First and Second Stage Risk Factors Associated with Perineal Lacerations.

OBJECTIVE: To determine intrapartum factors associated with perineal laceration at delivery. METHODS: This was a planned secondary analysis of a multicenter randomized clinical trial of delayed versus immediate pushing among term nulliparous women in labor with neuraxial analgesia conducted in the United States. Intrapartum characteristics were extracted from the medical charts. The primary outcome was perineal laceration, defined as second degree or above, characterized at delivery in women participating in longer term pelvic floor assessments post-delivery. Multivariable logistic regression was used to refine risk estimates while adjusting for randomization group, birth weight, and maternal age. RESULTS: Among the 941 women participating in the pelvic floor follow-up, 40.6% experienced a perineal laceration. No first stage labor characteristics were associated with perineal laceration, including type of labor or length of first stage. Receiving an amnioinfusion appeared protective of perineal laceration (adjusted odds ratio, 0.48; 95% confidence interval 0.26-0.91; P = 0.01). Second stage labor characteristics associated with injury were length of stage (2.01 h vs. 1.50 h; adjusted odds ratio, 1.36; 95% confidence interval 1.18-1.57; P < 0.01) and a prolonged second stage (adjusted odds ratio, 1.64; 95% confidence interval 1.06-2.56; P < 0.01). Operative vaginal delivery was strongly associated with perineal laceration (adjusted odds ratio, 3.57; 95% confidence interval 1.85-6.90; P < 0.01). CONCLUSION: Operative vaginal delivery is a modifiable risk factor associated with an increased risk of perineal laceration. Amnioinfusion appeared protective against injury, which could reflect a spurious finding, but may also represent true risk reduction similar to the mechanism of warm perineal compress.

Complete Bladder Eversion after Colpocleisis.

BACKGROUND: Because complete urinary bladder eversion is rare, a medical dilemma exists on the optimal treatment approach. The most extensive cases of this disorder have required a laparotomy for definitive management. Our transvaginal approach in this case provides an additional surgical perspective, which could potentially guide clinical care for patients with this disorder. CASE: We cared for a 76-year-old multiparous, postmenopausal woman with transurethral bladder eversion following a Le Fort colpocleisis, who presented with vaginal pain, bleeding, and renal failure. We used a transvaginal surgical approach rather than laparotomy as a novel surgical approach for treatment of the bladder eversion, which resulted in improved symptoms and renal function. We describe our diagnostic and decision making approach used for the care of this unique patient. CONCLUSION: Transvaginal bladder neck closure and suprapubic catheter placement is an acceptable and less invasive alternative to the laparotomy with cystopexy for the surgical management of recurrent bladder eversion.

Understanding the Pursuit of Third-Line Therapies for Overactive Bladder: A Mixed Methods Study.

IMPORTANCE: Overactive bladder (OAB) affects millions of women in the United States, with negative effects in multiple domains that have an impact on quality of life. Third-line therapies for OAB are as effective or superior to lifestyle/behavior modification and medical management, yet few women access these treatments and often spend more than 36 months to reach these treatments after starting medication. Factors associated with time to reach third-line therapy are not well studied, and little is known about how patients progress through care pathways for OAB. OBJECTIVES: The aim of the study was to determine factors associated with the time spent between second- and third-line therapy for OAB at an academic urogynecology and reconstructive pelvic surgery practice. We sought to identify demographic, treatment, clinical factors, and themes in barriers to receiving treatment for OAB. STUDY DESIGN: This was a mixed methods study consisting of a retrospective cohort study followed by qualitative key informant interviews. RESULTS: Eighty-five total participants were included in the analysis, and 42 (49.5%) spent more than 36 months between initiation of medical management and initial third-line therapy for OAB. No significant (P > 0.05) demographic, clinical, or treatment differences were found between groups. Facilitators and obstacles to receiving third-line therapy were identified among key informants, and a treatment decision framework was developed. CONCLUSIONS: Women often spend more than 36 months to pursue third-line therapy for OAB. Existing objective variables are poor predictors of pursuit of third-line treatment, and leveraging known facilitators and obstacles can be used to develop improved care pathways for OAB.

Impact of the Duration of the Second Stage of Labor on Postpartum Pelvic Floor Symptoms.

IMPORTANCE: The associated effect of duration of the second stage of labor (SSL) on pelvic floor symptoms development is not well studied. OBJECTIVE: This study aimed to examine the association between duration of SSL and pelvic floor symptoms at 6 months postpartum among primiparous women. STUDY DESIGN: A planned secondary analysis of a multicenter randomized trial evaluating the impact of immediate versus delayed pushing on vaginal delivery rates, maternal morbidity, and neonatal outcomes was conducted between 2014 and 2018. For pelvic floor arm participants, demographic, pelvic examination, and validated questionnaire data were collected postpartum. Primary outcome was change in Pelvic Floor Distress Inventory 20 (PFDI-20) score from immediate to 6 months postpartum. Secondary outcomes included changes in the Pelvic Floor Impact Questionnaire, Fecal Incontinence Severity Index, Modified Manchester Health Questionnaire scores, and Pelvic Organ Prolapse Quantification measurements at 6 months postpartum. Participants were analyzed by SSL duration ≤60 minutes or >60 minutes. RESULTS: Of the 2,414 trial participants, 767 (32%) completed pelvic floor assessments at 6 months. Pelvic Floor Distress Inventory 20 scores significantly improved at 6 months in the ≤60 minutes SSL group compared with >60 minutes SSL (-14.3 ± 48.0 and -3.2 ± 45.3, respectively; P = 0.04). Changes from immediate postpartum in total and subscale scores for other questionnaires at 6 months did not differ between groups. Prolapse stage did not differ between groups. Perineal body was significantly shorter in the >60 minutes SSL group (3.7 ± 0.7, 3.5 ± 0.8; P = 0.03). CONCLUSIONS: Women with SSL >60 minutes experience less improvement in PFDI-20 scores at 6 months. Greater tissue and innervation trauma in those with SSL >60 minutes may explain persistently less improvement in PFDI-20 scores.

Longitudinal Reoperation Risk After Apical Prolapse Procedures in Women Aged 65 Years and Older.

OBJECTIVE: To describe longitudinal reoperation risk among older women undergoing surgery for apical pelvic organ prolapse (POP) and to compare risk of reoperation for prolapse and complications among different surgical approaches. METHODS: This nationwide, retrospective cohort study evaluated older adult women (aged 65 years and older) within the Centers for Medicare & Medicaid Services' (CMS) 5% LDS (Limited Data Set) who underwent sacrocolpopexy, uterosacral ligament suspension (USLS), sacrospinous ligament fixation (SSLF), or colpocleisis, or their uterine-preserving equivalents, from January 1, 2011, to December 31, 2018, with follow-up through 2019. The primary outcome was overall reoperation, and secondary outcomes included reoperation for POP and for complications. Rates were compared using χ 2 tests for categorical variables, Wilcoxon rank-sum for continuous variables and Kaplan Meier estimates of cumulative incidence. Death and exit from CMS insurance were considered as censoring events. We used cumulative incidence to calculate reoperation risk as a function of time at 1 year or more, 3 years or more, and 7 years or more. RESULTS: This cohort included 4,089 women who underwent surgery to treat apical POP from 2011 to 2018: 1,034 underwent sacrocolpopexy, 717 underwent USLS, 1,529 underwent SSLF, and 809 underwent colpocleisis. Demographics varied among patients for each POP surgery. Patients who underwent the different surgeries had differences in age ( P <.01), Charlson Comorbidity Index score ( P <.01), diabetes ( P <.01), chronic obstructive pulmonary disease ( P <.01), hypertension ( P <.01), chronic pain ( P =.01), congestive heart failure ( P <.01), and concomitant hysterectomy ( P <.01). Reoperation rates were low and increased over time. The overall reoperation risk through 7 years was 7.3% for colpocleisis, 10.4% for USLS, 12.5% for sacrocolpopexy, and 15.0% for SSLF ( P <.01). Reoperation for recurrent POP through 7 years was 2.9% for colpocleisis, 7.3% for sacrocolpopexy, 7.7% for USLS, and 9.9% for SSLF ( P <.01). Reoperation for complications through 7 years was 5.3% for colpocleisis, 8.2% for sacrocolpopexy, 6.4% for USLS, and 8.2% for SSLF ( P <.01). CONCLUSION: The type of surgical repair is significantly associated with long-term risk of reoperation. Colpocleisis offers the least likelihood of reoperation for prolapse, followed by sacrocolpopexy; colpocleisis followed by USLS has the least risk of long-term reoperation for complication.

Examining the role of frailty on treatment patterns and complications among older women undergoing procedure-based treatment for urinary incontinence.

BACKGROUND: Aging beyond 65 years is associated with increased prevalence of urinary incontinence (UI), frailty, and increased complication rate with UI treatments. To investigate this relationship, we examined frailty as a predictor of procedure-based UI treatment patterns and urologic complications in Medicare-eligible women. METHODS: We identified women undergoing procedures for UI between 2011-2018 in the 5% limited Medicare data set. A Claims-based Frailty Index (CFI) using data from the 12-months prior to the index procedure defined frailty (CFI≥0.25). Urologic complications were assessed during the 12-months following the index procedure. We used unadjusted logistic regression models to calculate odds of having a specific type of UI procedure based on frailty status. Odds of post-procedure urologic complications were examined with logistic regression adjusted for age and race. RESULTS: We identified 21,783 women who underwent a procedure-based intervention for UI, of whom 3,826 (17.5%) were frail. Frail women with stress UI were 2.6 times more likely to receive periurethral bulking (95%CI 2.26-2.95), compared to non-frail. Conversely, frailty was associated with lower odds of receiving a Sling or Burch colposuspension. Among women with urgency UI or overactive bladder (OAB), compared to non-frail, frailty was associated with higher odds of both sacral neuromodulation (OR=1.21, 95%CI 1.11-1.33) and intravesical Botox (OR=1.16, 95%CI 1.06-1.28), but lower odds of receiving posterior tibial nerve stimulation. Frailty was associated with higher odds of post-procedure urologic complications (OR=1.64, 95%CI 1.47-1.81). CONCLUSIONS: Frailty status may influence treatment choice for treatment of stress or urgency UI symptoms and increase the odds of post-procedural complications in older women.

Effects of Same-Day Discharge on 30-Day Readmission Rates in Women Aged 65 Years and Older Undergoing Minimally Invasive Pelvic Organ Prolapse Surgery.

OBJECTIVE: To compare the effects of same-day discharge on 30-day readmission after minimally invasive pelvic organ prolapse (POP) surgery in older patients. METHODS: This retrospective cohort study examined all minimally invasive POP surgeries performed and included in the national Centers for Medicare & Medicaid Services 5% Limited Data Set (2011-2018). Our primary outcome was 30-day hospital readmission, and our secondary outcome was 30-day emergency department (ED) visits. RESULTS: Of the 7,278 patients undergoing surgery, patients who had same-day discharge were older (73.5 years vs 73.1 years, P =.04) and less likely to undergo concomitant hysterectomy (9.5% vs 34.9%, P <.01) or midurethral sling (36.8% vs 40.1%, P =.02). Same-day discharge increased over the study period from 15.7% in 2011 to 25.5% in 2018 ( P <.01). On propensity score-matching multiple logistic regression, the adjusted difference was statistically significant, with same-day discharge increasing the odds of 30-day readmission compared with next-day discharge (adjusted odds ratio [OR] 1.57, 95% CI 1.19-2.08). There was no difference (OR 0.81, 95% CI 0.63-1.05) for 30-day ED visits on propensity score-matching multiple logistic regression. CONCLUSION: After minimally invasive POP surgery, older women have low rates of readmission and ED visits within 30 days. After propensity score matching and adjustment for perioperative factors, there may be increased odds in readmission and no difference in ED visits risk in those who had same-day discharge. When considering patient factors, same-day discharge after minimally invasive POP surgery may be effective for older patients.

Web-Based Yoga-Pilates: A Prospective Cohort Study.

IMPORTANCE: There are limited data to determine the change in severity, efficacy, and mechanism of action of yoga-Pilates in the treatment of stress urinary incontinence (SUI). OBJECTIVES: The primary objective was to evaluate the effect of an 8-week web-based home yoga-Pilates exercise program on SUI severity and to evaluate the potential mechanism of action through ultrasound examination of the urethral rhabdosphincter cross-sectional area. STUDY DESIGN: This was a prospective cohort study of women with SUI. Participants underwent visits pre- and post-intervention, completed quality of life/severity surveys, and underwent pelvic examination and 3-dimensional transperineal ultrasonography to determine the urethral cross-sectional area. Pre- and post-intervention 24-hour voiding diaries were also collected. The intervention was an 8-week online yoga-Pilates video that tracked and prompted participation. RESULTS: Sixty women completed the study; they were predominantly premenopausal (67%) and vaginally parous (65%) and had done yoga (76%) and/or Pilates (44%). Seventy-three percent performed the exercises ≥3 times per week. For the primary outcome, the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form score improved from 9.5 (95% confidence interval [CI], 8.7-10.4) to 7.1 (95% CI, 6.3-7.9) (P < 0.001). The median (interquartile range) number of incontinence episodes per 24 hours decreased from 1 (1-3) to 1 (0-1) (P < 0.001). The Brink pelvic floor strength score improved from 7.1 (95% CI, 6.6-7.7) to 7.7 (95% CI, 7.2-8.2) (P = 0.01). Eighty-three percent reported that they were "better" on Patient Global impression of Improvement. There were no significant changes in urethral measurements. CONCLUSIONS: Although it did not meet the minimal clinically important difference, this 8-week web-based yoga-Pilates exercise program improved SUI symptoms and decreased the number of incontinence episodes in women with SUI.

Effect of Second-Stage Pushing Timing on Postpartum Pelvic Floor Morbidity: A Randomized Controlled Trial.

OBJECTIVE: To assess whether immediate or delayed pushing in the second-stage results in higher risk of pelvic floor morbidity. METHODS: This study was a planned secondary aim of a multicenter randomized clinical trial that included nulliparous patients at 37 weeks of gestation or greater in labor with neuraxial analgesia. Participants were randomized in the second stage to initiate pushing immediately or wait 60 minutes before pushing. Participants had pelvic floor assessments at 1-5 days postpartum, 6 weeks postpartum, and 6 months postpartum. Rates of perineal lacerations, pelvic organ prolapse quantification (POP-Q) measures, and scores on validated symptom-specific distress and quality-of-life questionnaires (PFDI-20 [Pelvic Floor Distress Inventory], PFIQ [Pelvic Floor Impact Questionnaire], FISI [Fecal Incontinence Severity Index], and MMHQ [Modified Manchester Health Questionnaire]) were compared. It was estimated that 630 participants would provide more than 80% power to detect a 40% difference in second-degree or greater perineal lacerations and approximately 80% power to detect a 40% difference in stage 2 or greater pelvic organ prolapse (POP). RESULTS: Among 2,414 participants in the primary trial conducted between May 19, 2014, and December 16, 2017, 941 (39%) had pelvic floor assessments: 452 immediate pushing and 489 delayed pushing. The mean age was 24.8 years, and 93.4% had vaginal delivery. There were no significant differences in perineal lacerations at delivery and POP at 6 weeks and 6 months postpartum. Changes from baseline in total and subscale scores for the PFDI-20, the PFIQ, and the MMHQ were not significantly different at 6 weeks postpartum and 6 months postpartum. The change in FISI score was higher in the immediate pushing group at 6 months (2.9±5.7 vs 2.0±4.5, difference 0.9, P =.01), but less than the minimum important difference of 4. CONCLUSION: Among nulliparous patients in the second stage with neuraxial analgesia, immediate pushing, compared with delayed pushing, did not increase perineal lacerations, POP-Q measures, or patient-reported pelvic floor symptoms at 6 weeks and 6 months postpartum. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02137200.

Longitudinal urinary microbiome characteristics in women with urgency urinary incontinence undergoing sacral neuromodulation.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the stability of the urinary microbiome communities in women undergoing sacral neuromodulation (SNM) for urgency urinary incontinence (UUI). We hypothesized that clinical response to SNM therapy would be associated with changes in the urinary microbiome. METHODS: Women completed the Overactive Bladder Questionnaire Short-Form, the International Consultation on Incontinence Questionnaire Short Form, and the Female Sexual Function Index at baseline and 3 months post-SNM implantation. Transurethral urinary specimens were obtained for microbiome analysis at baseline and 3 months postoperatively. The V4 region of the 16S rRNA gene (515F-806R) was amplified with region-specific primers, and Amplicon Sequence Variants (ASVs) were identified with a closed-reference approach of taxonomic classification. Alpha-diversity was calculated using the phylogenetic (i.e., Faith's phylogenetic diversity) and nonphylogenetic metrics (i.e., Shannon diversity, and Pielou's evenness) using the QIIME2 plugin. Longitudinal paired volatility analysis was performed using the DEICODE and Gemelli plugin to account for host specificity across both time and space. RESULTS: Nineteen women who underwent SNM and provided both baseline and 3-month urine samples were included in this analysis. Women reported improvement in objective (number of UUI episodes) and subjective (symptom severity and health-related quality of life) measures. Ninety percent of the bacteria were classified as Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. No significant differences were observed in each subject's beta-diversity at 3 months compared with their baseline microbiome. CONCLUSIONS: Our descriptive pilot study of a cohort of women who had achieved objective and subjective improvements in UUI following SNM therapy demonstrates that the urinary microbiome remains relatively stable, despite variability amongst the cohort.

Characterization of the GU microbiome in women with self-perceived bladder health over the life course.

BACKGROUND: A variety of factors influence bladder health, including environmental factors, life experiences, biologic foundations, and coexistent medical conditions. A biologically diverse microbial community exists in the urine that is likely influenced by the microbial inhabitants of the vagina. The relationship between the genitourinary (GU) microbiome and self-perceived bladder health is unknown. OBJECTIVE: To longitudinally define the GU microbiome in women with self-percieved bladder health sampled across multiple time points over a year. STUDY DESIGN: Women with no reported lower urinary tract dysfunction or symptoms (LUTS) were recruited from six clinical sites and assessed every 6 weeks for 1 year. Voided urine and vaginal samples were longitudinally collected. Self-perceived bladder health was assessed with select items from the LURN comprehensive assessment of self-reported urinary symptoms (CASUS) tool. We defined four life phases as follows: young (18-34 years, nulliparous), midlife (35-45 years, menstruating), transitional (46-60 years, perimenopausal), mature (>60 years, not using vaginal and/or systemic hormone replacement therapy). DNA was extracted from samples, and the V4 region of the 16S rRNA gene was amplified with region-specific primers. The 16S rRNA sequencing on an Illumina NovaSeq. Microbial beta-diversity was calculated using DEICODE to identify microbial taxa that cluster in the samples. Longitudinal volatility analysis was performed using the gemelli plugin. Log-abundance ratios of microbial features were explored and visualized in Qurro. RESULTS: Fifty-four (N = 16 young, N = 16 midlife, N = 15 transitional, N = 7 mature) women were enrolled and provided baseline data. Most women in each life phase (93%-98%) continued to report self-perceived bladder health throughout the 1-year follow-up as assessed by CASUS items. Temporal-based microbial diversity of urinary and vaginal microbiome remained relatively stable over 1 year in all subjects. The GU microbiomes of mature women were distinct and microbially diverse from that of young, midlife, and transitional women, with genera of Gardnerella, Cupriavidus, and Dialister contributory to the microbial features of the mature microbiome. The mature GU microbiome was statistically different (p < 0.0001) from the midlife, transitional, and young microbiome for the log ratio of Gardnerella and Cupriavidus (in the numerator) and Lactobacillus (in the denominator) for voided samples and Gardnerella and Dialister (in the numerator) and Lactobacillus (in the denominator) for vaginal samples. Differences in the GU microbiome were also demonstrated via longitudinal beta-diversity between women developing urinary frequency as reported by CASUS responses or objectively on bladder diary compared to women without urinary frequency. CONCLUSION: In women with a self-perceived healthy bladder, the GU microbiome remained stable in all age groups over a 1 year period. Differences were seen with respect to life phase, where mature women were distinct from all other groups, and with respect to self-reported LUTS.

Development and Validation of a Model for Predicting Surgical Site Infection After Pelvic Organ Prolapse Surgery.

IMPORTANCE: Surgical site infection (SSI) is a common and costly complication. Targeted interventions in high-risk patients may lead to a reduction in SSI; at present, there is no method to consistently identify patients at increased risk of SSI. OBJECTIVE: The aim of this study was to develop and validate a model for predicting risk of SSI after pelvic organ prolapse surgery. STUDY DESIGN: Women undergoing surgery between 2011 and 2017 were identified using Current Procedural Terminology codes from the Centers for Medicare and Medicaid Services 5% Limited Data Set. Surgical site infection ≤90 days of surgery was the primary outcome, with 41 candidate predictors identified, including demographics, comorbidities, and perioperative variables. Generalized linear regression was used to fit a full specified model, including all predictors and a reduced penalized model approximating the full model. Model performance was measured using the c-statistic, Brier score, and calibration curves. Accuracy measures were internally validated using bootstrapping to correct for bias and overfitting. Decision curves were used to determine the net benefit of using the model. RESULTS: Of 12,334 women, 4.7% experienced SSI. The approximated model included 10 predictors. Model accuracy was acceptable (bias-corrected c-statistic [95% confidence interval], 0.603 [0.578-0.624]; Brier score, 0.045). The model was moderately calibrated when predicting up to 5-6 times the average risk of SSI between 0 and 25-30%. There was a net benefit for clinical use when risk thresholds for intervention were between 3% and 12%. CONCLUSIONS: This model provides estimates of probability of SSI within 90 days after pelvic organ prolapse surgery and demonstrates net benefit when considering prevention strategies to reduce SSI.

Intrapartum risk factors associated with pelvic organ prolapse at 6 months postpartum.

BACKGROUND: Pregnancy and childbirth are known risk factors associated with the development of pelvic organ prolapse; specific intrapartum risk factors are not well characterized. OBJECTIVE: This study aimed to determine intrapartum factors associated with increased risk of pelvic organ prolapse identified after delivery. STUDY DESIGN: A planned secondary analysis of a multicenter randomized clinical trial of delayed vs immediate pushing among nulliparous women at ≥37 weeks of gestation in labor with neuraxial analgesia was conducted at 6 academic and community hospitals in the United States. Intrapartum characteristics were identified, and Pelvic Organ Prolapse Quantification assessments at 6 weeks and 6 months after delivery were performed. The primary outcome was pelvic organ prolapse, defined as stage 2 or greater prolapse using the Pelvic Organ Prolapse Quantification assessment at 6 months. Multivariable logistic regression was used to refine risk estimates while adjusting for randomization group, macrosomia, and maternal age. RESULTS: Among the 941 women participating in the pelvic floor follow-up, 793 women had Pelvic Organ Prolapse Quantification assessments at 6 weeks with 91 of 793 women (11.5%) demonstrating stage 2 or greater prolapse. Of the 728 women followed up at 6 months, stage 2 or greater prolapse was identified in 58 of 728 women (8.0%). Prostaglandin use for induction of labor was associated with an increased risk at 6 months (adjusted odds ratio, 2.15; 95% confidence interval, 1.18-3.91; P<.01). The length and type (spontaneous vs induced) of the first stage of labor were not significantly associated with stage 2 or greater prolapse. Moreover, increased length of the second stage of labor and duration of pushing were not associated with stage 2 or greater prolapse. After adjusting for confounding factors, cesarean delivery was protective of pelvic organ prolapse at 6 months (adjusted odds ratio, 0.12; 95% confidence interval, 0.02-0.90). CONCLUSION: The management of the first and second stages of labor, including time length, was not associated with stage 2 or greater prolapse at 6 months. The findings that prostaglandin exposure was associated with increased risk likely were not directly affecting the risk of prolapse but may be surrogates for other labor features that deserve exploration. Cesarean delivery was associated with protection from stage 2 or greater pelvic organ prolapse at 6 months, consistent with previous literature.

Network-Based Differences in the Vaginal and Bladder Microbial Communities Between Women With and Without Urgency Urinary Incontinence.

Background: Little is known about the relationship of proximal urogenital microbiomes in the bladder and the vagina and how this contributes to bladder health. In this study, we use a microbial ecology and network framework to understand the dynamics of interactions/co-occurrences of bacteria in the bladder and vagina in women with and without urgency urinary incontinence (UUI). Methods: We collected vaginal swabs and catheterized urine specimens from 20 women with UUI (cases) and 30 women without UUI (controls). We sequenced the V4 region of the bacterial 16S rRNA gene and evaluated using alpha and beta diversity metrics. We used microbial network analysis to detect interactions in the microbiome and the betweenness centrality measure to identify central bacteria in the microbial network. Bacteria exhibiting maximum betweenness centrality are considered central to the microbe-wide networks and likely maintain the overall microbial network structure. Results: There were no significant differences in the vaginal or bladder microbiomes between cases and controls using alpha and beta diversity. Silhouette metric analysis identified two distinct microbiome clusters in both the bladder and vagina. One cluster was dominated by Lactobacillus genus while the other was more diverse. Network-based analyses demonstrated that vaginal and bladder microbial networks were different between cases and controls. In the vagina, there were similar numbers of genera and subgroup clusters in each network for cases and controls. However, cases tend to have more unique bacterial co-occurrences. While Bacteroides and Lactobacillus were the central bacteria with the highest betweenness centrality in controls, Aerococcus had the highest centrality in cases and correlated with bacteria commonly associated with bacterial vaginosis. In the bladder, cases have less than half as many network clusters compared to controls. Lactobacillus was the central bacteria in both groups but associated with several known uropathogens in cases. The number of shared bacterial genera between the bladder and the vagina differed between cases and controls, with cases having larger overlap (43%) compared to controls (29%). Conclusion: Our study shows overlaps in microbial communities of bladder and vagina, with higher overlap in cases. We also identified differences in the bacteria that are central to the overall community structure.

A Randomized Trial of Social Media Versus Search Engine Advertising to Increase Awareness of Treatments for Female Stress Urinary Incontinence.

IMPORTANCE: Outreach based on user characteristics through social media advertising is significantly more effective than outreach based on user interests with search engine advertising for female stress urinary incontinence. OBJECTIVE: The aim of the study was to compare the effectiveness of 2 online outreach platforms to engage women at risk of stress urinary incontinence with a high-quality patient education website. STUDY DESIGN: A geographic randomized trial was performed comparing online advertising on Facebook, a social media site, versus Google Ads, a search engine, to direct viewers to VoicesForPFD.org. Advertisements were developed using health communication theory and pretested before the randomized trial. Counties in the Pacific Northwest were grouped into approximately equal populations, called "supercounties," and randomized to advertisement platforms. Educational website views resulting from each campaign, called sessions, were measured using Google Analytics; the primary outcome was the number of sessions per supercounty. County characteristics were obtained from national survey data. Effectiveness of the advertising platforms was compared between randomization arms using Welch's unequal variances t test, and crude and adjusted linear regression models. RESULTS: Mean user sessions were significantly higher in areas randomized to Facebook advertising (470 sessions) compared with areas randomized to Google Ads advertising [44 sessions; mean, 426 session difference (95% confidence interval, 199-653 sessions); P = 0.001]. After accounting for adult female population and rurality, randomization to Facebook instead of Google Ads still resulted in 409 additional sessions (95% confidence interval, 317-501 sessions; P < 0.001). CONCLUSIONS: Social media was 10 times more effective (470 versus 44 mean sessions per supercounty) than search engine outreach advertising and should be prioritized in outreach efforts. Future work is needed on engagement and behavior change with online outreach.

The Impact of Local Estrogen on the Urogenital Microbiome in Genitourinary Syndrome of Menopause: A Randomized-Controlled Trial.

IMPORTANCE: The postmenopausal urinary bladder microbiome is not well defined. OBJECTIVES: The aims of this study were to characterize the effect of vaginal estrogen on the vaginal and urinary bladder microbiome in postmenopausal women and describe any clinical associations with the symptoms of genitourinary syndrome of menopause. STUDY DESIGN: This was a participant-masked, randomized controlled trial comparing the effect of a 12-week course of an estrogen-containing vaginal ring to a placebo vaginal ring. Standardized evaluations were performed at baseline and 12 weeks. Vaginal samples were obtained for pH, vaginal maturation index, and microbiome analysis. Concomitant catheterized urine samples were obtained for microbiome analysis. 16S ribosomal RNA gene sequencing was performed to characterize the resident microbial communities, with Lactobacillus relative abundance as the primary outcome variable. Genitourinary syndrome of menopause symptoms was measured using validated questionnaires (Pelvic Floor Distress Inventory-Short Form, Female Sexual Function Index, Vulvovaginal Symptoms Questionnaire). RESULTS: Of the 39 postmenopausal women randomized, baseline characteristics were similar between arms, with a mean age of 62 years and mean vaginal pH of 5.0. Using intention-to-treat analysis, there were no significant changes in vaginal or urinary Lactobacillus relative abundance. Two participants in each arm removed their ring prior to the end of the study. Eighty percent of participants experienced at least 1 bothersome genitourinary syndrome of menopause symptom. Vulvovaginal dryness and urinary frequency were most common at baseline, whereas painful intercourse and urinary urgency were most common at the final visit, none of which were statistically significant. CONCLUSIONS: Our study did not show a significant change in the bacterial composition of the vaginal or urinary bladder microbiome after either vaginal ring in this relatively asymptomatic postmenopausal population.