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.

Genital Pain and the Spectrum of Bladder-Related Symptoms: Findings from the Prevention of Lower Urinary Tract Symptoms Research Consortium RISE FOR HEALTH Study, USA.

INTRODUCTION AND HYPOTHESIS: Women with vulvovaginal or genital pain more commonly experience interstitial cystitis/bladder pain syndrome (IC/BPS) and urinary tract infections. However, the relationship between genital pain and bladder health is lacking. METHODS: Women in the Prevention of Lower Urinary Tract Symptoms Consortium's RISE FOR HEALTH population-based study answered questions about bladder health globally, and across nine bladder health domains of holding, efficacy, social-occupation, physical activity, intimacy, travel, emotion, perception, and freedom. Bladder function was assessed across six indices including urinary frequency, sensation, continence, comfort, emptying, and dysbiosis (e.g., urinary tract infections). Participants were grouped by no pain beyond transitory events (i.e., minor headaches, toothaches, or sprains), nongenital-related pain only, and any genital pain using a validated pain diagram. Mean adjusted scores and indices were compared using general linear modelling. RESULTS: Of 1,973 eligible women, 250 (12.7%) reported genital pain, 609 (30.9%) reported nongenital pain only, and 1,114 (56.5%) reported no pain. Women with any genital pain had lower (worse) adjusted mean scores across all bladder health scales (BHS; BHS global adjusted mean 47.5; 95% CI 40.8-54.1), compared with those with nongenital pain only (53.7; 95% CI 47.6-59.8), and no pain (59.3; 95% CI 53.3-65.4). Similarly, adjusted mean total Bladder Functional Index scores were lower for those with genital pain (63.1; 95% CI 58.4-67.9) compared with nongenital pain (72.1; 95% CI 67.7-76.5) and no pain (77.4; 95% CI 73.0-81.8). CONCLUSIONS: Heightened awareness of the relationship between genital pain and bladder health should prompt clinicians caring for women with genital pain to assess bladder health and function.

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.

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.

The RISE FOR HEALTH study: Methods for in-person musculoskeletal assessment.

OBJECTIVES: To describe the methods for the in-person musculoskeletal (MSK) assessment of the RISE FOR HEALTH (RISE) study, a population-based multicenter prospective cohort study designed to identify factors associated with bladder health (BH) conducted by the Prevention of Lower Urinary Tract Symptoms Research Consortium (PLUS). METHODS: A subset of RISE participants who express interest in the in-person assessment are screened to ensure eligibility (planned n = 525). Eligible consenting participants are asked to complete a standardized MSK assessment to evaluate core stability (four component core stability test, lumbar spine pain (seated slump test), pelvic girdle pain, (sacroiliac joint, anterior superior iliac spine, pubic symphysis tenderness, and pelvic girdle pain provocation test), hip pain (flexion, abduction, internal rotation and flexion, adduction and external rotation) and pelvic girdle function (active straight leg raise). Participants are also asked to complete the Short Physical Performance Battery to measure balance, gait speed, lower extremity strength, and functional capacity. RESULTS: Detailed online and in-person MSK training sessions led by physical therapy were used to certify research staff at each clinical center before the start of RISE in-person assessments. All evaluators exceeded the pre-specified pass rates. CONCLUSIONS: The RISE in-person MSK assessment will provide further insight into the role of general body MSK health and dysfunction and the spectrum of BH.

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.

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.

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.

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.

Measuring Bladder Health: Development and Cognitive Evaluation of Items for a Novel Bladder Health Instrument.

PURPOSE: We describe the item development and cognitive evaluation process used in creating the Prevention of Lower Urinary Tract Symptoms Bladder Health Instrument (PLUS-BHI). MATERIALS AND METHODS: Questions assessing bladder health were developed using reviews of published items, expert opinion, and focus groups' transcript review. Candidate items were tested through cognitive interviews with community-dwelling women and an online panel survey. Items were assessed for comprehension, language, and response categories and modified iteratively to create the PLUS-BHI. RESULTS: Existing measures of bladder function (storage, emptying, sensation components) and bladder health impact required modification of time frame and response categories to capture a full range of bladder health. Of the women 167 (18-80 years old) completed individual interviews and 791 women (18-88 years) completed the online panel survey. The term "bladder health" was unfamiliar for most and was conceptualized primarily as absence of severe urinary symptoms, infection, or cancer. Coping mechanisms and self-management strategies were central to bladder health perceptions. The inclusion of prompts and response categories that captured infrequent symptoms increased endorsement of symptoms across bladder function components. CONCLUSIONS: Bladder health measurement is challenged by a lack of awareness of normal function, use of self-management strategies to mitigate impact on activities, and a common tendency to overlook infrequent lower urinary tract symptoms. The PLUS-BHI is designed to characterize the full spectrum of bladder health in women and will be validated for research use.

Success and failure are dynamic, recurrent event states after surgical treatment for pelvic organ prolapse.

BACKGROUND: The ideal measure of success after surgery for pelvic organ prolapse has long been debated. Historically, strict definitions based on anatomic perfection have dominated the literature. However, the importance of patient-centered perception of outcomes is equally or more important when comparing the success of various prolapse surgeries. Understanding the limitations of existing outcome definitions will guide surgical outcome reporting and comparisons of pelvic organ prolapse surgeries. OBJECTIVE: This study aimed to describe the relationships and overlap among the participants who met the anatomic, subjective, and retreatment definitions of success or failure after pelvic organ prolapse surgery; demonstrate rates of transition between success and failure over time; and compare scores from the Pelvic Organ Prolapse Distress Inventory, Short-Form Six-Dimension health index, and quality-adjusted life years among these definitions. STUDY DESIGN: Definitions of surgical success were evaluated at 3 or 6, 12, 24, 36, 48, and 60 months after surgery for ≥stage II pelvic organ prolapse in a cohort of women (N=1250) from 4 randomized clinical trials conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Surgical failure was defined by a composite measure requiring 1 or more of (1) anatomic failure (Pelvic Organ Prolapse Quantification point Ba, Bp, or C of >0), (2) subjective failure (presence of bothersome vaginal bulge symptoms), or (3) pessary or surgical retreatment for pelvic organ prolapse. Pelvic Organ Prolapse Distress Inventory, Short-Form Six-Dimension health index, and quality-adjusted life years were compared among participants who met a variety of definitions of success and failure including novel "intermittent" success and failure over time. RESULTS: Among the 433 of 1250 women (34.6%) who had surgical failure outcomes at ≥1 time point, 85.5% (370 of 433) met only 1 component of the composite outcome at the assessment of initial failure (anatomic failure, 46.7% [202 of 433]; subjective failure, 36.7% [159 of 433]; retreatment, 2.1% [9 of 433]). Only 12.9% (56 of 433) met the criteria for both for anatomic and subjective failure. Despite meeting the criteria for failure in primary study reporting, 24.2% of these (105 of 433) transitioned between success and failure during follow-up, of whom 83.8% (88 of 105) met the criteria for success at their last follow-up. There were associations between success or failure classification and the 1- and 2-year quality-adjusted life years and a time-varying group effect on Pelvic Organ Prolapse Distress Inventory and Short-Form Six-Dimension health index scores. CONCLUSION: True failure rates after prolapse surgery may be overestimated in the current literature. Only 13% of clinical trial subjects initially met both subjective and objective criteria for failure. Approximately one-quarter of failures were intermittent and transitioned between success and failure over time, with most intermittent failures being in a state of "surgical success" at their last follow-up. Current composite definitions of success or failure may result in the overestimation of surgical failure rates, potentially explaining, in part, the discordance with low retreatment rates after pelvic organ prolapse surgery.

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.

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 ).

Cost-Effectiveness of Sacral Neuromodulation versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: Results of the ROSETTA Randomized Trial.

PURPOSE: Sacral neuromodulation and intradetrusor onabotulinumtoxinA injection are therapies for refractory urgency urinary incontinence. Sacral neuromodulation involves surgical implantation of a device that can last 4 to 6 years while onabotulinumtoxinA therapy involves serial office injections. We assessed the cost-effectiveness of 2-stage implantation sacral neuromodulation vs 200 units onabotulinumtoxinA for the treatment of urgency urinary incontinence. MATERIALS AND METHODS: Prospective economic evaluation was performed concurrent with the ROSETTA (Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment) randomized trial of 386 women with 6 or more urgency urinary incontinence episodes on a 3-day diary. Analysis is from the health care system perspective with primary within-trial analysis for 2 years and secondary 5-year decision analysis. Costs are in 2018 U.S. dollars. Effectiveness was measured in quality adjusted life-years (QALYs) and reductions in urgency urinary incontinence episodes per day. We generated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. RESULTS: Two-year costs were higher for sacral neuromodulation than for onabotulinumtoxinA ($35,680 [95% CI 33,920-37,440] vs $7,460 [95% CI 5,780-9,150], p <0.01), persisting through 5 years ($36,550 [95% CI 34,787-38,309] vs $12,020 [95% CI 10,330-13,700], p <0.01). At 2 years there were no differences in mean reduction in urgency urinary incontinence episodes per day (-3.00 [95% CI -3.38 - -2.62] vs -3.12 [95% CI -3.48 - -2.76], p=0.66) or QALYs (1.39 [95% CI 1.34-1.44] vs 1.41 [95% CI 1.36-1.45], p=0.60). The probability that sacral neuromodulation is cost-effective relative to onabotulinumtoxinA is less than 0.025 for all willingness to pay values below $580,000 per QALY at 2 years and $204,000 per QALY at 5 years. CONCLUSIONS: Although both treatments were effective, the high cost of sacral neuromodulation is not good value for treating urgency urinary incontinence compared to 200 units onabotulinumtoxinA.

Defining the relationship between vaginal and urinary microbiomes.

BACKGROUND: Although the vaginal and urinary microbiomes have been increasingly well-characterized in health and disease, few have described the relationship between these neighboring environments. Elucidating this relationship has implications for understanding how manipulation of the vaginal microbiome may affect the urinary microbiome and treatment of common urinary conditions. OBJECTIVE: To describe the relationship between urinary and vaginal microbiomes using 16S rRNA gene sequencing. We hypothesized that the composition of the urinary and vaginal microbiomes would be significantly associated, with similarities in predominant taxa. STUDY DESIGN: This multicenter study collected vaginal swabs and catheterized urine samples from 186 women with mixed urinary incontinence enrolled in a parent study and 84 similarly aged controls. Investigators decided a priori that if vaginal and/or urinary microbiomes differed between continent and incontinent women, the groups would be analyzed separately; if similar, samples from continent and incontinent women would be pooled and analyzed together. A central laboratory sequenced variable regions 1-3 (v1-3) and characterized bacteria to the genus level. Operational taxonomic unit abundance was described for paired vaginal and urine samples. Pearson's correlation characterized the relationship between individual operational taxonomic units of paired samples. Canonical correlation analysis evaluated the association between clinical variables (including mixed urinary incontinence and control status) and vaginal and urinary operational taxonomic units, using the Canonical correlation analysis function in the Vegan package (R version 3.5). Linear discriminant analysis effect size was used to find taxa that discriminated between vaginal and urinary samples. RESULTS: Urinary and vaginal samples were collected from 212 women (mean age 53±11 years) and results from 197 paired samples were available for analysis. As operational taxonomic units in mixed urinary incontinence and control samples were related in canonical correlation analysis and since taxa did not discriminate between mixed urinary incontinence or controls in either vagina or urine, mixed urinary incontinence and control samples were pooled for further analysis. Canonical correlation analysis of vaginal and urinary samples indicated that that 60 of the 100 most abundant operational taxonomic units in the samples largely overlapped. Lactobacillus was the most abundant genus in both urine and vagina (contributing on average 53% to an individual's urine sample and 64% to an individual's vaginal sample) (Pearson correlation r=0.53). Although less abundant than Lactobacillus, other bacteria with high Pearson correlation coefficients also commonly found in vagina and urine included: Gardnerella (r=0.70), Prevotella (r=0.64), and Ureaplasma (r=0.50). Linear discriminant analysis effect size analysis identified Tepidimonas and Flavobacterium as bacteria that distinguished the urinary environment for both mixed urinary incontinence and controls as these bacteria were absent in the vagina (Tepidimonas effect size 2.38, P<.001, Flavobacterium effect size 2.15, P<.001). Although Lactobacillus was the most abundant bacteria in both urine and vagina, it was more abundant in the vagina (linear discriminant analysis effect size effect size 2.72, P<.001). CONCLUSION: Significant associations between vaginal and urinary microbiomes were demonstrated, with Lactobacillus being predominant in both urine and vagina. Abundance of other bacteria also correlated highly between the vagina and urine. This inter-relatedness has implications for studying manipulation of the urogenital microbiome in treating conditions such as urgency urinary incontinence and urinary tract infections.

Accidental Bowel Leakage Evaluation: A New Patient-Centered Validated Measure of Accidental Bowel Leakage Symptoms in Women.

BACKGROUND: Questionnaires assessing accidental bowel leakage lack important patient-centered symptoms. OBJECTIVE: We aimed to create a valid measure of accidental bowel leakage symptoms. DESIGN: We previously created a conceptual framework capturing patient-centered accidental bowel leakage symptoms. The framework included bowel leakage type, severity and bother, and ancillary bowel symptoms, including predictability, awareness, leakage control, emptying disorders, and discomfort. SETTINGS: The study was conducted in outpatient clinics. PATIENTS: Women with at least monthly accidental bowel leakage were included. INTERVENTIONS: Participants completed the Accidental Bowel Leakage Evaluation at baseline and 12 and 24 weeks, as well as bowel diaries and other validated pelvic floor questionnaires. A subset completed items twice before treatment. Final item selection was based on psychometric properties and clinical importance. MAIN OUTCOME MEASURES: Psychometric analyses included Cronbach α, confirmatory factor, and item response theory analyses. Construct validity was based on correlations with measures of similar constructs. RESULTS: A total of 296 women completed baseline items, and 70 provided test-retest data. The cohort was predominately white (79%) and middle aged (64 ± 11 y). Confirmatory factor analyses supported the conceptual framework. The final 18-item scale demonstrated good internal consistency (Cronbach α = 0.77-0.90) and test-retest reliability (intraclass correlation = 0.80). Construct validity was demonstrated with baseline and 12- and 24-week scale scores, which correlated with the Vaizey (r = 0.52, 0.68, and 0.69), Colorectal Anal Distress Inventory (r = 0.54, 0.65, 0.71), Colorectal Anal Impact Questionnaire (r = 0.48, 0.53, 0.53), and hygiene (r = 0.39, 0.43, 0.49) and avoidance subscales scores of the adaptive index (r = 0.45, 0.44, 0.43) and average number of pad changes per day on bowel diaries (r = 0.35, 0.38, 0.31; all p < 0.001). LIMITATIONS: The study was limited by nature of involving validation in a care-seeking population. CONCLUSIONS: The Accidental Bowel Leakage Evaluation instrument is a reliable, patient-centered measure with good validity properties. This instrument improves on currently available measures by adding patient-important domains of predictability, awareness, control, emptying, and discomfort. See Video Abstract at http://links.lww.com/DCR/B172. EVALUACIóN DE FUGA INTESTINAL ACCIDENTAL: UNA NUEVA MEDIDA VALIDADA Y CENTRADA EN PACIENTES FEMENINOS CON SíNTOMAS DE FUGA INTESTINAL ACCIDENTAL: Los cuestionarios que evalúan la fuga intestinal accidental, carecen de síntomas centrados en el paciente.Nuestro objetivo fue crear una medida válida de síntomas de fuga intestinal accidental.Previamente creamos un marco conceptual centrado en el paciente, para capturar síntomas de fuga intestinal accidental. El marco incluía tipo de fuga intestinal, gravedad, molestia, y síntomas intestinales auxiliares, incluyendo previsibilidad, conciencia, control de fugas, trastornos de vaciado e incomodidad.Clínicas de pacientes externos.Mujeres con al menos una fuga intestinal accidental mensual.Las participantes completaron la Evaluación de Fuga Intestinal Accidental al inicio del estudio y a las 12 y 24 semanas, así como diarios intestinales y otros cuestionarios validados del piso pélvico. Un subconjunto completó los elementos dos veces antes del tratamiento. La selección final del elemento se basó en las propiedades psicométricas y la importancia clínica.Los análisis psicométricos incluyeron el Alfa de Cronbach, factor confirmatorio y análisis de la teoría de respuesta al elemento. La validez de constructo se basó en correlaciones con medidas de constructos similares.Un total de 296 mujeres completaron los elementos de referencia y 70 proporcionaron datos de test-retest. La cohorte fue predominantemente blanca (79%) y de mediana edad (64 +/- 11 años). Análisis factorial confirmatorio respaldó el marco conceptual. La escala final de 18 elementos, demostró una buena consistencia interna (Alfa de Cronbach = 0,77-0,90) y fiabilidad test-retest (correlación intraclase = 0,80). La validez de constructo se demostró con puntajes de escala de referencia de 12 y 24 semanas que se correlacionaron con Vaizey (r = 0,52, 0,68 y 0,69), Inventario de Ansiedad colorecto anal (r = 0,54, 0,65, 0,71), Cuestionarios de Impacto colorecto anal (r = 0,48, 0,53, 0,53) e higiene (r = 0,39, 0,43, 0,49), puntuaciones de subescalas de evitación del índice adaptativo (r = 0,45, 0,44, 0,43), número promedio de cambios de almohadilla por día, de los diarios intestinales (r = 0.35, 0.38, 0.31), todos p <.001.Validación de una población en busca de atención.El instrumento de Evaluación de Fuga Intestinal Accidental es una medida confiable, centrada en el paciente y con buenas propiedades de validez. Este instrumento mejora las medidas actualmente disponibles, al agregar dominios importantes para el paciente de previsibilidad, conciencia, control, vaciado e incomodidad. Consulte Video Resumen en http://links.lww.com/DCR/B172. (Traducción-Dr. Fidel Ruiz Healy).

Performance, acceptability, and validation of a phone application bowel diary.

AIMS: To assess performance, acceptability, external validity, and reliability of a phone application electronic bowel diary (PFDN Bowel eDiary). METHODS: Women reporting refractory accidental bowel leakage (ABL) were enrolled in a randomized, crossover trial evaluating paper versus eDiary documentation of bowel movements (BM) and fecal incontinence episodes (FIE). Events were characterized by the presence or absence of urgency and Bristol stool scale consistency. The eDiary entries were date/time stamped and prompted by twice-daily phone notifications. Women were randomized to complete up to three consecutive 14-day diaries in two sequences. Diary events were compared between formats using the Pearson correlation. System usability scale (SUS) assessed eDiary usability. The eDiary test-retest reliability was assessed with intraclass correlations (ICCs). RESULTS: Paired diary data were available from 60/69 (87%) women 63.8 ± 9.8 years old with mean 13.2 BM per week and 6.5 FIE per week (nearly half with urgency). Among those providing diaries, adherence did not differ by paper or eDiary (93.3% vs. 95.0%). Notifications prompted 29.6% of eDiary entries, improving adherence from 70% to 95%. Paper and eDiaries were moderate to-strongly correlated for BMs per week (r = .61), urgency BMs per week (r = .76), FIE per week (r = .66), urgency FIE per week (r = .72). Test-retest reliability was good (ICC = .81 BMs per week, .79 urgency BMs per week, .74 FIE per week, and .62 urgency FIE per week). The mean SUS score was high, 82.3 ± 17.5 (range, 0-100) with 91.4% rating it easy to use, and 75.9% preferring the eDiary over paper. CONCLUSION: The PFDN Bowel eDiary correlated well with paper diary was considered easy to use, preferred to paper diaries, had high rates of confirmed real-time diary completion that obviated staff data entry.

Is the juice worth the squeeze? Transdisciplinary team science in bladder health.

AIMS: Prior research on lower urinary tract symptoms (LUTS) has focused on the treatment and management of these conditions with scant attention to prevention. The Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium was formed to address the complexities of preventing LUTS and promoting bladder health. METHODS: Herein, we describe challenges faced and strategies used to develop the PLUS Research Consortium into an engaged and productive transdisciplinary scientific team. We apply four previously defined team science phases (development, conceptualization, implementation, and translation) to frame our progress. RESULTS: Strategies to progress through the development phase included the generation of a shared mission, and valuing of other disciplinary perspectives. The conceptualization phase included generating a shared language and developing a team transdisciplinary orientation. During the implementation phase, the group developed roles and procedures and focused on conflict management. The translation phase includes continued refinement of the mission and goals, implementation of research protocols, and robust dissemination of the scientific work products related to bladder health. CONCLUSION: A diverse group has matured into a productive transdisciplinary team science consortium. Achieving this outcome required dedicated effort for each member to engage in activities that often required more time than single discipline research activities. Provision of the necessary time and tools has fostered a transdisciplinary team science culture and rich research agenda that reflects the complexity of the health issue to be addressed. Our experience may be useful for others embarking on team science projects.