Evolving to End a Toxic Relationship: ADP Ribosylation in Interbacterial Warfare.

Long before pathogenic interactions with eukaryotic cells evolved, bacteria were competing with one another for limited resources. In this issue, Ting et al. (2018) identify previously unappreciated players in the interbacterial arms race that may be the evolutionary ancestors of eukaryotic cell-targeting ADP-ribosyltransferase toxins.

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.

Physician awareness of patients' preferred level of involvement in decision-making at the initial urogynecology visit: a randomized trial.

BACKGROUND: Studies have shown up to a 40% discordance between patients' preferred roles in decision-making before and their perceived roles after their visit. This can negatively affect patients' experiences; interventions to minimize this discordance may significantly improve patient satisfaction. OBJECTIVE: We aimed to determine whether physicians' awareness of patients' preferred involvement in decision-making before their initial urogynecology visit affects patients' perceived level of involvement after their visit. STUDY DESIGN: This randomized controlled trial enrolled adult English-speaking women presenting for their initial visit at an academic urogynecology clinic from June 2022 to September 2022. Before the visit, participants completed the Control Preference Scale to determine the patient's preferred level of decision-making: active, collaborative, or passive. The participants were randomized to either the physician team being aware of their decision-making preference before the visit or usual care. The participants were blinded. After the visit, participants again completed a Control Preference Scale and the Patient Global Impression of Improvement, CollaboRATE, patient satisfaction, and health literacy questionnaires. Fisher exact, logistic regression, and generalized estimating equations were used. Based on a 21% difference in preferred and perceived discordance, we calculated the sample size to be 50 patients in each arm to achieve 80% power. RESULTS: Women (n=100) with a mean age of 52.9 years (standard deviation=15.8) participated in the study. Most participants identified as White (73%) and non-Hispanic (70%). Before the visit, most women preferred an active role (61%) and few preferred a passive role (7%). There was no significant difference between the 2 cohorts in the discordance between their pre- and post-Control Preference Scale responses (27% vs 37%; P=.39) or whether their symptoms were much better or very much better following the visit (18% vs 37%; P=.06). However, when asked whether they were completely satisfied with the visit, those assigned to the physician awareness cohort reported higher satisfaction than those in the treatment as usual cohort (100% vs 90%; P=.03). CONCLUSION: Although there was no significant decrease in discordance between the patient's desired and perceived level of decision-making following physician awareness, it had a significant effect on patient satisfaction. All patients whose physicians were aware of their preferences reported complete satisfaction with their visit. Although patient-centered care does not always entail meeting all of the patients' expectations, the mere understanding of their preferences in decision-making can lead to complete patient satisfaction.

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.

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.

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 patient burden of nocturnal polyuria in the United States: Results from the epidemiology of nocturnal polyuria (EpiNP) study.

OBJECTIVES: To explore the impact of nocturnal polyuria (NP) on health-related quality of life (HRQoL), work productivity, mental health, fatigue, bother, and daytime sleepiness. MATERIALS AND METHODS: This large-scale, US population-representative epidemiologic study was conducted in two parts: a web-based survey and 3-day bladder diary. Consenting participants completed the baseline Epidemiology of NP (EpiNP) survey online (Lower Urinary Tract Symptoms [LUTS] Tool, comorbidities, burden, and multiple HRQoL measures). Participants who reported ≥2 voids/night, and a random sample of 100 respondents each reporting 0 or 1 void/night, were sent urine measurement containers and asked to complete the 3-day bladder diary. NP was defined as Nocturnal Polyuria Index >0.33 (NPI33) or nocturnal urine production >90 ml/h (NUP90). Five subgroups were created: Idiopathic NP (NP with no underlying cause), NP associated with symptoms of overactive bladder (NPOAB) or bladder outlet obstruction (NPBOO; men only), NP associated with other comorbidities (NPCOM; e.g., diabetes, hypertension, heart disease, sleep apnea), and no NP (did not meet NP criteria). RESULTS: A total of 4893 men and 5297 women completed the EpiNP survey; mean age was 54.4 (SD = 14.7). Significantly greater patient burden (p < 0.0001) was evidenced in the nocturia group (≥2 voids/night) versus no nocturia group (0-1 void/night) on daily impact of nocturia, LUTS Bother, prostate symptoms (men only), work productivity, physical and mental health component scores, depression, fatigue, and daytime sleepiness. NP subgroup analyses showed men in the NPBOO group and women in the NPOAB group reported the greatest impact on LUTS bother, fatigue, physical health, work productivity impairment, daytime sleepiness, and depression (women only). CONCLUSION: This was the first large-scale, epidemiologic study to explore the impact of different forms of NP on patients' HRQoL. Findings demonstrate that NP associated with other urologic or comorbid conditions appears to have greater patient burden than idiopathic NP, in particular for women.

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.

Urobiome changes differ based on OAB treatment in adult females.

INTRODUCTION AND HYPOTHESIS: Representatives of two classes of oral medication are often used to treat urgency urinary incontinence (UUI): solifenacin, an M3-receptor-selective antimuscarinic, and mirabegron, a beta-3 agonist. Two previous asynchronous drug-specific studies suggested different interactions between these medications and the urobiome despite identical methodologies, including recruitment, sample procurement, medication dose escalation strategy, determination of 12-week responders versus nonresponders, and data collection. This analysis compares data from these two studies using a uniform analytic approach. METHODS: Urine was collected aseptically via transurethral catheter from consenting participants for subsequent processing by the Expanded Quantitative Urine Culture (EQUC) protocol in two cohorts (n=50 and n=47) that were demographically similar. Species accumulation curves were generated to compare the total number of unique species detected. Indices that measure richness, evenness, and/or abundance were used to compare alpha (within sample) diversity. The Bray-Curtis Dissimilarity Index was used to determine between sample (beta) diversity. RESULTS: The majority of the 40 species detected in the pre-treatment urobiomes were detected in both cohorts. Both pre-treatment urobiomes were substantially similar in species richness, evenness, and diversity. Differences in pre-treatment urobiomes were associated with treatment response for solifenacin-treated participants only. In contrast, the pre-treatment urobiomes of mirabegron-treated participants were not associated with treatment response. Changes in the post-treatment urobiomes were detected in both cohorts with an increase in richness for both solifenacin (5-mg dose only) and mirabegron. CONCLUSIONS: Pre-treatment urobiome characteristics were associated with treatment response in participants treated with solifenacin, but not mirabegron. Differences exist in urobiome response after treatment with two medications that have known differences in mechanism of action.

Nocturnal polyuria in women: results from the EpiNP study.

INTRODUCTION AND HYPOTHESIS: Data from a large US population-based, cross-sectional, epidemiological study (the EpiNP Study) were used to assess the symptoms and bother experienced by women with nocturnal polyuria (NP). METHODS: Consenting participants recruited from an online panel completed the baseline EpiNP survey online (Lower Urinary Tract Symptoms Tool and urological comorbidities). All reporting ≥2 voids/night and a random sample of 100 respondents, each reporting 0 or 1 void/night were asked to complete a 3-day web-based bladder diary recording time, volume, and urgency rating of each void. NP was calculated by the proportion of urine production that occurred during nocturnal hours using a Nocturnal Polyuria Index (NPI33) threshold of >0.33 or nocturnal urine production of >90 ml/h (NUP90). The frequency of participants reporting LUTS and bother was determined by age and NP: idiopathic NP, NP associated with overactive bladder (NPOAB), NP associated with comorbidities (NPCom), and no NP (did not meet NP criteria). RESULTS: A total of 5,290 women completed the baseline survey. Mean age (range) was 54.9 (30-95) years; 1,841 (34.8%) reported ≥2 nocturnal voids. The prevalence of LUTS increased across the lifespan; however, bother associated with each LUTS decreased with increasing age. The percentage of women rating bother by nocturia episodes ≥2 "> somewhat" ranged from 40.3% to 68.3%, with bother ratings highest in the NPOAB and No NP groups. CONCLUSIONS: NP is prevalent in women with considerable bother and is often associated with other urinary symptoms. Multifactorial causes and potential treatments of NP should be considered, particularly at a later age.

pH-dependent activation of cytokinesis modulates Escherichia coli cell size.

Cell size is a complex trait, derived from both genetic and environmental factors. Environmental determinants of bacterial cell size identified to date primarily target assembly of cytosolic components of the cell division machinery. Whether certain environmental cues also impact cell size through changes in the assembly or activity of extracytoplasmic division proteins remains an open question. Here, we identify extracellular pH as a modulator of cell division and a significant determinant of cell size across evolutionarily distant bacterial species. In the Gram-negative model organism Escherichia coli, our data indicate environmental pH impacts the length at which cells divide by altering the ability of the terminal cell division protein FtsN to localize to the cytokinetic ring where it activates division. Acidic environments lead to enrichment of FtsN at the septum and activation of division at a reduced cell length. Alkaline pH inhibits FtsN localization and suppresses division activation. Altogether, our work reveals a previously unappreciated role for pH in bacterial cell size control.

The active repertoire of Escherichia coli peptidoglycan amidases varies with physiochemical environment.

Nearly all bacteria are encased in peptidoglycan, an extracytoplasmic matrix of polysaccharide strands crosslinked through short peptide stems. In the Gram-negative model organism Escherichia coli, more than 40 synthases and autolysins coordinate the growth and division of the peptidoglycan sacculus in the periplasm. The precise contribution of many of these enzymes to peptidoglycan metabolism remains unclear due to significant apparent redundancy, particularly among the autolysins. E. coli produces three major LytC-type-N-acetylmuramoyl-L-alanine amidases, which share a role in separating the newly formed daughter cells during cytokinesis. Here, we reveal two of the three amidases that exhibit growth medium-dependent changes in activity. Specifically, we report acidic growth conditions stimulate AmiB-and to a lesser extent, AmiC-amidase activity. Combining genetic, biochemical, and computational analyses, we demonstrate that low pH-dependent stimulation of AmiB is mediated through the periplasmic amidase activators NlpD, EnvC, and ActS (formerly known as YgeR). Although NlpD and EnvC promote amidase activity across pH environments, ActS preferentially stimulates AmiB activity in acidic conditions. Altogether, our findings support partially overlapping roles for E. coli amidases and their regulators in cell separation and illuminate the physiochemical environment as an important mediator of cell wall enzyme activity.

Differences in the Prevalence of Nocturnal Polyuria in the U.S. by Definition: Results from the Epidemiology of Nocturnal Polyuria Study.

PURPOSE: Prevalence data on nocturnal polyuria (NP), nocturia caused by overproduction of urine during sleep, is primarily limited to men and varies by NP definition. This U.S.-representative epidemiological study of men and women ≥30 years old assessed the prevalence of NP. MATERIALS AND METHODS: Consenting participants completed the baseline EpiNP (Epidemiology of Nocturnal Polyuria) survey (eg Lower Urinary Tract Symptoms Tool, comorbidities). All reporting ≥2 voids/night and a target of 100 random respondents reporting 0 or 1 void/night were asked to complete 3-day bladder diaries. NP was defined as nocturnal polyuria index (NPI) >0.33 (NPI33) and nocturnal urine production >90 ml/hour (NUP90). Extrapolated prevalence was stratified by sex and subgroups: idiopathic (without underlying causes), associated with overactive bladder (NPOAB), bladder outlet obstruction (NPBOO; men) and comorbidities. Voided volumes and timing, including first uninterrupted sleep period, were assessed by subgroup. RESULTS: A total of 10,190 individuals completed the baseline survey; mean age (range) was 54.4 (30-95). A total of 3,938 individuals were invited to complete the diary; 1,763 (49.3%) completed 3-day bladder diaries. Urine production (maximum nighttime volume, total volume, nocturnal urine production, nocturia index) was higher in both men and women with idiopathic NP and comorbidities. The median number of nighttime voids was greatest for NPBOO in men and NPOAB in women. Bother associated with nighttime voiding differed by NP subgroup but was highest in NPBOO for men (NPI33: 69.6%; NUP90: 71.1%) and NPOAB for women (NPI33: 67.5%; NUP90: 66.0%). CONCLUSIONS: This population-based NP prevalence study including men and women characterizes NP subgroups and provides insights into nocturia treatment by emphasizing factors influencing urine production versus factors influencing bladder capacity.

Symptom improvement with mirabegron treatment is associated with urobiome changes in adult women.

INTRODUCTION AND HYPOTHESIS: Mirabegron, a beta-3 agonist, is prescribed for urgency urinary incontinence (UUI). We assessed the correlation of symptom improvement with urobiome characteristics in adult women participants prescribed mirabegron for UUI treatment. METHODS: We enrolled participants seeking UUI treatment who selected mirabegron and agreed to participate in this 12-week, open label study conducted at the Female Pelvic Medicine and Reconstructive Surgery Center at Loyola University Medical Center. Following eligibility screening and research consent, participants completed the overactive bladder questionnaire (OAB-Q) and provided a catheterized urine sample at baseline, 4, 8, and 12 weeks. The primary outcome, symptom improvement at 12 weeks, was based on the validated Patient Global Symptom Control questionnaire score to dichotomize symptom response (responder vs nonresponder [PGSC score ≤3]). Urine samples were processed by the Expanded Quantitative Urine Culture (EQUC) protocol. RESULTS: Eighty-three participants (mean age 68 years) completed baseline assessment. Of the 47 participants with primary outcome data and samples analysis, there were 16 responders and 31 nonresponders; responder groups were similar demographically. Living microbes were detected in most participants. There were no significant differences in alpha diversity (within sample) at baseline between groups. However, at the 12-week follow-up, the responder urobiome became significantly richer, with a larger number of genera (p = 0.027) and was significantly more diverse than the nonresponders. CONCLUSIONS: Longitudinal urobiome changes are associated with symptom improvement in adult women being treated with mirabegron for UUI. The mechanism for symptoms improvement may relate to the detected changes in the urobiome and warrants further study.

A Randomized Clinical Trial of Standard versus Expanded Cultures to Diagnose Urinary Tract Infections in Women.

PURPOSE: We compared urinary tract infection (UTI) symptom resolution rates at 7-10 days in symptomatic women randomized to treatment based on standard urine culture (SUC) versus expanded quantitative urine culture (EQUC) results. MATERIALS AND METHODS: Women ≥18 years old who responded "yes" to "do you feel you have a UTI?" agreed to urethral catheterization and followup. Symptoms were assessed using the validated UTI Symptom Assessment (UTISA) questionnaire. Culture method was randomized 2:1 (SUC:EQUC); antibiotics were prescribed to women with positive cultures. The primary outcome, UTI symptom resolution, was determined 7-10 days following enrollment on all participants regardless of treatment. RESULTS: Demographic data were similar between groups. Of the SUC and EQUC groups 63% and 74% had positive cultures (p=0.10), respectively. Of participants with positive cultures 97% received antibiotics. Primary outcome data were provided by 215 of 225 participants (SUC 143 [95%], EQUC 72 [97%]). At the primary outcome assessment, 64% and 69% in the SUC and EQUC groups, respectively, reported UTI symptom resolution (p=0.46); UTISA scores improved from baseline in the EQUC arm compared to the SUC arm (p=0.04). In the subset of women predominated by non-Escherichia coli (76), there was a trend toward more symptom resolution in the EQUC arm (21%, p=0.08). CONCLUSIONS: Symptom resolution was similar for the overall population (E. coli and non-E. coli) of women treated for UTI symptoms based on SUC or EQUC. Although the sample size limits conclusions regarding the utility of EQUC in women with non-E. coli uropathogens, the detected trend indicates that this understudied clinical subset warrants further study.

Urinary retention is rare after colpocleisis and concomitant midurethral sling: a 10-year experience.

OBJECTIVES: The optimal method of managing stress urinary incontinence (SUI) in women undergoing colpocleisis remains unclear, especially in a setting of urinary retention. We aim to compare postoperative retention after colpocleisis with or without concomitant midurethral sling (MUS). METHODS: A retrospective chart review of all women who underwent colpocleisis with or without MUS from October 2007 to October 2017 was performed. Women with preoperative and 2-week postoperative post-void residual volume (PVR) measurements were included. Urinary retention was defined as PVR of ≥100 ml. Analysis included t tests/Wilcoxon rank, Chi-squared/Fisher's exact, and multivariate linear regression models. RESULTS: A total of 231 women with a mean age of 77.7 years (± 6.0 years SD) met the inclusion criteria. One hundred and thirty-eight women underwent colpocleisis alone, whereas 93 women had colpocleisis with MUS. Preoperative retention rates were high (44.9% vs 34.4%, for colpocleisis alone versus with MUS, p = 0.114). Postoperative retention rates were lower and similar between the groups (10.1% vs 11.8%, for colpocleisis alone vs with MUS, p = 0.69). Linear regression models showed the adjusted odds ratio for postoperative urinary retention in patients with concomitant MUS was 1.68 (95% confidence interval: 0.64-4.41) compared with patients with colpocleisis alone and this did not reach statistical significance (p = 0.292). Fortunately, after colpocleisis, women had high rates of resolution of retention, regardless of MUS (80.3% vs 90.6% for colpocleisis alone vs with MUS; p = 0.20). Few women required reoperation for retention (3.1%). CONCLUSIONS: Placement of an MUS at the time of colpocleisis is a safe and effective therapy. This appears to be unaffected by preoperative urinary retention status.

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 ).

The Urethral Microbiota: A Missing Link in the Female Urinary Microbiota.

PURPOSE: We examined the urethral microbiota, determined if it differs from the bladder urinary microbiota, and assessed if its composition differs based on patient demographic factors and presence of lower urinary tract symptoms. MATERIALS AND METHODS: Patients presenting to our urogynecology clinic were enrolled in the study. Demographic information and responses to the Pelvic Floor Distress Inventory questionnaire were collected. All participants provided midstream voided urine, periurethral swab, transurethral swab and catheterized urine samples, which were analyzed by Expanded Quantitative Urine Culture and MALDI-TOF mass spectrometry. Bray-Curtis dissimilarity analysis assessed diversity between sample types for each participant. Kruskal-Wallis, chi-square, McNemar, Wilcoxon signed rank and Fisher's exact tests tested for significance. RESULTS: A total of 49 patients participated in the study. Bladder microbiota were dissimilar to urethral, periurethral and voided urine microbiota (p <0.0001). Urethral and periurethral microbiota were similar (p >0.05), but the urethral microbiota were dissimilar to voided urine microbiota (p=0.001) while the periurethral microbiota were not (p >0.05). Women less than 55 years old were more likely to be sexually active, premenopausal and Hispanic compared to women 55 years old or older. Women in the younger cohort had Lactobacillus and Gardnerella cultured from urethral samples more frequently and more abundantly than women in the older cohort. There was no significant association between lower urinary tract symptoms and the frequency or abundance of urethral bacteria species. CONCLUSIONS: Niches of microbiota along the female lower urinary tract may be influenced by age, menopausal status and sexual activity. More research is needed to determine the function and clinical significance of the urethral microbiome.

Vaginal estrogen therapy is associated with increased Lactobacillus in the urine of postmenopausal women with overactive bladder symptoms.

BACKGROUND: Previous work has shown that the vaginal microbiome decreases in Lactobacillus predominance and becomes more diverse after menopause. It has also been shown that estrogen therapy restores Lactobacillus dominance in the vagina and that topical estrogen is associated with overactive bladder symptom improvement. We now know that the bladder contains a unique microbiome and that increased bladder microbiome diversity is associated with overactive bladder. However, there is no understanding of how quickly each pelvic floor microbiome responds to estrogen or if those changes are associated with symptom improvement. OBJECTIVE: This study aimed to determine if estrogen treatment of postmenopausal women with overactive bladder decreases urobiome diversity. STUDY DESIGN: We analyzed data from postmenopausal participants in 2 trials (NCT02524769 and NCT02835846) who chose vaginal estrogen as the primary overactive bladder treatment and used 0.5 g of conjugated estrogen (Premarin cream; Pfizer, New York City, NY) twice weekly for 12 weeks. Baseline and 12-week follow-up data included the Overactive Bladder questionnaire, and participants provided urine samples via catheter, vaginal swabs, perineal swabs, and voided urine samples. Microbes were detected by an enhanced culture protocol. Linear mixed models were used to estimate microbiome changes over time. Urinary antimicrobial peptide activity was assessed by a bacterial growth inhibition assay and correlated with relative abundance of members of the urobiome. RESULTS: In this study, 12 weeks of estrogen treatment resulted in decreased microbial diversity within the vagina (Shannon, P=.047; Richness, P=.043) but not in the other niches. A significant increase in Lactobacillus was detected in the bladder (P=.037) but not in the vagina (P=.33), perineum (P=.56), or voided urine (P=.28). The change in Lactobacillus levels in the bladder was associated with modest changes in urgency incontinence symptoms (P=.02). The relative abundance of the genus Corynebacterium correlated positively with urinary antimicrobial peptide activity after estrogen treatment. CONCLUSION: Estrogen therapy may change the microbiome of different pelvic floor niches. The vagina begins to decrease in diversity, and the bladder experiences a significant increase in Lactobacillus levels; the latter is correlated with a modest improvement in the symptom severity subscale of the Overactive Bladder questionnaire.

Bladder bacterial diversity differs in continent and incontinent women: a cross-sectional study.

BACKGROUND: Since the discovery of the bladder microbiome (urobiome), interest has grown in learning whether urobiome characteristics have a role in clinical phenotyping and provide opportunities for novel therapeutic approaches for women with common forms of urinary incontinence. OBJECTIVE: This study aimed to test the hypothesis that the bladder urobiome differs among women in the control cohort and women affected by urinary incontinence by assessing associations between urinary incontinence status and the cultured urobiome. STUDY DESIGN: With institutional review board oversight, urine specimens from 309 adult women were collected through transurethral catheterization. These women were categorized into 3 cohorts (continent control, stress urinary incontinence [SUI], and urgency urinary incontinence [UUI]) based on their responses to the validated Pelvic Floor Distress Inventory (PFDI) questionnaire. Among 309 women, 150 were in the continent control cohort, 50 were in the SUI cohort, and 109 were in the UUI cohort. Symptom severity was assessed by subscale scoring with the Urinary Distress Inventory (UDI), subscale of the Pelvic Floor Distress Inventory. Microbes were assessed by expanded quantitative urine culture protocol, which detects the most common bladder microbes (bacteria and yeast). Microbes were identified to the species level by matrix-assisted laser desorption and ionization time-of-flight mass spectrometry. Alpha diversity indices were calculated for culture-positive samples and compared across the 3 cohorts. The correlations of UDI scores, alpha diversity indices, and species abundance were estimated. RESULTS: Participants had a mean age of 53 years (range 22-90); most were whites (65%). Women with urinary incontinence were slightly older (control, 47; SUI, 54; UUI, 61). By design, UDI symptom scores differed (control, 8.43 [10.1]; SUI, 97.95 [55.36]; UUI, 93.71 [49.12]; P<.001). Among 309 participants, 216 (70%) had expanded quantitative urine culture-detected bacteria; furthermore, the urinary incontinence cohorts had a higher detection frequency than the control cohort (control, 57%; SUI, 86%; UUI, 81%; P<.001). In addition, the most frequently detected species among the cohorts were as follows: continent control, Lactobacillus iners (12.7%), Streptococcus anginosus (12.7%), L crispatus (10.7%), and L gasseri (10%); SUI, S anginosus (26%), L iners (18%), Staphylococcus epidermidis (18%), and L jensenii (16%); and UUI, S anginosus (30.3%), L gasseri (22%), Aerococcus urinae (18.3%), and Gardnerella vaginalis (17.4%). However, only Actinotignum schaalii (formerly Actinobaculum schaalii), A urinae, A sanguinicola, and Corynebacterium lipophile group were found at significantly higher mean abundances in 1 of the urinary incontinence cohorts when compared with the control cohort (Wilcoxon rank sum test; P<.02), and no individual genus differed significantly between the 2 urinary incontinence cohorts. Both urinary incontinence cohorts had increased alpha diversity similar to continent control cohort with indices of species richness, but not evenness, strongly associated with urinary incontinence. CONCLUSION: In adult women, the composition of the culturable bladder urobiome is associated with urinary incontinence, regardless of common incontinence subtype. Detection of more unique living microbes was associated with worsening incontinence symptom severity. Culturable species richness was significantly greater in the urinary incontinence cohorts than in the continent control cohort.