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OBJECTIVE - To determine whether women overactive bladder symptoms would report more frequent unhealthy toileting behaviors.
METHODS - A community-based sample of adult women was electronically recruited to complete the Toileting Behavior Scale and the International Consultation on Incontinence Questionnaire - Overactive Bladder module, as well as clinical and demographic questionnaires. The associations between overactive bladder and toileting behavior subscales were assessed as continuous variables using Spearman's rank correlation and as dichotomous variables with multivariable logistic regression.
RESULTS - Of the 6562 adult women included in the analytic sample, 1059 (16.1%) were classified as having overactive bladder. Of the toileting behavior subscales, convenience voiding had the highest, positive association with overactive bladder score (r = 0.301, P < .0001). On multivariable logistic regression, women with overactive bladder (OAB) were more likely to report behaviors of convenience voiding (odds ratio [OR] 1.13, confidence intervals [CI] 1.11-1.15), delayed voiding (OR 1.05, CI 1.02-1.08), straining to void (OR 1.05, CI 1.03-1.07), and position preference (OR 1.13, CI 1.08-1.18).
CONCLUSION - OAB symptoms were associated with specific toileting behaviors of convenience voiding, delayed voiding, straining to void, and position preference. Further investigation is needed to determine if toileting behaviors are a risk factor for OAB or a compensatory adaptation to mitigate symptoms.
Copyright © 2019 Elsevier Inc. All rights reserved.

AIMS - To examine the current understanding and management of detrusor underactivity (DUA) and underactive bladder (UAB) in women.
METHODS - A review of the current literature was performed with a specific focus on new management strategies and treatment options for women with DUA and UAB.
RESULTS - DUA has become an area of increased interest in recent years. Affecting up to 45% of older women undergoing urodynamic evaluation for non-neurogenic lower urinary tract symptoms, DUA is common. There are a variety of possible etiologies including neurogenic or myogenic dysfunction. As there is currently no cure for DUA and no way to restore the ability of the detrusor muscle to contract, management of DUA in women is mostly focused on effective bladder drainage by urinary catheterization. Clean intermittent catheterization is the gold standard for bladder drainage however for a variety of reasons, women with DUA often are managed with indwelling urethral catheter or suprapubic tube. Medications, sacral neuromodulation, and the inFlow urinary prosthesis are also treatment alternatives or additions to catheterization. Novel therapies using stem cells and gene therapy are also under investigation for the treatment of DUA and UAB.
CONCLUSIONS - DUA is likely more prevalent than recognized and undertreated in women. It is vital that further research in treatment options beyond catheterization be developed for these patients to offer patients a variety of treatment options.
© 2019 Wiley Periodicals, Inc.

AIMS - To examine the impact of frailty on treatment outcomes for overactive bladder (OAB) in older adults starting pharmacotherapy, onabotulinumtoxinA, and sacral neuromodulation.
METHODS - This is a prospective study of men and women age ≥60 years starting pharmacotherapy, onabotulinumtoxinA, or sacral neuromodulation. Subjects were administered questionnaires at baseline and again at 1- and 3-months. Frailty was assessed at baseline using the timed up and go test (TUGT), whereby a TUGT time of ≥12 seconds was considered to be slow, or frail. Response to treatment was assessed using the overactive bladder symptom score (OABSS) and the OAB-q SF (both Bother and HRQOL subscales). Information on side effects/adverse events was also collected. Mixed effects linear modeling was used to model changes in outcomes over time both within and between groups.
RESULTS - A total of 45 subjects enrolled in the study, 40% (N = 18) of whom had a TUGT ≥12 seconds. Both TUGT groups demonstrated improvement in OAB symptoms over time and there were no statistically significant differences in these responses per group (all P-values >.05). Similar trends were found for both OAB-q SF Bother and OAB-q SF HRQOL questionnaire responses. Side effects and adverse events were not significantly different between groups (all P's >.05).
CONCLUSIONS - Adults ≥60 years of age starting second- and third-line treatments for OAB, regardless of TUGT time, demonstrated improvement in OAB symptoms at 3 months. These findings suggest that frail older adults may receive comparable benefit and similar rates of side effects compared with less frail older individuals.
© 2019 Wiley Periodicals, Inc.

OBJECTIVE - To estimate effective dose of kidney-ureter-bladder (KUB) radiographs in a contemporary population of patients with urolithiasis.
METHODS - A retrospective review was performed to identify patients visiting a urology clinic for urolithiasis where a KUB was obtained and whom had a recent computed tomography (CT). Effective dose for KUBs was estimated using a Monte Carlo based simulation program and for CT utilizing the reported dose-length-product. Age, gender, body mass index, and abdominal diameter were analyzed for association with effective dose. KUBs performed at outside facilities in referred patient were compared to those obtained locally when available.
RESULTS - Fifty-four patients were identified meeting criteria. The majority (92.6%) of KUBs contained multiple radiographs. Mean effective dose was 2.15 mSv ± 1.67 mSv. Only 26% of examinations effective dose was under 1 mSv. Body mass index, abdominal thickness, and image count were all associated with an increase in dose (P < .01 each). Similar to local KUBs, 88% of outside examinations contained multiple images.
CONCLUSION - KUB examinations in this contemporary setting are associated with a 2-fold higher effective dose then is often referenced. Increased effective dose is associated with increased patient size and number of images acquired. Nearly 1 in 5 patient's KUB effective dose was similar to a low-dose CT. KUBs role should be re-examined given its limited sensitivity, specificity, associated radiation, and other available imaging options.
Copyright © 2018. Published by Elsevier Inc.

OBJECTIVE - To identify nonclinical factors affecting postoperative complication rates in patients with neurogenic bladder undergoing benign genitourinary (GU) reconstruction.
METHODS - Adult patients with neurogenic bladder undergoing benign GU reconstruction between October 2010 and November 2015 were included. Patients were excluded if a diversion was performed for malignancy, if patients had a history of radiation or if a new bowel segment was not utilized at the time of the operation. Clinical and nonclinical factors were abstracted from the patients' electronic medical records. Health literacy was assessed via the Brief Health Literacy Screen (BHLS), a validated 3-question assessment. Education, marital status, and distance from the medical center were also queried.
RESULTS - Forty-nine patients with a neurogenic bladder undergoing complex GU reconstruction met inclusion and exclusion criteria. On average, patients lived 111 miles (standard deviation 89) from the hospital. Overall, mean BHLS score was 10.4 (standard deviation 4.6) with 35% of patients scoring a BHLS of ≤9. Mean years of educational attainment was 9.7, and only 31% of patients completed high school education. In the first month after surgery, 37 patients (76%) experienced a complication, and 22% were readmitted; however, analysis of complication data did not identify an association between any nonclinical variables and complication rates.
CONCLUSION - Nonclinical factors including unmarried status, poor health literacy, and marked distance from quaternary care are prevalent in patients with neurogenic bladder undergoing complex GU reconstruction. To mitigate these potential risk factors, the authors recommend acknowledgment of these factors and multidisciplinary support perioperatively to counteract them.
Copyright © 2018. Published by Elsevier Inc.

PURPOSE - The objective of this study was to assess toileting behaviors in community dwelling women.
MATERIALS AND METHODS - Women 18 years old or older were recruited through a national registry of research volunteers. They were asked to complete validated questionnaires assessing urinary symptoms and toileting behaviors, specifically place preference for voiding, convenience voiding, delayed voiding, straining during voiding and position preference for voiding. The PPBC (patient perception of bladder condition) was administered to assess the participant impression of bladder health. Analyses were done to determine the prevalence of each toileting behavior reported to occur sometimes or more often as well as differences in toileting behaviors in women with vs without self-perceived bladder problems based on the PPBC response.
RESULTS - The 6,695 women who completed the questionnaires were 18 to 89 years old (mean ± SD age 41.4 ± 15). Of the women 79.9% identified as white and 71.0% were college educated. Of the women 6,613 (98.8%) reported a place preference for voiding. The 3,552 women (53.1%) who reported a bladder problem were more likely to report convenience voiding, delayed voiding and strained voiding behaviors. While 6,657 women (99.4%) reported sitting to void at home only 5,108 (76.2%) reported sitting when using public toilets.
CONCLUSIONS - Certain toileting behaviors, of which some may be considered unhealthy, were common in this sample of women and most were associated with a perception of bladder problems. Voiding positions other than sitting were frequently used when away from home. These data have important implications for defining bladder health and implementing behavior based interventions for women with lower urinary tract symptoms.

PURPOSE - We investigated the relationship of painful bladder filling and urinary urgency to somatic and chronic pain symptoms in women with overactive bladder without an interstitial cystitis/bladder pain syndrome diagnosis.
MATERIALS AND METHODS - Women who met overactive bladder criteria based on symptoms were recruited, including 183 (83.9%) from the community and 35 (16.1%) from the urology clinic to complete validated questionnaires assessing urinary symptoms, somatic symptoms and pain syndromes. Participants were categorized into 1 of 3 groups, including 1) neither symptom, 2) either symptom or 3) both symptoms, based on their reports of painful urinary urgency and/or painful bladder filling. Multivariable regression analyses were performed to determine factors predictive of having painful urgency and/or painful filling.
RESULTS - Of 218 women with overactive bladder 101 (46%) had neither painful bladder filling nor urinary urgency, 94 (43%) had either symptom and 23 (11%) had both symptoms. When controlling for age, women with either or both urological pain symptoms were more likely to have irritable bowel syndrome, chronic pelvic pain and temporomandibular disorder than women in the neither group. Additionally, these women had higher pain intensity and somatic symptoms scores than women with neither symptom.
CONCLUSIONS - The majority of women with overactive bladder who had not been diagnosed with interstitial cystitis/bladder pain syndrome reported painful urgency and/or painful filling. Experiencing painful urgency and/or filling was associated with an increased somatic symptom burden and greater pain intensity. These findings support the hypothesis that overactive bladder and interstitial cystitis/bladder pain syndrome diagnoses may represent a continuum of bladder hypersensitivity.
Copyright © 2018. Published by Elsevier Inc.

PURPOSE - We sought to determine whether women with overactive bladder who required third line therapy would demonstrate greater central sensitization, indexed by temporal summation to heat pain stimuli, than those with overactive bladder.
MATERIALS AND METHODS - We recruited 39 women with overactive bladder from the urology clinic who were planning to undergo interventional therapy for medication refractory overactive bladder with onabotulinumtoxinA bladder injection or sacral neuromodulation. We also recruited 55 women with overactive bladder who were newly seen at our urology clinic or who responded to advertisements for study participation. Participants underwent quantitative sensory testing using a thermal temporal summation protocol. The primary study outcome was the degree of temporal summation as reflected in the magnitude of positive slope of the line fit to the series of 10 stimuli at a 49C target temperature. We compared the degree of temporal summation between the study groups using linear regression.
RESULTS - Women in the group undergoing third line therapy showed significantly higher standardized temporal summation slopes than those in the nontreatment group (β = 1.57, 95% CI 0.18-2.96, t = 2.25, p = 0.027). On exploratory analyses a history of incontinence surgery or hysterectomy was associated with significantly greater temporal summation.
CONCLUSIONS - In this study the degree of temporal summation was elevated in women undergoing third line overactive bladder therapy compared to women with overactive bladder who were not undergoing that therapy. These findings suggest there may be pathophysiological differences, specifically in afferent nerve function and processing, in some women with overactive bladder.
Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

While many adhesion receptors are known to influence tumor progression, the mechanisms by which they dynamically regulate cell-cell adhesion remain elusive. We previously identified Activated Leukocyte Cell Adhesion Molecule (ALCAM) as a clinically relevant driver of metastasis and hypothesized that a tunable mechanism of ectodomain shedding regulates its contribution to dissemination. To test this hypothesis, we examined an under-explored ALCAM splice variant (ALCAM-Iso2) and demonstrated that loss of the membrane-proximal region of ALCAM (exon 13) increased metastasis four-fold. Mechanistic studies identified a novel MMP14-dependent membrane distal cleavage site in ALCAM-Iso2, which mediated a ten-fold increase in shedding, thereby decreasing cellular cohesion. Importantly, the loss of cohesion is not limited to the cell capable of shedding because the released extracellular domain diminished cohesion of non-shedding cells through disruption of ALCAM-ALCAM interactions. ALCAM-Iso2-dominated expression in bladder cancer tissue, compared to normal bladder, further emphasizes that ALCAM alternative splicing may contribute to clinical disease progression. The requirement for both the loss of exon 13 and the gain of metalloprotease activity suggests that ALCAM shedding and concomitant regulation of tumor cell adhesion is a locally tunable process.

We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.
Copyright © 2017 Elsevier Inc. All rights reserved.