The AUA/SUFU Guideline on Adult Neurogenic Lower Urinary Tract Dysfunction: Treatment and Follow-up.

PURPOSE: The clinician treating patients with neurogenic lower urinary tract dysfunction (NLUTD) needs to balance a variety of factors when making treatment decisions. In addition to the patient's urologic symptoms and urodynamic findings, other issues that may influence management options of the lower urinary tract include cognition, hand function, type of neurologic disease, mobility, bowel function/management, and social and caregiver support. This Guideline allows the clinician to understand the options available to treat patients, understand the findings that can be seen in NLUTD, and appreciate which options are best for each individual patient. This allows for decisions to be made with the patient, in a shared decision-making manner, such that the patient's quality of life can be optimized with respect to their bladder management. MATERIALS AND METHODS: A comprehensive search for studies assessing patients undergoing evaluation, surveillance, management, or follow-up for NLUTD was conducted from January 2001 through October 2017 and was rerun in February 2021 to capture newer literature. The primary search returned 20,496 unique citations. Following a title and abstract screen, full texts were obtained for 3,036 studies. During full-text review, studies were primarily excluded for not meeting the PICO criteria. One hundred eight-four primary literature studies met the inclusion criteria and were included in the evidence base. RESULTS: This guideline was developed to inform clinicians on the proper evaluation, diagnosis, and risk stratification of adult patients with NLUTD and the non-surgical and surgical treatment options available. Additional statements on urinary tract infection and autonomic dysreflexia were developed to guide the clinician. CONCLUSIONS: NLUTD patients may undergo non-surgical and surgical treatment options depending on their level of risk, symptoms, and urodynamic findings. Appropriate follow-up, primarily based on their risk stratification, must be maintained after treatment.

The AUA/SUFU Guideline on Adult Neurogenic Lower Urinary Tract Dysfunction: Diagnosis and Evaluation.

PURPOSE: The clinician treating patients with neurogenic lower urinary tract dysfunction (NLUTD) needs to balance a variety of factors when making treatment decisions. In addition to the patient's urologic symptoms and urodynamic findings, other issues that may influence management options of the lower urinary tract include cognition, hand function, type of neurologic disease, mobility, bowel function/management, and social and caregiver support. This Guideline allows the clinician to understand the options available to treat patients, understand the findings that can be seen in NLUTD, and appreciate which options are best for each individual patient. This allows for decisions to be made with the patient, in a shared decision-making manner, such that the patient's quality of life can be optimized with respect to their bladder management. MATERIALS AND METHODS: A comprehensive search for studies assessing patients undergoing evaluation, surveillance, management, or follow-up for NLUTD was conducted from January 2001 through October 2017 and was rerun in February 2021 to capture newer literature. The primary search returned 20,496 unique citations. Following a title and abstract screen, full texts were obtained for 3,036 studies. During full-text review, studies were primarily excluded for not meeting the PICO criteria. One hundred eight-four primary literature studies met the inclusion criteria and were included in the evidence base. RESULTS: This guideline was developed to inform clinicians on the proper evaluation, diagnosis, and risk stratification of patients with NLUTD and the non-surgical and surgical treatment options available. Additional statements on urinary tract infection and autonomic dysreflexia were developed to guide the clinician. This Guideline is for adult patients with NLUTD and pediatric NLUTD will not be discussed. CONCLUSIONS: NLUTD patients should be risk-stratified as either low-, moderate-, high-, or unknown-risk. After diagnosis and stratification, patients should be monitored according to their level of risk at regular intervals. Patients who experience new or worsening signs and symptoms should be reevaluated and risk stratification should be repeated.

Anterior Vaginal Wall Prolapse Repair and the Rise and Fall of Transvaginal Mesh. Did We Come Full Circle? A Historical Perspective.

OBJECTIVE: To present a brief historical review of treatment options for pelvic organ prolapse with a focus on anterior vaginal wall defects and highlight changing practice patterns in the era of synthetic mesh controversy. METHODS: A MEDLINE and PubMed search was performed using the keywords pelvic organ prolapse, anterior colporrhaphy, and cystocele followed by a manual search of bibliographies. RESULTS: Ancient treatments included Hippocratic succession, local astringent, and use of pomegranates as crude pessaries. More sophisticated surgical techniques evolved in the 19th century with further refinement in the early 20th century. Numerous native tissue apposition techniques were popularized by Kelly, Kennedy, Burch, and Raz. Due to poor durability, surgeons sought alternate approaches including biologic and synthetic grafts. Synthetic transvaginal mesh (TVM) initially included use of Tantalum and Marlex to repair anterior wall defects. Both were eventually abandoned due to complications. TVM was re-designed, re-marketed, and re-introduced. Type 1 polypropylene monofilament TVM use became ubiquitous in female pelvic surgery peaking between 2004 and 2008. Initial promising outcomes were soon eclipsed by a surge of adverse events leading to multiple FDA warnings, reclassification to Class III, high-risk medical device, and ultimately a complete recall in 2019. CONCLUSION: The bidirectional pendulum swing on use of synthetic TVM has been occurring since its introduction 50 years ago. In the current era of mesh controversy, more practitioners are now revisiting previously described native tissue and biologic graft techniques. It appears that history has repeated itself.

Early and Consistent Improvements in Urinary Symptoms and Quality of Life With OnabotulinumtoxinA in Patients With Overactive Bladder and Urinary Incontinence: Results From a Randomized, Placebo-controlled, Phase IV Clinical Trial.

OBJECTIVES: This randomized, multicenter, placebo-controlled, phase IV study assessed the efficacy and tolerability of onabotulinumtoxinA in patients with overactive bladder. METHODS: Patients were randomized 1:1 to onabotulinumtoxinA 100 U or placebo. Assessments over 12 weeks included: change from baseline in urinary incontinence (UI) episodes/day; proportions of patients who achieved 100% and 50% or greater reductions in UI episodes/day; proportion of patients using no incontinence pads in the previous 24 hours; and changes from baseline in micturition frequency, nocturia, urgency UI, Incontinence-Quality of Life, King's Health Questionnaire, International Consultation on Incontinence Questionnaire-UI Short Form scores and time to request retreatment. RESULTS: Significant reductions in UI episodes/day were seen with onabotulinumtoxinA versus placebo within week 1 posttreatment (-2.9 vs -2.0, P = 0.005) through week 12 (coprimary endpoint: -3.5 vs -1.6, P < 0.001). Significantly more onabotulinumtoxinA-treated patients achieved 100% (coprimary endpoint) and 50% or greater reductions in UI episodes/day. Decreases in other urinary symptoms were also seen within 1 week with onabotulinumtoxinA that continued through at least week 12. More onabotulinumtoxinA-treated versus placebo-treated patients required no incontinence pads at weeks 1 to 12, and greater improvements in quality of life measurements were seen. Time to request retreatment was significantly longer with onabotulinumtoxinA versus placebo (30.0 weeks vs 13.1 weeks; P < 0.001). No unexpected safety signals were observed. Urinary tract infection was the most commonly observed adverse event. CONCLUSIONS: Urinary symptom and quality of life improvements were observed with onabotulinumtoxinA within 1 week of treatment and were sustained for at least 12 weeks.

Treatment of urethral stricture disease in women: A multi-institutional collaborative project from the SUFU research network.

AIM: Female urethral stricture disease is rare and has several surgical approaches including endoscopic dilations (ENDO), urethroplasty with local vaginal tissue flap (ULT) or urethroplasty with free graft (UFG). This study aims to describe the contemporary management of female urethral stricture disease and to evaluate the outcomes of these three surgical approaches. METHODS: This is a multi-institutional, retrospective cohort study evaluating operative treatment for female urethral stricture. Surgeries were grouped into three categories: ENDO, ULT, and UFG. Time from surgery to stricture recurrence by surgery type was analyzed using a Kaplan-Meier time to event analysis. To adjust for confounders, a Cox proportional hazard model was fit for time to stricture recurrence. RESULTS: Two-hundred and ten patients met the inclusion criteria across 23 sites. Overall, 64% (n = 115/180) of women remained recurrence free at median follow-up of 14.6 months (IQR, 3-37). In unadjusted analysis, recurrence-free rates differed between surgery categories with 68% ENDO, 77% UFG and 83% ULT patients being recurrence free at 12 months. In the Cox model, recurrence rates also differed between surgery categories; women undergoing ULT and UFG having had 66% and 49% less risk of recurrence, respectively, compared to those undergoing ENDO. When comparing ULT to UFG directly, there was no significant difference of recurrence. CONCLUSION: This retrospective multi-institutional study of female urethral stricture demonstrates that patients undergoing endoscopic management have a higher risk of recurrence compared to those undergoing either urethroplasty with local flap or free graft.

Surveillance and management of urologic complications after spinal cord injury.

PURPOSE: Neurogenic bladder due to spinal cord injury has significant consequences for patients' health and quality of life. Regular surveillance is required to assess the status of the upper and lower urinary lower urinary tracts and prevent their deterioration. In this review, we examine surveillance techniques in neurogenic bladder, describe common complications of this disease, and address strategies for their management. METHODS: This work represents the efforts of SIU-ICUD joint consultation on Urologic Management of the Spinal Cord injury. For this specific topic, a workgroup was formed and comprehensive literature search of English language manuscripts regarding neurogenic bladder management was performed using key words of neurogenic bladder. Articles were compiled, and recommendations in the chapter are based on group discussion and follow the Oxford Centre for Evidence-based Medicine system for Levels of Evidence (LOEs) and Grades of Recommendation (GORs). RESULTS: At a minimum, patients should undergo an annual history and physical examination, renal functional testing (e.g., serum creatinine), and upper tract imaging (e.g., renal ultrasonography). The existing evidence does not support the use of other modalities, such as cystoscopy or urodynamics, for routine surveillance. Urologic complications in neurogenic bladder patients are common and often more complex than in the general population. CONCLUSIONS: There is a shortage of high-quality evidence to support any particular neurogenic bladder surveillance protocol. However, there is consensus regarding certain aspects of regular genitourinary system evaluation in these patients. Proper surveillance allows the clinician to avoid or address common urological complications, and to guide, alter, or maintain appropriate therapeutic regimens for individual patients.

Long-Term Treatment with OnabotulinumtoxinA Results in Consistent, Durable Improvements in Health Related Quality of Life in Patients with Overactive Bladder.

PURPOSE: We present the long-term effects of repeat onabotulinumtoxinA 100 U treatment on health related quality of life in patients with overactive bladder and urinary incontinence who had an inadequate response to and/or were intolerant of an anticholinergic. MATERIALS AND METHODS: Patients who completed either of 2, 24-week phase III trials could enter a 3-year extension study and request multiple onabotulinumtoxinA 100 U treatments as needed. Results of the I-QOL (Incontinence-Quality of Life) and KHQ (King's Health Questionnaire) are reported for up to 6 treatments. Consistency of the response to repeat onabotulinumtoxinA treatments was evaluated by classifying patients by the I-QOL response to the first treatment and analyzing responses to treatments 2 to 6. RESULTS: After onabotulinumtoxinA treatments 1 to 6, improvements in I-QOL scores were consistently 2 to 3 times the minimally important difference, and improvements in KHQ role limitations and social limitations domain scores were 5 to 6 and 3 to 4 times the minimally important difference, respectively. Most patients achieved or exceeded the minimally important difference for I-QOL and KHQ domain scores. Furthermore, 72.9% of patients who achieved or exceeded the minimally important difference for I-QOL after treatment 1 did so for all subsequent treatments. Of patients with a poor response after treatment 1, 38.3% achieved improvements greater than the minimally important difference for all subsequent treatments. CONCLUSIONS: In patients with overactive bladder and incontinence consistent and clinically meaningful improvements in health related quality of life were observed with repeat onabotulinumtoxinA 100 U treatments. A positive response after treatment 1 tended to predict similar responses to subsequent treatments, whereas a lack of response to treatment 1 did not preclude positive response(s) to later treatments.

Mixed urinary incontinence: what first?

Mixed urinary incontinence (MUI) is the involuntary loss of urine associated with the sensation of urgency and also with exertion, effort, sneezing, or coughing. The underlying cause of MUI is poorly understood. Without clearly understanding the pathophysiological and anatomical changes associated with MUI, treatment is often misdirected. This review presents an analysis of the most recent studies and pathophysiological mechanisms thought to be associated with MUI-related voiding dysfunction. A suggested algorithm is provided for the workup of these women with a review of medical and surgical treatment options used to treat MUI.

OnabotulinumtoxinA is effective in patients with urinary incontinence due to neurogenic detrusor overactivity [corrected] regardless of concomitant anticholinergic use or neurologic etiology.

INTRODUCTION: To evaluate the efficacy and safety of onabotulinumtoxinA for the treatment of neurogenic detrusor overactivity (NDO) in subpopulations of etiology (multiple sclerosis [MS] or spinal cord injury [SCI]) and concomitant anticholinergics (use/non-use). METHODS: Data were pooled from two double-blind, placebo-controlled, pivotal, phase 3 studies including a total of 691 patients with ≥ 14 urinary incontinence (UI) episodes/week due to MS (n = 381) or SCI (n = 310). Patients received intradetrusor injections of onabotulinumtoxinA 200U (n = 227), 300U (n = 223), or placebo (n = 241). Change from baseline at week 6 in UI episodes/week (primary endpoint), urodynamics, quality of life (QOL), and adverse events (AEs) were assessed. RESULTS: Significant and similar reductions in UI episodes were observed regardless of etiology or anticholinergic use: at week 6, mean weekly decreases of -22.6 and -19.6 were seen in MS and SCI patients, respectively, and -20.3 and -22.5 in anticholinergic users and non-users, respectively, treated with onabotulinumtoxinA 200U. The 300U dose did not add to the clinical efficacy in any subpopulation. Similar proportions of patients achieved ≥ 50% or 100% reductions in UI episodes in all subgroups. Improvements in maximum cystometric capacity, maximum detrusor pressure during first involuntary detrusor contraction, and QOL were significant in both etiologies and were independent of anticholinergic use. The most common AEs in all groups were urinary tract infection and urinary retention. CONCLUSION: Regardless of concomitant anticholinergic use or etiology, onabotulinumtoxinA significantly improved UI symptoms, urodynamics, and QOL in patients with UI due to NDO. OnabotulinumtoxinA was well tolerated in all groups.

A phase III, randomized, double-blind, parallel-group, placebo-controlled, multicentre study to assess the efficacy and safety of the ß3 adrenoceptor agonist, mirabegron, in patients with symptoms of overactive bladder.

OBJECTIVE: To assess the efficacy and tolerability of mirabegron 25 mg and 50 mg once-daily vs placebo in patients with overactive bladder (OAB). MATERIALS AND METHODS: Patients ≥18 years with OAB symptoms were recruited to a 2-week, single-blind, placebo run-in. Those with ≥8 micturitions per 24 hours and ≥3 urgency episodes were randomized 1:1:1 to once-daily mirabegron 25 mg or 50 mg, or placebo for 12 weeks. Primary endpoints were changes to final visit in mean number of incontinence episodes and micturitions per 24 hours. Key secondary endpoints were changes to final visit in mean volume voided or micturition, change to week 4 in mean number of incontinence episodes and micturitions per 24 hours, changes to final visit in mean level of urgency, number of urgency incontinence episodes, and urgency (grade 3 or 4) episodes per 24 hours. Patient-reported outcomes were assessed using the OAB-questionnaire, Patient Perception of Bladder Condition, and Treatment-Satisfaction-Visual Analog Scale. RESULTS: Both mirabegron groups demonstrated statistically significant improvements in coprimary endpoints vs placebo. Mirabegron 50 mg demonstrated significantly greater improvements vs placebo in the following: change to final visit in mean volume voided per micturition and change to week 4 in mean number of incontinence episodes per 24 hours. Statistically significant improvements vs placebo were demonstrated by mirabegron 50 mg in all patient-reported outcome scales with no increase in the incidence of treatment-emergent adverse events vs placebo. CONCLUSION: Mirabegron 25 mg and 50 mg were associated with significant improvements in efficacy measures of incontinence episodes and micturition frequency. Mirabegron was well tolerated vs placebo.

Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity.

PURPOSE: We assessed the efficacy, safety and effects on quality of life of onabotulinumtoxinA in patients with neurogenic detrusor overactivity. MATERIALS AND METHODS: In this 52-week, international, multicenter, double-blind, randomized, placebo controlled trial 416 patients with neurogenic detrusor overactivity and urinary incontinence (14 or more episodes per week) resulting from multiple sclerosis (227) and spinal cord injury (189) were treated with intradetrusor injections of onabotulinumtoxinA (200 or 300 U) or placebo. The primary end point was the change from baseline in the mean number of urinary incontinence episodes per week at week 6. Maximum cystometric capacity, maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life total score were secondary end points. Adverse events were monitored. RESULTS: OnabotulinumtoxinA at a dose of 200 U in 135 patients and 300 U in 132 decreased mean urinary incontinence at week 6 by 21 and 23 episodes per week, respectively, vs 9 episodes per week in 149 on placebo (each dose p<0.001). Also, maximum cystometric capacity, maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life score were significantly improved over values in the placebo group (each dose p<0.001). Median time to patient re-treatment request was greater for onabotulinumtoxinA 200 and 300 U than for placebo (256 and 254 days, respectively, vs 92). The most common adverse events were urinary tract infection and urinary retention. Of patients who did not catheterize at baseline 10% on placebo, 35% on 200 U and 42% on 300 U initiated catheterization due to urinary retention. CONCLUSIONS: OnabotulinumtoxinA significantly improved neurogenic detrusor overactivity symptoms vs placebo. Clean intermittent catheterization initiation due to urinary retention appeared to increase in a dose dependent fashion. No clinically relevant benefit in efficacy or duration was identified for the 300 U dose over the 200 U dose.

Treatment satisfaction and goal attainment with onabotulinumtoxinA in patients with incontinence due to idiopathic OAB.

INTRODUCTION AND HYPOTHESIS: Clinically meaningful overactive bladder syndrome (OAB) symptom relief is associated with patient satisfaction. This study evaluated the effects of onabotulinumtoxinA on patient satisfaction and goal attainment. METHODS: In a 36-week, multicenter, double-blind study, 313 participants with idiopathic OAB and urinary urgency incontinence inadequately managed with anticholinergics were randomized to placebo or one of five onabotulinumtoxinA doses. Assessment included a modified OAB-Patient Satisfaction with Treatment Questionnaire (PSTQ) and four Patient Global Assessment questions assessed changes in symptoms, quality of life, activity limitations, and emotions. RESULTS: Mean changes from baseline in OAB-PSTQ scores for the main module (Q2-Q13) at week 12 were greater for each onabotulinumtoxinA group (range, -31.5% to -48.9%) versus placebo (-17.6%). Greater proportions of patients in onabotulinumtoxinA groups attained their primary goal (range, 34.5% to 65.3%) versus placebo (23.7%). CONCLUSIONS: Patients with OAB are more likely to be satisfied and/or achieve their primary treatment goal with onabotulinumtoxinA treatment than with placebo, consistent with symptom improvements.

Role of botulinum toxin-A in refractory idiopathic overactive bladder patients without detrusor overactivity.

BACKGROUND: To evaluate the efficacy of intradetrusor botulinum toxin-A (BTX-A) in idiopathic overactive bladder patients (OAB) refractory to anti-muscarinic therapy, without detrusor overactivity (DOA) on urodynamics. METHODS: Patients with refractory idiopathic OAB without DOA on urodynamics were prospectively enrolled. Subjects completed a 3-day voiding diary (3-VD), urogenital distress inventory-6 questionnaire (UDI-6) and graded their quality of life on a 10-cm visual analog scale (VAS) prior to study enrollment and at week 12 postinjection. All patients underwent multichannel urodynamics at study enrollment and 12 weeks postinjection. Improvement was analyzed based on 3-VD, UDI-6 questionnaire, VAS scores, and urodynamic parameters at week 12 postinjection compared to study enrollment. RESULTS: The study included 32 patients. Mean ± SD age was 56 ± 16. There were 27 women and 5 men. Nineteen patients had OAB without incontinence (OAB-dry) and 13 patients had OAB with incontinence (OAB-wet). In OAB-dry patients, mean ± SD urinary frequency dropped from 24 ± 11 to 10 ± 4 by week 12. In OAB-wet patients, mean ± SD urge incontinence episodes dropped from 7.9 ± 5 to 0 ± 2.6 by week 12. Mean UDI-6 and VAS scores improved significantly in both groups by week 12 (P = 0.0001). On comparing urodynamic parameters, OAB-wet patients showed significant decrease in maximum detrusor pressure during the voiding phase at week 12 compared to baseline values (P = 0.02). CONCLUSIONS: Refractory idiopathic OAB patients without DOA on urodynamics may benefit from intradetrusor BTX-A.

Bladder dysfunction in patients with diabetes.

With diabetes mellitus (DM) reaching epidemic proportions, the identification of voiding dysfunction as a common and burdensome complication of this disease is critical. Research into diabetic voiding dysfunction significantly lags behind other complications of DM, such as retinopathy and nephropathy. Recent studies have revealed that DM predisposes patients to a wide range of lower urinary tract dysfunction, from the classic diabetic cystopathy of incomplete emptying to urgency incontinence. In this review, we discuss the current concepts of diabetic voiding dysfunction with a critical analysis of the available evidence.

Voiding dysfunction in the female patient: is the "syndrome" paradigm valid?

Voiding dysfunction in the female patient significantly affects the patient's quality of life. The condition is poorly understood, has varied etiology and clinical presentation, and lacks standard definitions with no consensus on diagnostic criteria. It consists of a constellation of symptoms involving both phases of the micturition cycle. Appropriate diagnosis and treatment of female lower urinary tract symptoms (LUTS) is of paramount importance. However, the differentiation of female LUTS into various syndromes is currently controversial. This article comprehensively reviews the commonly encountered female non-neurogenic LUTS (overactive bladder, interstitial cystitis, and painful bladder syndrome); discusses the contemporary management of these syndromes; and emphasizes a syndromic approach to the condition.

Repeat intradetrusor injections of onabotulinum toxin a for refractory idiopathic overactive bladder patients: a single-center experience.

OBJECTIVES: : The objective of the study was to evaluate the safety and efficacy of repeat intradetrusor onabotulinum toxin A injection in patients with idiopathic overactive bladder refractory to anticholinergic medications. Furthermore, 2 doses, 100 and 150 U, were compared. METHODS: : We prospectively enrolled 60 patients in our investigator-initiated, single-center randomized trial. Thirty patients were randomized to each dosage arm. Total study duration was 3 years. Patients were eligible to receive 6 onabotulinum toxin A injections. Subjects completed a 3-day voiding diary and Urogenital Distress Inventory 6 (UDI-6) questionnaire and graded their quality of life on a visual analog scale (VAS) before study enrollment and at week 6 after every injection. The outcome was based on the amount of improvement noted on the UDI-6 and VAS scores at 6 weeks post every injection as compared with study enrollment. RESULTS: : There were 9 men and 51 women. The mean UDI-6 and VAS scores improved significantly (P = 0.0001) at week 6 after initial onabotulinum toxin A injection, and no change was seen when comparing repeat injections; 20% and 10% of the patients randomized to 150 and 100 U required performing clean intermittent catheterization, respectively. The mean UDI-6 scores after repeat onabotulinum toxin A injections did not differ significantly between 100 and 150 U. CONCLUSIONS: : Repeat injections of onabotulinum toxin A are capable of significantly improving UDI-6 scores and quality of life in refractory patients with idiopathic overactive bladder. There was no evidence of decreased efficacy after repeat injections. Lower clean intermittent catheterization rates were noted in patients randomized to 100 U as compared with 150 U. Both doses, 100 and 150 U, were equally efficacious.