Predictors of non-persistence in women with overactive bladder syndrome.

Persistence is important for the success in the treatment of women with overactive bladder syndrome (OAB). We aimed to identify the predictors of non-persistence in women with OAB after first-line medical treatment. All consecutive women with OAB (n = 608), who underwent urodynamic studies and received first-line medical treatment (5 mg of solifenacin or 25 mg of mirabegron per day) in a referral medical center, were reviewed. Mirabegron (hazard ratio [HR] = 0.711) was associated with a higher persistence rate, compared to solifenacin. Mirabegron treatment (HR = 0.269) was less likely to switch medication; however, a high Urogenital Distress Inventory score (HR = 1.082) was more likely to switch medication. Furthermore, old age (HR = 1.050, especially for ≥ 75 years) and high voided volume (dL, HR = 1.420, especially for voided volume ≥ 250 ml) were associated with added medication at follow-up. Additionally, women with low parity (HR = 0.653, especially for parity ≤ 3) and a low Incontinence Impact Questionnaire (IIQ-7) score (HR = 0.828, especially for IIQ-7 score ≤ 7) were associated with improvement without medication. In conclusion, mirabegron can be considered as the first frontline treatment to increase the persistence rate and decrease the rate of switched medications, compared to solifenacin. In addition, combination therapy or higher-dose monotherapy could be used as the first front-line treatment for women ≥ 75 years of age or with ≥ 250 ml of voided volume.

Comparison of the efficacy and safety of onabotulinum toxin A and mirabegron for overactive bladder in elderly patients.

OBJECTIVE: This study aimed to investigate the efficacy and tolerability of mirabegron and onabotulinum toxin A (BoNT/A) injections for overactive bladders. The treatment we provided was to patients over the age of 65 years who were not satisfied with the results of anticholinergic monotherapy. PATIENTS AND METHODS: This multicenter retrospective observational study was conducted between March 2017 and December 2021. Thirty patients who were unable to take anticholinergics or mirabegron due to side effects received a total of 100-unit intravesical injections of BoNT/A. Furthermore, 30 patients receiving 50 mg of mirabegron daily were compared. Micturition frequency, urgency of urinary incontinence, pad usage, and nocturia were all evaluated for efficacy. Patients' health-related quality of life and subjective satisfaction ratings were assessed before and six months after treatment using an incontinence-quality-of-life questionnaire. We documented all adverse events for all subjects. RESULTS: There was a statistically significant decrease in the frequency, daily pad usage, and incontinence episodes of both groups. The median (interquartile range) voiding frequency after onabotulinum toxin A treatment was lower than that after mirabegron treatment [9.4 (6.83-10.0) vs. 10.5 (8.37-11.67); p = 0.01]. Incontinence episodes showed similar differences [1.3 (1.17-3.67) vs. 2.53 (2.0-5.67); p = 0.05]. There was no significant difference in nocturia or maximum urine flow rate between the groups before and after treatment. CONCLUSIONS: We determined that mirabegron led to lower urinary retention, hematuria, infection and post-void residual urine volume rates than BoNT/A in the older patient population. In addition, mirabegron treatment had comparable incontinence-quality-of-life scores at six months post-treatment.

Long-term Outcomes With Macroplastique in Women With Stress Urinary Incontinence Secondary to Intrinsic Sphincter Deficiency.

OBJECTIVE: To evaluate the long-term outcomes of polydimethylsiloxane (Macroplastique (MPQ)) in women with stress urinary incontinence (SUI) secondary to intrinsic sphincter deficiency (ISD) using validated questionnaires. METHODS: Following IRB approval, charts of non-neurogenic women with SUI secondary to ISD who underwent MPQ injection were reviewed from a prospectively maintained database. ISD was defined as positive stress test with a well-supported urethra and low Valsalva leak point pressure when available. Excluded were women with follow-up <5years. Baseline data included validated questionnaire scores (UDI-6 question 3 (0-3), VAS Quality of Life, Incontinence Impact Questionnaire (IIQ-7)) and urodynamic study findings. Patients were followed with same questionnaires and three-dimensional ultrasound evaluating volume/configuration of MPQ. All three-dimensional ultrasound measurements were performed by the same imaging team blinded to clinical outcomes. Outcomes were evaluated in four groups based on prior SUI treatment. Success was defined as UDI-6 question 3 score of 0-1 and not requiring additional anti-incontinence therapy at the last visit after the last MPQ injection. RESULTS: From April 2011-December 2016, 106 patients (median age 67) met study criteria. Median follow-up time was 7.4years. Median MPQ injected was 5 mL. Overall success was 43%, with 54% successful after one injection and 46% requiring ≥2 injections. Across all groups, patients had improvement in Quality of Life and IIQ-7 Question 7 (frustration). Among the failure group, 17% opted for a secondary autologous sling procedure. CONCLUSION: MPQ demonstrated long-term favorable outcomes in a subset of women with SUI secondary to ISD.

Applying children's enuresis treatment with amitriptyline for canine post-spaying urinary incontinence: A pilot estriol-controlled randomized clinical trial.

Urinary incontinence due to urethral sphincter mechanism incompetence (USMI) affects up to 20% of bitches that undergo spaying surgery. Amitriptyline is a tricyclic antidepressant whose urinary retention is a reported side effect. This study aimed to assess the efficacy and safety of amitriptyline when compared to estriol orally. Fifteen bitches with a clinical diagnosis of post-spaying UI were evaluated during 60 days in a non-blinded randomized clinical trial. All patients were enrolled after clinical evaluation consisting of anamnesis, physical examination, and complementary exams (complete blood count, biochemical parameters, urinalysis, and abdominal ultrasound). The amitriptyline (AMT) group consisted of 8 bitches, which received the initial dose of 1 mg/kg every 12 h, whereas the estriol (EST) group consisted of 7 bitches which were initially treated with 1 mg/animal every 24 h. Patients underwent clinical evaluation at 7 days, and then at 21 and 60 days of treatment to assess safety and efficacy, as well as adjustments of dose when necessary. A urinary incontinence scale was used to assess the level of incontinence and therapeutic response to treatment. During the period of the study, estriol was fully effective in 71% of cases and amitriptyline in 62%. Both drugs proved safe in the medical treatment of USMI, with adverse effects such as somnolence (AMT, n = 5/8) and male attraction (EST, n = 1/7). The results support the amitriptyline recommendation as a substitute for estriol in USMI treatment.

Treatment of urge incontinence in postmenopausal women: A systematic review.

BACKGROUND: Urinary incontinence and other urinary symptoms tend to be frequent at menopause because of hormonal modifications and aging. Urinary symptoms are associated with the genitourinary syndrome of menopause which is characterized by physical changes of the vulva, vagina and lower urinary tract. The treatment strategies for postmenopausal urinary incontinence are various and may include estrogens, anticholinergics, and pelvic floor muscle training. A comparison of these treatments is difficult due to the heterogeneity of adopted protocols. We systematically reviewed the evidence from randomized controlled trials (RCTs) focusing on treatment of postmenopausal women with urge incontinence. METHODS: We conducted a systematic review and meta-analysis by searching PubMed and EMBASE databases for randomized controlled trials (RCTs) reporting results of treatments for postmenopausal urinary urge incontinence. Odds ratios for improvement of urinary incontinence were calculated using random effect Mantel-Haenszel statistics. RESULTS: Out of 248 records retrieved, 35 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared with placebo, systemic estrogens were associated with decreased odds of improving urinary incontinence in postmenopausal women (OR = 0.74, 95% CI: 0.61-0.91, 7 series, 17132 participants, Z = 2.89, P = 0.004, I2 = 72%). In most studies, no significant improvement in urinary symptoms was observed in patients treated with local estrogens, although they showed to be helpful in improving vaginal symptoms. Vitamin D, phytoestrogens and estrogen modulators were not effective in improving symptoms of incontinence and other symptoms of genitourinary menopause syndrome or yielded contradictory results. A randomized controlled trial demonstrated that oxybutynin was significantly better than placebo at improving postmenopausal urgency and urge incontinence. The combination of anticholinergics with local estrogens has not been shown to be more effective than anticholinergics alone in improving urinary incontinence symptoms in postmenopausal women. Physical therapy showed an overall positive outcome on postmenopausal urinary incontinence symptoms, although such evidence should be further validated in the frame of quality RCTs. CONCLUSIONS: The evidence for effective treatment of postmenopausal urinary incontinence is still lacking. Welldesigned large studies having subjective and objective improvement primary endpoints in postmenopausal urinary incontinence are needed. At present, a combination of different treatments tailored to the characteristics of the individual patient can be suggested.

Impact of microbiota and host immunologic response on the efficacy of anticholinergic treatment for urgency urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Studies within the past decade have suggested associations among composition of the urinary microbiota, local immune responses, and urinary incontinence symptoms. To investigate these relationships, we evaluated the structure of the urinary microbiome, local inflammatory markers, and patient responses prior to and at 6-weeks after treatment with anticholinergic medication for urgency urinary incontinence (UUI). METHODS: Using a prospective pilot study, we enrolled women who presented with UUI symptoms and were prescribed treatment with anticholinergics. Catheterized urine samples were collected from participants at their baseline and 6-week follow-up visits for microbiological (standard and 16S rRNA gene phylotyping analyses) and cytokine analysis along with the UDI-6 questionnaire and 2-day bladder diary. RESULTS: Patients were Caucasian, post- menopausal, with a median age of 64 and median BMI of 30.1 kg/m2. Among the patients, 75% had UUI symptoms for less than 2 years, but with a frequency of at least a few times a week or every day. Most women were prescribed 10 mg oxybutynin ER daily at enrollment. Patients had varied urinary microbiota by culture and 16S phylotyping, with species of Lactobacillus being the most common, in six samples, in addition to taxa associated with Enterococcus, Staphylococcus, and mixed flora. Cytokine levels showed no differences before and after treatment with anticholinergics, nor correlation with urinary bacteria or microbiome composition. CONCLUSIONS: Our pilot study suggests factors in addition to the urinary microbiome and local immune responses may be involved in patients' response to anticholinergics for UUI.

La irrigación transanal como opción terapéutica para los pacientes con incontinencia y estreñimiento crónico severo refractarios a primera línea / Transanal irrigation as a therapeutic option for patients with incontinence and severe chronic constipation refractory to first line treatment

Introducción: El objetivo es evaluar la utilidad de la irrigación transanal como tratamiento de la incontinencia y estreñimiento crónico severo refractario a primera línea terapéutica, y valorar su impacto en la sintomatología y calidad de vida. Métodos: Estudio retrospectivo descriptivo de pacientes con incontinencia y estreñimiento crónico que han iniciado irrigación transanal en dos hospitales de la región. Se recogen variables sociodemográficas, comorbilidades, tratamientos previos, pruebas realizadas, parámetros e incidencias durante la irrigación, puntuación en las escalas de gravedad de incontinencia y estreñimiento de la Cleveland Clinic y calidad de vida EuroQol-5D antes y después del tratamiento. Resultados: Un total de 40 pacientes, 20 con incontinencia y 20 con estreñimiento crónico. Tras una media de 9 meses de tratamiento, en 14 pacientes con incontinencia hemos objetivado una media de mejoría de 7,45 puntos pre-post tratamiento en la escala de gravedad de incontinencia de la Cleveland Clinic, y una media de mejoría en la calidad de vida de 23 puntos pre-post tratamiento en la escala EQ5D (p<0,001); y en 16 pacientes con estreñimiento una media de mejoría de 7,6 puntos pre-post tratamiento en la escala de gravedad de estreñimiento de la Cleveland Clinic, y una media de mejoría en la calidad de vida de 31,5 puntos pre-post tratamiento en la escala EQ5D (p<0,001). Conclusiones: La irrigación transanal es una terapia efectiva para pacientes con incontinencia y estreñimiento crónico no respondedores a primera línea terapéutica. Es sencilla, autoadministrable y segura. Cuando el paciente aprende a emplearla, mejora su sintomatología y calidad de vida. (AU)

Introduction: The aim is to evaluate the utility of transanal irrigation such as treatment of incontinence and severe chronic constipation which is refractory to first-line therapy, and to assess its impact into the symptomatology and quality of life. Methods: Observational retrospective study of patients with incontinence and chronic constipation that had initiated transanal irrigation in two hospitals of the region. We collect sociodemographic variables, comorbidity, previous treatments, tests, parameters and incidences during the irrigation, and punctuation in the Cleveland Clinic Incontinence and Constipation Scores and EuroQol-5D Quality Of Life Scale before and after the treatment. Results: 40 patients, 20 with incontinence and 20 with chronic constipation. After an average period of 9 months of treatment, in 14 patients with incontinence we have observed a mean clinical improvement of 7,45 points before-after treatment measured with Cleveland Clinic Incontinence Score, and a mean improvement of 23 points in their quality of life before-after treatment measured with EQ5D Scale (p<0.001); and in 16 patients with constipation a mean clinical improvement of 7,6 points before-after treatment measured with Cleveland Clinic Constipation Score, and a mean improvement of 31,5 points in their quality of life before-after treatment measured with EQ5D Scale (p<0.001). Conclusions: Transanal irrigation is an effective therapy for patients with incontinence and chronic constipation that are refractory to first-line therapies. It's an easy, self-administered and safe procedure. When the patient learns how to use it, the symptomatology and quality of life are improved. (AU)

Pelvic floor muscle exercise with or without duloxetine for postprostatectomy urinary incontinence: A retrospective single-center study.

This study aimed to evaluate the effectiveness of combined pelvic floor muscle exercise (PFME) and duloxetine treatment in the recovery from postprostatectomy urinary incontinence (PPUI). Participants were patients who underwent radical prostatectomy (RP) between 2018 and 2021 and who were able to attend follow-up appointments every 3 months for at least 12 months. Continence was defined as the use of ≤1 pad per day. PPUI was compared at each follow-up period by dividing the participants into the PFME group (PFME only after RP) and the PFME + DUL group (PFME and 30 mg duloxetine daily after RP). A total of 197 patients were included. No significant differences were observed in the baseline characteristics between the 2 groups. In the PFME group (n = 127), the PPUI was 77.17%, 27.56%, 17.32%, 12.60%, and 9.45% at 2 weeks, 3 months, 6 months, 9 months, and 12 months, respectively. In the PFME + DUL group (n = 70), the PPUI was 62.50%, 17.86%, 12.50%, 8.93%, and 5.36%, respectively, at the same follow-up period. At 2 weeks, the PFME + DUL group demonstrated a better incontinence rate than the PFME group (P = .019). However, no significant differences were found in the incontinence rates between the 2 groups at each follow-up period after 3 months. Compared to PFME monotherapy, the combination therapy of PFME and duloxetine has short-term effectiveness in improving PPUI, but it does not have a significant long-term impact. Therefore, for early recovery from PPUI, duloxetine should be administered for a short period during PFME.

Heterogeneity of placebo effects on urinary incontinence in overactive bladder syndrome: A meta-analysis of Japanese placebo-controlled clinical trials.

OBJECTIVES: The effect sizes, changes over time, and heterogeneity of placebo effects on frequency of urination for voiding disorders in Japanese clinical trials have been published. This study evaluated the characteristics of placebo effects on overall and urge incontinence in overactive bladder patients. METHODS: A meta-analysis of Japanese placebo-controlled clinical trials was conducted to determine placebo effects on the daily frequency of overall (n = 16) and urge (n = 11) incontinence and identify factors that should be considered in clinical trials. RESULTS: The between-study heterogeneity variance of placebo effects for overall and urge incontinence at 8 weeks was estimated as I2 = 70.3% and 64.2%, and the prediction interval for the ratio of means ranged from g = 0.31-0.91 and 0.32-0.81, respectively. Subgroup analysis using the random-effects model showed placebo effects in overall incontinence (p = 0.08) and urge incontinence (p < 0.0001). The ratio of means (95% confidence interval) of urge incontinence frequency from baseline to 4 (n = 10), 8 (n = 10), and 12 (n = 7) weeks were 0.65 (0.57, 0.74), 0.51 (0.42, 0.62), and 0.48 (0.36, 0.64), respectively, for the random-effects model. Regression analysis did not reveal any significant factors that influenced placebo effects. CONCLUSIONS: This meta-analysis confirmed the characterization of placebo effects on overall and urge incontinence, which demonstrates heterogeneity between trials. The impact of population, follow-up period, and endpoints on placebo effects should be considered when designing clinical trials for overactive bladder syndrome.

One treatment with onabotulinumtoxinA relieves symptoms of overactive bladder in patients refractory to one or more oral medications.

INTRODUCTION AND HYPOTHESIS: Patients with overactive bladder (OAB) often undergo prolonged treatment with one or more oral OAB medications. OnabotulinumtoxinA (onabotA), a type A botulinum toxin, may provide an appropriate alternative to oral treatments in patients intolerant of or refractory to one or more oral OAB medications. The GRACE study demonstrated real-world benefits of onabotA treatment for OAB in patients refractory to oral medications. This exploratory post hoc analysis of data from the GRACE study aims to determine if treatment history impacts benefit from treatment with onabotA. METHODS: This is a subanalysis of the GRACE study, a prospective observational study (NCT02161159) that enrolled patients with symptomatic OAB inadequately managed by at least one oral OAB medication. Patients had a treatment history of one or more anticholinergics (AC) and/or ß-3 adrenoreceptor agonists (ß-3) for relief of OAB; results were stratified according to treatment history. Patients in this analysis elected to discontinue oral medications upon treatment with onabotA. Safety was followed for 12 months in all patients that received at least 1 dose of onabotA; efficacy was determined over a 12-week period. RESULTS: Compared to baseline levels, significant reductions in urinary incontinence (UI), urgency, micturition, and nocturia were noted as early as 1 week and were sustained at 12 weeks, regardless of the type and number of oral medications taken before treatment with onabotA. At 12 weeks post-onabotA, the mean change from baseline UI episodes/day for those with a treatment history of only one AC was -2.4 (n = 43, p ≤ 0.001); more than one AC, -2.4 (n = 52, p ≤ 0.001); one ß-3, -3.3 (n = 12, p < 0.05); at least one AC and at least one ß-3, -3.2 (n = 56, p ≤ 0.001). Pad and liner use was significantly decreased at 12 weeks post-onabotA across all treatment history groups. Reductions in diaper pant use varied, with less of a reduction in patients with a treatment history of more than one AC compared to patients with a history of at least one AC and one ß-3 (p < 0.05) or those with a history of only one AC (p < 0.05). Overall, a total of 253/288 of patients (88%) reported improvements on the treatment benefit scale 12 weeks after treatment with onabotA, regardless of type and number of prior oral medications. In the population of patients that received at least one dose of onabotA (N = 504), 57 adverse events were reported in 38 patients (7.5%); 9 were serious (1.8%). Urinary retention was reported in 5 patients (1.0%); 1 was severe (0.2%). Symptomatic urinary tract infection was reported in 2 patients (0.4%). CONCLUSIONS: In this exploratory post hoc analysis of real-world data from the GRACE study, there were few significant differences in outcomes based on the type and number of prior oral medications. Thus, patients who are refractory to one or more oral OAB medications may benefit from earlier treatment with onabotA.

Seminal papers in urology: anticholinergic therapy vs. onabotulinumtoxina for urgency urinary incontinence.

In this critical review, we explore the study design, strengths, and limitations of landmark trial "Anticholinergic therapy vs. onabotulinumtoxinA for urgency urinary incontinence". This trial was the first to directly compare two key treatment options for urge urinary incontinence - anticholinergic medication and intravesical botox, and still influences clinical guidelines a decade after publication. This non-inferiority, double-blinded, multi-centre randomised controlled trial administered Solifenacin or intra-detrusor botox to women, measuring outcomes six months post-treatment. Non-inferiority of the treatments was established, though Botox had a higher rate of retention and infection, with side effect profile rising as the key discriminator in selecting first-line therapy.

Treating Neurogenic Lower Urinary Tract Dysfunction in Chronic Spinal Cord Injury Patients-When Intravesical Botox Injection or Urethral Botox Injection Are Indicated.

Lower urinary tract symptoms (LUTS), such as urgency, urinary incontinence, and/or difficulty voiding, hamper the quality of life (QoL) of patients with spinal cord injury (SCI). If not managed adequately, urological complications, such as urinary tract infection or renal function deterioration, may further deteriorate the patient's QoL. Botulinum toxin A (BoNT-A) injection within the detrusor muscle or urethral sphincter yields satisfactory therapeutic effects for treating urinary incontinence or facilitating efficient voiding; however, adverse effects inevitably follow its therapeutic efficacy. It is important to weigh the merits and demerits of BoNT-A injection for LUTS and provide an optimal management strategy for SCI patients. This paper summarizes different aspects of the application of BoNT-A injection for lower urinary tract dysfunctions in SCI patients and provides an overview of the benefits and drawbacks of this treatment.

TReating Incontinence for Underlying Mental and Physical Health (TRIUMPH): a study protocol for a multicenter, double-blinded, randomized, 3-arm trial to evaluate the multisystem effects of pharmacologic treatment strategies for urgency-predominant urinary incontinence in ambulatory older women.

BACKGROUND: Urgency-type urinary incontinence affects one in four older community-dwelling women and overlaps with other common aging-associated health syndromes such as cognitive impairment, physical mobility impairment, and depression. Observational studies have raised concern about potentially higher rates of delirium and dementia in older adults taking anticholinergic bladder medications, but few prospective data are available to evaluate the effects of these and other pharmacologic treatments for urgency incontinence on cognition and other multisystem functional domains important to older women. METHODS: The TRIUMPH study is a randomized, double-blinded, 3-arm, parallel-group trial comparing the multisystem effects of anticholinergic versus beta-3-adrenergic agonist bladder therapy and versus no active bladder anti-spasmodic pharmacotherapy in older women with urgency incontinence. Women aged 60 years and older (target N = 270) who have chronic urgency-predominant urinary incontinence and either normal or mildly impaired cognition at baseline are recruited from the community by investigators based in northern California, USA. Participants are randomized in equal ratios to take identically encapsulated oral anticholinergic bladder therapy (in the form of tolterodine 2 mg extended release [ER]), oral beta-3 adrenergic agonist bladder therapy (mirabegron 25 mg ER), or placebo daily for 24 weeks, with the option of participant-directed dose titration (to tolterodine 4 mg ER, mirabegron 50 mg ER, or matching placebo daily). Participants also receive patient-oriented information and instructions about practicing first-line behavioral management strategies for incontinence. The primary outcome is change in composite cognitive function over 24 weeks assessed by a comprehensive battery of cognitive tests, with a secondary exploration of the persistence of change at 36 weeks. Secondary outcomes include changes over 24 and 36 weeks in domain-specific cognitive function; frequency, severity, and impact of urgency-associated urinary symptoms; physical function and balance; sleep quality and daytime sleepiness; psychological function; and bowel function. DISCUSSION: The TRIUMPH trial addresses the need for rigorous evidence to guide counseling and decision-making for older women who are weighing the potential multisystem benefits and risks of pharmacologic treatments for urgency incontinence in order to preserve their day-to-day functioning, quality of life, and independence in older age. TRIAL REGISTRATION: ClinicalTrials.gov NCT05362292. Registered on May 5, 2022.

The impact of postinjection urinary tract infection on efficacy of intravesical onabotulinumtoxinA-A secondary analysis.

OBJECTIVES: To compare treatment response in women who did and did not develop a urinary tract infection (UTI) within 14 days after intravesical onabotulinumtoxinA injections for treatment of refractory urgency urinary incontinence (UUI). METHODS: This is a secondary analysis of women who received Onabotulinumtoxin A in the Refractory Overactive Bladder: Sacral Neuromodulation vs Botulinum Toxin Assessment (ROSETTA) Trial. Participants were grouped by presence or absence of UTI within 14 days of injection. UTI was defined as symptomatic with positive urine culture per the primary ROSETTA protocol. Our primary outcome was change from baseline in mean number of UUI episodes based on monthly 3-day bladder diaries averaged over 6 months. We performed t tests and chi-square/Fisher's exact for continuous and categorical variables. A p value of <0.05 was considered statistically significant. RESULTS: Of 187 participants in the onabotulinumtoxinA arm, 10 (5.3%) experienced UTI within 14 days of injection, and 177 (94.7%) did not. At baseline, groups did not differ in demographics, mean UUI episodes per day (no UTI [5.37 ± 2.65] vs. UTI [6.40 ± 3.02], p = 0.24), or other diary parameters. For our primary outcome, groups did not differ in the change in mean daily UUI episodes at 1 month (no UTI [-4.29 ± 2.75] vs. UTI [-3.74 ± 2.01]; mean difference [95% confidence interval, CI] -0.55 [-2.39 to 1.28], p: 0.55) or 6 months (no UTI [-3.63 ± 2.89] vs. UTI [-2.15 ± 3.18]; mean difference [95% CI] -1.48 [-3.44 to 0.48], p: 0.14). CONCLUSIONS: UTI within 14 days after intravesical injection of onabotulinumtoxinA for refractory UUI was not significantly associated with inferior treatment response at 1 or 6 months.

Application of urethral injection of calcium hydroxyapatite as a natural bulking agent for improvement of urinary incontinence in children with spinal dysraphism.

PURPOSE: The aim of this report is to evaluate the efficacy of endoscopic injection of calcium hydroxyapatite (CaHA) into the bladder neck and posterior urethra in children with refractory urinary incontinence due to spinal dysraphism. METHODS: A retrospective study was performed on patients with neuropathic bladder due to spinal dysraphism who had undergone submucosal urethral injections of CaHA from 2010 until 2019. All patients were totally incontinent without voiding per urethra and did not respond to 1-year standard pharmacotherapy with anticholinergic drugs. All children underwent a precise physical exam and urodynamic studies. Patients underwent urethrocystoscopy and injection of pure soluble CaHA into the bladder neck and posterior urethra except for the verumontanum. The outcomes were determined as no change, improvement (social continent), or cure (total continent). RESULTS: Fifteen children (ten boys, five girls, mean age of 7.6 years) with a history of spinal dysraphism and refractory urinary incontinence were included. Endoscopic injections of CaHA were performed one or two times for each patient. At the median follow-up of 2 years (interquartile range = 6), seven (46.7%), three (20.0%), and five (33.3%) of the patients were total continent, social continent, and total incontinent, respectively. In four patients, intradetrusor botulinum toxin injection was performed simultaneously with CaHA injection. Also, one patient experienced a febrile urinary tract infection between two CaHA injections. Among 15 patients, 9 had atonic/hypotonic bladders both before and after CaHA injections; at the last follow-up, 4 of these children (44.4%) were totally continent. No injection-related or other complications were observed in the patients. CONCLUSION: Injection of CaHA into the bladder neck is relatively safe, reproducible, and effective for total dribbling urinary incontinence in children with spinal dysraphism. The bladder neck reconstruction with or without a urethral sling or other surgical procedures could be postponed until puberty in selected cases. However, further multicenter clinical trials are highly recommended.

Effects of ospemifene on overactive bladder in postmenopausal women with vulvovaginal atrophy.

OBJECTIVE: Overactive bladder (OAB) is a complex and multifactorial syndrome associated with urinary frequency, urgency and incontinence. The menopause-associated hormonal changes play a role in the development of this condition. Vaginal estrogens are effective in improving OAB in postmenopausal women (PMW) with vulvovaginal atrophy (VVA). Ospemifene is a selective estrogen receptor modulator licensed for the treatment of VVA. This study aimed to evaluate the effects of ospemifene on OAB symptoms in PMW with VVA. METHODS: Forty PMW suffering from OAB and VVA received oral ospemifene (60 mg/day) for 12 weeks. All patients were assessed with a urodynamic study, a 3-day bladder diary and validated questionnaires (International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form [ICIQ-UI SF] and International Consultation on Incontinence Questionnaire - Overactive Bladder [ICIQ-OAB]) at enrollment and at the end of the study. RESULTS: Cytometric capacity, bladder compliance and verbal sensory threshold responses during bladder filling were improved after treatment. The voiding diary showed a significant reduction of daily voids, urge urinary incontinence episodes and nocturnal events. The median overall scores of the ICIQ-UI and ICIQ-OAB were also significantly improved. CONCLUSIONS: Our study suggest that treatment with ospemifene in PMW suffering from OAB is associated with a reduction of OAB symptoms due to a decreased bladder sensitivity and with an improvement in quality of life.

Current and Emerging Pharmacological Targets and Treatments of Urinary Incontinence and Related Disorders.

Overactive bladder syndrome with and without urinary incontinence and related conditions, signs, and disorders such as detrusor overactivity, neurogenic lower urinary tract dysfunction, underactive bladder, stress urinary incontinence, and nocturia are common in the general population and have a major impact on the quality of life of the affected patients and their partners. Based on the deliberations of the subcommittee on pharmacological treatments of the 7th International Consultation on Incontinence, we present a comprehensive review of established drug targets in the treatment of overactive bladder syndrome and the aforementioned related conditions and the approved drugs used in its treatment. Investigational drug targets and compounds are also reviewed. We conclude that, despite a range of available medical treatment options, a considerable medical need continues to exist. This is largely because the existing treatments are symptomatic and have limited efficacy and/or tolerability, which leads to poor long-term adherence. SIGNIFICANCE STATEMENT: Urinary incontinence and related disorders are prevalent in the general population. While many treatments have been approved, few patients stay on long-term treatment despite none of them being curative. This paper provides a comprehensive discussion of existing and emerging treatment options for various types of incontinence and related disorders.

Role of Urological Botulinum Toxin-A Injection for Overactive Bladder and Voiding Dysfunction in Patients with Parkinson's Disease or Post-Stroke.

Botulinum toxin A (BoNT-A) paralyzes muscle by blocking acetylcholine release at the synaptic junction. BoNT-A has shown its therapeutic effects in neurological disorders such as Parkinson's disease (PD) and post-stroke spasticity. A high proportion of patients with PD and post-stroke develop neurogenic detrusor overactivity (nDO) and then develop urinary incontinence and overactive bladder (OAB) symptoms. This study aimed to disclose the safety and efficacy of BoNT-A injection in treating bladder and voiding dysfunction in PD and post-stroke patients by reviewing the current evidence. At present, intradetrusor injection of BoNT-A is a Food and Drug Administration (FDA)-approved third-line therapy for nDO and idiopathic OAB. Although intradetrusor injection of onaBoNT-A 200 U is already approved for nDO treatment, most researchers would like to manage PD and post-stroke patients by using onaBoNT-A 100 U intradetrusor injection to achieve long-term efficacy and reduce adverse effects. However, in contrast to its inclusion in the International Continence Society guidelines for PD treatment, the clinical use of BoNT-A for post-stroke patients is limited to experimental use due to the development of urinary retention in about one-fifth of patients. For treating urethral pseudodyssynergia, half of patients may respond to onaBoNT-A 100 U urethral injection. However, refinement is needed to reduce unwanted urinary incontinence.

Efficacy of abobotulinumtoxinA versus onabotulinumtoxinA for the treatment of refractory neurogenic detrusor overactivity: a systematic review and indirect treatment comparison.

AIMS: To compare the efficacy and safety of abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) for the treatment of refractory neurogenic detrusor overactivity (NDO), using an indirect treatment comparison (ITC). MATERIALS AND METHODS: A systematic literature review was used to identify randomized controlled trials (RCTs) that evaluated botulinum toxin type A for the treatment of refractory NDO. Treatments were compared using a Bucher ITC approach. Efficacy outcomes were reduction in number of weekly urinary incontinence (UI) episodes at 6, 12, and 24 weeks of follow-up. The safety outcome was the proportion of patients with treatment-emergent urinary tract infections (TE-UTIs) during follow-up. Subgroup/sensitivity analyses were performed to investigate the impact of heterogeneity. RESULTS: Fifteen studies of botulinum toxin type A were identified. Among these, onaBoNT-A 200 U was the only botulinum toxin type A considered an appropriate comparator for aboBoNT-A 600 U and 800 U. As such, six RCTs that evaluated onaBoNT-A or aboBoNT-A were included in the ITC. In base-case analyses, there were no statistically significant differences between aboBoNT-A and onaBoNT-A in terms of UI episodes or TE-UTIs. Numerically, the trend favored aboBoNT-A (either dose) for all endpoints and time points. At 12 and 24 weeks, the difference in reduction of UI episodes per week was considered clinically relevant when comparing aboBoNT-A 800 U with onaBoNT-A 200 U, but not when comparing the lower dose of aboBoNT-A (600 U) with onaBoNT-A 200 U. Results from subgroup/sensitivity analyses were consistent with the base case. LIMITATIONS: Heterogeneity across studies was observed; however, strong consistency of trends across analyses suggests the impact of heterogeneity is low. CONCLUSIONS: There may be potential advantages of aboBoNT-A over onaBoNT-A, in terms of UI reduction, in patients with refractory NDO. More confirmatory studies are needed owing to the sparsity of current evidence.

Neurogenic detrusor overactivity (NDO) is a condition in which the bladder muscle wall is overactive and does not function normally. This can lead to urinary incontinence (i.e. accidental leakage of urine). NDO may also cause urinary tract infections and upper urinary tract damage if it is left untreated or if treatment does not work (i.e. refractory NDO).Botulinum toxin is a treatment that relaxes muscles in patients with refractory NDO, so they have less chance of experiencing urinary incontinence. This study used results from clinical trials to compare two types of botulinum toxin ­ abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) ­ to see if one works better than the other.Clinical trials are experiments to assess how well treatments work by giving different treatments to different patients and observing the results. When there is no clinical trial that compares the two treatments you are interested in, it is possible to combine results from a number of different clinical trials instead. This is known as an indirect treatment comparison.We used an indirect treatment comparison to compare aboBoNT-A and onaBoNT-A for the treatment of refractory NDO. Results showed that aboBoNT-A may be more effective than onaBoNT-A in reducing the frequency of urinary incontinence episodes. On average, patients treated with aboBoNT-A had at least three fewer episodes of urinary incontinence per week than those treated with onaBoNT-A. These results suggest that patients treated with aboBoNT-A could have a better quality of life than those treated with onaBoNT-A.