Search

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.

IntroductionTo 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.MethodsWomen 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.ResultsOf 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.DiscussionAlthough 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.

BackgroundThe urogenital microbiome is associated with urgency and mixed urinary incontinence symptoms and differential treatment responses to pharmacotherapy for urgency urinary incontinence.ObjectiveThis 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 designThis 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.ResultsObjective 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

ObjectivesHigh-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.MethodsThe 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.ResultsSample 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.ConclusionsThe 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.

BackgroundBladder 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.MethodsThree 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.DiscussionWe 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 ).

BackgroundTreatment 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.ObjectiveThis 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 designOutcomes 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.ResultsSurgical 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.ConclusionIn 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.

BackgroundProlapse recurrence after transvaginal surgical repair is common; however, its mechanisms are ill-defined. A thorough understanding of how and why prolapse repairs fail is needed to address their high rate of anatomic recurrence and to develop novel therapies to overcome defined deficiencies.ObjectiveThis study aimed to identify mechanisms and contributors of anatomic recurrence after vaginal hysterectomy with uterosacral ligament suspension (native tissue repair) vs transvaginal mesh (VM) hysteropexy surgery for uterovaginal prolapse.Study designThis multicenter study was conducted in a subset of participants in a randomized clinical trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Overall, 94 women with uterovaginal prolapse treated via native tissue repair (n=48) or VM hysteropexy (n=46) underwent pelvic magnetic resonance imaging at rest, maximal strain, and poststrain rest (recovery) 30 to 42 months after surgery. Participants who desired reoperation before 30 to 42 months were imaged earlier to assess the impact of the index surgery. Using a novel 3-dimensional pelvic coordinate system, coregistered midsagittal images were obtained to assess study outcomes. Magnetic resonance imaging-based anatomic recurrence (failure) was defined as prolapse beyond the hymen. The primary outcome was the mechanism of failure (apical descent vs anterior vaginal wall elongation), including the frequency and site of failure. Secondary outcomes included displacement of the vaginal apex and perineal body and change in the length of the anterior wall, posterior wall, vaginal perimeter, and introitus of the vagina from rest to strain and rest to recovery. Group differences in the mechanism, frequency, and site of failure were assessed using the Fisher exact tests, and secondary outcomes were compared using Wilcoxon rank-sum tests.ResultsOf the 88 participants analyzed, 37 (42%) had recurrent prolapse (VM hysteropexy, 13 of 45 [29%]; native tissue repair, 24 of 43 [56%]). The most common site of failure was the anterior compartment (VM hysteropexy, 38%; native tissue repair, 92%). The primary mechanism of recurrence was apical descent (VM hysteropexy, 85%; native tissue repair, 67%). From rest to strain, failures (vs successes) had greater inferior displacement of the vaginal apex (difference, -12 mm; 95% confidence interval, -19 to -6) and perineal body (difference, -7 mm; 95% confidence interval, -11 to -4) and elongation of the anterior vaginal wall (difference, 12 mm; 95% confidence interval, 8-16) and vaginal introitus (difference, 11 mm; 95% confidence interval, 7-15).ConclusionThe primary mechanism of prolapse recurrence following vaginal hysterectomy with uterosacral ligament suspension or VM hysteropexy was apical descent. In addition, greater inferior descent of the vaginal apex and perineal body, lengthening of the anterior vaginal wall, and increased size of the vaginal introitus with strain were associated with anatomic failure. Further studies are needed to provide additional insight into the mechanism by which these factors contribute to anatomic failure.

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.

BackgroundLower urinary tract symptoms (LUTS) are common in children and adolescents. Non-invasive tests evaluating bladder function are generally preferred over invasive tests, yet few studies have explored the range of normative values for these tests in healthy, asymptomatic children.ObjectiveTo define normative reference ranges for non-invasive tests of bladder function in healthy, asymptomatic girls and adolescents.Study designA comprehensive search strategy was performed in seven electronic databases through October 2019. English-language studies reporting data on voiding frequency, voided and postvoid residual volumes (PVR) and uroflowmetry results in healthy, asymptomatic girls (mean age ≥ 5 years) were included. Two independent reviewers performed study review, data extraction, and quality assessment. Overall mean estimates and 95% confidence intervals for each bladder function parameter were calculated using random effects models, and 95% normative reference values were estimated.ResultsTen studies met eligibility criteria for the meta-analysis (n = 2143 girls, age range: 3-18). Mean estimates of maximum voided volume and PVR were 233.4 ml (95% CI 204.3-262.6; n = 1 study) and 8.6 ml (95% CI 4.8-12.4; n = 2 studies) respectively. Pooled mean estimates for uroflowmetry parameters were: 21.5 ml/s (95% CI 20.5-2.5) for maximum flow rate (n = 6 studies), 12.5 ml/s (95% CI 11.2-13.8) for mean flow rate (n = 6 studies), 6.8 s (95% CI 4.4-9.3) for time to maximum flow (n = 3 studies), 15.7 s (95% CI 13.0-18.5) for flow time (n = 3 studies), and 198.7 ml (95% CI 154.2-234.2) for voided volume (n = 9 studies). No studies reported estimates of voiding frequency. Between-study heterogeneity was high (89.0-99.6%).ConclusionsAlthough we were able to calculate pooled mean estimates for several parameters, the small number of included studies and the wide age ranges of participants preclude generalization of reference values to all healthy girls. Further research is needed to determine normative reference values within specific age groups.

PurposeWe 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 methodsQuestions 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.ResultsExisting 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.ConclusionsBladder 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.

ObjectivesThe 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.MethodsThis 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.ResultsWomen 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]).ConclusionsA higher dose of onabotulinumtoxinA may not directly result in improved outcomes, but rather baseline disease severity may be a more important prediction of outcomes.

ObjectivesWe 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).MethodsThis 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.ResultsThirty-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).ConclusionsCommonly prescribed forms of vaginal estrogen with contemporary dosing schedules prevent UTIs in postmenopausal women with an active diagnosis of rUTI.

ObjectivesThere 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.MethodsThis 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.ResultsA 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).ConclusionsIn this study, symptomatic SUI occurred more frequently in women with lower self-reported exercise levels 2 years after MUS surgery.

Introduction and hypothesisWe describe the responsiveness and minimally important difference (MID) of the Accidental Bowel Leakage Evaluation (ABLE) questionnaire.MethodsWomen with bowel leakage completed ABLE, Patient Global Impression of Improvement, Colo-Rectal Anal Distress Inventory, and Vaizey questionnaires pretreatment and again at 24 weeks post-treatment. Change scores were correlated between questionnaires. Student's t tests compared ABLE change scores for improved versus not improved based on other measures. The MID was determined by anchor- and distribution-based approaches.ResultsIn 266 women, the mean age was 63.75 (SD = 11.14) and 79% were white. Mean baseline ABLE scores were 2.32 ± 0.56 (possible range 1-5) with a reduction of 0.62 (SD = 0.79) by 24 weeks. ABLE change scores correlated with related measures change scores (r = 0.24 to 0.53) and differed between women who improved and did not improve (all p

AimsTo assess performance, acceptability, external validity, and reliability of a phone application electronic bowel diary (PFDN Bowel eDiary).MethodsWomen 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).ResultsPaired 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.ConclusionThe 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.

Introduction and hypothesisLimited data exist comparing different surgical approaches in women with advanced vaginal prolapse. This study compared 2-year surgical outcomes of uterosacral ligament suspension (ULS) and sacrospinous ligament fixation (SSLF) in women with advanced prolapse (stage III-IV) and stress urinary incontinence.MethodsThis was a secondary analysis of a multicenter 2 × 2 factorial randomized trial comparing (1) ULS versus SSLF and (2) behavioral therapy with pelvic floor muscle training versus usual care. Of 374 subjects, 117/188 (62.7%) in the ULS and 113/186 (60.7%) in the SSLF group had advanced prolapse. Two-year surgical success was defined by the absence of (1) apical descent > 1/3 into the vaginal canal, (2) anterior/posterior wall descent beyond the hymen, (3) bothersome bulge symptoms, and (4) retreatment for prolapse. Secondary outcomes included individual success outcome components, symptom severity measured by the Pelvic Organ Prolapse Distress Inventory, and adverse events. Outcomes were also compared in women with advanced prolapse versus stage II prolapse.ResultsSuccess did not differ between groups (ULS: 58.2% [57/117] versus SSLF: 58.5% [55/113], aOR 1.0 [0.5-1.8]). No differences were detected in individual success components (p > 0.05 for all components). Prolapse symptom severity scores improved in both interventions with no intergroup differences (p = 0.82). Serious adverse events did not differ (ULS: 19.7% versus SSLF: 16.8%, aOR 1.2 [0.6-2.4]). Success was lower in women with advanced prolapse compared with stage II (58.3% versus 73.2%, aOR 0.5 [0.3-0.9]), with no retreatment in stage II.ConclusionsSurgical success, symptom severity, and overall serious adverse events did not differ between ULS and SSLF in women with advanced prolapse. ClinicalTrials.gov Identifier: NCT01166373.

ObjectiveTo describe sexual activity and risks for dyspareunia after pelvic organ prolapse surgery.MethodsThis was a secondary analysis of data from four randomized trials conducted between 2002 and 2018. Standard assessments and validated measures of sexual function were assessed at baseline and at 12 months postoperatively. Anterior apical surgeries were grouped by approach: transvaginal native tissue repairs, transvaginal mesh or graft-augmented repairs, and abdominal sacrocolpopexy. Additional surgeries, which included posterior repair, hysterectomy, and slings, were analyzed. Bivariate analyses and logistic regression models identified risk factors for postoperative dyspareunia.ResultsOf the 1,337 women enrolled in the trials, 932 had sufficient outcome data to determine dyspareunia status. Of these before surgery, 445 (47.8%) were sexually active without dyspareunia, 89 (9.6%) were sexually active with dyspareunia, 93 (10.0%) were not sexually active owing to fear of dyspareunia, and 305 (32.7%) were not sexually active for other reasons. At 12 months, dyspareunia or fear of dyspareunia was present in 63 of 627 (10.0%); occurred de novo in 17 of 445 (3.8%) and resolved in 136 of 182 (74.7%). Multivariable regression demonstrated baseline dyspareunia as the only factor associated with postoperative dyspareunia (adjusted odds ratio 7.8, 95% CI 4.2-14.4). No other factors, including surgical approach, were significantly associated with postoperative dyspareunia. Too few had de novo dyspareunia to perform modeling.ConclusionDyspareunia is common in one in five women before undergoing prolapse surgery. Surgical repair resolves dyspareunia in three out of four women with low rates of de novo dyspareunia at less than 4%. Preoperative dyspareunia appears to be the only predictor of postoperative dyspareunia.Clinical trial registrationClinicalTrials.gov, NCT00065845, NCT00460434, NCT00597935, and NCT01802281.

Background: Little research to date has investigated the spectrum of bladder health in women, including both bladder function and well-being. Therefore, we expanded our previous baseline analysis of bladder health in the Boston Area Community Health (BACH) Survey to incorporate several additional measures of bladder-related well-being collected at the 5-year follow-up interview, including one developed specifically for women. Methods: At follow-up, participants reported their frequency of 15 lower urinary tract symptoms (LUTS), degree of life impact from and thought related to urinary symptoms or pelvic/bladder pain/discomfort, and perception of their bladder condition. Prevalence ratios were calculated by generalized linear models with robust variance estimation, adjusting for LUTS risk factors and individual LUTS. The BACH Survey was approved by the New England Research Institutes Institutional Review Board and all participants provided written informed consent. Results: Generally similar findings were observed in the 5-year cross-sectional analysis as at baseline, irrespective of how we categorized LUTS or measured bladder-related well-being. Approximately one in five women (16.2%-18.0% of 2527 eligible women) reported no LUTS and no diminished bladder-related well-being, the majority (55.8%-65.7%) reported some LUTS and/or diminished well-being, and a further one in five (16.9%-26.6%) reported the maximum frequency, number, or degree of LUTS and/or diminished well-being. Measures of storage function (urinating again after

This applied paper is intended to serve as a "how to" guide for public health researchers, practitioners, and policy makers who are interested in building conceptual models to convey their ideas to diverse audiences. Conceptual models can provide a visual representation of specific research questions. They also can show key components of programs, practices, and policies designed to promote health. Conceptual models may provide improved guidance for prevention and intervention efforts if they are based on frameworks that integrate social ecological and biological influences on health and incorporate health equity and social justice principles. To enhance understanding and utilization of this guide, we provide examples of conceptual models developed by the Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium. PLUS is a transdisciplinary U.S. scientific network established by the National Institutes of Health in 2015 to promote bladder health and prevent lower urinary tract symptoms, an emerging public health and prevention priority. The PLUS Research Consortium is developing conceptual models to guide its prevention research agenda. Research findings may in turn influence future public health practices and policies. This guide can assist others in framing diverse public health and prevention science issues in innovative, potentially transformative ways.

AimsPrior 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.MethodsHerein, 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.ResultsStrategies 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.ConclusionA 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.

PurposeSacral 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 methodsProspective 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.ResultsTwo-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

BackgroundQuestionnaires assessing accidental bowel leakage lack important patient-centered symptoms.ObjectiveWe aimed to create a valid measure of accidental bowel leakage symptoms.DesignWe 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.SettingsThe study was conducted in outpatient clinics.PatientsWomen with at least monthly accidental bowel leakage were included.InterventionsParticipants 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 measuresPsychometric analyses included Cronbach α, confirmatory factor, and item response theory analyses. Construct validity was based on correlations with measures of similar constructs.ResultsA 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).LimitationsThe study was limited by nature of involving validation in a care-seeking population.ConclusionsThe 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

BackgroundAlthough 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.ObjectiveTo 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 designThis 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.ResultsUrinary 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

Background/aimsIn this study, we compared two research consent techniques: a standardized video plus usual consent and usual consent alone.MethodsIndividuals who completed 24-month outcomes (completers) in the Operations and Pelvic Muscle Training in the Management of Apical Support Loss study were invited to participate in an extended, longitudinal follow-up study (extended Operations and Pelvic Muscle Training in the Management of Apical Support Loss). Potential participants who were (1) able to provide consent and (2) not in long-term care facilities were randomized 1:1 to a standardized video detailing the importance of long-term follow-up studies of pelvic floor disorders followed by the usual institutional consent process versus the usual consent process alone. Randomization, stratified by site, used randomly permuted blocks. The primary outcome was the proportion of participants who enrolled in the extended study and completed data collection events 5 years after surgery. Secondary outcomes included the proportion enrolled in the extended study, completion of follow-up at each study year, completion of data collection points, completion of in-person visits, and completion of quality of life calls. Motivation and barriers to enrollment (study-level and personal-level) and satisfaction with the study consent process were measured by questionnaire prior to recruitment into extended Operations and Pelvic Muscle Training in the Management of Apical Support Loss. Groups were compared using an intention-to-treat principle, using unadjusted Student's t-test (continuous) and chi-square or Fisher's exact (categorical) test. A sample size of 340 (170/group) was estimated to detect a 15% difference in enrollment and study completion between groups with p

ImportanceMixed urinary incontinence, including both stress and urgency incontinence, has adverse effects on a woman's quality of life. Studies evaluating treatments to simultaneously improve both components are lacking.ObjectiveTo determine whether combining behavioral and pelvic floor muscle therapy with midurethral sling is more effective than sling alone for improving mixed urinary incontinence symptoms.Design, setting, and participantsRandomized clinical trial involving women 21 years or older with moderate or severe stress and urgency urinary incontinence symptoms for at least 3 months, and at least 1 stress and 1 urgency incontinence episode on a 3-day bladder diary. The trial was conducted across 9 sites in the United States, enrollment between October 2013 and April 2016; final follow-up October 2017.InterventionsBehavioral and pelvic floor muscle therapy (included 1 preoperative and 5 postoperative sessions through 6 months) combined with midurethral sling (n = 209) vs sling alone (n = 207).Main outcomes and measuresThe primary outcome was change between baseline and 12 months in mixed incontinence symptoms measured by the Urogenital Distress Inventory (UDI) long form; range, 0 to 300 points; minimal clinically important difference, 35 points, with higher scores indicating worse symptoms.ResultsAmong 480 women randomized (mean [SD] age, 54.0 years [10.7]), 464 were eligible and 416 (86.7%) had postbaseline outcome data and were included in primary analyses. The UDI score in the combined group significantly decreased from 178.0 points at baseline to 30.7 points at 12 months, adjusted mean change -128.1 points (95% CI, -146.5 to -109.8). The UDI score in the sling-only group significantly decreased from 176.8 to 34.5 points, adjusted mean change -114.7 points (95% CI, -133.3 to -96.2). The model-estimated between-group difference (-13.4 points; 95% CI, -25.9 to -1.0; P = .04) did not meet the minimal clinically important difference threshold. Related and unrelated serious adverse events occurred in 10.2% of the participants (8.7% combined and 11.8% sling only).Conclusions and relevanceAmong women with mixed urinary incontinence, behavioral and pelvic floor muscle therapy combined with midurethral sling surgery compared with surgery alone resulted in a small statistically significant difference in urinary incontinence symptoms at 12 months that did not meet the prespecified threshold for clinical importance.Trial registrationClinicalTrials.gov Identifier: NCT01959347.

Standardized conditions for collection, preservation and storage of urine for microbiome research have not been established. We aimed to identify the effects of the use of preservative AssayAssure® (AA), and the effects of storage time and temperatures on reproducibility of urine microbiome results. We sequenced the V3-4 segment of the 16S rRNA gene to characterize the bacterial community in the urine of a cohort of women. Each woman provided a single voided urine sample, which was divided into aliquots and stored with and without AA, at three different temperatures (room temperature [RT], 4 °C, or -20 °C), and for various time periods up to 4 days. There were significant microbiome differences in urine specimens stored with and without AA at all temperatures, but the most significant differences were observed in alpha diversity (estimated number of taxa) at RT. Specimens preserved at 4 °C and -20 °C for up to 4 days with or without AA had no significant alpha diversity differences. However, significant alpha diversity differences were observed in samples stored without AA at RT. Generally, there was greater microbiome preservation with AA than without AA at all time points and temperatures, although not all results were statistically significant. Addition of AA preservative, shorter storage times, and colder temperatures are most favorable for urinary microbiome reproducibility.

AimTo report research terminology and definitions for describing healthy bladder function among women and girls.MethodsThe Prevention of Lower Urinary tract Symptoms (PLUS) Consortium developed research terminology and definitions for elements of healthy bladder function based on existing understanding of storage and emptying functions of the bladder and accepted definitions of lower urinary tract symptoms (LUTS). The novel concept of a bladder "bioregulatory" function was also proposed. Elements of bladder function corresponding to bladder health (BH) and LUTS were developed and refined using an iterative process. A comprehensive reference table structured by bladder function (Storage, Emptying, and Bioregulatory) and elements of each function was created to document proposed research terminology and definitions.ResultsThe BH research definitions for each bladder function are: (1) Storage: the ability to hold urine for a reasonable duration of time and sense bladder fullness without fear of or concern about urgency, discomfort or leakage; (2) Emptying: the ability to empty the bladder completely in a timely, efficient, effortless, comfortable manner; and (3) Bioregulatory: the bladder barrier protects the individual/host from pathogens, chemicals, and malignancy. Research definitions for seven Storage, seven Emptying, and three Bioregulatory elements of function are presented. Novel LUTS research definitions were developed when gaps in existing definitions were identified or nonclinical language was desired.ConclusionsPLUS BH definitions reflect a transdisciplinary approach to standardizing research definitions for elements of bladder function from a perspective of health rather than dysfunction and provide a framework for studying BH in clinical practice, public health promotion, and LUTS prevention.

Background: Little research to date has focused on lower urinary tract symptom (LUTS) prevention and bladder health promotion in women. To address this gap, the Prevention of LUTS Research Consortium developed the following working bladder health definition: "A complete state of physical, mental, and social well-being related to bladder function [that] permits daily activities [and] allows optimal well-being." To begin to inform and quantify this definition, we used data from the Boston Area Community Health Survey, drawing upon its rare collection of information on LUTS and LUTS-specific interference with activities. Methods: At baseline, participants reported their frequency of 15 LUTS and interference with 7 activities. Prevalence ratios (PRs) were calculated by generalized linear models with robust variance estimation, adjusting for LUTS risk factors and individual LUTS. Results: Of the 3169 eligible participants, 17.5% reported no LUTS or interference, whereas the remaining 82.5% reported some frequency of LUTS/interference: 15.1% rarely; 21.7% a few times; 22.6% fairly often/usually; and 22.9% almost always. LUTS independently associated with interference were urgency incontinence, any incontinence, urgency, nocturia, perceived frequency, and urinating again after

INTRODUCTION & HYPOTHESIS:Previous studies have suggested that women with urinary incontinence have an altered urinary microbiome. We hypothesized that the microbiome in women with mixed urinary incontinence (MUI) differed from controls and tested this hypothesis using bacterial gene sequencing techniques. METHODS:This multicenter study compared the urinary microbiome in women with MUI and similarly aged controls. Catheterized urine samples were obtained; v4-6 regions of the 16S rRNA gene were sequenced to identify bacteria. Bacterial predominance (> 50% of an individual's genera) was compared between MUI and controls. Bacterial sequences were categorized into "community types" using Dirichlet multinomial mixture (DMM) methods. Generalized linear mixed models predicted MUI/control status based on clinical characteristics and community type. Post-hoc analyses were performed in women < 51 and ≥ 51 years. Sample size estimates required 200 samples to detect a 20% difference in Lactobacillus predominance with P

Introduction: Uroflowmetry is often used to assess lower urinary tract symptoms (LUTS). Criteria for characterization of flow patterns are not well established, and subjective interpretation is the most common approach for flow curve classification. We assessed the reliability of uroflowmetry curve interpretation in adult women. Materials and Methods: Uroflowmetry studies were obtained in 296 women who participated in an observational cohort study. Four investigators with expertise in female LUTS and urodynamics reviewed and categorized each tracing for interrater reliability. A random subset of 50 tracings was re‐reviewed by each investigator for intrarater reliability. The uroflowmetry tracings were rated using categories of continuous, continuous fluctuating, interrupted, and prolonged. Other parameters included flow rate, voided volume, time to maximum flow, and voiding time. Agreement between raters is summarized with kappa (k) statistics and percentage where at least three raters agreed. Results: The mean age of participants was 44.8 ± 18.3 years. Participant age categories were 18–24 years: 20%; 25–34 years: 17%; 35–64 years: 42%; 65+ years: 18%. Nine percent described their race as Asian, 31% Black, 62% White, and 89% were of non‐Hispanic ethnicity. The interrater reliability was highest for the continuous flow category (k = 0.65), 0.47 for prolonged, 0.41 for continuous fluctuating, and 0.39 for interrupted flow curves. Agreement among at least three raters occurred in 74.3% of uroflow curves (69% for continuous, 33% for continuous fluctuating, 23% for interrupted, and 25% for prolonged). For intrarater reliability, the mean k was 0.72 with a range of 0.57–0.85. Conclusions: Currently accepted uroflowmetry pattern categories have fair to moderate interrater reliability, which is lower for flow curves that do not meet "continuous" criteria. Given the subjective nature of interpreting uroflowmetry data, more consistent and clear parameters may enhance reliability for use in research and as a screening tool for LUTS and voiding dysfunction. Trial Registration: Parent trial: Validation of Bladder Health Instrument for Evaluation in Women (VIEW); ClinicalTrials.gov ID: NCT04016298. [ABSTRACT FROM AUTHOR]

AimsThe Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium was established by the National Institutes of Health in 2015 to expand research beyond the detection and treatment of lower urinary tract symptoms (LUTS) to the promotion and preservation of bladder health and prevention of LUTS in girls and women. While many multi-disciplinary scientific networks focus on pelvic floor dysfunction and LUTS, the PLUS Consortium stands alone in its focus on prevention. This article describes the PLUS approach to developing a conceptual framework to guide the Consortium's initial prevention research agenda.MethodsThe conceptual framework was informed by traditional social ecological models of public health, biopsychosocial models of health, Glass and McAtee's Society-Behavior-Biology Nexus, and the World Health Organization's conceptual framework for action on the social determinants of health.ResultsThe PLUS conceptual framework provides a foundation for developing prevention interventions that have the greatest likelihood of promoting and preserving bladder health among diverse populations.ConclusionsPLUS Consortium work is premised on the notion that programs, practices, and policies designed to promote health will have optimal impact if the conceptual foundation upon which efforts are based is comprehensive and informed by multiple disciplines. The PLUS conceptual framework is broadly applicable to domains of health that have historically focused on the treatment of illness and symptoms rather than the promotion of health. It is also applicable to domains of health that have been examined from a predominantly biological or social ecological perspective, without integration of both perspectives.

ObjectiveTo develop statistical models predicting recurrent pelvic organ prolapse, surgical complications, and change in health status 12 months after apical prolapse surgery.MethodsLogistic regression models were developed using a combined cohort from three randomized trials and two prospective cohort studies from 1,301 participants enrolled in surgical studies conducted by the Pelvic Floor Disorders Network. Composite recurrent prolapse was defined as prolapse beyond the hymen; the presence of bothersome bulge symptoms; or prolapse reoperation or retreatment within 12 months after surgery. Complications were defined as any serious adverse event or Dindo grade III complication within 12 months of surgery. Significant change in health status was defined as a minimum important change of SF-6D utility score (±0.035 points) from baseline. Thirty-two candidate risk factors were considered for each model and model accuracy was measured using concordance indices. All indices were internally validated using 1,000 bootstrap resamples to correct for bias.ResultsThe models accurately predicted composite recurrent prolapse (concordance index=0.72, 95% CI 0.69-0.76), bothersome vaginal bulge (concordance index=0.73, 95% CI 0.68-0.77), prolapse beyond the hymen (concordance index=0.74, 95% CI 0.70-0.77), serious adverse event (concordance index=0.60, 95% CI 0.56-0.64), Dindo grade III or greater complication (concordance index=0.62, 95% CI 0.58-0.66), and health status improvement (concordance index=0.64, 95% CI 0.62-0.67) or worsening (concordance index=0.63, 95% CI 0.60-0.67). Calibration curves demonstrated all models were accurate through clinically useful predicted probabilities.ConclusionThese prediction models are able to provide accurate and discriminating estimates of prolapse recurrence, complications, and health status 12 months after prolapse surgery.

BACKGROUND:Bladder health in women and girls is poorly understood, in part, due to absence of a definition for clinical or research purposes. This article describes the process used by a National Institutes of Health funded transdisciplinary research team (The Prevention of Lower Urinary Tract Symptoms [PLUS] Consortium) to develop a definition of bladder health. METHODS:The PLUS Consortium identified currently accepted lower urinary tract symptoms (LUTS) and outlined elements of storage and emptying functions of the bladder. Consistent with the World Health Organization's definition of health, PLUS concluded that absence of LUTS was insufficient and emphasizes the bladder's ability to adapt to short-term physical, psychosocial, and environmental challenges for the final definition. Definitions for subjective experiences and objective measures of bladder dysfunction and health were drafted. An additional bioregulatory function to protect against infection, neoplasia, chemical, or biologic threats was proposed. RESULTS:PLUS proposes that bladder health be defined as: "A complete state of physical, mental, and social well-being related to bladder function and not merely the absence of LUTS. Healthy bladder function permits daily activities, adapts to short-term physical or environmental stressors, and allows optimal well-being (e.g., travel, exercise, social, occupational, or other activities)." Definitions for each element of bladder function are reported with suggested subjective and objective measures. CONCLUSIONS:PLUS used a comprehensive transdisciplinary process to develop a bladder health definition. This will inform instrument development for evaluation of bladder health promotion and prevention of LUTS in research and public health initiatives.

AIMS:Traditional technology to characterize urethral pressure changes during dynamic conditions is limited by slow response times or artifact-inducing withdrawal maneuvers. The 8F high-resolution manometry (HRM) catheter (ManoScan™ ESO, Covidien) has advantages of fast response times and the ability to measure urethral pressures along the urethral length without withdrawal. Our objective was to determine static and dynamic maximum urethral closure pressures (MUCPs) and resting functional urethral length (FUL) in women using HRM before and after transurethral bulking and compare results to other women who underwent midurethral sling (MUS). METHODS:We recorded rest, cough, and strain MUCPs and FUL in 24 women before and after transurethral bulking with polydimethylsiloxane (Macroplastique®) using the HRM catheter and compared these changes to HRM values from 26 women who had the same measures before and after MUS. RESULTS:At rest, MUCPs increased minimally after both urethral bulking and MUS (3 vs 0.4 cm H2 O respectively, P = 0.4). Under dynamic conditions there were statistically insignificant small increases in MUCP and these increases were markedly less than after MUS (cough: 1.5 vs 63.8 cm H2 O, P

Lower urinary tract symptoms (LUTS) are highly prevalent in women, and are expected to impose a growing burden to individuals and society as the population ages. The predominance of research related to LUTS has focused on underlying pathology, disease mechanisms, or the efficacy of treatments for women with LUTS. Although this research has been vital for helping to reduce or ameliorate LUTS conditions, it has done little to prevent the onset of LUTS. Health promotion and prevention require an expansion of scientific inquiry beyond the traditional paradigm of studying disease mechanisms and treatment to the creation of an evidence base to support recommendations for bladder health promotion and, in turn, prevention of LUTS. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) introduced the concept of prevention as an important priority for women's urologic research as a prelude to supporting the formation of the Prevention of Lower Urinary Tract Symptoms (PLUS) research consortium. In this article, we introduce the PLUS research consortium to the scientific community; share the innovative paradigms by which the consortium operates; and describe its unique research mission: to identify factors that promote bladder health across the life course and prevent the onset of LUTS in girls and women.

ObjectiveTo investigate whether infant temperament and childhood internalizing, externalizing, and inattention symptoms increase the likelihood of daytime urinary incontinence or nocturnal enuresis at 10 years and adolescence (11.9-17.8 years).MethodData were from a longitudinal cohort of 1119 healthy Chilean children. We assessed behavioral symptoms at infancy, 5 years, and 10 years and their relationship with subsequent daytime urinary incontinence and nocturnal enuresis.ResultsDaytime urinary incontinence and nocturnal enuresis occurred in, respectively, 3.3% and 11.4% at 10 years and 1.1% and 2.7% at adolescence. Difficult infant temperament was associated with increased odds of 10-year daytime urinary incontinence. Inattention at 5 years was associated with increased odds for nocturnal enuresis at 10 years and adolescence. Internalizing and externalizing symptoms at 5 years were associated with increased odds of 10-year daytime urinary incontinence and nocturnal enuresis. Internalizing and externalizing symptoms at 10 years were associated with adolescent nocturnal enuresis.ConclusionTemperament and internal/externalizing symptoms may be risk factors for school-age and adolescent urinary incontinence.

ImportanceUrinary incontinence, the involuntary loss of urine, is a common health condition that may decrease quality of life. Ten to twenty percent of women and up to 77% of women residing in nursing homes have urinary incontinence, yet only 25% seek or receive treatment.ObservationsThis review summarizes the evaluation and therapeutic options for women affected by urinary incontinence. The initial assessment should focus on understanding the effect of incontinence on quality of life, the patient's goals and preferences for treatment, the results of previous treatments, and the presence of concomitant conditions, such as advanced pelvic organ prolapse, that may require referral. Infection and hematuria need to be ruled out. In the absence of urinary infection or serious underlying pathology (such as cancer or serious neurologic disease) associated with urinary incontinence, the clinician should initiate unsupervised pelvic muscle exercises and lifestyle modifications appropriate to the patient to reduce her symptoms. These recommendations can include weight loss, adequate hydration, avoidance of excessive fluids, and regular voiding intervals that reduce urgency incontinence episodes. Urgency incontinence medications, with timely reassessment of symptoms, can be started without extensive evaluation. Specialist treatments for urgency incontinence include onabotulinumtoxinA and percutaneous or implanted neuromodulators. Stress incontinence surgery, the midurethral sling, is associated with symptom improvement in 48% to 90% of women and has low rates of mesh complications (

BackgroundWound complications (WC) following cesarean delivery (CD) result in significant morbidity. A randomized trial in 2013, which demonstrated lower WC rates with suture closure compared to staple closure, resulted in a practice change within our academic institution.ObjectiveTo determine the impact of this practice change on WC rates and identify other modifiable risk factors for WC.Study designThis is a retrospective cohort study of all women undergoing CD at the University of California, San Diego between 1 March 2011 and 28 February 2012 (primarily staple) and 1 March 2013 and 28 February 2014 (primarily suture). WC rates were compared between the two time intervals using Chi-square and Student's t-tests. Risk factors (OR, 95%CI) for WC were assessed using multiple logistic regression modeling.ResultsOf 1580 women delivered by CD, rates of WC were higher with staple closure compared to sutures (10.1% versus 4.5%; OR 2.4, 1.4-4.1). Additionally, WC were more likely with vertical skin incisions (OR 3.6, 1.6-8.1), CD for failed labor (OR 2.9, 1.1-7.4) and diabetes (OR 2.1, 1.4-3.9).ConclusionsAfter adjusting for confounders, there were over twofold increased odds of WC with staple closure. Vertical incisions, failed labor and diabetes also contributed to WC. Suture closure appears to decrease the risks of WC post CD.

To establish validity for the Pelvic Floor Disorders Network (PFDN) self-administered Adaptive Behavior Index (ABI) and to assess whether ABI assesses known discordance between severity of pelvic floor symptoms and self-reported bother.In addition to the ABI questionnaire, participants in 1 of 6 Pelvic Floor Disorders Network trials completed condition-specific measures of pretreatment symptom severity (including Pelvic Floor Distress Inventory; PFDI) and health-related quality of life (Pelvic Floor Impact Questionnaire; PFIQ). The final survey was developed from an iterative process using subject and expert endorsement, factor analyses, and response distributions. Domains were created using a development cohort (n = 304 women), reliability and validity were established using a validation cohort (n = 596 women), and test-retest reliability was assessed (n = 111 women).Factor analyses supported an 11-item avoidance domain and a 6-item hygiene domain. Cronbach' alphas were 0.88 and 0.68, respectively. Test-retest reliability was 0.84 for both domains. Construct validity was demonstrated in correlations between the ABI domains and baseline PFDI and PFIQ (r values, 0.43-0.79 with all P values

Introduction and hypothesisWe describe the rationale and methods of a study designed to compare vaginal and urinary microbiomes in women with mixed urinary incontinence (MUI) and similarly aged, asymptomatic controls.MethodsThis paper delineates the methodology of a supplementary microbiome study nested in an ongoing randomized controlled trial comparing a standardized perioperative behavioral/pelvic floor exercise intervention plus midurethral sling versus midurethral sling alone for MUI. Women in the parent study had at least "moderate bother" from urgency and stress urinary incontinence symptoms (SUI) on validated questionnaire and confirmed MUI on bladder diary. Controls had no incontinence symptoms. All participants underwent vaginal and urine collection for DNA analysis and conventional urine culture. Standardized protocols were designed, and a central lab received samples for subsequent polymerase chain reaction (PCR) amplification and sequencing of the bacterial16S ribosomal RNA (rRNA) gene. The composition of bacterial communities will be determined by dual amplicon sequencing of variable regions 1-3 and 4-6 from vaginal and urine specimens to compare the microbiome of patients with controls. Sample-size estimates determined that 126 MUI and 84 control participants were sufficient to detect a 20 % difference in predominant urinary genera, with 80 % power and 0.05 significance level.ResultsSpecimen collection commenced January 2015 and finished April 2016. DNA was extracted and stored for subsequent evaluation.ConclusionsMethods papers sharing information regarding development of genitourinary microbiome studies, particularly with control populations, are few. We describe the rigorous methodology developed for a novel urogenital microbiome study in women with MUI.

BackgroundFemale urinary microbiota are associated with urgency urinary incontinence and response to medication. The urinary microbiota of women with stress urinary incontinence has not been described.ObjectiveWe sought to study the cross-sectional relationships between urinary microbiota features and demographic and clinical characteristics of women undergoing stress urinary incontinence surgery.Study designPreoperative urine specimens were collected from women without urinary tract infection and were available from 197 women (174 voided, 23 catheterized) enrolled in a multicenter prospective randomized trial, the Value of Urodynamic Evaluation study. Demographic and clinical variables were obtained including stress and urgency urinary incontinence symptoms, menopausal status, and hormone use. The bacterial composition of the urine was qualitatively assessed by sequencing the bacterial 16S ribosomal RNA gene. Phylogenetic relatedness and microbial alpha diversity were compared to demographics and symptoms using generalized estimating equation models.ResultsThe majority of 197 urine samples (86%) had detectable bacterial DNA. Bacterial diversity was significantly associated with higher body mass index (P = .02); increased Medical, Epidemiologic, and Social Aspects of Aging urge index score (P = .04); and hormonal status (P < .001). No associations were detected with stress urinary incontinence symptoms. Increased diversity was also associated with a concomitant lower frequency of Lactobacillus in hormone-negative women.ConclusionWomen undergoing stress urinary incontinence surgery have detectable urinary microbiota. This cross-sectional analysis revealed that increased diversity of the microbiota was associated with urgency urinary incontinence symptoms, hormonal status, and body mass index. In contrast, the female urinary microbiota were not associated with stress urinary incontinence symptoms.

Introduction and hypothesisWe hypothesized that there would be a significant difference in changes in obstructed defecation symptoms and posterior compartment prolapse between women who underwent posterior vaginal wall prolapse repair (PR) and those who did not.MethodsThis was a two-site prospective cohort study of women undergoing prolapse or incontinence surgery in which a PR was, or was not, performed at the discretion of the surgeon. Women were assessed using validated obstructed defecation questionnaires and standardized examination measures (including POP-Q, measurement of transverse gh, and assessment for a rectovaginal pocket and laxity) prior to pelvic surgery and 12 weeks after surgery.ResultsOf 68 women who underwent surgery, 43 had PR. The PR group had higher obstructed defecation symptoms and greater posterior compartment prolapse at baseline. At 12 weeks, obstructed defecation symptoms had improved significantly more in the PR group than in the no PR group (all p

Introduction and hypothesisMixed urinary incontinence (MUI) can be a challenging condition to manage. We describe the protocol design and rationale for the Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence (ESTEEM) trial, designed to compare a combined conservative and surgical treatment approach versus surgery alone for improving patient-centered MUI outcomes at 12 months.MethodsESTEEM is a multisite, prospective, randomized trial of female participants with MUI randomized to a standardized perioperative behavioral/pelvic floor exercise intervention plus midurethral sling versus midurethral sling alone. We describe our methods and four challenges encountered during the design phase: defining the study population, selecting relevant patient-centered outcomes, determining sample size estimates using a patient-reported outcome measure, and designing an analysis plan that accommodates MUI failure rates. A central theme in the design was patient centeredness, which guided many key decisions. Our primary outcome is patient-reported MUI symptoms measured using the Urogenital Distress Inventory (UDI) score at 12 months. Secondary outcomes include quality of life, sexual function, cost-effectiveness, time to failure, and need for additional treatment.ResultsThe final study design was implemented in November 2013 across eight clinical sites in the Pelvic Floor Disorders Network. As of 27 February 2016, 433 total/472 targeted participants had been randomized.ConclusionsWe describe the ESTEEM protocol and our methods for reaching consensus for methodological challenges in designing a trial for MUI by maintaining the patient perspective at the core of key decisions. This trial will provide information that can directly impact patient care and clinical decision making.