Lower Urinary Tract Symptoms in US Women: Contemporary Prevalence Estimates from the RISE FOR HEALTH Study.

PURPOSE: We aimed to estimate the prevalence of a wide range of lower urinary tract symptoms (LUTS) in US women, and explore associations with bother and discussion with health care providers, friends, and family. MATERIALS AND METHODS: We analyzed baseline data collected from May 2022 to December 2023 in the RISE FOR HEALTH study-a large, regionally representative cohort study of adult female community members. LUTS and related bother were measured by the 10-item Symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index, and discussion was assessed by a study-specific item. RESULTS: Of the 3000 eligible participants, 73% (95% CI 71%-74%) reported any storage symptoms, 52% (95% CI 50%-53%) any voiding or emptying symptoms, and 11% (95% CI 10%-13%) any pain with bladder filling, for an overall LUTS prevalence of 79% (95% CI 78%-81%). This prevalence estimate included 43% (95% CI 41%-45%) of participants with mild to moderate symptoms and 37% (95% CI 35%-38%) with moderate to severe symptoms. Over one-third of participants reported LUTS-related bother (38%, 95% CI 36%-39%) and discussion (38%, 95% CI 36%-40%), whereas only 7.1% (95% CI 6.2%-8.1%) reported treatment. Urgency and incontinence (including urgency and stress incontinence) were associated with the greatest likelihood of bother and/or discussion (adjusted prevalence ratios = 1.3-2.3), even at mild to moderate levels. They were also the most commonly treated LUTS. CONCLUSIONS: LUTS, particularly storage LUTS such as urgency and incontinence, were common and bothersome in the RISE study population, yet often untreated. Given this large burden, both prevention and treatment-related interventions are warranted to reduce the high prevalence and bother of LUTS.

Effects of variation in sample storage conditions and swab order on 16S vaginal microbiome analyses.

IMPORTANCE: The composition of the human vaginal microbiome has been linked to a variety of medical conditions including yeast infection, bacterial vaginosis, and sexually transmitted infection. The vaginal microbiome is becoming increasingly acknowledged as a key factor in personal health, and it is essential to establish methods to collect and process accurate samples with self-collection techniques to allow large, population-based studies. In this study, we investigate if using AssayAssure Genelock, a nucleic acid preservative, introduces microbial biases in self-collected vaginal samples. To our knowledge, we also contribute some of the first evidence regarding the impacts of multiple swabs taken at one time point. Vaginal samples have relatively low biomass, so the ability to collect multiple swabs from a unique participant at a single time would greatly improve the replicability and data available for future studies. This will hopefully lay the groundwork to gain a more complete and accurate understanding of the vaginal microbiome.

Healthy bladder storage and emptying functions in community-dwelling women measured by a 2-day bladder health diary.

INTRODUCTION: The prevalence of healthy bladder storage and emptying function in community-dwelling women is not well established. METHODS: A planned secondary analysis of a US cross-sectional study designed to validate a bladder health instrument was conducted in women aged ≥18 years. A subset was invited to complete the novel 2-day bladder health diary capturing bladder storage and emptying experiences. Overall healthy bladder function was defined as ≤8 waking/daytime voids and ≤1 void during sleeping/nighttime; along with the absence of leakage, urgency, emptying difficulties (initiation, flow, efficacy, relief of urge sensation) and pain. Descriptive statistics of healthy bladder functions and regression models of factors associated with healthy function are reported. RESULTS: Of the 383 invited, 237 (62%) eligible women returned complete dairies. Of these, 12% (29/237) met criteria for overall healthy bladder function. Most (96%) denied pain, 74% had healthy daytime and 83% had healthy nighttime voiding frequency, 64% were continent, 36% reported healthy emptying and 30% denied any urgency episodes. Middle income (odds ratio [OR]:95% confidence interval [CI] = 11.4:1.9-67.4 for $75k-$99 999 vs. $25 000-$49 999), Graduate education (4.8:1.4-17) and previously seeking treatment for bladder problems (OR:95%CI = 0.1; 0-0.9) were associated with overall healthy function. CONCLUSION: The prevalence of overall healthy bladder function was very low based on our strict definition of health as measured on a 2-day diary. However, most women had healthy voiding frequency and denied pain or urinary leakage. Postvoid dribbling and urgency most commonly contributed to an overall unhealthy bladder. Further investigation is needed to determine whether these diary derived measures are meaningful for patient-oriented bladder health research.

Validation of bladder health scales and function indices for women's research.

BACKGROUND: Existing bladder-specific measures lack the ability to assess the full range of bladder health, from poor to optimal health. OBJECTIVE: This study aimed to report evidence of validity of the self-administered, multidimensional bladder health scales and function indices for research in adult women. STUDY DESIGN: A cross-sectional population-based validation study with random assignment to paper or electronic administration was conducted using national address-based probability sampling supplemented by purposive sampling of women with lower urinary tract symptoms in 7 clinical research centers. Construct validity of the bladder health scales and function indices was guided by a multitrait-multimethod approach using health and condition-specific questionnaires, bladder diaries, expert ratings of bladder health, and noninvasive bladder function testing. Internal dimensional validity was evaluated using factor analysis; internal reliability was assessed using paired t-tests and 2-way mixed-effects intraclass correlation coefficient models. Chi-square, Fisher exact, or t-tests were used for mode comparisons. Convergent validity was evaluated using Pearson correlations with the external construct measures, and known-group validity was established with comparison of women known and unknown to be symptomatic of urinary conditions. RESULTS: The sample included 1072 participants. Factor analysis identified 10 scales, with Cronbach's alpha ranging from 0.74 to 0.94. Intraclass correlation coefficients of scales ranged from 0.55 to 0.94. Convergent validity of the 10 scales and 6 indices ranged from 0.52 to 0.83. Known-group validity was confirmed for all scales and indices. Item distribution was similar by mode of administration. CONCLUSION: The paper and electronic forms of the bladder health scales and function indices are reliable and valid measures of bladder health for use in women's health research.

Comprehensive pelvic muscle assessment: Developing and testing a dual e-Learning and simulation-based training program.

OBJECTIVE: The Prevention of Lower Urinary Tract Symptoms (PLUS) research consortium launched the RISE FOR HEALTH (RISE) national study of women's bladder health which includes annual surveys and an in-person visit. For the in-person exam, a standardized, replicable approach to conducting a pelvic muscle (PM) assessment was necessary. The process used to develop the training, the products, and group testing results from the education and training are described. METHODS: A comprehensive pelvic muscle assessment (CPMA) program was informed by literature view and expert opinion. Training materials were prepared for use on an electronicLearning (e-Learning) platform. An in-person hands-on simulation and certification session was then designed. It included a performance checklist assessment for use by Clinical Trainers, who in collaboration with a gynecology teaching assistant, provided an audit and feedback process to determine Trainee competency. RESULTS: Five discrete components for CPMA training were developed as e-Learning modules. These were: (1) overview of all the clinical measures and PM anatomy and examination assessments, (2) visual assessment for pronounced pelvic organ prolapse, (3) palpatory assessment of the pubovisceral muscle to estimate muscle integrity, (4) digital vaginal assessment to estimate strength, duration, symmetry during PM contraction, and (5) pressure palpation of both myofascial structures and PMs to assess for self-report of pain. Seventeen Trainees completed the full CPMA training, all successfully meeting the a priori certification required pass rate of 85% on checklist assessment. CONCLUSIONS: The RISE CPMA training program was successfully conducted to assure standardization of the PM assessment across the PLUS multicenter research sites. This approach can be used by researchers and healthcare professionals who desire a standardized approach to assess competency when performing this CPMA in the clinical or research setting.

Characteristics associated with subjective and objective measures of treatment success in women undergoing percutaneous tibial nerve stimulation vs sham for accidental bowel leakage.

INTRODUCTION AND HYPOTHESIS: In randomized trials both percutaneous tibial nerve stimulation (PTNS) and sham result in clinically significant improvements in accidental bowel leakage (ABL). We aimed to identify subgroups who may preferentially benefit from PTNS in women enrolled in a multicenter randomized trial. METHODS: This planned secondary analysis explored factors associated with success for PTNS vs sham using various definitions: treatment responder using three cutoff points for St. Mark's score (≥3-, ≥4-, and ≥5-point reduction); Patient Global Impression of Improvement (PGI-I) of ≥ much better; and ≥50% reduction in fecal incontinence episodes (FIEs). Backward logistic regression models were generated using elements with significance of p<0.2 for each definition and interaction terms assessed differential effects of PTNS vs sham. RESULTS: Of 166 women randomized, 160 provided data for at least one success definition. Overall, success rates were 65% (102 out of 158), 57% (90 out of 158), and 46% (73 out of 158) for ≥3-, ≥4-, and ≥5-point St Mark's reduction respectively; 43% (68 out of 157) for PGI-I; and 48% (70 out of 145) for ≥50% FIEs. Of those providing data for all definitions of success, 77% (109 out of 142) met one success criterion, 43% (61 out of 142) two, and 29% (41 out of 142) all three success criteria. No reliable or consistent factors were associated with improved outcomes with PTNS over sham regardless of definition. CONCLUSIONS: Despite exploring diverse success outcomes, no subgroups of women with ABL differentially responded to PTNS over sham. Success results varied widely across subjective and objective definitions. Further investigation of ABL treatment success definitions that consistently and accurately capture patient symptom burden and improvement are needed.

The RISE FOR HEALTH study: Methods for in-person assessment and biospecimen collection.

OBJECTIVES: To describe the methods for the in-person assessment of the RISE FOR HEALTH (RISE) study, a population-based multicenter prospective cohort study designed to identify factors that promote bladder health and/or prevent lower urinary tract symptoms in adult women, conducted by the Prevention of Lower Urinary Tract Symptoms Research Consortium (PLUS). METHODS AND RESULTS: A subset of RISE participants who express interest in the in-person assessment will be screened to ensure eligibility (planned n = 525). Eligible consenting participants are asked to complete 15 physical assessments in addition to height and weight, to assess pelvic floor muscle function, musculoskeletal (MSK) status, and pain, and to provide urogenital microbiome samples. Pelvic floor muscle assessments include presence of prolapse, strength, levator attachment integrity (tear) and myofascial pain. MSK tests evaluate core stability, lumbar spine, pelvic girdle and hip pain and function. Participants are asked to complete the Short Physical Performance Battery to measure balance, lower extremity strength, and functional capacity. All participants are asked to provide a voided urine sample and a vaginal swab for microbiome analyses; a subset of 100 are asked to contribute additional samples for feasibility and validation of a home collection of urinary, vaginal, and fecal biospecimens. RESULTS: Online and in-person training sessions were used to certify research staff at each clinical center before the start of RISE in-person assessments. Standardized protocols and data collection methods are employed uniformly across sites. CONCLUSIONS: The RISE in-person assessment is an integral portion of the overall population-based RISE study and represents an innovative approach to assessing factors hypothesized to promote bladder health and/or prevent lower urinary tract symptoms. Data collected from this assessment will be used to prioritize future research questions and prevention strategies and interventions. This description of the assessment methods is intended to provide methodologic transparency and inform other researchers who join efforts to understand and improve bladder health.

RISE FOR HEALTH: Rationale and protocol for a prospective cohort study of bladder health in women.

INTRODUCTION: The spectrum of bladder health and the factors that promote bladder health and prevent lower urinary tract symptoms (LUTS) among women are not well understood. This manuscript describes the rationale, aims, study design, sampling strategy, and data collection for the RISE FOR HEALTH (RISE) study, a novel study of bladder health in women conducted by the Prevention of Lower Urinary Tract Symptom (PLUS) Research Consortium. METHODS AND RESULTS: RISE is a population-based, multicenter, prospective longitudinal cohort study of community-dwelling, English- and Spanish-speaking adult women based in the United States. Its goal is to inform the distribution of bladder health and the individual factors (biologic, behavioral, and psychosocial) and multilevel factors (interpersonal, institutional, community, and societal) that promote bladder health and/or prevent LUTS in women across the life course. Key study development activities included the: (1) development of a conceptual framework and philosophy to guide subsequent activities, (2) creation of a study design and sampling strategy, prioritizing diversity, equity, and inclusion, and (3) selection and development of data collection components. Community members and cross-cultural experts shaped and ensured the appropriateness of all study procedures and materials. RISE participants will be selected by simple random sampling of individuals identified by a marketing database who reside in the 50 counties surrounding nine PLUS clinical research centers. Participants will complete self-administered surveys at baseline (mailed paper or electronic) to capture bladder health and LUTS, knowledge about bladder health, and factors hypothesized to promote bladder health and prevent LUTS. A subset of participants will complete an in-person assessment to augment data with objective measures including urogenital microbiome specimens. Initial longitudinal follow-up is planned at 1 year. DISCUSSION: Findings from RISE will begin to build the necessary evidence base to support much-needed, new bladder health promotion and LUTS prevention interventions in women.

Effects of Variation in Urine Sample Storage Conditions on 16S Urogenital Microbiome Analyses.

Replicability is a well-established challenge in microbiome research with a variety of contributing factors at all stages, from sample collection to code execution. Here, we focus on voided urine sample storage conditions for urogenital microbiome analysis. Using urine samples collected from 10 adult females, we investigated the microbiome preservation efficacy of AssayAssure Genelock (Genelock), compared with no preservative, under different temperature conditions. We varied temperature over 48 h in order to examine the impact of conditions samples may experience with home voided urine collection and shipping to a central biorepository. The following common lab and shipping conditions were investigated: -20°C, ambient temperature, 4°C, freeze-thaw cycle, and heat cycle. At 48 h, all samples were stored at -80°C until processing. After generating 16S rRNA gene amplicon sequencing data using the highly sensitive KatharoSeq protocol, we observed individual variation in both alpha and beta diversity metrics below interhuman differences, corroborating reports of individual microbiome variability in other specimen types. While there was no significant difference in beta diversity when comparing Genelock versus no preservative, we did observe a higher concordance with Genelock samples shipped at colder temperatures (-20°C and 4°C) when compared with the samples shipped at -20°C without preservative. Our results indicate that Genelock does not introduce a significant amount of microbial bias when used on a range of temperatures and is most effective at colder temperatures. IMPORTANCE The urogenital microbiome is an understudied yet important human microbiome niche. Research has been stimulated by the relatively recent discovery that urine is not sterile; urinary tract microbes have been linked to health problems, including urinary infections, incontinence, and cancer. The quality of life and economic impact of UTIs and urgency incontinence alone are enormous, with $3.5 billion and $82.6 billion, respectively, spent in the United States. annually. Given the low biomass of urine, novelty of the field, and limited reproducibility evidence, it is critical to study urine sample storage conditions to optimize scientific rigor. Efficient and reliable preservation methods inform methods for home self-sample collection and shipping, increasing the potential use in larger-scale studies. Here, we examined both buffer and temperature variation effects on 16S rRNA gene amplicon sequencing results from urogenital samples, providing data on the consequences of common storage methods on urogenital microbiome results.

Percutaneous Tibial Nerve Stimulation vs Sham Stimulation for Fecal Incontinence in Women: NeurOmodulaTion for Accidental Bowel Leakage Randomized Clinical Trial.

INTRODUCTION: To determine whether percutaneous tibial nerve stimulation (PTNS) is superior to sham stimulation for the treatment of fecal incontinence (FI) in women refractory to first-line treatments. METHODS: Women aged 18 years or older with ≥3 months of moderate-to-severe FI that persisted after a 4-week run-in phase were randomized 2:1 (PTNS:sham stimulation) to 12 weekly 30-minute sessions in this multicenter, single-masked, controlled superiority trial. The primary outcome was change from baseline FI severity measured by St. Mark score after 12 weeks of treatment (range 0-24; minimal important difference, 3-5 points). The secondary outcomes included electronic bowel diary events and quality of life. The groups were compared using an adjusted general linear mixed model. RESULTS: Of 199 women who entered the run-in period, 166 (of 170 eligible) were randomized, (111 in PTNS group and 55 in sham group); the mean (SD) age was 63.6 (11.6) years; baseline St. Mark score was 17.4 (2.7); and recording was 6.6 (5.5) FI episodes per week. There was no difference in improvement from baseline in St. Mark scores in the PTNS group when compared with the sham group (-5.3 vs -3.9 points, adjusted difference [95% confidence interval] -1.3 [-2.8 to 0.2]). The groups did not differ in reduction in weekly FI episodes (-2.1 vs -1.9 episodes, adjusted difference [95% confidence interval] -0.26 [-1.85 to 1.33]). Condition-specific quality of life measures did not indicate a benefit of PTNS over sham stimulation. Serious adverse events occurred in 4% of each group. DISCUSSION: Although symptom reduction after 12 weeks of PTNS met a threshold of clinical importance, it did not differ from sham stimulation. These data do not support the use of PTNS as conducted for the treatment of FI in women.

Association between the urogenital microbiome and surgical treatment response in women undergoing midurethral sling operation for mixed urinary incontinence.

BACKGROUND: The urogenital microbiome is associated with urgency and mixed urinary incontinence symptoms and differential treatment responses to pharmacotherapy for urgency urinary incontinence. OBJECTIVE: This study aimed to describe whether the preoperative urinary and vaginal microbiomes were associated with surgical treatment responses at 12 months after a midurethral sling operation in women with mixed urinary incontinence. STUDY DESIGN: This cohort study compared the preoperative microbiome compositions of urine and vaginal samples from a subset of women undergoing a midurethral sling operation in the Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence trial (NCT01959347) and compared the microbiota in women who were surgical responders vs surgical nonresponders. Twelve-month objective response was defined as a ≥70% reduction from baseline urinary incontinence episodes on a 3-day diary. Subjective response was defined as a change from baseline in the Urogenital Distress Inventory scores. Bacterial abundance and beta diversity were assessed using 16S ribosomal RNA sequencing. The primary differential abundance analysis described predominant bacterial operational taxonomic units associated with responders vs nonresponders using unadjusted and age-adjusted linear models. RESULTS: Objective nonresponders (n=28) compared with responders (n=72) were older (58.5±10.7 vs 51.6±10.2 years) and more likely postmenopausal without hormone use (odds ratio, 6.4; 95% confidence interval, 1.8-22.6). Vaginal and urinary microbiota beta diversities were associated with age (P<.05) for both responders and nonresponders. Overall, predominant operational taxonomic units (genera) were Lactobacillus, Gardnerella, Tepidimonas, Escherichia, Streptococcus, and Prevotella. Operational taxonomic units from baseline urine samples were not significantly associated (P threshold=.05) with surgical treatment responses. A greater abundance of baseline vaginal Lactobacillus was associated with an objective response (P=.04) and Prevotella with an objective nonresponse (P=.01). Adjusting for age, only a greater abundance of baseline vaginal Prevotella was associated with an objective nonresponse (P=.01). Moreover, less abundant vaginal operational taxonomic units were associated with objective and subjective responses and persistent urinary incontinence symptoms (P<.05). CONCLUSION: Women meeting a 70% reduction of urinary incontinence treatment episodes (objective responders) had greater vaginal Lactobacillus at the time of the surgical procedure; however, controlling for age diminished this association. Women not meeting a 70% reduction of urinary incontinence episodes 1 year after a midurethral sling operation had greater vaginal Prevotella at the time of the midurethral sling operation. Further research is needed to determine whether therapy altering the vaginal microbiome may impact surgical treatment responses in women with mixed urinary incontinence.

Impact of Vaginal Estrogen on the Urobiome in Postmenopausal Women With Recurrent Urinary Tract Infection.

OBJECTIVE: The aim of this study was to describe effects of vaginal estrogen (VE) on the urogenital microbiome in postmenopausal women with recurrent urinary tract infections (rUTIs). METHODS: This is a secondary analysis of 17 participants enrolled in a randomized controlled trial of VE versus placebo on urinary tract infection recurrence in postmenopausal women with rUTIs. Paired clean-catch urine samples were collected at baseline and after 6 months of VE and sequenced using 16S rRNA gene sequencing. Sequence reads were analyzed using Quantitative Insights Into Microbial Ecology 2. Changes in α diversity, ß diversity, and differentially abundant genera were measured between paired baseline and 6-month samples and between those with a urinary tract infection at 6 months (failures) and those without (successes). RESULTS: Of the 17 women, 11 were successes and 6 were failures after 6 months of VE treatment. There was a significant change in α diversity from baseline to month 6 in samples overall (Kruskal-Wallis χ2 = 3.47, P = 0.037) and in the treatment success group (Yuen T = -2.53, P = 0.035). The increase in relative abundance of Lactobacillus crispatus, Lactobacillus gasseri, and Lactobacillus iners AB-1 was correlated with month 6. A relative bloom of L. crispatus compared with L. gasseri was associated with treatment success (Kruskal-Wallis χ2 = 4.9, P = 0.0014). CONCLUSIONS: Lactobacillus increases in the urogenital microbiome of postmenopausal women with rUTI after 6 months of VE. However, only the relative increase in L. crispatus specifically may be associated with treatment success.

Forming Consensus To Advance Urobiome Research.

Urobiome research has the potential to advance the understanding of a wide range of diseases, including lower urinary tract symptoms and kidney disease. Many scientific areas have benefited from early research method consensus to facilitate the greater, common good. This consensus document, developed by a group of expert investigators currently engaged in urobiome research (UROBIOME 2020 conference participants), aims to promote standardization and advances in this field by the adoption of common core research practices. We propose a standardized nomenclature as well as considerations for specimen collection, preservation, storage, and processing. Best practices for urobiome study design include our proposal for standard metadata elements as part of core metadata collection. Although it is impractical to follow fixed analytical procedures when analyzing urobiome data, we propose guidelines to document and report data originating from urobiome studies. We offer this first consensus document with every expectation of subsequent revision as our field progresses.

Subgroups of failure after surgery for pelvic organ prolapse and associations with quality of life outcomes: a longitudinal cluster analysis.

BACKGROUND: Treatment outcomes after pelvic organ prolapse surgery are often presented as dichotomous "success or failure" based on anatomic and symptom criteria. However, clinical experience suggests that some women with outcome "failures" are asymptomatic and perceive their surgery to be successful and that other women have anatomic resolution but continue to report symptoms. Characterizing failure types could be a useful step to clarify definitions of success, understand mechanisms of failure, and identify individuals who may benefit from specific therapies. OBJECTIVE: This study aimed to identify clusters of women with similar failure patterns over time and assess associations among clusters and the Pelvic Organ Prolapse Distress Inventory, Short-Form Six-Dimension health index, Patient Global Impression of Improvement, patient satisfaction item questionnaire, and quality-adjusted life-year. STUDY DESIGN: Outcomes were evaluated for up to 5 years in a cohort of participants (N=709) with stage ≥2 pelvic organ prolapse who underwent surgical pelvic organ prolapse repair and had sufficient follow-up in 1 of 4 multicenter surgical trials conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Surgical success was defined as a composite measure requiring anatomic success (Pelvic Organ Prolapse Quantification system points Ba, Bp, and C of ≤0), subjective success (absence of bothersome vaginal bulge symptoms), and absence of retreatment for pelvic organ prolapse. Participants who experienced surgical failure and attended ≥4 visits from baseline to 60 months after surgery were longitudinally clustered, accounting for similar trajectories in Ba, Bp, and C and degree of vaginal bulge bother; moreover, missing data were imputed. Participants with surgical success were grouped into a separate cluster. RESULTS: Surgical failure was reported in 276 of 709 women (39%) included in the analysis. Failures clustered into the following 4 mutually exclusive subgroups: (1) asymptomatic intermittent anterior wall failures, (2) symptomatic intermittent anterior wall failures, (3) asymptomatic intermittent anterior and posterior wall failures, and (4) symptomatic all-compartment failures. Each cluster had different bulge symptoms, anatomy, and retreatment associations with quality of life outcomes. Asymptomatic intermittent anterior wall failures (n=150) were similar to surgical successes with Ba values that averaged around -1 cm but fluctuated between anatomic success (Ba≤0) and failure (Ba>0) over time. Symptomatic intermittent anterior wall failures (n=82) were anatomically similar to asymptomatic intermittent anterior failures, but women in this cluster persistently reported bothersome bulge symptoms and the lowest quality of life, Short-Form Six-Dimension health index scores, and perceived success. Women with asymptomatic intermittent anterior and posterior wall failures (n=28) had the most severe preoperative pelvic organ prolapse but the lowest symptomatic failure rate and retreatment rate. Participants with symptomatic all-compartment failures (n=16) had symptomatic and anatomic failure early after surgery and the highest retreatment of any cluster. CONCLUSION: In particular, the following 4 clusters of pelvic organ prolapse surgical failure were identified in participants up to 5 years after pelvic organ prolapse surgery: asymptomatic intermittent anterior wall failures, symptomatic intermittent anterior wall failures, asymptomatic intermittent anterior and posterior wall failures, and symptomatic all-compartment failures. These groups provide granularity about the nature of surgical failures after pelvic organ prolapse surgery. Future work is planned for predicting these distinct outcomes using patient characteristics that can be used for counseling women individually.

Design of a Randomized Controlled Trial of Percutaneous Posterior Tibial Nerve Stimulation for the Treatment of Refractory Fecal Incontinence in Women: The NeurOmodulaTion for Accidental Bowel Leakage Study.

OBJECTIVES: High-level evidence for second-line noninvasive treatments for fecal incontinence in women is limited. We present the rationale for and design of the NeuromOdulaTion for Accidental Bowel Leakage trial, a randomized controlled trial of percutaneous tibial nerve stimulation (PTNS) and validated sham stimulation in women with refractory accidental bowel leakage. METHODS: The rationale and goals for a 2-part study with a run-in phase, use of a generic pulse generator for PTNS and sham stimulation, masking, participant inclusion, primary and secondary outcome measures, and adverse event collection are described. A superiority design will be used to compare change from baseline in St. Mark's score after 12 weekly stimulation sessions between PTNS and sham. Responders to initial treatment (PTNS or sham) will be assigned to scheduled or "as needed" intervention for up to 1 year. Secondary outcome measures include incontinence episodes and other bowel events recorded in a 14-day electronic bowel diary, general and condition-specific quality of life instruments, adaptive behavior, global impression of improvement, symptom control, and sexual function. RESULTS: Sample size calculations determined that 165 participants (110 PTNS and 55 sham) would provide 90% power to detect greater than or equal to 4-point difference between PTNS and sham in change from baseline in St. Mark's score at 12 weeks. CONCLUSIONS: The methods for the NeuromOdulaTion for Accidental Bowel Leakage trial will provide high-level evidence of the effectiveness and optimal maintenance therapy schedule of a low-cost PTNS protocol in community-dwelling women seeking second-line intervention for refractory accidental bowel leakage.

Comparison of 100 U With 200 U of Intradetrusor OnabotulinumToxinA for Nonneurogenic Urgency Incontinence.

OBJECTIVES: The objective of this study was to compare efficacy and adverse events between 100 U and 200 U of onabotulinumtoxinA for 6 months in women with nonneurogenic urgency incontinence. METHODS: This is a secondary analysis of 2 multicenter randomized controlled trials assessing efficacy of onabotulinumtoxinA in women with nonneurogenic urgency incontinence; one compared 100 U to anticholinergics and the other 200 U to sacral neuromodulation. Of 307 women who received onabotulinumtoxinA injections, 118 received 100 U, and 189 received 200 U. The primary outcome was mean adjusted change in daily urgency incontinence episodes from baseline over 6 months, measured on monthly bladder diaries. Secondary outcomes included perceived improvement, quality of life, and adverse events. The primary outcome was assessed via a multivariate linear mixed model. RESULTS: Women receiving 200 U had a lower mean reduction in urgency incontinence episodes by 6 months compared with 100 U (-3.65 vs -4.28 episodes per day; mean difference, 0.63 episodes per day [95% confidence interval (CI), 0.05-1.20]). Women receiving 200 U had lower perceptions of improvement (adjusted odds ratio, 0.32 [95% CI, 0.14-0.75]) and smaller improvement in severity score (adjusted mean difference, 12.0 [95% CI, 5.63-18.37]). Upon subanalysis of only women who were treated with prior anticholinergic medications, these differences between onabotulinumtoxinA doses were no longer statistically significant. There was no statistically significant difference in adverse events in women receiving 200 U (catheterization, 32% vs 23%; adjusted odds ratio, 1.4 [95% CI, 0.8-2.4]; urinary tract infection, 37% vs 27%; adjusted odds ratio, 1.5 [95% CI, 0.9-2.6]). CONCLUSIONS: A higher dose of onabotulinumtoxinA may not directly result in improved outcomes, but rather baseline disease severity may be a more important prediction of outcomes.

Rationale and design of the validation of bladder health instrument for evaluation in women (VIEW) protocol.

BACKGROUND: Bladder health is an understudied state and difficult to measure due to lack of valid and reliable instruments. While condition specific questionnaires assess presence, severity and degree of bother from lower urinary tract symptoms, the absence of symptoms is insufficient to assume bladder health. This study describes the methodology used to validate a novel bladder health instrument to measure the spectrum of bladder health from very healthy to very unhealthy in population based and clinical research. METHODS: Three samples of women are being recruited: a sample from a nationally representative general population and two locally recruited clinical center samples-women with a targeted range of symptom severity and type, and a postpartum group. The general population sample includes 694 women, 18 years or older, randomly selected from a US Postal delivery sequence file. Participants are randomly assigned to electronic or paper versions of the bladder health instrument along with a battery of criterion questionnaires and a demographic survey; followed by a retest or a two-day voiding symptom diary. A total of 354 women around 7 clinical centers are being recruited across a spectrum of self-reported symptoms and randomized to mode of completion. They complete the two-day voiding symptom diary as well as a one-day frequency volume diary prior to an in-person evaluation with a standardized cough stress test, non-invasive urine flowmetry, chemical urine analysis and post void residual measurement. Independent judge ratings of bladder health are obtained by interview with a qualified health care provider. A total of 154 postpartum women recruited around 6 of the centers are completing similar assessments within 6-12 weeks postpartum. Dimensional validity will be evaluated using factor analysis and principal components analysis with varimax rotation, and internal consistency with Cronbach's alpha. Criterion validity will be assessed using multitrait-multimethod matrix including correlations across multiple data sources and multiple types of measures. DISCUSSION: We aim to validate a bladder health instrument to measure the degree of bladder health within the general population and among women (including postpartum) recruited from local clinical centers. Trial registration NCT04016298 Posted July 11, 2019 ( https://www.clinicaltrials.gov/ct2/show/NCT04016298?cond=bladder+health&draw=2&rank=1 ).

Vaginal Estrogen for the Prevention of Recurrent Urinary Tract Infection in Postmenopausal Women: A Randomized Clinical Trial.

OBJECTIVES: We aimed to compare the efficacy of 2 commonly used contemporary vaginal estrogen administrations versus placebo for the prevention of urinary tract infection (UTI) in postmenopausal women with a clinical diagnosis of recurrent UTI (rUTI). METHODS: This was an investigator-initiated, multicenter, single-blind, randomized, placebo-controlled trial of vaginal estrogen (delivered via ring or cream) compared with placebo. Postmenopausal women with documented rUTI were randomized to receive either vaginal estrogen (via ring or cream) or placebo cream in a 1:1:1 fashion. The primary outcome was occurrence of UTI at 6 months. After 6 months, open-label use of ring or active cream was offered to all participants for an additional 6 months. Because of slower than expected recruitment, sample size calculations and block randomization schema were revised to combine estrogen groups (ring or cream) for statistical comparisons to placebo cream in a 1:1 fashion. RESULTS: Thirty-five women were randomized with 9 dropouts (1 ring, 2 cream, and 6 placebo) prior to the 6 months. Intention-to-treat analysis (assuming dropouts as failures) revealed fewer women treated with vaginal estrogen had a UTI within 6 months versus placebo (11/18 vs 16/17, respectively; P = 0.041). Per-protocol analysis revealed fewer subjects treated with vaginal estrogen had a UTI at 6 months (8/15 vs 10/11, respectively; P = 0.036). CONCLUSIONS: Commonly prescribed forms of vaginal estrogen with contemporary dosing schedules prevent UTIs in postmenopausal women with an active diagnosis of rUTI.

Do Women Who Self-report More Exercise Have Increased Rates of Symptomatic Stress Urinary Incontinence After Midurethral Slings?

OBJECTIVES: There is a paucity of data on postoperative exercise and how it relates to surgical failure, specifically after midurethral sling (MUS) surgery. We aimed to assess if women with higher self-reported activity levels as measured by strenuous exercise are more likely to experience stress urinary incontinence (SUI) symptoms after MUS than women with lower self-reported activity. METHODS: This is a secondary analysis of Operations and Pelvic Muscle Training in the Management of Apical Support Loss: the OPTIMAL Trial, a randomized trial comparing sacrospinous ligament suspension versus uterosacral ligament suspension, both with concomitant retropubic MUS. Participants completed a validated assessment of activity preoperatively and postoperatively. Women in the upper quartile for strenuous exercise (≥90 minutes per week) were compared with the remaining participants. Symptomatic SUI was defined as retreatment or reoperation for SUI and/or any positive response to Pelvic Floor Disorders Inventory stress incontinence questions 20 to 22. RESULTS: A total of 351 participants in the OPTIMAL study received MUS along with their prolapse repair and had postoperative exercise and Pelvic Floor Disorders Inventory data. At 2 years, 87 (29%) of 305 exercised strenuously for at least 90 minutes per week, and 63 (23%) of 277 experienced SUI. Women who were less active at 2 years were significantly more likely to experience SUI than women who were more active (26.6% vs 12.8%, P = 0.0138). CONCLUSIONS: In this study, symptomatic SUI occurred more frequently in women with lower self-reported exercise levels 2 years after MUS surgery.