Yuko M. Komesu

A Baseline for the Multivariate Comparison of Resting-State Networks

As the size of functional and structural MRI datasets expands, it becomes increasingly important to establish a baseline from which diagnostic relevance may be determined, a processing strategy that efficiently prepares data for analysis, and a statistical approach that identifies important effects in a manner that is both robust and reproducible. In this paper, we introduce a multivariate analytic approach that optimizes sensitivity and reduces unnecessary testing. We demonstrate the utility of this mega-analytic approach by identifying the effects of age and gender on the resting-state networks (RSNs) of 603 healthy adolescents and adults (mean age: 23.4 years, range: 12–71 years). Data were collected on the same scanner, preprocessed using an automated analysis pipeline based in SPM, and studied using group independent component analysis. RSNs were identified and evaluated in terms of three primary outcome measures: time course spectral power, spatial map intensity, and functional network connectivity. Results revealed robust effects of age on all three outcome measures, largely indicating decreases in network coherence and connectivity with increasing age. Gender effects were of smaller magnitude but suggested stronger intra-network connectivity in females and more inter-network connectivity in males, particularly with regard to sensorimotor networks. These findings, along with the analysis approach and statistical framework described here, provide a useful baseline for future investigations of brain networks in health and disease.

OnabotulinumtoxinA vs Sacral Neuromodulation on Refractory Urgency Urinary Incontinence in Women: A Randomized Clinical Trial.

Importance Women with refractory urgency urinary incontinence are treated with sacral neuromodulation and onabotulinumtoxinA with limited comparative information. Objective To assess whether onabotulinumtoxinA is superior to sacral neuromodulation in controlling refractory episodes of urgency urinary incontinence. Design, Setting, and Participants Multicenter open-label randomized trial (February 2012-January 2015) at 9 US medical centers involving 381 women with refractory urgency urinary incontinence. Interventions Cystoscopic intradetrusor injection of 200 U of onabotulinumtoxinA (n = 192) or sacral neuromodulation (n = 189). Main Outcomes and Measures Primary outcome, change from baseline mean number of daily urgency urinary incontinence episodes over 6 months, was measured with monthly 3-day diaries. Secondary outcomes included change from baseline in urinary symptom scores in the Overactive Bladder Questionnaire Short Form (SF); range, 0-100, higher scores indicating worse symptoms; Overactive Bladder Satisfaction questionnaire; range, 0-100; includes 5 subscales, higher scores indicating better satisfaction; and adverse events. Results Of the 364 women (mean [SD] age, 63.0 [11.6] years) in the intention-to-treat population, 190 women in the onabotulinumtoxinA group had a greater reduction in 6-month mean number of episodes of urgency incontinence per day than did the 174 in the sacral neuromodulation group (-3.9 vs -3.3 episodes per day; mean difference, 0.63; 95% CI, 0.13 to 1.14; P = .01). Participants treated with onabotulinumtoxinA showed greater improvement in the Overactive Bladder Questionnaire SF for symptom bother (-46.7 vs -38.6; mean difference, 8.1; 95% CI, 3.0 to 13.3; P = .002); treatment satisfaction (67.7 vs 59.8; mean difference, 7.8; 95% CI, 1.6 to 14.1; P = .01) and treatment endorsement (78.1 vs 67.6; mean difference; 10.4, 95% CI, 4.3 to 16.5; P < .001) than treatment with sacral neuromodulation. There were no differences in convenience (67.6 vs 70.2; mean difference, -2.5; 95% CI, -8.1 to 3.0; P = .36), adverse effects (88.4 vs 85.1; mean difference, 3.3; 95% CI, -1.9 to 8.5; P = .22), and treatment preference (92.% vs 89%; risk difference, -3%; 95% CI, -16% to 10%; P = .49). Urinary tract infections were more frequent in the onabotulinumtoxinA group (35% vs 11%; risk difference, -23%; 95% CI, -33% to -13%; P < .001). The need for self-catheterization was 8% and 2% at 1 and 6 months in the onabotulinumtoxinA group. Neuromodulation device revisions and removals occurred in 3%. Conclusions and Relevance Among women with refractory urgency urinary incontinence, treatment with onabotulinumtoxinA compared with sacral neuromodulation resulted in a small daily improvement in episodes that although statistically significant is of uncertain clinical importance. In addition, it resulted in a higher risk of urinary tract infections and need for transient self-catheterizations.

Functional MRI of the Brain in Women with Overactive Bladder: Brain Activation During Urinary Urgency

Objectives: To identify abnormal function of the limbic cortex (LC) in response to urinary urgency among patients with overactive bladder (OAB) using brain functional magnetic resonance imaging. Methods: For this study, 5 OAB subjects and 5 controls underwent bladder filling and rated urgency sensations while functional magnetic resonance imaging measured activation in discrete volumes (voxels) within the brain. Changes in brain activation were related to bladder distension and individual subjects rating of urgency via multiple regression analysis. &bgr; Weights from regression equations were converted into percent signal change for each voxel and percent signal change compared with the null hypothesis using t tests. Significance threshold of P < 0.05 was applied along with a cluster size threshold of 0.32 mL (5005 voxels left ACG). Results: Patients with OAB showed increased brain activation in LC, specifically the insula (IN) and anterior cingulate gyrus, associated with increased urgency. Urgency sensations during low volumes were associated with bilateral IN activation in OAB subjects (7621 voxels right IN and 4453 voxels left IN, mean &bgr; weights = 0.018 ± 0.014 and 0.014 ± 0.011). Minimal activation was present in controls (790 voxels right IN, &bgr; weight = 0.010 ± 0.007). Urgency sensations during high volumes were associated with bilateral anterior cingulate gyrus activation in OAB subjects (2304 voxels right ACG and 5005 voxels left IN, mean &bgr; weights = 0.005 ± 0.003 and 0.004 ± 0.003) without activation in controls. Conclusions: Urinary urgency in patients with OAB is associated with increased activation of the LC. This activation likely represents abnormal processing of sensory input in brain regions associated with emotional response to discomfort.

The association between fecal incontinence and sexual activity and function in women attending a tertiary referral center

Introduction and hypothesisTo determine whether fecal incontinence (FI) is associated with sexual activity and to compare sexual function in women with and without FI.MethodsWe conducted a retrospective chart review of all new patients seen in an academic urogynecology clinic. Women who reported fecal incontinence, as defined by loss of fecal material on the Wexner scale, were compared with those without fecal incontinence. We compared sexual activity and Pelvic Organ Prolapse Incontinence Sexual Questionnaire-12 (PISQ-12) scores between groups.ResultsIn our population of women with pelvic floor disorder, 588 women reported FI compared with 527 who did not. On multivariate analysis, FI was not associated with sexual activity status, but was associated with worsened PISQ-12 scores (p < 0.001). PISQ-12 item analysis found that women with FI reported more dyspareunia, fear, and avoidance of sexual activity with greater partner problems (all p <0.05) than women without FI.ConclusionsWomen with FI were as likely to engage in sexual relations as women without FI; however, sexually active women with FI had poorer sexual function than those without FI.

Patient-selected goal attainment for pessary wearers: what is the clinical relevance?

OBJECTIVE The purpose of this study was to evaluate whether patient determined goal achievement is associated with pessary continuation. STUDY DESIGN Patients identified goals they wished to achieve from pessary use. Patients were asked whether they continued pessary use and if goals were met 6-12 months later. Goals were divided into 8 categories. Fisher exact test was used to evaluate categorical variables, t tests for continuous variables, and regression methods to calculate odds ratios (OR). RESULTS Eighty women enrolled in the study. Sixty-four had follow-up data. Goals commonly listed were bladder (36%), activity (20%), general health (13%), and prolapse related (11%). Thirty-four women continued and 30 discontinued pessary use. Women who continued pessary use were more likely to meet 1 or 2 goals (OR 17.5, 21.1 and 95% CI 4.8-64.4, 5.7-78.9, respectively). CONCLUSION Patient goals are variable and subjective. However, when assessed for achievement, they are associated with pessary continuation. Women who attain self-determined goals are likely to continue pessary use.

Incidence and remission of urinary incontinence in a community-based population of women ≥ 50 years.

Introduction and hypothesisThe objective of the study was to determine incidence, remission, and predictors of change in urinary incontinence in women ≥50 in a racially diverse population.MethodsSubjects were women ≥50 with 4-year follow-up incontinence information in the Health and Retirement Study. Women with Any UI (AUI) and Severe UI (SVUI) were evaluated. Repeated measures logistic regression determined predictors of progression to and improvement of SVUI.ResultsWomen (11,591) were evaluated. AUI 4-year cumulative incidence was 12.7–33.8% (fifth vs. ninth decades). SVUI incidence was lower but also increased with age. Among the predictors of improvement in SVUI were age (ninth vs. fifth decade odds ratios (OR) = 6.06) and ethnicity (Black vs. White OR = 0.57). Improvement of SVUI (45.8% overall) decreased with age (ninth vs. fifth decade OR = 0.12).ConclusionsSVUI incidence increased and remission decreased with age. Ethnicity and age predicted SVUI progression while age predicted improvement. Rates of the latter were high, particularly in younger patients.

Genetic contributions to urgency urinary incontinence in women

PURPOSE We identify genetic variants associated with urgency urinary incontinence in postmenopausal women. MATERIALS AND METHODS A 2-stage genome-wide association analysis was conducted to identify variants associated with urgency urinary incontinence. The WHI GARNET substudy with 4,894 genotyped post-reproductive white women was randomly split into independent discovery and replication cohorts. Genome-wide imputation was performed using IMPUTE2 with the 1000 Genomes ALL Phase I integrated variant set as a reference. Controls reported no urgency urinary incontinence at enrollment or followup. Cases reported monthly or greater urgency urinary incontinence and leaked sufficiently to wet/soak underpants/clothes. Logistic regression models were used to predict urgency urinary incontinence case vs control status based on genotype, assuming additive inheritance. Age, obesity, diabetes and depression were included in the models as covariates. RESULTS Following quality control, 975,508 single nucleotide polymorphisms in 2,241 cases (discovery 1,102; replication 1,133) and 776 controls (discovery 405, replication 371) remained. Genotype imputation resulted in 9,077,347 single nucleotide polymorphisms and insertions/deletions with minor allele frequency greater than 0.01 available for analysis. Meta-analysis of the discovery and replication samples identified 6 loci on chromosomes 5, 10, 11, 12 and 18 associated with urgency urinary incontinence at p <10(-6). Of the loci 3 were within genes, the zinc finger protein 521 (ZFP521) gene on chromosome 18q11, the ADAMTS16 gene on chromosome 5p15 and the CIT gene on chromosome 12q24. The other 3 loci were intergenic. CONCLUSIONS Although environmental factors also likely contribute, this first exploratory genome-wide association study for urgency urinary incontinence suggests that genetic variants in the ZFP521, CIT and ADAMTS16 genes might account for some of the observed heritability of the condition.

Elder American Indian women's knowledge of pelvic floor disorders and barriers to seeking care.

Objectives The objectives of this study are to evaluate urinary incontinence and pelvic organ prolapse knowledge among elder southwestern American Indian women and to assess barriers to care for pelvic floor disorders through community-engaged research. Methods Our group was invited to provide an educational talk on urinary incontinence and pelvic organ prolapse at an annual meeting of American Indian elders. Female attendees aged 55 years or older anonymously completed demographic information and 2 validated questionnaires, the Prolapse and Incontinence Knowledge Questionnaire (PIKQ) and Barriers to Incontinence Care Seeking Questionnaire (BICS-Q). Questionnaire results were compared with historical controls from the original PIKQ and BICS-Q validation study. Results One hundred forty-four women completed the questionnaires. The mean age was 77.7 ± 9.1 years. The mean (SD) for PIKQ of urinary incontinence score was 6.6 (3.0) (similar to historic gynecology controls 6.8 [3.3], P = 0.49), and the mean (SD) for PIKQ on pelvic organ prolapse score was 5.4 (2.9) (better than historic gynecology controls 3.6 [3.2], P < 0.01). Barriers to care seeking reported by the elder women were highest on the BICS-Q subscales of “cost” and “inconvenience.” Conclusions Urinary incontinence knowledge is similar to historic gynecology controls, and pelvic organ prolapse knowledge is higher than historic gynecology controls among elder southwestern American Indian women. American Indian elder women report high levels of barriers to care. The greatest barriers to care seeking for this population were related to cost and inconvenience, reflecting the importance of assessing socioeconomic status when investigating barriers to care. Addressing these barriers may enhance care-seeking southwestern American Indian women.

Ethnicity and variations of pelvic organ prolapse bother

Introduction and hypothesisTo determine if prolapse symptom severity and bother varies among non-Hispanic white, Hispanic, and Native American women with equivalent prolapse stages on physical examination.MethodsThis was a retrospective chart review of new patients seen in an academic urogynecology clinic from January 2007 to September 2011. Data were extracted from a standardized intake form, including patients’ self-identified ethnicity. All patients underwent a Pelvic Organ Prolapse Quantification (POPQ) examination and completed the Pelvic Floor Distress Inventory-20 (PFDI-20) with its Pelvic Organ Prolapse Distress Inventory (POPDI) subscale.ResultsFive hundred and eighty-eight new patients were identified with pelvic organ prolapse. Groups did not differ by age, prior prolapse, and/or incontinence surgery, or sexual activity. Based on POPDI scores, Hispanic and Native American women reported more bother compared with non-Hispanic white women with stage 2 prolapse (p < 0.01). Level of bother between Hispanic and Native American women with stage 2 prolapse (p = 0.56) was not different. In subjects with ≥ stage 3 prolapse, POPDI scores did not differ by ethnicity (p = 0.24). In multivariate stepwise regression analysis controlling for significant factors, Hispanic and Native American ethnicity contributed to higher POPDI scores, as did depression.ConclusionsAmong women with stage 2 prolapse, both Hispanic and Native American women had a higher level of bother, as measured by the POPDI, compared with non-Hispanic white women. The level of symptom bother was not different between ethnicities in women with stage 3 prolapse or greater. Disease severity may overshadow ethnic differences at more advanced stages of prolapse.

Urgency urinary incontinence in women 50 years or older: incidence, remission, and predictors of change.

Objectives: To estimate 2-year incidence, remission, and predictors of urgency urinary incontinence (UUI) in a community-based population of women 50 years or older. Methods: We analyzed the 2004 to 2006 data in the Health and Retirement Study. Subjects were women 50 years or older with baseline and follow-up UUI information. Urgency urinary incontinence incidence and remission were calculated. Predictors of UUI progression and improvement were estimated controlling for age, ethnicity, body mass index, parity, psychiatric illness, medical comorbidities, functional limitations, and stress urinary incontinence. We evaluated whether baseline UUI status predicted follow-up status and used multivariable logistic regression to identify predictor variables. Results: A total of 8581 women reported UUI status at baseline and follow-up. Of 7244 women continent at baseline, 268 affirmed UUI at follow-up for a 2-year incidence of 3.7%. Of 581 women with UUI at baseline, 150 were continent at follow-up for a 2-year remission of 25.8%. Predictors of UUI development included increased age (7th and 10th decades compared with 6th decade; OR, 1.5 and 7.2; confidence interval [CI], 1.1-2.1 and 4.2-12.5, respectively), obesity (OR, 1.6; CI, 1.2-2.1), history of psychiatric illness (OR, 1.6; CI, 1.3-2.0), functional limitations (OR, 6.2; CI, 4.2-9.2), and stress urinary incontinence (OR, 5.0; CI, 3.0-8.3). Women who denied UUI at baseline were also likely to deny UUI at follow-up (OR, 47.4; CI, 22.9-98.1). Conclusions: In this community-based population of women 50 years or older, UUI incidence was low and remission was high. Predictors of UUI included increased age, severe obesity, functional limitations, a positive psychiatric history, and incontinence status at baseline.