Intradetrusor Versus Suburothelial Onabotulinum Toxin A in Adults with Neurogenic and Non-neurogenic Overactive Bladder Syndrome: A Meta-Analysis.

PURPOSE: This systematic review and meta-analysis aimed to compare the effectiveness and safety of submucosal injection of onabotulinum toxin A (OnabotA) with intradetrusor injection for overactive bladder syndrome (OAB). METHODS: This systematic review is registered with PROSPERO (CRD42021237964). A licensed librarian surveyed Medline, EMBASE, Scopus, and Google Scholar databases to conduct a comprehensive search. Studies comparing suburothelial and intradetrusor techniques of OnabotA injection for OAB were included, along with clinical and urodynamic variables and complications. The studies were assessed for quality on the basis of Cochrane Collaboration guidelines and evaluated using statistical analysis via a random-effect model and I2 statistic. Data extraction and analysis were conducted using Covidence systematic review platform and Review Manager software. RESULTS: Six studies with 299 patients were included in the systematic review, with four reporting that suburothelial injection of OnabotA was as effective as intradetrusor injection and two reporting intradetrusor injection to be more effective. The meta-analysis found no significant difference between the suburothelial and intradetrusor groups for mean daily catheter or voiding frequency (mean difference: 2.12 [95% confidence interval (CI): -1.61, 5.84]) and the mean number of urgency/urge incontinence episodes (mean difference: 0.08 [95% CI: -1.42, 1.57]). However, a significant heterogeneity was found among the studies. Only the mean volume at first detrusor contraction showed a significant difference, being higher for suburothelial injection (mean difference: 33.39 [95% CI: 0.16, 66.63]). No significant difference was noted for mean compliance, mean bladder capacity, and mean maximum detrusor pressure. Urinary tract infections (UTIs) (p = 0.24) and acute urinary retention (p = 0.92) showed no significant difference between the two groups. The risk of bias varied among the studies. CONCLUSIONS: Suburothelial injection of OnabotA is as effective as intradetrusor injection in improving OAB symptoms, and it has similar complication rates. A higher mean volume of the first detrusor contraction was found in a urodynamic study with suburothelial injection.

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.

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

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: DKI is a promising approach to the investigation of the pathophysiology of OAB and a potential biomarker for clinical diagnosis of OAB.

Percutaneous Tibial Nerve Stimulation in the Treatment of Refractory Idiopathic Overactive Bladder Syndrome: A Retrospective Cohort Study.

BACKGROUND: Overactive bladder (OAB) is a syndrome defined as urinary urgency, accompanied by increased frequency and nocturia with or without urge incontinence, in the absence of urinary tract infection or other obvious pathology. The standard therapies are anticholinergic agents, selective beta-3 adrenoreceptor agonists, or intradetrusor injections of botulinum toxin (BTX-A). For patients with contraindications for BTX-A or drug therapies, percutaneous tibial nerve stimulation (PTNS) may be used. PTNS shows fewer side effects than anticholinergic drugs and costs less than BTX-A. The primary outcome of this study was to assess the efficacy of PTNS in women with refractory OAB. METHODS: Women with refractory OAB undergoing PTNS at our tertiary referral center from 2017 to 2019 were included. The validated German Female Pelvic Floor Questionnaire and a micturition protocol were filled out before and after PTNS. PTNS was applied weekly for 12 weeks. RESULTS: Improvements in OAB symptoms were seen in daily micturition frequency, urgency, and urgency incontinence from pre- to post-PTNS (p < 0.006). Impairments to quality of daily life were significantly (p < 0.0002) less severe after PTNS. There was a significant reduction in daytime voiding frequency from a median of nine to five (p < 0.0001). CONCLUSIONS: Substantial reductions in OAB symptoms, daily micturition frequency, urgency, and urgency incontinence were found in patients with refractory OAB after PTNS.

Aggressive Bladder Tumour Following Clam Ileocystoplasty: A Rare Long-Term Complication.

Overactive bladder syndrome (OAB) is a common, chronic, complex, often under-reported and under-treated condition with a significant impact on quality of life. It poses a high burden on healthcare systems. Clam ileocystoplasty is an invasive procedure typically reserved for the treatment of severe refractory cases. Malignant transformation in the area of anastomosis remains a rare but real, life-threatening risk in the patient group and requires active life-long surveillance and follow-up. We report the case of a 51-year-old woman who presented with recurrent urinary tract infections and non-visible haematuria 30 years after clam ileocystoplasty for urge incontinence. Imaging revealed an anterior bladder tumour with hepatic metastases. On multiple occasions, she was unfit for any invasive surgical sampling options to obtain tissue samples to allow for treatment planning, and was provided with best supportive care. The disease rapidly progressed to death within 10 weeks of presentation. This case buttresses the need for informed consent regarding the risks, including malignant transformation several years after the procedure, and the necessity for lifelong follow-up and surveillance cystoscopy, with frequency tailored to individual patient risk assessment.

Real-life after sacral nerve modulation implantation: Rate, reasons, and risk factors for mid-term follow-up discontinuation.

OBJECTIVES: To evaluate follow-up after implantation of a sacral nerve modulation implantable pulse generator (IPG) and to investigate the reasons and risk factors for follow-up discontinuation. MATERIALS AND METHODS: All patients who underwent an IPG implantation to treat lower urinary tract symptoms between 2014-2019 within 6 hospital centers located in the district of "Hauts-de-France" (France) were systematically called during the year 2020 for a standardized (tele)consultation. Patients were divided into 3 distinct profiles according to the regularity of their 5-year postoperative follow-up: "Regular follow-up", "Irregular follow-up" and "Lost to follow-up". The primary outcome was the change in the annual proportion of the 3 follow-up profiles over the 5 years following IPG implantation. As secondary outcomes we described the reasons reported for follow-up discontinuation and looked for risk factors associated with. RESULTS: Overall, 259 patients were included. At the time of data collection, after a mean follow-up of 28.4 (± 19.8) months, 139 patients (53.7%) had a "Regular follow-up", 54 (20.8%) had an "Irregular follow-up" and 66 (25.5%) were "Lost to follow-up". The proportion of patients with a "Regular follow-up" decreased year by year, representing only 46.2% of patients at five-years. 175 patients (67.6%) underwent a standardized (tele)consultation. In multivariate analysis, only "lack of knowledge of the follow-up protocol" was statistically associated with follow-up discontinuation (OR=5.16; 95% CI [2.12-13.57]). CONCLUSION: The proportion of patients followed up after IPG implantation decreased steadily over the years, often related to a lack of therapeutic education.

Bladder neck incompetence could be an etiology of overactive bladder syndrome in women with stress urinary incontinence after anti-incontinence surgery: insights from transrectal sonography.

PURPOSE: To investigate the prevalence of bladder neck incompetence (BNI) and the anatomic differences between different types of urinary incontinence (UI) and overactive bladder (OAB) by transrectal sonography, and to investigate these differences among those with stress UI (SUI) or mixed UI (MUI) who exhibited de novo or persistent OAB symptoms following anti-incontinence surgery. METHODS: A retrospective analysis was conducted on a total of 184 patients with SUI, MUI, urge UI (UUI), or OAB dry who underwent transrectal ultrasound between 2017 and 2022. The presence of BNI and urethral incompetence assessed by transrectal ultrasound were recorded in all included patients, and recorded preoperatively and postoperatively among patients with SUI and MUI who underwent anti-incontinence surgery. RESULTS: Among the patients, 91%, 84%, 76%, and 71% exhibited BNI in MUI, SUI, UUI, OAB dry group, respectively. Significantly higher rate of patients with BNI were found in MUI than in OAB dry group. Patients with OAB symptoms after anti-incontinence surgery exhibited significantly higher rates of BNI and urethral incompetence than those who did not have postoperative OAB symptoms. Among MUI patients with preoperative BNI, significantly lower rate of postoperative BNI and urethral incompetence was observed in individuals who had improved OAB symptoms after surgery, compared to those without improvement. CONCLUSION: A higher BNI rate was observed in the MUI group. A significantly higher BNI rate was observed in women with OAB symptoms after anti-incontinence surgery. Patients with MUI had improved OAB symptoms if BNI was successfully corrected after anti-incontinence surgery.

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.

Progress in Functional Urology Reflected in Recent Papers in the Journal of Clinical Medicine.

Benign conditions of the lower urinary tract, including benign prostatic hyperplasia, overactive bladder syndrome, and stress urinary incontinence, are frequent in the general population. Despite their benign nature, they have major adverse effects on the quality of life of the afflicted patients and their partners. Despite major progress in the diagnosis and treatment of these conditions, improved understanding and management of these patients remain substantial medical needs. This editorial discusses some recent high-quality articles published in the Journal of Clinical Medicine on the understanding of the epidemiology, pathophysiology, diagnostic, and treatment of benign diseases of the lower urinary tract tissues such as the bladder and prostate.

Implantable Multi-Cross-Linked Membrane-Ionogel Assembly for Reversible Non-Faradaic Neurostimulation.

Neural interfaces play a major role in modulating neural signals for therapeutic purposes. To meet the demand of conformable neural interfaces for developing bioelectronic medicine, recent studies have focused on the performance of electrical neurostimulators employing soft conductors such as conducting polymers and electronic or ionic conductive hydrogels. However, faradaic charge injection at the interface of the electrode and nerve tissue causes irreversible gas evolution, oxidation of electrodes, and reduction of biological ions, thus causing undesired tissue damage and electrode degradation. Here we report a conformable neural interface engineering based on multicross-linked membrane-ionogel assembly (termed McMiA), which enables nonfaradaic neurostimulation without irreversible charge transfer reaction. The McMiA consists of a genipin-cross-linked biopolymeric ionogel coupled with a dopamine-cross-linked graphene oxide membrane to prevent ion exchange between biological and synthetic McMiA ions and to function as a bioadhesive forming covalent bonds with the target tissues. In addition, the demonstration of bioelectronic medicine via the McMiA-based neurostimulation of sciatic nerves shows the enhanced clinical utility in treating the overactive bladder syndrome. As the McMiA-based neural interface is soft, robust for bioadhesion, and stable in a physiological environment, it can offer significant advancement in biocompatibility and long-term operability for neural interface engineering.

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

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Efficacy and safety of mirabegron in the treatment of overactive bladder syndrome after radical prostatectomy: a prospective randomized controlled study.

Objectives: To evaluate the effects of mirabegron in the treatment of overactive bladder syndrome (OAB) after radical prostatectomy (RP). Patients and methods: A total of 108 post-operative RP patients were randomly assigned to either the mirabegron (study) or the placebo (control) group. The Overactive Bladder Syndrome Self-Assessment Scale (OABSS) was selected as the primary endpoint, and the International Prostate Symptom Score (IPSS) and Quality of Life (QOL) score were selected as secondary endpoints. Statistical analysis was performed using IBM SPSS Statistics 26, and the treatment effects were compared between the two groups using independent samples t-test. Results: In total, 55 patients were included in the study group and 53 patients in the control group. The mean age was(70.08 ± 7.54)years. There was no statistical difference in the baseline data between the two groups. OABSS scores decreased significantly in the study group compared to the control group during drug treatment (6.67 ± 1.06 vs. 9.14 ± 1.83, p < 0.01) and were better than the control group during the follow-up at week 8 and week 12. In addition, the decrease in IPSS scores (11.29 ± 3.89 and 15.34 ± 3.54, p<0.01) and the increase in QOL scores (2.40 ± 0.81 vs. 3.20 ± 1.00) were statistically significant in the study group. And the patients in the study group had better improvement in voiding symptoms and quality of life than the control group during the follow-up period. Conclusion: Daily administration of 50 mg mirabegron after RP surgery significantly improved the symptoms of OAB after surgery with fewer side effects. Additional randomized controlled trials should be conducted in the future to further evaluate the efficacy and safety of mirabegron.

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 45 mg/d for 12 weeks 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.

Comparative study of different combinations of mirabegron and antimuscarinics in treatment for overactive bladder syndrome in elderly patients.

Objectives: To compare the therapeutic efficacy, adverse events (AEs), and patient preference in elderly patients with overactive bladder (OAB) receiving different combinations of mirabegron and solifenacin. Materials and Methods: Elderly OAB patients received mirabegron 25 mg (M25) daily for 1 month (1M) followed by randomization to receive M25 (Group 1), mirabegron 50 mg (M50, Group 2), solifenacin 5 mg (S5, group 3); or M25 plus S5 (Group 4) for further 2 months. Efficacy and AEs were evaluated. At the end of 3M, patients' preferred option for future treatment was investigated. Results: A total of 168 patients were enrolled, and 100 completed 3-month treatment. At 1M, all parameters improved significantly except postvoid residual (PVR), 23 (13.7%) patients had no symptom, 16 (9.5%) had no improvement, and 10 (6.0%) withdrew from the trial. Compared parameters at 3M with 1M revealed that quality of life, Patient's Perception of Bladder Condition scores, and voided volume improved significantly in group 1; the OAB Symptom Score (OABSS) increased in group 2; mean PVR and Global Response Assessment (GRA) deteriorated in group 3; and the OABSS and GRA improved in group 4. At 3M, the AEs prevalence increased significantly in group 3. Only 38.1% in group 4 preferred long-term usage of combination therapy. Conclusion: M25 daily is effective and safe in treating elderly OAB patients. Dose escalation to 50 mg or shifting to S5 does not increase the therapeutic efficacy. Combining M25 with S5 provides better treatment efficacy but is associated with lower patient compliance than M25 alone.

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.

Role of Protopine and Nuciferine in the Management of Nocturia, Urgency, and Dysuria in Pre- and Postmenopausal Women: A Prospective Pilot Study.

OBJECTIVES: Nocturia was commonly treated with drugs burdened with high costs and numerous side effects; in fact, more than 70% of patients drop out of long-term treatment. Protopine and nuciferine are two alkaloids that have different effects on the neurotransmitter receptors involved in the regulation mechanism of the onset of urinary stimuli. The aim of the study was to evaluate the efficacy in controlling primarily nocturia and secondarily urgency and dysuria after 3 months of treatment with combination therapy of protopine and nuciferine syrup. DESIGN: This is a prospective cohort study in which all patients were diagnosed with overactive bladder syndrome (OAB) and the presence of the following symptoms: nocturia, urgency, and dysuria. Thirty patients were administered 10 mL/die (16.6 mg of nuciferine, 0.09 mg of protopine) of syrup for 3 months. Patients were evaluated at baseline (T0) with the International Consultation on Incontinence Questionnaire (ICIQ), Visual Analogue Scale (VAS) for the evaluation of dysuria, Patient Perception of Intensity of Urgency Scale (PPIUS) and at 3 months (T1) with the Patients' Global Impression of Change (PGI-C) scale, PPIUS, VAS, and ICIQ. PARTICIPANTS: Women with diagnosis of OAB; the presence of nocturia, urgency, and dysuria symptoms agreeing to undergo treatment and compiling informed consent; and the absence of contraindications to the use of active ingredients were included in the study. SETTING: Patients were recruited at T0 during the visit to the Uro-Gynecology clinic of the University of "Campus Bio-Medico" and visited again 3 months (T1) after the initiation of therapy. METHODS: We explored survey data by descriptive statistics: in particular, continuous values (i.e., ICIQ) have been summarized by mean and standard deviation of discrete ordinal values (i.e., VAS, PPIUS, and bladder diary parameters at T0 and T1) by median, minimum, and maximum reported scores. Where we could assume normality in distribution, assessed by the Shapiro-Wilk test and the evaluation of the QQ plot, we compared the observation of T0 and T1 with the paired Student's t test; otherwise, we tested differences in distribution with the paired Mann-Whitney U test. RESULTS: Thirty patients completed a 3-month therapy. The ICIQ and VAS questionnaires for the assessment of dysuria, both, reported an improvement in dysuria at T1 (p < 0.001). The PPIUS questionnaire reported an improvement in urinary urgency at T1 (p < 0.001). The PGI-C scale in T1 indicated an improvement in symptoms: 93% for nocturia, 70% for urinary urgency, and 63% for dysuria. LIMITATIONS: The weaknesses of this study are the small number of patients; as a pilot study, the study design was not randomized with a placebo and without blinding; and the short follow-up. CONCLUSIONS: Protopine and nuciferine can be an interesting alternative to primarily treat and reduce nocturia episodes, in addition to improving OAB-related urgency and dysuria.

Safety and tolerability of solifenacin in children and adolescents with overactive bladder- a systematic review.

BACKGROUND: Solifenacin is an anticholinergic that is used to treat overactive bladder syndrome (OAB) in children. It is important to ascertain the safety and tolerability of solifenacin in the paediatric population as solifenacin offers an alternative, is more bladder specific, and should have less anticholinergic side effects than other therapies. OBJECTIVE: The aim of this study is to systematically evaluate the safety and tolerability of solifenacin in children and adolescents with OAB. STUDY DESIGN: We included studies that reported the safety and tolerability of solifenacin in children and adolescents. All study types were included. Electronic searches were conducted in Ovid MEDLINE, Ovid Embase, TRIP, CINAHL and ICTRP on the 18th of January 2022. Risk of bias was assessed with the Cochrane Risk of Bias tool 2.0 (ROB-2) for randomised controlled trials (RCTs) and the Newcastle-Ottowa scale for cohort studies. RESULTS: A total of twelve studies including two RCTs were included in this review. Results from the meta-analysis of RCTs showed the commonest side effects were constipation (RR 3.5, 95%CI 0.9-13.7) and dry mouth (RR 3.1 95%CI 0.2-53). In terms of tolerability, the effect estimate of ceasing solifenacin due to an adverse effect was 2.7 (95%CI 0.8-9.1). Within the cohort studies, out of the 779 patients 21.7% experienced side effects. The most common side effects were constipation (6.8%) and dry mouth/lips (6.0%) and 3.5% of patients ceased solifenacin due to adverse effects. Overall, the certainty of the evidence for side effects and tolerability were very low. DISCUSSION: The reported incidence of side effects is low, and less than reported with oxybutynin use. However, the very low certainty of the evidence means the findings should be interpreted with caution. There is limited reporting of a prolonged QTc interval on ECG. Studies that described this only had an increase of QTc from baseline and not a clinically significant prolonged QTc that resulted in arrhythmias. CONCLUSION: Solifenacin is an alternative anticholinergic for the treatment of OAB in children. However, given the paucity of good quality data on safety and tolerability it should be used cautiously in children with close monitoring for potential side effects.

Are ß3 -adrenoceptor gene polymorphisms relevant for urology?

AIMS: ß3 -adrenoceptors (ARs) are an important drug target for the treatment of overactive bladder syndrome (OAB) and are under investigation for other indications. The human ß3 -AR gene is polymorphic; an exchange of amino acid tryptophan (Trp) for arginine (Arg) in position 64 of the receptor protein is the most frequent and best-studied polymorphism. A narrative review on the impact of ß3 -AR polymorphisms on urological disease and its treatment is presented. RESULTS: Two out of four studies have reported that the 64Arg allele was found more frequently in subjects with OAB than in healthy controls. A large study in a highly selective population (men undergoing prostatectomy for cancer treatment) did not confirm this. On the other hand, studies examining symptom severity typically found little difference between 64Arg and 64Trp carriers. In vitro studies with endogenously expressed ß3 -AR reported a decreased lipolytic response in human adipose tissue. Studies with heterologously expressed receptors sometimes found a decreased responsiveness to agonists including ß3 -AR agonists, but others did not confirm that. CONCLUSIONS: The overall evidence points to carriers of the 64Arg genotype expressing fewer and/or hypofunctional ß3 -ARs and being associated with the presence of OAB but such findings were only detected inconsistently. If this hypofunctionality exists, the consequences may be of insufficient magnitude to allow a robust detection. Only adequately powered studies comparing responses with a ß3 -AR agonist in 64Arg carriers versus wild-type patients can address this.

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.

Depression and anxiety in patients with pelvic floor disorders.

Pelvic floor disorders are very common health problems in adult women affecting their quality of life in many aspects. One of them, still poorly recognised, is depression as well as anxiety. As the main goal of treatment is achievement of improvement of life quality we have to be aware of the incidence and severity of mood disorders in urogynecological patients. It is very important to be sure whether treatment of main disease is enough to solve depression and anxiety or we have to cope with them separately. The review sums up current knowledge on that very important topic.