthy peers. Fourteen healthy older volunteers experienced voids with urge 3 (need to void now), however at a higher mean voided volume compared to the older OAB patients. They both experienced the same amount of nocturia. Conclusions:Storage symptoms are widespread throughout the population in a continuum of frequency and severity of symptoms. Ageing healthy volunteers shift on this continuum, from never having any urinary complaints towards experiencing (a severity of) symptoms that fit within the ICS definition of OAB. Hence, there is an important distinction between storage symptoms and storage complaints.

Antibiotic prophylaxis for onabotulinum toxin A injections: systematic review and meta-analysis.

To our knowledge, there are no evidence-based recommendations regarding the optimal prophylactic antibiotic regimen for intradetrusor onabotulinum toxin type A (BTX) injections. This systematic review and meta-analysis was aimed at investigating the optimal prophylactic antibiotic regimen to decrease urinary tract infection (UTI) in patients undergoing BTX for overactive bladder syndrome (OAB). A systematic search of MEDLINE, Embase, CINAHL, and Web of Science was conducted from inception through 30 June 2022. All randomized controlled trials and prospective trials with > 20 subjects undergoing BTX injections for OAB in adults that described prophylactic antibiotic regimens were included. Meta-analysis performed to assess UTI rates in patients with idiopathic OAB using the inverse variance method for pooling. A total of 27 studies (9 randomized controlled trials, 18 prospective) were included, representing 2,100 patients (69% women) with 19 studies of idiopathic OAB patients only, 6 of neurogenic only, and 2 including both. No studies directly compared antibiotic regimens for the prevention of UTI. Included studies favor the use of antibiotics in patients with idiopathic OAB and favor continuing antibiotics for 2-3days after the procedure for prevention of UTI. Given the heterogeneity of the data, direct comparisons of antibiotic type or duration could not be performed. Meta-analysis found a 10% UTI rate at 4 weeks and 15% at 12 weeks post-injection. Although there are insufficient data to support the use of a specific antibiotic regimen, available studies favor the use of prophylactic antibiotics for 2-3days in idiopathic OAB patients undergoing BTX injection. Future trials are needed to determine the optimal regimens to prevent UTI in patients undergoing BTX for OAB.

Progress in overactive bladder: novel avenues from psychology to clinical opinions.

Overactive bladder (OAB) is a common, distressing condition that worsens with age and impacts quality of life significantly. As a results of its clinical symptoms, patients suffer from serious physical and mental health issues, have a poor quality of life, and participate in a serious economic burden. The key social-psychological factors include living habits, eating habits, and personality characteristics on this disease, even though the pathogenesis of OAB is complex. However, there is few cognitions and research on OAB in the field of psychology. Between 2000 and 2022, two electronic databases were systematically searched in accordance with Cochrane library guidelines (PubMed/Medline, Web of Science). An analysis of the remaining articles with relevant information was conducted using a data extraction sheet. An itemized flow diagram was adopted and used to report systematic reviews and meta-analysis. A systematic review of studies published from 2000 to 2022 in English language were conducted and included in the review. Urological surgeon and psychologists majoring in urinary diseases. As a result of this information, we are able to develop a better understanding of the role of psychological factors in the development of OAB and suggest potential therapeutic directions for OAB patients. This may benefit the recovery of OAB patients.

Bladder Capacity in Women With Overactive Bladder Syndrome: A Cross-sectional Study

To evaluate bladder capacity in women with idiopathic overactive bladder syndrome (OAB) through bladder diary, cystomanometry, and uroflowmetry and assess the concordance of the different measures of bladder capacity. A secondary objective is to describe the relationship between bladder capacity and urinary frequency in OAB patients. An observational cross-sectional multicentric study was conducted, including female patients diagnosed with idiopathic OAB. All participants underwent a urodynamic study and completed a 3-day bladder diary (3dBD). Different parameters were used to calculate bladder capacity: maximum cystometric capacity (MCC) assessed at the end of filling cystometry, voided volume (VV) during the uroflowmetry, maximum voided volume (VVmax), and average voided volume (VVmed), both assessed through the 3dBD. Reproducibility analysis was performed to assess the agreement among the different bladder capacity measures. Intraclass correlation coefficient (ICC) and weighted Kappa index were used. Bladder capacity parameters were also assessed in relation to urinary frequency. Bladder capacity measures were diminished in this population, except for VVmax. Poor correlation was found between the different bladder capacity variables (ICC and weighted Kappa index <0.4). Twenty-four-hour frequency and average VV present a weak negative linear relationship (Pearson coefficient -0.344). MCC and average VV are reduced in OAB patients. MCC does not correlate well with functional bladder volumes determined by voiding diary in the OAB population.

Decrease in the Ratio proBDNF/BDNF in the Urine of Aging Female Patients with OAB.

Imbalance in the levels of neurotrophins, growth factors crucial in the development, function, and survival of neurons is commonly observed in many pathological states. Concentrations of brain-derived neurotrophic factor (BDNF) and its precursor (proBDNF) were measured in the urine of a cohort of aging female patients with overactive bladder disease (OAB). When reported to creatinine, levels were similar between OAB patients and healthy controls. However, the ratio proBDNF/BDNF was significantly decreased in the OAB group. Receiver operating characteristic (ROC) curve analysis of the ratio proBDNF/BDNF displayed a good diagnostic value for OAB (AUC = 0.729). Clinical questionnaires of symptom severity (OABSS and IIQ-7) were negatively correlated with this ratio. On the other hand, microRNAs (miRNA) involved in proBDNF gene translation were expressed at comparable levels between groups. However, urinary enzymatic activity of matrix metalloproteinase-9 (MMP-9), the enzyme that cleaves proBDNF into BDNF, was increased in OAB compared to controls. Levels of miR-491-5p, the main miRNA that downregulates MMP-9 synthesis, were greatly decreased in urine from OAB patients. These results suggest that the ratio proBDNF/BDNF could be useful in the phenotyping of OAB in an aging population, and the difference could originate from enhanced MMP-9 enzymatic activity rather than translational control.

Differences in the Urinary Microbiome of Patients with Overactive Bladder Syndrome with and without Detrusor Overactivity on Urodynamic Measurements.

It has been hypothesized that the urinary microbiome might play an important role in OAB. Studies have been conducted on the association between OAB symptoms and the microbiome, although a possible causality still has to be determined. In this study, 12 female patients, ≥18 years of age, with 'OAB DO+' and 9 female patients with 'OAB DO-' were included. Patients were excluded if they met one of the following exclusion criteria: bladder tumors and previous bladder operations; sacral neuromodulation; injection of Botox in the bladder; and TOT or TVT operations. Urine samples were collected and stored with patient informed consent and with the approval of the Hospital Ethical Review Board (Arnhem-Nijmegen). All OAB patients underwent urodynamics before collecting urine samples, and the diagnosis of detrusor overactivity was confirmed by two individual urologists. In addition, samples from 12 healthy controls who did not undergo urodynamic evaluation were analyzed. The 16S rRNA V1-V2 region amplification and gel electrophoresis were used to determine the microbiota. 12 of the OAB patients had DO shown on their urodynamic studies; the remaining 9 patients had a normoactive detrusor on their urodynamic measurements. Overall, there were no substantial differences among the demographic characteristics of the subjects. The samples were classified as the following: 180 phyla, 180 classes, 179 orders, 178 families, 175 genera, and 138 species. The least commonly observed phyla were Proteobacteria, with an average presence of 10%, followed by Bacteroidetes with 15%, Actinobacteria with 16%, and Firmicutes with 41%. Most of the sequences could be classified according to the genus level for each sample. Significant differences were observed in the urinary microbiome of patients with overactive bladder syndrome who have detrusor overactivity on urodynamics compared to OAB patients without detrusor overactivity and matched controls. OAB patients with detrusor overactivity have a significantly less diverse microbiome and show a higher proportion of Lactobacillus, particularly Lactobacillus iners. The results imply that the urinary microbiome could be involved in the pathogenesis of a specific phenotype of OAB. The urinary microbiome could be a new starting point to study the causes and treatments of OAB.

Vibegron 50 mg Once Daily Improves OABSS, OAB-q SF Score in OAB Patients ≥80 Years Old in Real-World Clinical Settings and Switching from Other OAB Drugs May Reduce Residual Urine Volume.

The treatment effects of vibegron have not previously been evaluated in a prospective, non-interventional observational study of elderly Japanese patients, particularly those ≥80 years old. In addition, no reports have referred to residual urine volume in switching cases. We therefore grouped patients by condition and investigated the treatment effects of vibegron on Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Short Form (OAB-q SF), and residual urine volume in each group. This multicenter, prospective, non-interventional, observational study consecutively enrolled OAB patients with total OABSS score ≥3 and OABSS question 3 score ≥2. Sixty-three patients from six centers were recruited. Vibegron 50 mg once daily was administered for 12 weeks as first-line monotherapy (first-line group), monotherapy switching from antimuscarinics or mirabegron due to failure of prior therapy (no washout period), or combination therapy with antimuscarinics (second-line group). OABSS, OAB-q SF, and residual urine volume were collected after 4 and 12 weeks. Adverse events were also recorded at each visit. Of the 63 patients registered, 61 were eligible for analysis (first line, n=36; second line, n=25). The OABSS, excluding daytime frequency scores, and OAB-q SF scale showed significant improvement in all conditions. Switching from mirabegron to vibegron significantly reduced residual urine volume. No serious treatment-related adverse events were encountered. Vibegron 50 mg once daily significantly improved OABSS and OAB-q SF even in patients ≥80 years old. Notably, switching from mirabegron to vibegron resulted in significant improvements to residual urine volume.

MP24-08 THE CLINICAL FEATURE AND SIGNIFICANCE OF VESICAL ADAPTATION RESPONSE TO DIURESIS IN MALE LUTS PATIENTS

You have accessJournal of UrologyCME1 Apr 2023MP24-08 THE CLINICAL FEATURE AND SIGNIFICANCE OF VESICAL ADAPTATION RESPONSE TO DIURESIS IN MALE LUTS PATIENTS Kanako Matsuoka, Kei Yaginuma, Yu Endo, Yuki Harigane, Yuta Matsuoka, Yuki Yoshida, Hitomi Imai, Akifumi Onagi, Seiji Hoshi, Tomoyuki Koguchi, Junya Hata, Yuichi Sato, Hidenori Akaihata, Masao Kataoka, and Yoshiyuki Kojima Kanako MatsuokaKanako Matsuoka More articles by this author , Kei YaginumaKei Yaginuma More articles by this author , Yu EndoYu Endo More articles by this author , Yuki HariganeYuki Harigane More articles by this author , Yuta MatsuokaYuta Matsuoka More articles by this author , Yuki YoshidaYuki Yoshida More articles by this author , Hitomi ImaiHitomi Imai More articles by this author , Akifumi OnagiAkifumi Onagi More articles by this author , Seiji HoshiSeiji Hoshi More articles by this author , Tomoyuki KoguchiTomoyuki Koguchi More articles by this author , Junya HataJunya Hata More articles by this author , Yuichi SatoYuichi Sato More articles by this author , Hidenori AkaihataHidenori Akaihata More articles by this author , Masao KataokaMasao Kataoka More articles by this author , and Yoshiyuki KojimaYoshiyuki Kojima More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003249.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The bladder storage function has a homeostatic system that continuously varies voided volume at each void in response to changes in bladder filling rate. Specifically, high diuresis increases the voided volume at each voiding, and low diuresis decreases the voided volume at each voiding. Attention has recently focused on this system named vesical adaptation response to diuresis (VARD). We have reported that patients with lower urinary tract symptoms (LUTS) lacked VARD (Haga et al. PLoS One, 2016). Although VARD seems to be important to maintain lower urinary tract function, the clinical feature and significance of VARD remains unknown. Therefore, the aim of this study is to determine what factors influence VARD in male patients with LUTS. METHODS: Ninety-four male patients older than 60 years old (age 76.5±6.6 years) with LUTS who attended our hospital between 2017 and 2019 were included in this study. Overactive Bladder Symptom Score (OABSS), 24-h frequency-volume charts (FVCs), uroflowmetry, and ultrasonography to measure prostate volume were evaluated. Exclusion criteria were apparent neurogenic lower urinary tract dysfunction, acute urinary tract infection, and needed urethral catheterization. VARD was defined by the presence of a significant correlation coefficient (γ) between urine output rate and voided volume at each voiding on FVCs (γ>0.4, p<0.05). According to the presence or absence of VARD, patients were divided into two groups: VARD presence (n=48) and VARD absence groups (n=46). The patient characteristics and parameters of lower urinary tract functions were compared between two groups, with p<0.05 considered significant. RESULTS: The number of OAB patients was significantly higher in the VARD absence group than in the VARD presence group (p=0.04). The prostate volume tended to be higher in VARD absence group. The multivariate analysis revealed that OAB and prostate enlargement (BPE) were significantly related to the VARD absence group (OAB: aOR 3.76, 95%CI: 1.34-10.6, p=0.01, BPE: aOR = 1.04, 95% CI: 1.01-1.07, p=0.02). CONCLUSIONS: The OAB and BPE were independent risk factors for the lack of VARD in male LUTS patients. Increased afferent nerve activity from the lower urinary tract associated with OAB and BPE might lack VARD, resulting in increased urinary frequency during a high-diuretic phase. The VARD could be more a useful objective marker to measure the bladder storage function than the symptom questionnaire for LUTS. Source of Funding: Nothing © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e320 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kanako Matsuoka More articles by this author Kei Yaginuma More articles by this author Yu Endo More articles by this author Yuki Harigane More articles by this author Yuta Matsuoka More articles by this author Yuki Yoshida More articles by this author Hitomi Imai More articles by this author Akifumi Onagi More articles by this author Seiji Hoshi More articles by this author Tomoyuki Koguchi More articles by this author Junya Hata More articles by this author Yuichi Sato More articles by this author Hidenori Akaihata More articles by this author Masao Kataoka More articles by this author Yoshiyuki Kojima More articles by this author Expand All Advertisement PDF downloadLoading ...

Assessment of bladder pressure and discomfort symptoms: How do overactive bladder differ from interstitial cystitis/bladder pain syndrome patients?

BackgroundTo better understand the sensation of bladder “pressure” and “discomfort”, and how they are similar or distinct from the “pain” and “urgency” symptoms in IC/BPS and OAB.MethodsIC/BPS and OAB patients rated their bladder pain, pressure, discomfort, and urinary urgency on separate 0–10 numeric rating scales (NRS). Their NRS ratings were compared between IC/BPS and OAB, and Pearson correlations were performed.ResultsAmong IC/BPS patients (n = 27), their mean numeric ratings of pain, pressure, discomfort, and urinary urgency were almost identical (6.6 ± 2.1, 6.0 ± 2.5, 6.5 ± 2.2, and 6.0 ± 2.8 respectively). The three-way correlations between pain, pressure, or discomfort were very strong (all > 0.77). Among OAB patients (n = 51), their mean numeric ratings of pain, pressure, and discomfort (2.0 ± 2.6, 3.4 ± 2.9, 3.4 ± 2.9) were significantly lower than urgency (6.1 ± 2.6, p < 0.001). The correlations between urgency and pain, and between urgency and pressure were weak in OAB (0.21 and 0.26). The correlation between urgency and discomfort was moderate in OAB (0.45). The most bothersome symptom of IC/BPS was bladder/pubic pain, while the most bothersome symptom of OAB was urinary urgency and daytime frequency.ConclusionsIC/BPS patients interpreted bladder pain, pressure, or discomfort as the similar concepts and rated their intensity similarly. It is unclear whether pressure or discomfort provide additional information beyond pain in IC/BPS. Discomfort may also be confused with urgency in OAB. We should re-examine the descriptors pressure or discomfort in the IC/BPS case definition.

Association of diabetes, hypertension, and their combination with basal symptoms and treatment responses in overactive bladder patients.

Introduction: Pelvic hypoperfusion caused by atherosclerosis has been proposed as a cause of lower urinary tract dysfunction including overactive bladder syndrome (OAB). Limited data indicate that OAB patients with concomitant diabetes or hypertension, known risk factors of atherosclerosis, may exhibit greater baseline OAB symptoms and slightly smaller therapeutic responses to treatment, but the impact of a combined presence of diabetes and hypertension has not been reported. Therefore, we have explored whether the combined presence of both comorbidities is associated with greater baseline OAB symptoms than that of either comorbidity alone. Secondary questions were exploration of the impact of either comorbidity on baseline symptoms, and of the impact of either comorbidity alone and their combination on therapeutic responses. Methods: Data from two non-interventional studies applying treatment with propiverine ER 30 or 45mg/d for 12weeks were analyzed. Results: Number of urgency episodes in the combination group was greater than with each comorbidity alone. The impact of comorbidities on baseline intensity of incontinence, frequency or nocturia or Patient Perception of Bladder Condition was less consistent or absent. Either comorbidity alone was associated with a smaller % improvement of symptoms, and their combination had a greater effect than either alone. However, all attenuations associated with comorbidity were small relative to the overall improvement. Conclusions: We conclude that comorbidities of diabetes and hypertension have detectable effects on OAB symptoms and treatment responses, but the small magnitude of these alterations does not justify changing existing paradigms for the clinical management of OAB.

The peripheral nerve evaluation: determining which symptoms lead to a successful test

Objective: To identify the symptom or set of symptoms most improved in patients undergoing a successful peripheral nerve evaluation (PNE) for refractory overactive bladder syndrome (OAB). Methods: An analysis was conducted on refractory OAB patients to determine which symptom (nocturia, daytime voids, urgency, leaks per day, pad use per day and time to reach the bathroom) most improved following a PNE. This was measured in two ways: 1) by patient responses to a questionnaire and 2) by determining changes in symptoms with use of a voiding diary. Patients completed a pre- and post-questionnaire by phone interview. Descriptive statistics were used to analyze demographic and baseline characteristics as well as responses to questionnaires. Changes in voiding patterns were analyzed using a paired-samples t-test. Results: Overall, 28 patients were included. Prior to their evaluation patients indicated they were most bothered by urgency (n=26, 92.8%), followed by number of leaks per 24 hours (n = 24, 85.7%). After their evaluation, symptom improvement was highest for number of voids at night (n = 20, 71.4%) followed by sense of urgency (n = 18, 64.3%). Paired-samples t-tests on pre- and post-PNE voiding diaries revealed significant improvements in number of daytime voids (p = 0.015), number of leaks per 24 hours (p = 0.001), and number of urges per 24 hours (p = 0.001). Conclusion: Voiding diaries alone cannot be used to accurately determine symptom improvement. Clinicians must take into account the degree to which their patients are bothered by their symptoms. In an elderly population, improvement in nocturia has important implications including decreased morbidity.

Overactive bladder with urodynamic study-induced bladder pain: An overactive bladder subtype with symptoms similar to those of interstitial cystitis/painful bladder syndrome.

Overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS) are 2 lower urinary tract disorders with urgency and bladder pain for diagnosis and with several other shared symptoms. Because of their overlapping symptoms, precise differential diagnosis of OAB and IC/PBS remains difficult. Thus, we characterize a subgroup of OAB with bladder pain (OAB-BP) that can be differentiated from OAB alone by urodynamic study (UDS) findings. We also further examined the clinical presentations and urodynamic parameters of OAB alone, OAB-BP, and IC/PBS. Data were collected between September 2018 and April 2019. Patients were categorized into 3 groups, OAB-alone (no bladder pain during UDS, n = 39), OAB-BP (with bladder pain during UDS, n = 35), and IC/PBS (the comparator, n = 39). Chi-square tests were used to compare OAB alone, OAB-BP, and IC/PBS with respect to their clinical presentations and urodynamic parameters. Factors with P < .05 were further analyzed through post hoc comparisons with Bonferroni adjustment. An unique subgroup of OAB patients was identified (i.e., OAB-BP), bladder pain can only be induced at maximal cytometric capacity during UDS. We also identified that the case histories and UDS parameters (e.g., low first desire, normal desire, and maximum cytometric capacity) of the OAB-BP group were more similar to those of the IC/PBS group than to those of the OAB-alone group. The OAB-BP group and the IC/PBS group reported more intrusive, longer-lasting symptoms before their final diagnoses, more extensive family history of urinary tract disorder, and more associated comorbidities (e.g., irritable bowel syndrome, and myofascial pain) than the OAB-alone group. The UDS assessment induced bladder pain in the OAB-BP group to reveal their hidden symptoms. Careful attention to patient history and sophisticated UDS evaluation may help to identify this unique OAB group.

Assessment of Brainstem Functional Organization in Healthy Adults and Overactive Bladder Patients Using Ultra-High Field fMRI

The pathophysiological mechanisms of overactive bladder syndrome (OAB) remain largely unknown, with major involvement of the central nervous system (CNS). The periaqueductal gray (PAG) is a brainstem area which is indicated to play an essential role in bidirectional communication between the bladder and the CNS. We aimed to assess consistency of PAG functional organization across different bladder sensory states in OAB patients. We propose, that PAG functional organization patterns across sensory states will differ between controls and OAB patients. We analyzed fMRI scans at 7 Tesla from six controls and two OAB patients. The Louvain module detection algorithm was applied to parcellate the PAG in empty and full bladder states. We assessed within-subject consistency and investigated differences in this consistency between both groups. High within-subject agreement of PAG parcellations between empty and full bladder states was demonstrated in both groups. Additionally, we showed that the correlations between PAG clusters in both bladder states were significantly different in patients compared to controls (p = 0.039). The methods introduced here offer a promising tool to assess functional organization of the PAG and understand the underlying pathology and the role of this region in OAB syndrome.

β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus.

We previously reported the novel finding that β3-AR is functionally expressed in the renal tubule and shares its cellular localization with the vasopressin receptor AVPR2, whose physiological stimulation triggers antidiuresis by increasing the plasma membrane expression of the water channel AQP2 and the NKCC2 symporter in renal cells. We also showed that pharmacologic stimulation of β3-AR is capable of triggering antidiuresis and correcting polyuria, in the knockout mice for the AVPR2 receptor, the animal model of human X-linked nephrogenic diabetes insipidus (XNDI), a rare genetic disease still missing a cure. Here, to demonstrate that the same response can be evoked in humans, we evaluated the effect of treatment with the β3-AR agonist mirabegron on AQP2 and NKCC2 trafficking, by evaluating their urinary excretion in a cohort of patients with overactive bladder syndrome, for the treatment of which the drug is already approved. Compared to baseline, treatment with mirabegron significantly increased AQP2 and NKCC2 excretion for the 12 weeks of treatment. This data is a step forward in corroborating the hypothesis that in patients with XNDI, treatment with mirabegron could bypass the inactivation of AVPR2, trigger antidiuresis and correct the dramatic polyuria which is the main hallmark of this disease.

Sex and Gender Differences in the Pharmacology of the Overactive Urinary Bladder.

Dysfunction of the lower urinary tract in general and the overactive bladder syndrome (OAB) in particular are prevalent and have major impact on the quality of life of the afflicted patients and their partners. We concisely review sex and gender differences in patients and animal models in physiological bladder function, its alterations in disease (mostly OAB), and its responses to treatment. Women appear to have a smaller functional bladder capacity and, therefore, must void more often than men. On the other hand, men have a greater bladder outlet resistance, which is partly attributed to a longer urethra and partly to the presence of the prostate. Sex and gender differences in bladder contractility appear small and were not found consistently. The ability of bladder smooth muscle to relax may be somewhat smaller in females. However, females are heavily underrepresented in experimental studies on bladder function. Stress urinary incontinence is found predominantly in women (particularly those after childbirth). OAB is similarly prevalent in men and women.Females seek treatment much more often and are overrepresented in clinical trials. Treatment responses in OAB patients are similar in both genders for oral medications, but improvements upon injections of onabotulinum toxin type A appear smaller in men. We conclude that there is no evidence for major sex and gender differences in bladder dysfunction as related to OAB and its treatment responses, but female animals are heavily underrepresented in experimental studies.

Functional Polymorphism in the ADRB3 Gene, Encoding the Beta-3 Adrenergic Receptor, and Response to Intra-Detrusor Injection of Botulinum Toxin-A in Women with Overactive Bladder.

There are reports suggesting an association between the rs4994 polymorphism in the ADRB3 gene encoding the beta-3 adrenergic receptor and OAB risk in females. The injection of botulinum toxin-A into the bladder wall is recommended as a possible treatment for OAB patients in whom first-line therapies have failed. The aim of our study was to analyze the possible association between the ADRB3:rs4994 polymorphism and the patient-perceived response to a single intra-detrusor injection of botulinum toxin-A in Polish women with overactive bladder. The study group consisted of 115 consecutive female patients with OAB. The response to botulinum toxin-A was evaluated at three months after injection, as absolute or relative reductions in OAB symptoms or in scores from questionnaires ICIQ-OAB (parts A and B) and ICIQ-LUTS-QoL (parts A and B). ADRB3:rs4994 variants were identified by the sequencing of genomic DNA extracted from buccal swabs. There were no statistically significant differences between ADRB3:rs4994 [T];[T] homozygotes and [T];[C]+[C];[C] subjects for absolute or relative reductions in symptoms or in scores from all four questionnaire parts at three months after the injection of botulinum toxin-A. Our results do not support the hypothesis that ADRB3:rs4994 polymorphism is associated with the response to the intra-detrusor injection of botulinum toxin-A in Polish females with overactive bladder.

Weak association between arterial hypertension and overactive bladder baseline symptoms and treatment responses.

While animal studies have suggested an association between the presence of hypertension and the presence and/or severity of overactive bladder syndrome (OAB) symptoms, little clinical data is available. We have conducted a pre-specified secondary analysis of a non-interventional study involving 4450 OAB patients being treated with solifenacin to explore the existence of an association between OAB and hypertension using three parallel and overlapping definitions of hypertension to enhance robustness of analysis. Regardless of definition, patients with hypertension were older and had greater OAB symptom severity in univariate analyses. In multiple regression models including age as explanatory covariate, most relationships held up but effect sizes of concomitant hypertension on OAB severity were small (odds ratios <1.35 in all cases) and were deemed to be unlikely of clinical relevance. % Changes in symptom severity were somewhat smaller in univariate analysis, but effect sizes were small. We conclude that OAB and arterial hypertension are associated but effect sizes are too small to justify adaptation of clinical practice for OAB patients with concomitant hypertension.