Antimuscarinic Therapy Research Articles

2216 Geriatric overactive bladder and botulinum toxin a: feasibility and tolerability in the outpatient setting under local anaesthetic

Abstract Introduction Urinary incontinence significantly impacts the lives of older adults increasing their susceptibility to falls, social isolation and long term care Intravesical Botulinum Toxin A (Botox) offers a well-established treatment for overactive bladders in women. In select centres, it can be administered under local anaesthetic, allowing access for frailer patients at higher risk from general anaesthetic and in whom anti-muscarinic therapies are best avoided. This project performed an analysis of geriatric patients who underwent intravesical Botox under local anaesthetic in an outpatient setting and assessed the tolerability and feasibility. Method 50 women (mean age 66, range 34–88) with overactive bladders underwent Botox administration in 2023. The procedure utilised local anaesthesia (Instillagel) while patients held a supine position with abducted hips on an outpatient couch. A LiNA OperaScope and injeTAK® needle facilitated administration. A sub-analysis focused on patients aged 75+. Pain levels were compared to past cervical smear experiences for reference. Results All 50 patients successfully completed the procedure. 15 were aged 75+ (mean 80.8, range 76–88), with 8 classified as ‘frail’ based on the Prisma 7 score (mean 2.3, range 0–5). The geriatric cohort reported lower average pain levels (1.8/10, range 1–3) compared to the non-geriatric group (2.2/10, range 1–5). Both groups pain perception was also lower than for past smears (2.9/10, range 1–4 vs. 3.4/10, range 1–7). Total ‘operative’ time was <3 minutes for all patients. Two non-geriatric participants experienced post-procedure UTIs, successfully treated with oral antibiotics (Clavien-Dindo II). Conclusion Intravesical Botox under local anaesthesia demonstrated promise as a safe and well-tolerated treatment for geriatric patients with overactive bladder, where lower levels of pain were reported compared to their younger counterparts. Tolerability was also better than previous smear tests and notably offers a relatable and novel comparison point to facilitate clearer counselling for patients and their families regarding this procedure.

Predictors of the effectiveness of initial therapy with antimuscarinic agents in children with neurogenic urination disorders

BACKGROUND: Almost a third of patients with neurogenic urinary disorders have a refractory nature to therapy with antimuscarinic agents. The aim of the current trial was to identify predictors of the effectiveness of initial therapy with antimuscarinic agents in children with neurogenic urination disorders. For this, a comprehensive analysis of clinical parameters and video urodynamic findings in children was made. AIM: The purpose of this study was to identify predictors of the successful initial therapy with M-anticholinergic preparations in children with neurogenic urinary disorders. For this, results of a comprehensive analysis of initial clinical and video urodynamic parameters were used.. METHODS: A prospective longitudinal cohort study involved 62 patients, aged 1.8–18 years, with neurogenic urination. In addition to the standard examination, all patients underwent a video urodynamic examination at Laborite Delphis UDS-600 device with parallel cystography at Siemens X-ray C-arc (Siemens, Germany). By the obtained results, 52 out of 62 patients were prescribed antimuscarinic agents as the first line therapy. Therapy effectiveness was assessed in 3 months. Analysed parameters were age, presence/absence of self-catheterization, as well as presence/absence of vesicoureteral reflux (VUR) revealed at conventional retrograde urethrocystography and/or video urodynamic examination. RESULTS: The multivariate regression analysis demonstrated that the risk of ineffective antimuscarinic therapy increases by 75,6% in patients with VUR revealed at retrograde uretrocystography, regardless of patient's age and self-catheterization (OR=0.244; 95% CI=0.063-0.937; p=0.040) and by 89.8% (OR=0.102; 95% CI=0.019-0.554; p=0.008) when VUR is detected at video urodynamic examination. Unlike patients with a positive effect (n=24; 50%), 24 patients (50%) who had no response to antimuscarinic therapy were younger (median age 8 years); they also were self-catheterized and had VUR revealed at video urodynamic examination. Outcomes of the prescribed therapy were not associated with other video urodynamic parameters. The identified significant predictors (age, self-catheterization and VUR at video urodynamic examination) have allowed to develop a model for predicting antimuscarinic therapy effectiveness before its administration. This model can promote a rational selection of patients for antimuscarinic therapy, as the first line therapy, with a high probability of positive outcome in 84.9% of patients. CONCLUSION: When prescribing antimuscarinic agents, patient's age, self-catheterization, VUR revealed at retrograde urethrocystography and video urodynamic examination should be taken into account. Predictors of effective antimuscarinic therapy in children with neurogenic urinary disorders, which increase the likelihood of successful outcomes, are patient's age (over 12 years), no self-catheterization and no VUR at video urodynamic examination. Patients younger than 12 years, with self-catheterization and VUR are less likely to respond to antimuscarinic therapy.

Efficacy and Safety of Mirabegron Add-on Therapy After Failure With Solifenacin in Multiple Sclerosis Patients With Overactive Bladder: A Pilot Study.

Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative progressive disease of central nervous system that mostly affects young adults. (1) Because of involvement of spinal cord and brain, lower urinary dysfunction symptoms are commonly encountered. MS patients mostly show overactive bladder symptoms like urgency, frequent daytime urination, and urgency incontinence. Among MS patients, antimuscarinic therapy is the first-line treatment with overactive bladder symptoms as well as in general population yet 30% of the patients show insufficient improvement or intolerance to the treatment (2). In our study, our aim is to evaluate the efficacy and safety of mirabegron add-on treatment in MS patients after inadequate response to antimuscarinic monotherapy. University of Kyrenia and Dr Burhan Nalbantoglu State hospital's databases were screened for the study. Seventy patients who were residents diagnosed with MS according to McDonald criteria were questioned. Among these patients, a total of 22 of them were included in the study. Inclusion criteria was at least 3 years of MS diagnosis, score of <6 at Expanded Disability Status Scale, and a score of ≥3 at Overactive Bladder Symptom Score Scale. Among selected patients, 10 mg solifenacin treatment was daily started and followed for 4 weeks. Mirabegron add-on treatment was initiated to the 11 patient who had inadequate improvement in overactive bladder symptom score. After mirabegron add-on treatment among 11 patient, there was a sufficient improvement in overactive bladder symptom score ( P < 0.008). In our study, we have found that antimuscarinic and mirabegron combination causes improved efficacy for overactive bladder in MS population.

Unrecognised autonomic dysreflexia in neurogenic lower urinary tract dysfunction with spinal cord injury as a reason for admission to a cardiac surgical unit

BACKGROUND: In Russia, spinal cord injury occurs in 0.7–6.8% of total injuries. Due to emergence of new rehabilitation protocols, it is extremely important to know the time of occurrence of consequences of spinal cord injury and adequate diagnosis of complications, which allows timely identification of life-threatening conditions of one of the body systems.&#x0D; Clinical case description. We present a clinical case of autonomic dysreflexia in neurogenic lower urinary tract dysfunction after traumatic cervical spinal cord injury in a 17-year-old girl. In traumatic spinal cord injury above the level of the sixth thoracic vertebra, autonomic dysreflexia as a variant of autonomic dysfunction is a common complication. This clinical case will be of interest to clinicians of all specialties who encounter patients with spinal cord injury. It is shown that misinterpreted symptoms of increased blood pressure during bladder filling were the cause of observation and treatment by a cardiologist for arterial hypertension, as well as hospitalization in the cardiac surgery department for planned surgical treatment of renal artery stenosis, which was thought to be the cause of the episodic increases in blood pressure. Lack of knowledge about the presence of autonomic dysfunction in spinal cord injury patients may have led to unnecessary surgical treatment. During the joint management of the patient with a pediatric cardiac surgeon, signs of autonomic dysreflexia were detected against the background of traumatic spinal cord disease at the level of the cervical spine, hypotensive treatment and planned surgical intervention were canceled.&#x0D; Conclusion. Subsequently, an adequate regimen of periodic bladder catheterization and antimuscarinic drug therapy was prescribed, which successfully reduced the dysreflexia.

Re: Bhide AA et al. Bladder contractility index changes with short-term antimuscarinic therapy in patients with detrusor overactivity: A placebo controlled randomised study. Continence 8 (2023) 101047

Re: Bhide AA et al. Bladder contractility index changes with short-term antimuscarinic therapy in patients with detrusor overactivity: A placebo controlled randomised study. Continence 8 (2023) 101047

A Retrospective Database Analysis to Investigate Treatment Patterns and Health Care Resource Utilisation in Patients who CYCLe AntiMuscarinics in ENgland (CYCLAMEN)

BackgroundPatients with overactive bladder may cycle through different antimuscarinic medications even though there is limited evidence to support this approach. ObjectiveTo describe treatment patterns and the associated health care resource utilisation (HCRU) according to antimuscarinic cycling groups. Design, setting, and participantsThe CYCLe AntiMuscarinics in ENgland (CYCLAMEN) study was a retrospective observational investigation that used primary care records from the Clinical Practice Research Datalink GOLD database linked to Hospital Episode Statistics secondary care data. Eligible patients (≥18 yr) were prescribed their first antimuscarinic between January 2014 and December 2017. Patients were categorised into groups prescribed one, two, or three or more (groups 1–3) consecutive unique antimuscarinics over 18 mo. Outcome measurements and statistical analysisThe HCRU rate and costs were calculated for the period of continuous antimuscarinic therapy (first antimuscarinic treatment episode) and the 18-mo follow-up period. Treatment sequence patterns were displayed using sunburst plots and Kaplan-Meier analysis was used to assess time on treatment. Results and limitationsOverall, 35 369 patients were included, of whom 31 760 (89.8%) received one antimuscarinic (group 1), 3182 (9.0%) received two (group 2), and 427 (1.2%) received three or more (group 3). The most common initial antimuscarinics were solifenacin (13 628 patients, 42.9%) in group 1, and oxybutynin in group 2 (1267 patients, 39.8%) and group 3 (200 patients, 46.8%). The median duration of the first antimuscarinic treatment episode was 57 d and <20% of patients were receiving any antimuscarinic after 18 mo. The number of primary care visits and mean costs increased across groups. The reasons for cycling could not be identified in this study. ConclusionsApproximately 10% of patients underwent sequential cycling with two or more antimuscarinics. Furthermore, as the majority discontinued treatment within 18 mo, there is a need to improve the management of these patients in the clinical care setting. Patient summaryWe investigated treatment patterns and health care use for patients with overactive bladder who were prescribed at least one antimuscarinic drug (AMD), which are drugs that reduce some of the impulses passing from the bladder to the brain. Around 10% of patients accessing primary health care in England received more than one sequential AMD. Most patients discontinued treatment, which may indicate inadequate management of their condition. Prescription of a higher number of AMDs was associated with higher health care costs.

Bladder contractility index changes with short-term antimuscarinic therapy in patients with detrusor overactivity: A placebo controlled randomised study

Aims:Bladder contractility is altered by high doses of anticholinergics. It is unknown if anticholinergics at doses used for treating overactive bladder alter bladder contractility. This is a randomised, double-blind, placebo controlled cross-over multicentre study with two 2-week treatment periods. Patients with a previous diagnosis of detrusor overactivity and reporting urinary frequency of at least seven times a day, one or more episodes of urge urinary incontinence per week and at least seven episodes of urgency per week were included. Methods:After a two-week washout period, subjects were randomised to receive propiverine 20 mg od, propiverine 15 mg tds, oxybutynin 5 mg tds or placebo for 2 weeks. After a second washout period, they were randomised to receive 2 weeks of another treatment not previously used. Ambulatory urodynamic monitoring was performed according to ICS standards for 4 h, using a standardised protocol before and after treatment. The bladder contractility index (BCI) was given by the formula: BCI = PdetQmax+ 5Qmax. The main outcome measure was the average BCI for the first 2 voids for each of the treatment. Results:77 participants were recruited. The average BCI for the first two voids was 143 (range 24–314). The BCI was not statistically different before and after antimuscarinic therapy or placebo although there were reductions in urinary frequency and urgency over placebo indicating efficacy over placebo in the treatment of detrusor overactivity. Conclusions:The bladder contractility index did not change significantly in response to antimuscarinic therapy despite a therapeutic effect. This suggests efficacy is mediated by an effect on another system such as sensory rather than motor function.

Cost, resource utilization, and treatment-taking behaviors among patients with OAB initiating combination mirabegron and antimuscarinic therapy in the US

Cost, resource utilization, and treatment-taking behaviors among patients with OAB initiating combination mirabegron and antimuscarinic therapy in the US

Comparison Of Solifenacin And Mirabegron For The Treatment Of Overactive Bladder.

Overactive bladder is mostly treated with a combination of behavioural interventions and commonly prescribed anti-muscarinic medication therapy, including solifenacin, which has considerable side effects and lowers the quality of life. Mirabegron relaxes the detrusor muscle and is a recently approved drug for the treatment of OAB. This study examined the effectiveness and safety of two medications, solifenacin and mirabegron. This study was a comparative cross-sectional study conducted at Sami Medical Center, Abbottabad for a period of 6 months from August 2022 to January 2023. Female patients of aged ≥18 years with symptoms of OAB were enrolled. Current study showed that the average age of patients was 37.47±12.48 years in Group S and 39.93±7.93 in Group M. The population consists of 60 (100%) females. After 4 weeks of follow up dizziness, dry mouth, constipation hypertension and blurred vision were found insignificant between both groups with p-values of 0.312, 0.161, 0.076, 0.076, and 0.313 respectively. OABSS score improved significantly and after therapy 4.20±1.32 in Group S and 3.43±1.13 in Group M. There was no significant difference in frequency of treatment withdrawal p-value 0.150. When it comes to relieving symptoms of OAB, both solifenacin and mirabegron are effective. The OABSS improved with both drugs; however, mirabegron was associated with fewer treatment-related adverse events. We advocate using mirabegron as the first-line treatment. Solifenacin can be utilized if patients are no longer getting the desired effects from Mirabegron.

Small airway disease: A new “phenotype” of obstructive airway disease

Small airways are usually defined as noncartilaginous airways with an internal diameter &lt;2 mm. Robust data are available regarding small airway involvement in various obstructive airway diseases such as bronchial asthma and chronic obstructive pulmonary disease (COPD). Small airway disease (SAD) can present as a starting point of emphysema, and in few cases, SAD can present with emphysema. Thus, SAD in COPD is a different phenotype along with emphysema and chronic bronchitis. Although bronchial asthma is a disease of large and medium size airways, small airway involvement has been documented in asthma in late stage. Involvement of small airways in asthma is a clinical clue toward the role of inhaled antimuscarinic therapy in this phenotype. Spirometry is a simple and cost-effective but less reliable test to diagnose SAD in comparison to impulse oscillometry. Inhalation therapy with small particle size aerosol long-acting beta-agonist plus inhaled corticosteroids is recommended for treatment of SAD. Targeting small airways in asthma and COPD with ultrafine particle-size inhaled medicines with antimuscarinic drugs will have a successful treatment outcome.

One Month Dosing of Atomoxetine plus Oxybutynin in Obstructive Sleep Apnea: A Randomized, Placebo-controlled Trial.

Rationale: The combination of noradrenergic and antimuscarinic agents has recently been shown to improve upper-airway function and reduce obstructive sleep apnea (OSA) severity in short-term (⩽1 wk) proof-of-concept studies. Objectives: To determine the safety, tolerability, and potential efficacy of longer term use of different doses of the noradrenergic agent atomoxetine combined with the antimuscarinic oxybutynin (ato-oxy). Methods: Thirty-nine people with predominantly severe OSA received 80/5 mg ato-oxy, 40/5 mg ato-oxy, 40/2.5 mg ato-oxy, or placebo nightly for 30 days in a double-blind, randomized, parallel design. Participants completed three in-laboratory sleep studies (baseline, Night 1, and Night 30) to assess efficacy. Vital signs and objective measures of alertness and memory were assessed. In men, potential effects on prostate function were assessed using the International Prostate Symptom Score at baseline and Night 30. Potential adverse events were assessed during in-laboratory visits and via weekly phone calls. Results: Side effects were generally mild and consistent with known side-effect profiles of each individual drug (i.e., dose-dependent increases in dry mouth with oxybutynin). Heart rate increased by Night 30 in two active drug arms (mean ± standard deviation 8 ± 10 beats/min [P = 0.01] with 80/5 mg and 9 ± 14 beats/min [P = 0.02] with 40/2.5 mg vs. placebo). No clinically relevant changes in blood pressure, International Prostate Symptom Score, and measures of alertness and memory were observed between conditions. Apnea-hypopnea index (AHI) with 4% oxygen desaturation and hypoxic burden decreased by ∼50% with 80/5 mg ato-oxy from baseline but not versus placebo (e.g., AHI with 3% oxygen desaturation and AHI with 4% oxygen desaturation difference at Night 30 was -8.2 [95% confidence interval, -22.5 to 6.2] and -8.5 [95% confidence interval, -18.3 to 1.3] events/h, respectively). Conclusions: One month of nightly noradrenergic and antimuscarinic combination therapy was generally well tolerated, with a side-effect profile consistent with each agent alone, and was associated with an ∼50% reduction from baseline in a key OSA severity metric, the hypoxic burden with the highest dose combination. These findings highlight the potential to target noradrenergic and antimuscarinic mechanisms for OSA pharmacotherapy development. Clinical trial registered with www.anzctr.org.au (ACTRN 12619001153101).

Peroxinitrite and Malondialdehyde as Biomarkers for Overactive Bladder.

To measure urine malondialdehyde (MDA) and urine peroxynitrite (ONOO) levels in patients with overactive bladder (OAB), and compare them with healthy individuals; to determine the change of those markers in OAB patients prescribed antimuscarinic drugs. An observational study. The Department of Urology, School of Medicine, University of Gaziantep, Gaziantep, Turkey, between August 2021 and February 2022. Patients diagnosed with OAB (Group 1), and healthy controls (Group 2) were compared. Urinary MDA (µmol/L) and ONOO (µmol/L) levels were measured in all participants. The patients diagnosed with OAB were underwent antimuscarinic therapy with propiverine 30 mg. The levels of MDA (µmol/L) and ONOO (µmol/L) were reanalysed during the third month of antimuscarinic therapy. Patients with stress urinary incontinence, neurogenic bladder, pelvic organ prolapse stage ≥3 (POP-Q ≥3), interstitial cystitis (bladder pain syndrome), history of pelvic radiotherapy, symptoms of bladder outlet obstruction, Qmax <10 ml/sec for men and <15 ml/sec for women measured by uroflowmetry, and history of pelvic and incontinence surgery were excluded from the study. There was no difference in the mean age and or gender distribution of the two groups (p=0.166 and p=0.774, respectively). While the mean MDA levels were significantly higher in patients with OAB, (3.34 ± 1.06µmol/L vs. 2.62 ± 1.45µmol/L, p=0.036), no significant change was detected in ONOO levels between the groups (1.03 ± 0.75 µmol/L vs. 0.71 ± 022 µmol/L, p >0.05). Although no significant change was detected in MDA levels after antimuscarinic therapy (3.50 ± 1.19 µmol/L, p=0.529), there was a statistically significant increase in ONOO levels (1.49 ± 1.45 µmol/L, p=0.013). MDA might be used in the diagnosis of OAB, as a biomarker, similar to recent studies. ONOO was evaluated for the first time in the literature for the diagnosis of OAB, unfortunately, no significant outcomes were obtained. In addition, both MDA and ONOO had no role in monitoring antimuscarinic therapy. Overactive bladder, Peroxynitrite, Malondialdehyde.

Fesoterodine treatment of pediatric patients with neurogenic detrusor overactivity: A 24-week, randomized, open-label, phase 3 study

Neurogenic detrusor overactivity (NDO) can damage the upper urinary tract leading to chronic renal impairment. Antimuscarinic therapy is used to improve urinary incontinence and protect the upper urinary tract in patients with NDO. This study investigated safety and efficacy of fesoterodine, a muscarinic receptor antagonist, in 6‒<18-year-old patients with NDO (NCT01557244). This open-label phase 3 study included 2 pediatric cohorts. Patients in Cohort 1 (bodyweight >25kg) were randomized to fesoterodine 4 or 8mg extended-release tablets or oxybutynin XL tablets administered over the 12-week active comparator-controlled phase. The safety extension phase evaluated fesoterodine 4 and 8mg for a further 12 weeks, with patients in the oxybutynin arm allocated to fesoterodine 4 or 8mg. Patients in Cohort 2 (bodyweight ≤25kg) were randomized to fesoterodine 2 or 4mg extended-release beads-in-capsule (BIC) administered over a 12-week efficacy phase and 12-week safety extension phase. Patients with stable neurologic disease and clinically or urodynamically proven NDO were included. The primary endpoint was change from baseline to Week 12 in maximum cystometric bladder capacity (MCC). Secondary efficacy endpoints included detrusor pressure at maximum bladder capacity, bladder volume at first involuntary detrusor contraction, bladder compliance, and incontinence episodes. Safety endpoints included adverse event incidence, and specific assessments of cognition, behavior and vision. The pharmacokinetics of 5-hydroxymethyl tolterodine (5-HMT; fesoterodine's active metabolite) was determined using population-pharmacokinetic analysis. In Cohort 1 (n=124), fesoterodine 4 and 8mg treatment resulted in significant increases from baseline in the primary endpoint of MCC at Week 12. In Cohort 2 (n=57), fesoterodine 2 and 4mg BIC treatment resulted in improvements in MCC from baseline. Fesoterodine 4 and 8mg and fesoterodine 4mg BIC led to improvements in some secondary efficacy endpoints. The most common treatment-related adverse reactions were gastrointestinal effects, such as dry mouth, which occurred more frequently with oxybutynin than fesoterodine. No detrimental effects on visual accommodation or acuity, or on cognitive function or behavior were observed. These safety and efficacy results are consistent with limited published data on fesoterodine treatment in pediatric populations with overactive bladder or NDO. Study limitations include the lack of placebo control and the small sample size, which limits the ability to make formal efficacy comparisons and detect rare adverse reactions. Fesoterodine has a favorable benefit-risk profile in 6‒<18-year-old patients with NDO and may represent an additional option for pediatric NDO treatment.

Neurogenic Lower Urinary Tract Dysfunction in the First Year After Spinal Cord Injury: A Descriptive Study of Urodynamic Findings.

We aimed to provide a real-world description of neurogenic lower urinary tract dysfunction within the first year after spinal cord injury with a focus on unfavorable urodynamic parameters that are associated with urological morbidity. Urodynamic investigations from 97 patients with traumatic or ischemic acute spinal cord injury and managed according to the European Association of Urology Guidelines on Neuro-Urology were analyzed at a single university spinal cord injury center at 1 month, 3 months, 6 months, and 12 months after injury. Unfavorable urodynamic parameters were defined as detrusor overactivity in combination with detrusor sphincter dyssynergia, maximum storage detrusor pressure of 40 cm H2O or higher, bladder compliance less than 20 mL/cm H2O, and vesicoureteral reflux of any grade. One or more unfavorable urodynamic parameter was observed in 87 out of 97 patients (90%) within the first year after spinal cord injury. Eighty-eight percent of the patients showed detrusor overactivity with detrusor sphincter dyssynergia, 39% a maximum storage detrusor pressure of 40 cm H2O or higher, and 7% vesicoureteral reflux. No patient developed a low-compliance bladder. Using a standardized urodynamic follow-up schedule, we found unfavorable urodynamic parameters in a majority of the population within the first year after spinal cord injury. As early treatment based on urodynamic findings might reduce the risk of deterioration of upper and lower urinary tract function, thereby improving long-term outcomes, there is need for further research regarding recommendations for a urodynamic follow-up schedule during the first year after spinal cord injury.

Review of the clinical management of current organophosphate poisoning treatments in humans

Although they have several uses, organophosphates (OPs) are mostly employed in agriculture as insecticides. Every year, OPs are too accountable for the deaths of hundreds of thousands of individuals. Acute toxicity is caused by overstimulating the central and autonomic nervous systems with nicotinic and muscarinic receptors, as well as the neuromuscular junction, as a result of acetylcholinesterase (AChE) enzyme suppression. Based on the poisoning history, the odor of pesticides, the distinctive clinical symptoms, and decreased cholinesterase activity are used to make the diagnosis of OP poisoning. The keys to successful outcomes are appropriate supportive care, decontamination, intensive anti-muscarinic therapy, early seizure management, and the administration of antidotal oxime medication.

Long-term follow-up of intravesical abobotulinumtoxinA (Dysport®) injections in women with idiopathic detrusor overactivity

ObjectiveOnly a few numbers of studies have been published on the use of abobotulinumtoxinA (Dysport®) in idiopathic detrusor overactivity (IDO). This study reported the long-term follow-up of women with IDO who were treated with intravesical Dysport® injections. MethodsTwo hundred and thirty-six patients with IDO who had failed first-line conservative and antimuscarinic therapy received 500–900 units of Dysport® between April 2014 and July 2015. All patients were followed up for 5 years after their initial injection and interviewed on the phone. ResultsA total of 236 women with IDO aged from 18 years to 84 years (mean±standard deviation: 49.6±15.9 years) were included in our study. The median follow-up time for patients was 36.5 (range: 10–70) months, and the median recovery time after injection was 18.5 (range: 0–70) months. A total of 83 (35.2%) patients stated that they had subjective improvement of their symptoms whereas 84 (35.6%) patients did not report any improvement in symptoms. The initial International Consultation on Incontinence Questionnaire Overactive Bladder mean score was 6.9 (standard deviation 3.4). There was a positive association between the median recovery time and the components of the International Consultation on Incontinence Questionnaire Overactive Bladder questionnaire. ConclusionIn a sub-population of overactive bladder patients with IDO who have failed first-line therapy, a single intravesical Dysport® injection can resolve patient symptoms completely or reduce the symptoms to an acceptable level that can be controlled with antimuscarinics or re-injection on demands.

Combination therapy of solifenacin and mirabegron vs monotherapy in overactive bladder

Introduction and Objectives: Overactive bladder (OAB) with symptoms of frequency, urgency with or without urgency incontinence and nocturia is one of the most bothersome symptom affecting the quality of life of both men and women. Antimuscarinics and Beta 3 agonists both play an important role in reducing the bothersome symptoms. In this study we find the efficacy of low dose combination therapy of solifenacin 5 mg with mirabegron 25 mg vs the monotherapy solifenacin 10 mg or Mirabegron 50 mg.Materials and Methods: It is a prospective study conducted on 150 patients at Madras medical college and were divided into 3 groups. Group A received solifenacin 10 mg/day, Group B received solifenacin 5 mg/day + Mirabegron 25 mg/day and Group C received Mirabegron 50 mg/day. Patients were evaluated for improvement in frequency, urgency, leak episodes, voided volume and improvement in quality of life after a period of 4 weeks and 12 weeks. The three groups were compared using anova test and chi square test and p value was calculated.Results and Observations: Majority of patients of OAB belong to age group > 50 years and majority were females showing female predilection towards OAB. The mean duration of symptoms was 36.01± 7.91 months. Compared with monotherapy, the combination therapy resulted in a significant improvement in reducing the mean number of micturition/24hr from baseline to End of Treatment (EoT). The frequency of urgency episodes and mean number of nocturia episodes/24hr was significantly reduced in patients taking combination therapy as compared to monotherapy. In all the groups a decrease in mean number of incontinence episodes/24hr was observed from baseline to EoT but was not statistically significant. The frequency of antimuscarinic side effects (dry mouth, constipation, urinary retention) had lower incidence in combination therapy compared with solifenacin group. Conclusions: Combination therapy of solifenacin and mirabegron demonstrated significant improvement over monotherapy (solifenacin 10 mg & mirabegron 50 mg) in frequency of micturition, urgency and nocturia episodes without increasing bothersome adverse effects associated with antimuscarinic therapy.

Urodynamic evaluation of the efficacy of vibegron, a new β3-adrenergic receptor agonist, on lower urinary tract function in children and adolescents with overactive bladder

Idiopathic overactive bladder (OAB) is defined as an urgency symptom with or without urge incontinence, which is not due to known neurological abnormalities. Since children present with variable symptoms, pediatric nonneurogenic idiopathic OAB is a condition that is difficult to diagnose and treat. Although there are few reports on bladder function in pediatric patients compared to adult patients, it can be useful for diagnosis. Antimuscarinic therapy is the pharmacological mainstay of OAB management. However, antimuscarinic use is limited by side effects and Insufficient effects. Vibegron, a new drug with a different mechanism of action (β3-adrenoreceptor agonist), was recently introduced for treating OAB in adults but has not been studied in the pediatric population. This study aimed to determine the efficacy and tolerability of vibegron in children and adolescents with idiopathic OAB. We conducted a retrospective study enrolling pediatric patients with OAB whose symptoms did not improve with behavioral therapy or pharmaceutical therapy. Efficacy and tolerability were assessed via a question, and patients underwent video-urodynamic testing before and during treatment with once-daily 50mg vibegron. Statistical differences were evaluated using Wilcoxon matched-pairs signed-rank tests. Out of the 17 patients that were recruited, full study with two urodynamic studies were confirmed by 11 patients. OAB symptoms improved in 14 (82.4%) patients, and 3 patients discontinued treatment because of ineffectiveness. No patients discontinued treatment because of intolerance to vibegron. The median (IQR) first desire to void (133 [82-185]-161 [123-227] mL), bladder capacity (158 [136-238]-204 [150-257] mL), and bladder compliance (18.1 [9.1-76.7]-34.0 [30.0-82.3] mL/cm H2O) improved significantly post treatment compared to before treatment. Detrusor overactivity disappeared in one of the eight patients with this condition. The parameters of voiding function did not change significantly after the administration of vibegron. Treatment with vibegron significantly improved clinical and urodynamic parameters of pediatric OAB with no adverse effects. Little information is available regarding the feasibility of switching drugs when patients discontinue prior pharmacological therapy because of insufficient efficacy or poor tolerability in children. Vibegron may be a promising OAB treatment option with a better balance of efficacy and tolerability. Vibegron is an alternative agent for pediatric patients with idiopathic OAB for improving both subjective symptoms and lower urinary tract function. Future prospective randomized studies with larger sample sizes must be conducted to validate the results of the present study.

PD02-05 EFFICACY AND SAFETY OF VIBEGRON AS ADJUVANT TREATMENT ON REFRACTORY NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN WITH SPINA BIFIDA

You have accessJournal of UrologyCME1 May 2022PD02-05 EFFICACY AND SAFETY OF VIBEGRON AS ADJUVANT TREATMENT ON REFRACTORY NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN WITH SPINA BIFIDA Kazuyuki Nishinaka, and Naoya Masumori Kazuyuki NishinakaKazuyuki Nishinaka More articles by this author , and Naoya MasumoriNaoya Masumori More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002517.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of vibegron with improved selectivity and metabolic stability in comparison with previously disclosed β3-adrenoceptor agonists for treating antimuscarinic-resistant neurogenic bladder dysfunction in children with spina bifida. METHODS: In this retrospective study, 19 patients below 15 years of age, with antimuscarinic-resistant neurogenic bladder dysfunction due to spina bifida, underwent a video-urodynamic study before and during the prescription of vibegron. The dosage was 12.5, 25 or 50 mg once daily, based on age and body weight, for at least 12 weeks from January 2020 to July 2021, in addition to antimuscarinic therapy. The video-urodynamic study was conducted to evaluate bladder compliance, maximum cystometric bladder capacity, detrusor overactivity, detrusor leak point pressure, and vesicoureteral reflux. This was done subsequently prior to the beginning and after three months of vibegron administration. Patient-reported efficacy and adverse events were measured. RESULTS: Treatment with vibegron add-on therapy drastically improved bladder compliance and maximum cystometric bladder capacity compared to treatment with antimuscarinic agents alone (6.2; IQR: 5.2–10.4 vs. 28.3; IQR: 22.7–50.7 mL/cmH2O, P < 0.0001; and 178; IQR: 135–235 vs. 450; IQR: 358–502 mL, P<0.0001, respectively). Bladder deformity in 12 patients improved after taking the drug (image 1: before taking vibegron and image 2: after taking vibegron, obtained from the same case). Moreover, vesicoureteral reflux, confirmed in four patients, disappeared post administration. All the 18 patients who were incontinent before remained dry after initiating therapy with vibegron during the daytime. None of the patients showed side effects or discontinued treatment owing to intolerance to vibegron. CONCLUSIONS: Vibegron as adjuvant treatment in children with antimuscarinic-resistant neurogenic bladder dysfunction due to spina bifida showed favorable video-urodynamic efficacy with no apparent adverse events. Vibegron helped to achieve urinary continence in the entire sample population. Vibegron is a favorable treatment option for the treatment of refractory neurogenic bladder dysfunction in children with spina bifida. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e37 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazuyuki Nishinaka More articles by this author Naoya Masumori More articles by this author Expand All Advertisement PDF DownloadLoading ...

Solifenacin and Mirabegron Monotherapies Versus Combination Therapy in Overactive Bladder: A Prospective Observational Study

Overactive bladder (OAB) is a common medical condition, especially in the elderly population, that affects the quality of life. The primary treatment of OAB is a combination of behavioural measures and widely used anti-muscarinic drug therapy like solifenacin, which brings about significant side effects, thereby affecting the quality of life adversely. Mirabegron, a recently approved drug for treatment of OAB is a β3 - adrenergic agonist, which relaxes the detrusor muscle. With this background, the current study was done to compare the efficacy and safety of solifenacin, mirabegron and combination of low doses of solifenacin and mirabegron on various parameters of OAB. A total no. of 70 patients with OAB symptoms coming to urology OPD were included in this study and they were divided into 3 groups - Group 1: 24 patients receiving solifenacin 10mg/day, Group 2: 23 patients receiving solifenacin 5mg/day plus mirabegron 25mg/day, Group 3: 23 patients receiving mirabegron 50 mg/day. Patients were assessed for change in mean numbers of micturition, urgency, incontinence per 24 hour and quality of life using Patient Perception of Bladder Control (PPBC) Questionnaire. They were followed up after 4 weeks and 12 weeks and change in the above parameters from baseline were noted. Patients receiving combination therapy achieved a significant reduction in urgency, frequency, nocturia and urge incontinence and decrease in side effects when compared with solifenacin and mirabegron alone. Combination therapy with solifenacin and mirabegron significantly improved quality of life and reduced side effects like dry mouth, blurred vision, constipation in OAB patients in comparison to solifenacin and mirabegron monotherapy.