OAB Patients Research Articles

PD34-08 PIVOTAL STUDY OF A LEADLESS TIBIAL NERVE STIMULATOR FOR URGENCY URINARY INCONTINENCE (UUI): 2-YEAR OUTCOMES FROM A SINGLE SITE

You have accessJournal of UrologyCME1 May 2022PD34-08 PIVOTAL STUDY OF A LEADLESS TIBIAL NERVE STIMULATOR FOR URGENCY URINARY INCONTINENCE (UUI): 2-YEAR OUTCOMES FROM A SINGLE SITE Alexandra Rogers Alexandra RogersAlexandra Rogers More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002585.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A novel leadless, fully-implantable tibial nerve stimulator has unique attributes compared to current OAB treatments including automated compliance, a brief procedure using only local anesthetic and reliance on minimal resources. Patient experience with this device (eCoin®) was evaluated after 96 weeks of therapy at a single site. METHODS: This was a prospective, single-arm trial involving 15 US sites with patients who were intolerant of, or showed an inadequate response to, at least one 2nd or 3rd line therapy prior to enrollment. The coin-sized, leadless device is composed of electrodes lining the rim and bottom center, emitting a dome-shaped electrical field with a wide radius. It is implanted subcutaneously in the medial lower leg above the fascia using just local anesthetic. After a short healing period, it delivers automated 30-minute therapy sessions every 3-4 days. The primary endpoint for this study was assessed at 48 weeks post-activation, with patients given the option to participate in an extension phase including a follow up visit at 96 weeks post-activation. This visit included the collection of a 3-day voiding diary, Overactive Bladder Questionnaire (OABq), Patient Global Impression of Improvement in Incontinence (PGI-I), and an assessment of any adverse events. RESULTS: All 26 subjects reached 96-weeks post-activation. Mean age is 65.8 (±8.8) years, all patients are female, and at baseline patients had an average of 4.6 (±2.7) UUI episodes per day. At 96 weeks post-activation, 81% of subjects were “responders,” indicating they improved by at least 50% in their UUI. Additionally, 54% of patients achieved ≥75% reduction in UUI, and 23% had complete resolution in UUI (dry). Results from the OABq indicate the symptom bother scale was reduced by an average of 35 points, and the HRQoL scale was improved by an average of 30 points at 96 weeks. 82% indicated they were at least “Better” after treatment, and 50% indicated they were “Very Much Better” on the PGI-I. There were no related adverse events recorded during the extension phase of the study. CONCLUSIONS: These single site results suggest long term UUI management with eCoin is efficacious and safe, with the percentage of “responders” increasing from 77% at 48 weeks to 81% at 96 weeks post-activation. Potentially, the eCoin device will greatly treat more OAB patients by eliminating many of the barriers which reduce progression to current third-line therapies often compromised by poor adherence. Source of Funding: Valencia Technologies © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e563 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexandra Rogers More articles by this author Expand All Advertisement PDF DownloadLoading ...

Sacral neuromodulation for the treatment of overactive bladder: systematic review and future prospects

ABSTRACT Introduction Sacral Neuromodulation (SNM) is a minimally invasive treatment for OAB patients following failure of conventional interventions. Patient selection, lead placement, and testing technique are important pillars in optimizing success rates. Areas covered A comprehensive literature search was conducted on ‘sacral neuromodulation’ and ‘overactive bladder.’ There was no date restriction, with the last search dated 31 May 2021. Patient selection, lead placement, test phases, safety, efficacy, and available devices are thoroughly discussedLastly, future perspectives will be presented with the anticipated trajectory of sacral neuromodulation over the next five years. Expert opinion/commentary SNM has proved to be a safe and effective therapy on the short-, medium- and long-term without precluding any other treatment options. In all studies reviewed, no life threatening or major irreversible complications were presented. However, surgical re-intervention rates were high with a median of 33.2% (range: 8–34%) in studies with at least 24 months follow-up. No true consensus could be made regarding prognostic factors. However, optimized lead placement, consequent ideal motor thresholds, and the use of a curved stylet theoretically facilitates reaching maximal success with SNM. Test phase success rates increased to such a level that from a cost-effective point of view, single-stage implants could be considered. Abbreviations: OAB: overactive bladder; SNM: sacral neuromodulation; BoNT-A: Botulinum toxin A; PFM EMG: pelvic floor muscle electromyography; IPG: implantable pulse generator; PNE: percutaneous nerve evaluation; FSTLP: first-stage tined lead procedure; NLUTD: neurogenic lower urinary tract dysfunction; ITT: intention to threat; PPMC: per protocol modified completers; PPC: per protocol completers; AE: adverse event; MRI: magnetic resonance imaging; RCT: randomized controlled trial

PD27-12 ANTAGONISM OF THE P75NTR RECEPTOR INCREASES THE RELEASE OF NERVE GROWTH FACTOR IN UROTHELIAL CELLS BY INHIBITING MATRIX METALLOPROTEINASE-9

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (PD27)1 Sep 2021PD27-12 ANTAGONISM OF THE P75NTR RECEPTOR INCREASES THE RELEASE OF NERVE GROWTH FACTOR IN UROTHELIAL CELLS BY INHIBITING MATRIX METALLOPROTEINASE-9 Aalya Hamouda, Philippe Cammisotto, Stephanie Sirmakesyan, Uri Saragovi, and Lysanne Campeau Aalya HamoudaAalya Hamouda More articles by this author , Philippe CammisottoPhilippe Cammisotto More articles by this author , Stephanie SirmakesyanStephanie Sirmakesyan More articles by this author , Uri SaragoviUri Saragovi More articles by this author , and Lysanne CampeauLysanne Campeau More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002020.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Decreased levels of nerve growth factor (NGF) have been observed in the urine of patients with overactive bladder syndrome (OAB) and of diabetic animal models. This unbalance appeared to result from an increased activity of the proteolytic enzyme metalloproteinase-9 (MMP-9). On the other hand, THX-B, an inhibitor of p75NTR, restored normal levels of NGF in mice with type 1 diabetes. We here examine in vitro the effect of THX-B on the activity of MMP-9 in bladder cells. METHODS: Primary culture of urothelial and smooth muscle cells (SMCs) were grown from mouse bladder and exposed to p75NTR antagonist THX. The expression of NGF and MMP-9 were assessed by RT-qPCR, by immunohistochemistry and by immunoblotting. Levels of microRNAs were measured by RT-qPCR. NGF and proNGF secretion were measured by ELISA kits and MMP-9 activity by enzymatic assays. RESULTS: The mRNAs for NGF and MMP-9 were detected and found expressed in both cell types at similar level. Microscopy confirmed the localization of both proteins in cells. Urothelial cells and SMCs were both major source of NGF and proNGF. On the other hand, MMP-9 protein content was 7 times higher in SMCs than in urothelial cells, which was confirmed by high levels of miR-491-5p in the latter. However, secretion of active MMP-9 in the medium was 40 times higher in urothelial cells medium. Incubation with THX-B (5 µg/mL) for 24 hours abolished the synthesis and secretion of MMP-9 and doubled the concentration of NGF in the medium of urothelial cells. ProNGF secretion levels were not affected. THX-B had little effects on SMCs both at the level of NGF and MMP-9. CONCLUSIONS: Urothelial cells appear to be the primary target for THX-B to modulate secretion of NGF and MMP-9. These results are in accordance with our previous publications on OAB patients and diabetes type 1 in rodents, and suggest that THX-B could be a therapeutic tool to improve OAB by targeting primarily the urothelium. Source of Funding: Canadian Urology AssociationQuebec Network for Research on Aging © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e448-e448 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Aalya Hamouda More articles by this author Philippe Cammisotto More articles by this author Stephanie Sirmakesyan More articles by this author Uri Saragovi More articles by this author Lysanne Campeau More articles by this author Expand All Advertisement Loading ...

Solifenacin/Mirabegron Induces an Acute Compliance Increase in the Filling Phase of the Capacity-Reduced Urinary Bladder: A Pressure-Volume Analysis in Rats.

Aims: Pressure in the bladder, which is a high compliance organ, is only slightly elevated to a considerable filling volume during storage. Although cystometry off-line offers mean compliance, no protocol is available for real-time assays of the dynamics of bladder compliance, and the potential impact of solifenacin and mirabegron on dynamic bladder compliance has not been established. Methods: Along with constantly infused cystometry, a pressure-volume analysis (PVA) was performed by plotting intra-vesical volume against pressure in Sprague-Dawley rats. The instant compliance was assayed as the slope of the trajectory, and the mean compliance (Cm) was determined by the slope of the line produced by regression of the data points at the end of the first, second, and third quarters of the filling phase. Results: Under a steady-state, the PVA trajectory moved clockwise which shaped coincident enclosed loops with stable compliance. Though administering to naïve animals solifenacin, but not mirabegron (both 1 × 10−5−1 × 10−1 mg/kg, i.a.) decreased the peak pressure, both of these reagents exhibited acute increments in the trajectory slope and Cm of the filling phase in a dose-dependent manner (ED50 = 1.4 × 10−4 and 2.2 × 10−5 mg/kg, respectively). Resembling urine frequency/urgency in OAB patients, the voiding frequency of a capacity-reduced bladder was increased in association with decreased compliance which was ameliorated by both acute solifenacin and mirabegron injections (both 1 × 10−1 mg/kg). Conclusion: In addition to their well-known anti-inotropic/relaxative effects, solifenacin, and mirabegron induce an acute increase in bladder compliance to ameliorate OAB-like syndromes. Together with time-domain cystometry, PVA offers a platform for investigating the physiology/pathophysiology/pharmacology of bladder compliance which is crucial for urine storage.

Role of vasoactive drugs in the OAB complex treatment

Aim of the study.To investigate the vasoactive drugs for urinary bladder wall ischemia correction, based on its role in OAB pathogenesis.
 Patients and methods.OAB treatment in 150 women was performed. In addition to the standard anticholinergic therapy microcirculation corrector was prescribed to some patients with insufficient treatment efficacy.
 Results.The combination of simultaneous prescription of anticholinergic and vasoactive drugs was effective for OAB treatment. The treatment resulted in significant decrease of the OAB symptoms.
 Conclusion.Low efficacy of M-cholinolytic therapy of the OAB patients is determined by the blood flow disturbances in the urinary bladder wall. It is reasonable to include the vasoactive drugs in complex OAB therapy.

Treatment of Overactive Bladder in the Frail Patient

To understand how frailty interacts with overactive bladder. To explore how frailty should be considered when devising an individualized treatment plan for OAB patients. Frailty can be assessed in the outpatient office without undue burden. The urology community is increasingly aware of the importance of evaluating a patient for frailty and including this assessment in treatment algorithms. Frailty should be considered when treating OAB patients, since frail OAB patients are more susceptible to the potential deleterious consequences of medical therapy, onabotulinumtoxinA therapy, and sacral neuromodulation. A patient’s frailty status should be considered during counseling regarding OAB therapy. Additional studies are needed to examine the treatment effects and risks in the frail OAB population.

Are Beta 3 Adrenergic Agonists Now the Preferred Pharmacologic Management of Overactive Bladder?

This paper discusses the recent evidence supporting beta 3 adrenergic agonists as the preferred pharmacological management of overactive bladder syndrome. Mirabegron has a similar efficacy profile to first-line antimuscarinics with favorable adverse effects profile. Treatment of OAB with beta-3 adrenergic agonist should be favored in patients at higher risk of anticholinergic adverse events. The efficacy and tolerability of beta-3 adrenergic agonists are consistently reported in older OAB patients, whether used alone or with other antimuscarinics. Mirabegron is cost-effective in treating OAB unless the symptoms were severe or refractory. Combination therapy of mirabegron and other pharmacotherapy has proven to be efficient in controlling OAB symptoms without inducing serious add-on adverse effects. While beta-3 adrenergic agonists bear favorable advantages in OAB treatment, physicians should perform a thorough and careful pre-treatment planning to optimize treatment benefits and adherence.

Evaluating vibegron for the treatment of overactive bladder

ABSTRACT Introduction Vibegron is a very selective new β3-adrenergic receptor agonist introduced recently to clinical practice for OAB patients, which offers an alternative option for to antimuscarinic drugs. Areas covered This review presents the current knowledge concerning the mechanism of action, pharmacokinetics, and pharmacodynamics of vibegron. Moreover, it presents an overview of preclinical and phase II and phase III clinical studies on the efficacy, tolerability, and safety of this agent in patients suffering from OAB. Expert opinion Clinical studies confirmed efficacy and safety of vibegron in OAB patients. Vibegron differ from well-known mirabegron with regards to its pharmacological profile because it is metabolized independently from CYP3A4, 2D6, or 2C9 and therefore is less likely to cause a drug–drug interaction. Moreover, since this drug does not penetrate the blood-brain barrier, it could become the drug of choice in OAB patients with cognitive impairment. These properties have paved the way in near future for better-tailored treatments for OAB patients.

Recent advances in managing overactive bladder.

Overactive bladder syndrome (OAB) is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency incontinence, in the absence of urinary tract infection or other obvious pathology. In this review, we focus on recent advances in the management of OAB. We examine the evidence on the effect of anticholinergic load on OAB patients. Advances in medical treatment include a new beta-3 agonist, vibegron, which is thought to have fewer drug interactions than mirabegron. Treatment of genitourinary syndrome of the menopause with oestrogens and ospemifene have also shown promise for OAB. Botulinum toxin has been shown to be an effective treatment option. We discuss the new implantable neuromodulators that are on the market as well as selective bladder denervation and laser technology.

Treatment for refractory overactive bladder: a systematic review and meta-analysis of sacral neuromodulation and onabotulinumtoxinA.

This systematic review and meta-analysis aim to evaluate the outcomes between SNM and BTX in the treatment of refractory OAB. PubMed, Embase, and CENTRAL were comprehensively searched from their inception to December 2019. Randomized and nonrandomized controlled trials evaluating OAB patients who underwent SNM and BTX were included. Data extraction and quality assessment were conducted by two independent reviewers. The outcomes, side effects, and cost-effectiveness values of both procedures were compared in meta-analysis. This review involved six articles (2629 patients). Specifically, three articles were based on the same trial, and the other studies were retrospective cohort studies. No significant difference was found in successful treatment between BTX and SNM at 6months after procedures [risk ratio (RR) = 0.93, 95% confidence interval (CI) 0.63-1.39]. BTX exhibited a significantly higher total adverse event rate than SNM through 6months (RR = 1.55, 95% CI 1.28-1.88). Patients suffered more urinary tract infection (UTI) risk under BTX injection at the early stage (RR = 1.58, 95% CI 1.10-2.25); however, the difference in UTI events was not significant between the two groups (RR = 1.13, 95% CI 1.10-2.25) during the period of 7-12months postoperatively. Obviously, the short-term cost (1-2years) of BTX was significantly lower than that of the SNM procedure. Both treatments were effective; however, because of the high complication rate of BTX, it may not be a better way to treat refractory OAB than SNM, although BTX is more cost-effective for short-term treatment at present.

Development of a flowchart reflecting the current attitude and approach towards idiopathic overactive bladder treatment in Belgium: A Delphi study.

Idiopathic overactive bladder syndrome (iOAB) is a prevalent condition in urological practice. The variability in management between specialists and between centers remains high. Even existing guidelines contain inconsistencies. We aimed to develop a treatment algorithm for iOAB for use in daily clinical practice. From October 2018 till November 2019, a Delphi study was conducted to obtain expert consensus on the management of iOAB. Members from the Belgian Working Group of Functional Urology were asked to rate online statements, based on gaps and variabilities between the American Urology Association (AUA), European Association of Urology (EAU) and International Consultation on Incontinence (ICI) guidelines on iOAB. The consensus was reached if ≥75% of the panel agreed on the level of appropriateness. Two Delphi rounds and an open discussion session were held. Twenty out of 49 members completed the first round and 18 completed the second round. The consensus was reached on 44/143 statements and 15/56 statements in the first and second round, respectively. The consensus was reached on criteria by which to phenotype OAB patients, the terminology relating to the first-, second- and third-line treatment, the duration of therapies, the chronological order, and the choice between therapies. No consensus was reached on the role of percutaneous tibial nerve stimulation (PTNS) in the treatment algorithm. A flowchart reflecting the current attitude and approach of a Delphi expert panel towards the treatment of iOAB was developed. We propose its use in daily clinical practice to increase the standardization of OAB treatment.

Posterior Urethral Valves with Lower Urinary Tract Symptoms: Perspective on Urodynamics

Background Lower urinary tract symptoms (LUTs) are common in young boys with posterior urethral valves (PUVs). It is crucial to investigate the characteristics of PUV patients with and without LUTs after valve ablation. Methods Between January 2017 and December 2019, PUV patients visited Children’s Hospital, Fudan University for following up were enrolled. Medical records and information from the patients’ urodynamic studies (UDS) were reviewed. Results A total of 54 enrolled PUV patients were divided into symptomatic PUV group (28 cases) and non-symptomatic PUV group (26 cases) according to daytime incontinence or not, and 21 OAB cases without structural abnormalities were set as UDS control group. The non-symptomatic PUV patients had lager filling volume (135 ± 46% of EBC) than the symptomatic PUV patients and OAB patients (106.1 ± 44.4% of EBC, p = 0.0255 and 88.1 ± 39.6% of EBC, p = 0.0007, respectively). The detrusor pressure at 1/4 and 3/4 of full filling was higher in PUV groups than the control group, but no significant difference was found between the PUV groups. PUV patients with LUTs had a higher rate (19/28, 67.9%) of impaired bladder compliance than non-symptomatic PUV patients (11/26, 42.3%, p = 0.0489). The PUV patients with LUTs had a trend of worse kidney functions in lower GFR, higher serum creatinine and lower estimated GFR. Conclusion PUV patients have higher detrusor pressure regardless of the presence or absence of LUT symptoms. Bladder function assessments are needed in boys with PUV, even without incontinence symptoms after valve ablation.

MP31-12 OVERACTIVE BLADDER SYNDROME IS ASSOCIATED WITH ELEVATED URINARY PRONGF TO NGF RATIO IN AN AGING FEMALE POPULATION

INTRODUCTION AND OBJECTIVE: The clinical relevance of the ratio NGF/creatinine in urine as a biomarker for overactive bladder syndrome (OAB) diagnosis is a matter of debate. ProNGF, the precursor form of nerve growth factor (NGF) was recently found to possess degenerative roles by signalling through its receptor p75NTR. The present study aims to identify the changes in concentration of NGF and proNGF, and the soluble factors involved in their proteolysis in the urine of an aging female population with OAB. METHODS: Urine samples were obtained from 20 females of 50-80 years of age with OAB and from 20 controls of the same age group. Analyses were carried out with highly specific ELISA and enzymatic kits. Participants completed a full clinical evaluation and validated self-reported questionnaires of lower urinary tract symptoms as well as a one-day voiding diary. RESULTS: NGF ELISA kit specificity was confirmed. ProNGF/NGF ratio was significantly increased in the urine of OAB subjects. Enzymatic activities of plasmin and matrix metalloproteinase 7 (MMP-7), the main enzymes responsible for extracellular processing of proNGF to NGF, were similar between controls and OAB when normalized to their respective inhibitors, α2-antiplasmin inhibitor and TIMP-1. On the other hand, metalloproteinase 9 (MMP-9), the enzyme responsible for the proteolysis of NGF into peptides, displayed a marked increased activity even when normalized to its inhibitor TIMP-1. On the other hand, nitric oxide and PGE2, two factors increasing expression and activity of MMP-9, also displayed higher concentrations in urine of OAB patients. CONCLUSIONS: The ratio ProNGF/NGF could constitute a more reliable biomarker for OAB rather than NGF level alone. This increase could originate from MMP-9 overactivity enhancing NGF proteolysis in OAB. This suggests that MMP9 inhibitors could constitute a new therapeutic target to treat OAB patients. Source of Funding: Urology Care Foundation Rising Star in Urology Research Award and the Quebec Network for Research on Aging

PD44-09 A BLADDER INJECTION SYSTEM AND A SPECIFIC INJECTION PROTOCOL REDUCE URINARY RETENTION FOLLOWING ONABOTULINUMTOXINA TREATMENT OF OVERACTIVE BLADDER (OAB)

INTRODUCTION AND OBJECTIVE:Injecting onabotulinumtoxinA into the bladder wall effectively treats OAB but many patients find the risk of post procedure urinary retention unacceptable. Two recent stu...

Is There a Link Between Carotid Atherosclerosis and Idiopathic Overactive Bladder Among Women with Metabolic Syndrome?

PurposeTo evaluate the association between increased intima-media thickness (IMT) and atherosclerotic carotid plaque (CP) with idiopathic overactive bladder syndrome (OAB) in women with metabolic syndrome (MetS).MethodsThis is a cross-sectional study, which included consecutive women aged 40–75 years with MetS, seeking medical assistance at a reference center between April and December 2016. OAB-V8 questionnaire was used to estimate the prevalence of OAB symptoms, which were defined by a score ≥8 points. All patients underwent bilateral carotid artery ultrasound to assess IMT and CP. Atherosclerosis was defined by the identification of CP during ultrasound, which was diagnosed according to the Mannheim carotid intima-media thickness and plaque consensus.ResultsForty-five women were prospectively included. Mean age was 60±9.3 years (range 40–75 ys). Eighteen (40%) patients were diagnosed with OAB. IMT in the general population was 0.72 mm (SD = 0.20). Overall prevalence of atherosclerosis, defined by the presence of the carotid artery plaque, was 51%. OAB prevalence among women with atherosclerosis was higher than in those without atherosclerosis (56.52% versus 22.73%), with a prevalence ratio of 2.49 (p=0.04). Additionally, OAB was associated with degree of carotid stenosis (p = 0.029).ConclusionIn this cohort of female patients with MetS, there was an association between carotid atherosclerosis and OAB. Identification of carotid ultrasound abnormalities may lead to refined treatment decision-making among OAB patients.

Relation of ADRB3, GEF, ROCK2 gene polymorphisms to clinical findings in overactive bladder.

Adrenergic and cholinergic pathways play an important role in contraction-relaxation harmony in human bladder. Functional changes in any proteins in these pathways may result in overactive bladder. We aimed to investigate whether single gene polymorphisms affecting adrenergic and cholinergic pathways are associated with OAB syndrome. 60 patients with idiopathic OAB and 60 healthy controls were included in the study. A validated OAB-V8 questionnaire was given to all patients. Polymorphisms of ADRB3, ROCK2, and GEF gene were detected by PCR from whole blood samples. Genotypic structures of patients and controls were compared. The relationship between genotypic structures and OAB symptom scores were investigated. We found no significant difference in the genotype and allele frequencies between the patients and controls for all three SNP. While there was no relationship between ADRB3 and GEF gene polymorphisms and OAB scores in OAB patients, the OAB score in heterozygous polymorphic individuals was significantly higher than in homozygous polymorphic individuals in the ROCK2 gene (p = 0.039). The polymorphisms of the ADRB3, ROCK2, and GEF genes were present in both OAB group and healthy controls, but were not associated with OAB syndrome.

The efficacy of nebivolol on spontaneously hypertensive rats with overactive bladder - an experimental study.

IntroductionOveractive bladder (OAB) is a disease that significantly decreases quality of life. Adverse effects of the drugs currently used in OAB treatment limit their use in patients with hypertension. Nebivolol (a β1-adrenergic receptor blocker) is approved for hypertension treatment, but also shows agonistic activity on β3-adrenergic receptor, located in the urinary bladder. The aim of this study was to assess the impact of nebivolol on OAB symptoms and cardiovascular parameters in spontaneously hypertensive rats (SHR) – an animal model of OAB and hypertension.Material and methodsFemale Wistar-Kyoto (WHY) and SHR rats were used in the experiments. Nebivolol was administered intra-arterially at a single daily dose of 0.05 mg/kg for 14 days. Subsequently, cystometry and bladder blood flow assessment were performed. Then, 24-hour measurement of heart rate, blood pressure, and urine production was carried out. In addition, the bladders of experimental rats were removed and processed to conduct biochemical analyses.ResultsThe main finding of this study is that the treatment with nebivolol resulted in an improvement of cystometric parameters characteristic for OAB in SHR. Nebivolol normalised blood pressure in SHR, while in WHY the cardiovascular parameters remained unchanged. Biomarkers characteristic for OAB were elevated in SHR compared to WHY, and nebivolol decreased their values in SHR while it had no influence on WHY.ConclusionsNebivolol alleviates OAB symptoms and normalises blood pressure in SHRs. These results suggest that nebivolol may be a useful treatment alternative for OAB patients with pre-existing hypertension.

Abnormal Brain Functional Connectivity Strength in the Overactive Bladder Syndrome: A Resting-State fMRI Study

ObjectiveTo investigate the whole-brain functional connectivity strength (FCS) of patients with the overactive bladder syndrome (OAB). MethodsThis study investigates the changes of intrinsic whole brain functional connectivity pattern in OAB using FCS. We acquired resting-state fMRI data from 26 OAB patients and 28 healthy controls. FCS was used to compute the long-range and short-range FCS values for each voxel in the brain of each subject. The long or short-range FCS maps were compared between OAB patients and healthy controls. Pearson's correlation coefficients was also performed between abnormal FCS regions and clinical/psychometric scores in patients. ResultsCompared with healthy control subjects, the OAB patients exhibited significantly decreased short-range FCS in the right medial superior frontal gyrus and bilateral anterior cingulate gyrus, and increased short-range FCS in the middle frontal gyrus, the precentral gyrus, and bilateral caudate nucleus. In addition, significantly decreased long-range FCS was found in bilateral middle cingulate gyrus and posterior cingulate gyrus. Furthermore, the abnormal FCS values in the right caudate nucleus showed significantly negative correlation with Self-Rating Depression Scale of OAB patients. ConclusionPatients with OAB have abnormal short-range and long-range FCS in brain regions associated with brain-bladder network. Our study provides new insights into the underlying brain network topology of OAB.

PT237 - Chance of OAB patients to become symptom-free upon anti-muscarinic treatment depends on age and gender

PT237 - Chance of OAB patients to become symptom-free upon anti-muscarinic treatment depends on age and gender

Modeling the possibility of occurrence of overactive bladder in women of different ages, depending on anthropo-somatotypological indicators or hormonal background with the help of discriminant analysis

One of the most important problems of modern urogynecology is the improvement of the treatment-diagnostic algorithm and prevention of overactive bladder syndrome (OAB). The purpose of the work is to construct and analyze discriminant models of the possibility of OAB occurrence in pregnant women of different age groups depending on the characteristics of anthropo-somatotypological indicators or hormonal background. 75 pregnant women with clinical signs of OAB syndrome and 60 healthy pregnant women had hormonal screening in the 1st and 3rd trimester of pregnancy and at 16 weeks postpartum using radioimmunoassay and immune enzyme methods (estradiol, progesterone, thyroid stimulating hormone and testosterone levels were determined). The anthropometry was carried out according to the method of V. V. Bunak, the components of the somatotype were determined according to the method of J. Carter and B. Heath, as well as the components of the body composition according to the method of J. Matiegka and the American Institute of Nutrition (AIN). By age, all pregnant women were divided into 3 subgroups: І - from 17 to 25 years, ІІ - from 26 to 35 years, ІІІ - from 36 to 41 years. A discriminant analysis of the possibility of OAB occurrence, depending on the anthropo-somatotypological or hormonal indices in women of different age groups, was conducted using the licensing program “Statistica 5.5”. When taken into account anthropo-somatotypological indices in women aged from 17 to 25 years, the model is correct in 86.7% of cases; in women aged from 26 to 35 years - in 90.9% of cases; in women between the ages of 36 and 41 years - in 89.3% of cases. Between healthy and OAB patients, women aged from 17 to 25 years discriminating variables are the width of the distal epiphysis of the shoulder (which has the greatest contribution to discrimination), conjugata externa, the muscle component of the body weight by AIN and the forearm's girth in the upper third; women from 26 to 35 years - dist. Іntеrtrochantericа, the width of the distal epiphyses of the forearm (the greatest contribution to discrimination), hip circumference, conjugata externa, mesomorphic component of the somatotype according to by Heath-Carter, fat mass component of the body by Matiegka, the forearm's girth in the upper third and the shoulder girth; women of age from 36 to 41 years - the width of the distal epiphysis of the leg (which has the greatest contribution to discrimination) and the length of the body. In general, the aggregate of all variables has a low level of discrimination between healthy and sick with OAB women between the ages of 17 and 25 (Wilkes Lambda statistics = 0.531; F = 5.521; p <0.01) and 36-41 years (Wilkes Lambda statistics = 0.445; F = 15.62; p <0.001), while among women between the ages of 26 and 35 - the average level of discrimination (Wilkes Lambda statistics = 0.386; F = 13.52; p <0.001). When taken into account characteristics of the hormonal background in women of all ages, the model is correct in 100% of cases. Between healthy and OAB patients, of 17-25 years age, discriminant variables are estradiol levels at 16 weeks of postpartum (with the largest contribution to discrimination) and prolactin levels in the first trimester of pregnancy; women aged from 26 to 35 years - estradiol levels at 16 weeks of postpartum (the most contributing to discrimination), testosterone in the third trimester of pregnancy, estradiol in the third trimester of pregnancy, prolactin in the third trimester of pregnancy, estradiol in the first trimester of pregnancy, and testosterone levels in the first trimester of pregnancy; women aged from 36 to 41 years - estradiol in the third trimester of pregnancy (has the largest contribution to discrimination) and estradiol in the 16 weeks of postpartum period. In general, the totality of all variables has a low level of discrimination between healthy and sick at OAB women between the ages of 17 and 25 (Wilkes Lambda statistics = 0.619; F = 131.4; p <0.001) and ages 26-35 (Wilks Lambda statistics = 0.493; F = 224.9; p <0.001), while among women between the ages of 36 and 41 - the average level of discrimination (Wilkes Lambda statistics = 0.371; F = 207.4; p <0.001). Thus, with the aid of discriminant analysis, reliable models of the possibility of OAB occurrence, based on anthropo-somatotypological or hormonal indices in women of different age groups, are constructed. In all age groups, the greatest contribution to discrimination between healthy and sick with OAB pregnant women, in most cases, make parameters of the width of distal epiphyses of long limb bones or the level of estradiol.