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

Objective:Only 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.Methods:Two 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.Results:A 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.Conclusion:In 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.

Significance of preoperatively observed detrusor overactivity as a predictor of continence status early after robot-assisted radical prostatectomy

Several recent studies have reported the involvement of bladder dysfunction in the delayed recovery of urinary continence following radical prostatectomy （RP）. The objective of this study was to investigate the significance of detrusor overactivity （DO） as a predictor of the early continence status following robot-assisted RP （RARP）. This study included 84 consecutive patients with prostate cancer undergoing RARP. Urodynamic studies, including filling cystometry, pressure flow study, electromyogram of the external urethral sphincter and urethral pressure profile, were performed in these patients before surgery. Urinary continence was defined as the use of either no or one pad per day as a precaution only. DO was preoperatively observed in 30 patients （35.7%）, and 55 （65.5%） and 34 （40.5%） were judged to be incontinent 1 and 3 months after RARP, respectively. At both 1 and 3 months after RARP, the incidences of incontinence in patients with DO were significantly higher than in those without DO. Of several demographic and urodynamic parameters, univariate analyses identified DO and maximal urethral closure pressure （MUCP） as significant predictors of the continence status at both 1 and 3 months after RARP. Furthermore, DO and MUCP appeared to be independently associated with the continence at both I and 3 months after RARP on multivariate analysis. These findings suggest that preoperatively observed DO could be a significant predictor of urinary incontinence early after RARP; therefore, it is recommended to perform urodynamic studies for patients who are scheduled to undergo RARP in order to comprehensively evaluate their preoperative vesicourethral functions.

Electroacupuncture at points Baliao and Huiyang (BL35) for post-stroke detrusor overactivity

Acupuncture is used extensively in China for the treatment of stroke and other neurological disorders. The National Institutes of Health recommends acupuncture as an adjunctive therapy for stroke recovery. This study included patients with post-stroke detrusor overactivity who were treated in the Department of Neurology, Fourth Hospital of Harbin Medical University, China. Subjects received either electroacupuncture or sham electroacupuncture at points Baliao [including bilateral Shangliao （BL31）, bilateral Ciliao （BL32）, bilateral Zhongliao （BL33）, and bilateral Xialiao （BL34）] and Huiyang （BL35）. Our results showed that electroacupuncture significantly improved cystometric capacity and bladder compliance, decreased detrusor leak point pressure, ameliorated lower urinary tract symptoms, and decreased the risk of upper urinary tract damage. These findings indicate that electroacupuncture at points Bafiao and Huiyang is an effective treatment for post-stroke detrusor overactivity.

Pioneering drugs for overactive bladder and detrusor overactivity: Ongoing research and future directions

The ongoing research on pioneering drug candidates for the overactive bladder （OAB） aimed to overcome the limitations of currently licensed pharmacotherapies, such as antimuscarinics, β3-adrenergic agents, and botulinum neurotoxin, has been reviewed performing a systematic literature review and web search. The review covers the exploratory agents alternative to available medications for OAB and that may ultimately prove to be therapeutically useful in the future mana-gement of OAB patients based on preclinical and early clinical data. It emerges that many alternative pharmacological strategies have been discovered or are under investigation in disease-oriented studies. Several potential therapeutics are known for years but still fnd obstacles to pass the clinical stages of development, while other completely novel compounds, targeting new pharmacological targets, have been recently discovered and show potential to translate into clinical therapeutic agents for idiopathic and neurogenic OAB syndrome. The global scenario of investigational drugs for OAB gives promise for the development of innovative thera-peutics that may ultimately prove effective as first, combined or second-line treatments within a realistic timescale of ten years.

How botulinum toxin in neurogenic detrusor overactivity can reduce upper urinary tract damage?

Intradetrusor injections of botulinum toxin are the cornerstone of medical treatment of neurogenic detrusor overactivity. The primary aim of this treatment is to ensure a low pressure regimen in the urinary bladder, but the mechanisms leading to long-term protection of the urinary tract remain poorly understood. In this paper, we highlight the potential benefts of intradetrusor injections of botulinum toxin regarding local effects on the bladder structures, urinary tract infections, stone disease, vesico ureteral refux, hydronephrosis, renal function based on a comprehensive literature review.

Clinical Nursing Recommendations for the Treatment of the BTX-A Injections Due to Neurological Detrusor Overactivity

Background: Neurological detrusor overactivity (NDO) is commonly associated with various neurogenic diseases. Botulinum toxin A (BTX-A) has been proposed as alternatives to traditional treatments. Objective: To summarize the clinical experience of nursing care for the treatment of the Botulinum toxin A (BTX-A) injections due to neurological detrusor overactivity (NDO). Methods: We reviewed the data of 32 inpatients who received BTX-A injections between August 2014 to July 2016. Their mean age was 27.4 years old (range: 19 - 38). They were all on clean intermittent catheterization. All patients presented detrusor overactivity resistant to oral anticholinergic treatment. Results: There were significant difference between outcomes at baseline and week12 for Pdetmax (60.08 cmH2O vs. 28.04 cmH2O, P Conclusions: Patients were satisfied with the treatment and nursing by targeted perioperative nursing.

Combined Detrusor and External Urethral Sphincter BTX-A Injections for Detrusor Overactivity and Detrusor External Sphincter Dyssynergia Secondary to Spinal Cord Injury

Objective: To evaluate the efficacy and safety of Combined detrusor and external urethral sphincter BTX-A injections for detrusor overactivity (DO) and detrusor external sphincter dyssynergia (DESD) secondary to spinal cord injury. Study Design: Prospective study. Methods: The study was carried out in 18 SCI patients with detrusor overactivity (DO) and detrusor external sphincter dyssynergia (DESD) receiving Combined detrusor and external urethral sphincter BTX-A injections treatment. Contain 200 U botulinum toxin intradetrusor and 100 U external urethral sphincter injections. The effective outcomes included maximum detrusor pressure at first DO and DESD (PdetmaxDO-DESD), volume at first DO and DESD (VDO-DESD), maximum urethral closure pressure (MUCP), and Incontinence-Specific Quality-of-Life Instrument (I-QoL). Adverse events were recorded. Results: All patients experienced a significant mean reduction in PdetmaxDO-DESD (50.75%), maximum urethral closure pressure (26.34%) and a significant mean increase in VDO-DESD (63.00%) 12-weeks post-injection. Significant (p < 0.001) improvement in mean Incontinence-Specific Quality-of-Life Instrument was also found. No obvious adverse event and toxic effect was observed. Conclusion: Combined detrusor and external urethral sphincter BTX-A injections is a good choice for patients with DO and DESD secondary to spinal cord injury. It could not only protect the upper urinary tract but also improve quality of life.

Effect of Varenicline on Detrusor Overactivity in Rat Model of Parkinson’s Disease Induced by Intranigral 6-Hydroxydopamine

Background: Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Bladder dysfunction is the common non-motor symptom of PD, most often presenting with detrusor overactivity (DO). Treatment of DO is currently limited, poorly tolerated and sometimes ineffective. Bladder responses are not only mediated by muscarinic cholinergic receptors (mAChR) but also by nicotinic cholinergic receptors (nAChR). However, nicotinic receptor subtypes and functions in the bladder are not clearly identified. Purpose: This study aimed at investigating the effect of varenicline, an alpha7 full agonist and alpha4beta2/alpha3 partial agonist, on detrusor strips in rat PD model induced by substantia nigra injection of 6-hydroxydopamine. Method: The detrusor activity was studied in an isolated organ bath system. Results: In PD group, the detrusor activity was increased, whereas varenicline decreased the DO. Conclusion: Alpha7 nAChR agonists may have therapeutic potential in treatment of bladder overactivity in PD.

Multiple factors related to detrusor overactivity in Chinese patients with benign prostate hyperplasia

Background Detrusor overactivity （DO） is a known cause of lower urinary tract symptoms and occurs in 50%-75% of benign prostate hyperplasia （BPH） patients. We sought to investigate the clinical and urodynamic factors that are associated with the presence of DO in Chinese BPH patients.

Efficacy and Safety of OnabotulinumtoxinA in Treating Neurogenic Detrusor Overactivity： A Systematic Review and Meta-analysis

Background： OnabotulinumtoxinA is widely used in treating neurogenic detrusor overactivity （NDO）. We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug for treating NDO. Methods： We searched the following databases： Medline, EMBASE, and the Cochrane Controlled Trials Register. All published randomized double-blind, placebo-controlled trials of onabotulinumtoxinA for the treatment of NDO were identified in the analysis. The reference lists of the retrieved studies were also investigated. Results： Four publications involving a total of 807 patients were identified in the analysis, which compared onabotulinumtoxinA with placebo. The changes of the mean number of urinary incontinence per week （the standardized mean difference [SMD] = -10.91, 95% confidence intervals [C/s] = -14.18-7.63, P 〈 0.0001）; maximum cystometric capacity （SMD = 146.09, 95% CI = 126.19-165.99, P 〈 0.0001） and maximum detrusor pressure （SMD = -32.65, 95% CI = -37.83--27.48, P 〈 0.0001 ） indicated that onabotulinumtoxinA was more effective than the placebo, despite the doses ofonabotulinumtoxinA. Safety assessments primarily localized to the urinary tract indicated onabotulinumtoxinA were often associated with more complications. Urinary tract infections （relative risk [RR] = 1.48, 95% CI = 1.20- 1.81, P = 0.0002）; hematuria （RR = 1.81, 95% CI = 1.00-3.24, P = 0.05） and urinary retention （RR = 5.87, 95% CI = 3.61-9.56, P 〈 0.0001 ）. Conclusions： This meta-analysis indicates that onabotulinumtoxinA to be an effective treatment for NDO with side effects primarily localized to urinary tract.

Evaluation, treatment, and surveillance of neurogenic detrusor overactivity in spinal cord injury patients

Neurogenic detrusor overactivity is a common urodynamic finding in patients with supra-sacral spinal cord injury. Early evaluation, stepped management, and close follow-up reduce the risk of upper urinary tract deterioration, renal failure and incontinence. In this article, we aim to outline the modern pathway of the management of this complex disease. Evaluation of patients with history, physical examination, renal function assessment, cystoscopy, and urodynamic study are essential. Management of neurogenic detrusor overactivity with adequate bladder drainage, medical therapy, intradetrusor botulinum injections, and surgery can be offered in a stepwise manner. Follow-up after specific interventions should be done in a timely fashion to detect treatment response and to avoid complications of poorly managed neurogenic detrusor overactivity.

Does local vaginal estrogen after tension-free transobturator vaginal tape reduce overactive bladder symptoms in postmenopausal women? A prospective randomized, controlled study

Objective:We aimed to evaluate the efficacy of topical estrogen after transvaginal tension-free vaginal tape-obturator(TVT-O)in the treatment of de novo overactive bladder symptoms that appear after surgery.Methods:This is a prospective randomized controlled study performed in the Urology and Gynecology Departments,Kasr Al Ainy Hospital,Cairo University,Cairo,Egypt.Two hundred and ten postmenopausal females presenting during the period between January 2017 and November 2020 with stress urinary incontinence were included in the study.Patients were divided into two groups,105 patients in Group A(treatment group)and 105 patients in Group B(control group).Patients in Group A underwent transvaginal TVT-O followed by local vaginal estrogen treatment for 6 months,while patients in Group B underwent transvaginal TVT-O only.The study included any postmenopausal female with urodynamic stress urinary incontinence.All patients had to fulfill a 3-day bladder diary,overactive bladder symptoms score,urine analysis,urodynamic study,and post-voiding residual urine measurement by abdominal ultrasound preoperatively and at 3-month and 6-month follow-ups.Results:At 6-month follow-up,daytime frequency was reduced to 8%in Group A(increased to 21%in Group B)with a statistically significant difference between both groups(p=0.009).At 6-month follow-up,nocturia was 8%in Group A(11%in Group B)with no statistically significant difference between both groups(p=0.469).There was a statistically significant difference between both groups as regards to urinary urgency at 6-month follow-up(p=0.024).There was a statistically significant difference in postoperative wound healing events as regards to cure,hyperemia,gapping,and wound infection 1 week after intervention between both groups(p=0.008).No local or systemic side-effects were reported from local estrogen use.Conclusion:Local vaginal estrogen treatment given to postmenopausal patients after midurethral sling procedures can reduce the symptoms of daytime frequency and urinary urgency.Long-term follow-up is needed.

Acupuncture for overactive bladder in adults:Study protocol for a randomized controlled trial

Background:Overactive bladder(OAB)is a prevalent condition that substantially degrades patient quality of life.Acupuncture is recognized as an effective therapeutic approach for various urological diseases.However,there is limited evidence validating the effectiveness and safety of acupuncture for OABs.Objective:To assess the therapeutic efficacy of acupuncture for OAB and to investigate the potential mechanisms by analyzing its effects on relevant urinary biomarkers.Methods:This is a randomized,participants and outcome assessors blinded,sham acupuncture controlled trial.A total of 110 patients with OABs will be randomly divided in a 1:1 ratio between the acupuncture and sham acupuncture groups.Participants in the acupuncture group will undergo 30-min authentic acupuncture,while their counterparts in the sham acupuncture group will undergo sham acupuncture needling non-acupoints superficially three times weekly for a duration of 8 weeks.The two co-primary outcomes will be the change in the mean number of micturitions per 24 h from baseline to the end of the 8-week treatment and 20-week follow-up.The secondary outcomes will encompass the change in Overactive Bladder Symptom Score,Overactive Bladder Questionnaire Short Form,and average 24 h values of urgency,daytime micturition,nocturia,and mean volume voided per micturition from baseline to weeks 8 and 20.Urinary nerve growth factor,brain-derived neurotrophic factor,and monocyte chemoattractant protein-1 levels will be measured at baseline and week 8.Adverse events will also be documented.Discussion:The results of this trial will provide evidence for the effectiveness and safety of acupuncture in the management of OAB.

Relationship between urodynamic patterns and lower urinary tract symptoms in Chinese women with a non-neurogenic bladder

Objective:To investigate the urodynamic study(UDS)patterns,obstruction status,continence status,and their correlations among neurologically intact women with lower urinary tract symptoms(LUTS)through an epidemiological and logistic regression analyses.Methods:We retrospectively analyzed the UDS data of 3265 neurologically intact women with LUTS(2002e2014).Five UDS patterns were identified:normo-active detrusor/sphincter(NA,or DSI,detrusor/sphincter intact),idiopathic detrusor overactivity(IDO),idiopathic sphincter overactivity(ISO),IDO+ISO,and detrusor underactivity(DUA).Analyses of UDS pattern distribution and stratification were performed(based on a modification of the European Urological Association-Madersbacher classification system),and their correlations with bladder outlet obstruction(BOO)and stress urinary incontinence(SUI)status were evaluated via logistic regression analysis.Results:NA,IDO,IDO+ISO,ISO,and DUA were noted in 927(28.4%),678(20.8%),320(9.8%),689(21.1%),and 651(19.9%)cases,respectively.Moreover,storage,storage+voiding,and voiding symptoms were noted in 62.4%,21.1%,and 16.5% cases,respectively,whereas BOO and SUI were observed in 12.1%and 29.0%cases,respectively.The risk factors for BOO included NA,IDO,ISO,and IDO+ISO,whereas the protective factors against BOO included storage symptoms,SUI,storage+voiding symptoms,and complaint duration within 1e12 months.NA was the only risk factor for SUI,whereas BOO,storage+voiding symptoms,IDO,and storage symptoms were protective factors for SUI.Conclusion:Five UDS patterns were identified among neurologically intact women with LUTS.Functional abnormalities of the detrusor and/or sphincter were the main causes of LUTS,and were correlated with the BOO or SUI status.Thus,the UDS pattern can provide additional information regarding the risk factors for BOO or SUI status,as compared to symptomatic typing.

Beyond prostate, beyond surgery and beyond urology: The “3Bs” of managing non-neurogenic male lower urinary tract symptoms

Lower urinary tract symptoms(LUTS),consisting storage,voiding and postmicturition symptoms,is a comprehensive definition involving symptoms that may occur due to several causes.Instead of simply focusing on the enlarged prostate,more attention has to be paid to the entire urinary tract as well as multiple system comorbidities.Therefore,prostate surgery alone does not necessarily provide adequate management and cross-disciplinary collaborations are sometimes required.Based on current literature,this paper proposes the“3Bs”concept for managing non-neurogenic male LUTS,namely,“beyond prostate”,“beyond surgery”and“beyond urology”.The clinical application of the“3Bs”enables urologists to carry out integrated,individualized and precise medical care for each non-neurogenic male LUTS patient.

Comprehensive urodynamics: Being devoted to clinical urologic practice

As a combined electrophysiological system for evaluating the lower urinary tract(LUT), comprehensive urodynamics(UDS) aims at duplicating patient's micturition process, either normal or abnormal, and further seeking for possible causative origin, either neurogenic or non-neurogenic, in order to guide treatment. Through thorough analysis, some so-called cutoff values, for example, bladder outlet obstruction(BOO) degree or dyssynergic degree between the detrusor and sphincter, could be gained; however, in most cases, their qualitative description, such as stress urinary incontinence, idiopathic detrusor underactivity(DUA), detrusor overactivity(IDO), low compliance, and idiopathic sphincter overactivity(ISO), is more preferable and important. In aged neurologically intact male patients with symptoms of the LUT(LUTS) including benign prostatic hyperplasia, a combined UDS system, which coupled BOO with compliance, was constructed. The patients may be categorized into one of the seven subgroups, including equivocal or mild BOO with sphincter synergia with or without IDO(pattern A), equivocal or mild BOO with ISO(B), classic BOO with sphincter synergia(C) or ISO(D), BOO with only low compliance(E), BOO with both DUA and low compliance(F), and potential BOO with DUA(G). This new system can be used to optimize diagnosis and treatment according to a derived guideline diagram.

A Review on Urinary Incontinence after Surgery for Benign Prostatic Hyperplasia

Background: Benign prostatic hyperplasia (BPH) is characterized by the abnormal proliferation of cells, leading to structural changes. It is one of the most common diseases in ageing men. Its clinical presentations are dominated by lower urinary tract symptoms (LUTS). The therapeutic methods can be grouped into two options: the medical option and the surgical option in which prostate enucleation is found. In recent years many studies have reported the onset of urinary incontinence (UI) after prostate enucleation. The management of UI occurring after prostate enucleation is embarrassing for both the practitioner and the patient, and generates additional costs. Purpose: Cite the causes of UI after prostate enucleation for BPH, as well as ways to prevent the onset of UI after this surgery, specifically by the study of the vesicosphincteric system aimed at improving the technique of enucleation;our review will also deal with the therapeutic means of UI. Method: We retrieved studies from Science Direct, Wiley and Pubmed. Results: There are multiple etiologies of UI after prostate enucleation including urethral sphincter insufficiency (USI) and bladder dysfunction (BD). The management of UI after surgery could be conservative, surgical, or use new technologies. Urodynamic assessment before prostate enucleation for BPH is relevant. Conclusion: UI is a common post-operative complication of prostate enucleation. The study of the vesicosphincteric system leads us to believe that prostate enucleation for BPH, partially sparing the mucosa and the external urethral sphincter could decrease the incidence of UI after surgery.

Efficacy and safety of onabotulinum toxin A for overactive bladder

Overactive bladder(OAB) syndrome is a condition which affects 16.9% of women and 16.2% of men with a significant negative impact on quality of life. It is a condition characterized by urgency, with or without urge incontinence, frequency and nocturia. Behavioral modifications and oral anti-muscurinic medications are first and second-line therapies for OAB but are frequently ineffective or poorly tolerated. For refractory cases of OAB, onabotulinum toxin can be offered and this therapy was approved by the Food and Drug Administration in January of 2013. In this editorial, we will review the indications, usage, efficacy and safety data for intradetrusor injection of onabotulinum toxin A.

Non-pharmacologic options for the management of voiding dysfunction in multiple sclerosis

Multiple sclerosis is a neuroinflammatory condition that can cause significant bladder dysfunction manifesting either as overactive bladder or impaired bladder emptying.Patients will often complain of urgency,frequency,nocturia,urgency incontinence,hesitancy,straining to void,and incomplete bladder emptying.While these symptoms can be treated with pharmacologic agents,often patients will require more significant treatments.Patients should first be evaluated with urodynamics in order to adequately diagnose the pathologic condition causing their symptoms.These interventions include catheter use,injection of botulinum toxin,neuromodulation,urethral stenting,sphincterotomy,suprapubic catheter with bladder neck closure,bladder augmentation and urinary diversion.The purpose of this review is to examine the evidence supporting each of these treatment options so urologic providers can better provide for this unique and complex patient population.

Metabolic syndrome and lower urinary tract symptoms

Recently,clinical and epidemiologic data indicating the involvement of metabolic syndrome(Met S)in the pathogenesis and progression of lower urinary tract symptom(LUTS)/benign prostatic hyperplasia(BPH)are reported.This review evaluates the reports on the influence of MetS in the development and progression of LUTS/BPH,and discusses possible clinical implications for the management and treatment of this disease.Recent studies on the epidemiological relationship between MetS and LUTS hypothesize that MetS may be associated with an overactivity of the autonomic nervous system for which hyperinsulinemia,a key element of the Met S,might be responsible.An alternative explanation is that LUTS are associated with chronic ischemia of pelvis resulting from atherosclerotic changes in blood vessels,which leads the production of reactive oxygen species,which can damage the bladder detrusor.Control of autonomic nervous system overactivity and control of chronic bladder ischemia have potential as new targets for LUTS treatment.Studies suggest an association of Met S with LUTS/BPH,although further research is needed to understand how MetS influences LUTS/BPH.Met S should be considered a new domain in basic and clinical research in patients with LUTS/BPH and as a target for treatment.