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Purpose: Our objective was to investigate structural changes in brain white matter tracts using diffusion tensor imaging (DTI) in patients with overactive bladder (OAB)., Materials and Methods: Treatment-seeking OAB patients and matched controls enrolled in the cross-sectional case-control LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Neuroimaging Study received a brain DTI scan. Microstructural integrity of brain white matter was assessed using fractional anisotropy (FA) and mean diffusivity. OAB and urgency urinary incontinence (UUI) symptoms were assessed using the OAB Questionnaire Short-Form and International Consultation on Incontinence Questionnaire-Urinary Incontinence. The Lower Urinary Tract Symptoms Tool UUI questions and responses were correlated with FA values., Results: Among 221 participants with evaluable DTI data, 146 had OAB (66 urinary urgency-only without UUI, 80 with UUI); 75 were controls. Compared with controls, participants with OAB showed decreased FA and increased mean diffusivity, representing greater microstructural abnormalities of brain white matter tracts among OAB participants. These abnormalities occurred in the corpus callosum, bilateral anterior thalamic radiation and superior longitudinal fasciculus tracts, and bilateral insula and parahippocampal region. Among participants with OAB, higher OAB Questionnaire Short-Form scores were associated with decreased FA in the left inferior fronto-occipital fasciculus, P < .0001. DTI differences between OAB and controls were driven by the urinary urgency-only (OAB-dry) but not the UUI (OAB-wet) subgroup., Conclusions: Abnormalities in microstructural integrity in specific brain white matter tracts were more frequent in OAB patients. More severe OAB symptoms were correlated with greater degree of microstructural abnormalities in brain white matter tracts in patients with OAB., Trial Registration: ClinicalTrials.gov: NCT02485808.

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.

Purpose: Overactive bladder (OAB) may be attributed to dysfunction in supraspinal brain circuits. Overactive bladder participants enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) study reported sensations of urinary urgency during a bladder-filling paradigm while undergoing brain functional MRI to map supraspinal dysfunction., Materials and Methods: OAB participants and controls (CONs) completed 2 resting-state functional MRI scans following consumption of 350 mL water. Scans were conducted at fuller and emptier bladder states, interleaved with voiding. Urgency ratings (0-10) were assessed. Patterns of urgency during bladder filling were investigated using latent class trajectory models. Clusters of participants encompassing each pattern (ie, subtype) were derived from aggregated groups of OAB and CON independent of diagnosis., Results: Two distinct patterns of urgency trajectories were revealed: first subtype with OAB and CON who were unresponsive to bladder filling (OAB-1 and CON-1) and second highly responsive subtype predominantly containing OAB (OAB-2). OAB-2 participants scored significantly higher on urinary symptoms but not pain or psychosocial measures. Neuroimaging analyses showed change in urgency due to both bladder filling and voided volume related to multiple loci of brain network connectivity in OAB-2, and in some cases, different than OAB-1 and/or CON-1. Sensorimotor to dorsomedial/dorsolateral prefrontal connectivity mediated the relationship between stimulus (voided volume) and percept (urgency) in OAB-2., Conclusions: Our results reveal different OAB subtypes with latent class trajectory models of urgency ratings during natural bladder filling. Functional MRI revealed differences in pathophysiology between subtypes, namely sensorimotor-prefrontal connectivity is a key locus in OAB patients with higher urinary symptoms.

Purpose: We characterize patients with urinary urgency with vs without urgency urinary incontinence who presented to clinics actively seeking treatment for their symptoms., Materials and Methods: Participants who enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network were categorized into urinary urgency with vs without urgency urinary incontinence. Participants were followed for 1 year; their urinary symptoms, urological pain, psychosocial factors, bowel function, sleep disturbance, physical activity levels, physical function, and quality of life were compared. Mixed effects linear regression models were used to examine the relationships between urgency urinary incontinence and these factors., Results: Among 683 participants with urinary urgency at baseline, two-thirds (n=453) also had urgency urinary incontinence; one-third (n=230) had urinary urgency-only without urgency urinary incontinence. No differences were detected in urological pain between urinary urgency-only and urgency urinary incontinence. Those with urgency urinary incontinence had more severe urgency and frequency symptoms, higher depression, anxiety, perceived stress scores, more severe bowel dysfunction and sleep disturbance, lower physical activity levels, lower physical function, and worse quality of life than those with urinary urgency-only. Among those with urinary urgency-only at baseline, 40% continued to have urinary urgency-only, 15% progressed to urgency urinary incontinence, and 45% had no urgency at 12 months. Fifty-eight percent with urgency urinary incontinence at baseline continued to report urgency urinary incontinence at 12 months, while 15% improved to urinary urgency-only, and 27% had no urgency., Conclusions: Patients with urgency urinary incontinence have severe storage symptoms, more psychosocial symptoms, poorer physical functioning, and worse quality of life. Our data suggested urgency urinary incontinence may be a more severe manifestation of urinary urgency, rather than urinary urgency and urgency urinary incontinence being distinct entities.

Purpose: The impact of nonurological factors on male lower urinary tract symptoms (LUTS) remains unclear. We investigated cross-sectional and longitudinal associations among anxiety, depression, physical function, sleep quality and urinary symptom subdomains., Materials and Methods: Data from 518 men in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) study were analyzed to identify associations between Patient-Reported Outcomes Measurement Information System® (PROMIS®) depression, anxiety, sleep disturbance and physical function measures and LUTS subdomains, as derived from the American Urological Association Symptom Index and LUTS Tool. Multivariable linear regression was used to assess the relationships between PROMIS measures and LUTS subdomains at baseline and at 3- and 12-month followup., Results: Baseline depression and anxiety were associated with urinary incontinence (p <0.001), voiding symptoms (p <0.001) and quality of life (p=0.002), whereas baseline sleep disturbance was associated with voiding and storage symptoms and quality of life (p <0.001 for all). Urinary symptom severity improved in all subdomains at 3 and 12 months. Similar associations between PROMIS measures and LUTS subdomains were observed at all time points, but baseline depression, anxiety, sleep disturbance and physical function measures were not associated with longitudinal trajectories of LUTS., Conclusions: Urinary symptom subdomains are independently associated with modifiable clinical variables including sleep quality and depression at all time points, but these variables do not predict the degree of improvement in LUTS following urological evaluation and treatment over the medium term. Bidirectional assessment and randomized experiments may improve our understanding of these relationships.

Purpose: The objective of this study was to investigate the presence of nonbladder sensory abnormalities in participants with overactive bladder syndrome (OAB)., Materials and Methods: Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) study participants with OAB symptoms and controls were recruited from 6 U.S. tertiary referral centers. Quantitative sensory testing (QST) was performed to determine pressure pain sensitivity at the thumbnail bed and auditory sensitivity. Fixed and mixed effect multivariable linear regressions and Weibull models were used to compare QST responses between groups. Pearson correlations were used to assess the relationship between QST measures. Associations between QST and self-reported symptoms were explored with linear regression., Results: A total of 297 participants were analyzed (191 OAB, 106 controls; 76% white, 51% male). OAB cases were older than controls (57.4 vs 52.2 years, p=0.015). No significant differences in experimental thumbnail (nonbladder) pain or auditory sensitivity were detected between OAB cases and controls. Correlations between pressure and auditory derived metrics were weak to moderate overall for both groups, with some significantly stronger correlations for cases. Exploratory analyses indicated increased pressure pain and auditory sensitivity were modestly associated with greater self-reported bladder pain and pain interference with physical function., Conclusions: As a group, no significant differences between OAB cases and controls were observed in experimental nonbladder pain or auditory sensitivity during QST. Associations between QST outcomes and clinical pain raise the possibility of centrally mediated sensory amplification in some individuals with OAB.

Purpose: Lower urinary tract symptoms are common in men and women. Members of the LURN (Lower Urinary Tract Dysfunction Research Network) sought to create a brief, clinically relevant tool to improve existing measurements of lower urinary tract symptoms in men and women., Materials and Methods: Using a modified Delphi methodology during an expert consensus meeting we reduced the LURN CASUS (Comprehensive Assessment of Self-Reported Urinary Symptoms) questionnaire to a brief set of clinically relevant items measuring lower urinary tract symptoms. The sum score of these items was evaluated by comparing it to the AUA SI (American Urological Association Symptom Index), the UDI-6 (Urinary Distress Inventory Short Form) in women only and the CASUS lower urinary tract symptoms screening questions using the Pearson correlation, regression analysis and ROC curves., Results: The LURN SI-10 (10-Item LURN Symptom Index) assesses urinary frequency, nocturia, urgency, incontinence, bladder pain, voiding and post-micturition symptoms (score range 0 to 38). The correlation between LURN SI-10 and AUA SI scores was 0.77 in men and 0.70 in women. The UDI-6 and the LURN SI-10 correlated highly in women (r=0.76). The LURN SI-10 showed good accuracy to predict moderate and severe lower urinary tract symptoms as defined by the AUA SI (ROC AUC range 0.82-0.90). Similar accuracy was shown in predicting different levels of symptom status using the UDI-6 (AUC range 0.84-0.86)., Conclusions: The LURN SI-10 correlates well with the AUA SI and the UDI-6. It includes items related to a broader spectrum of lower urinary tract symptoms, particularly incontinence, bladder pain and post-micturition symptoms, and it applies to men and women.

Purpose: Conventional classification of patients with lower urinary tract symptoms into diagnostic categories based on a predefined symptom complex or predominant symptom appears inadequate. This is due to the frequent presentation of patients with multiple urinary symptoms which could not be perfectly categorized into traditional diagnostic groups. We used a novel clustering method to identify subtypes of male patients with lower urinary tract symptoms based on detailed multisymptom information., Materials and Methods: We analyzed baseline data on 503 care seeking men in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Observational Cohort Study. Symptoms and symptom severity were assessed using the LUTS (Lower Urinary Tract Symptoms) Tool and the AUA SI (American Urological Association Symptom Index), which include a total of 52 questions. We used a resampling based consensus clustering algorithm to identify patient subtypes with distinct symptom signatures., Results: Four distinct symptom clusters were identified. The 166 patients in cluster M1 had predominant symptoms of frequency, nocturia, hesitancy, straining, weak stream, intermittency and incomplete bladder emptying suggestive of bladder outlet obstruction. The 93 patients in cluster M2 mainly endorsed post-micturition symptoms (eg post-void dribbling and post-void leakage) with some weak stream. The 114 patients in cluster M3 reported mostly urinary frequency without incontinence. The 130 patients in cluster M4 reported severe frequency, urgency and urgency incontinence. Most other urinary symptoms statistically differed between cluster pairs. Patient reported outcomes of bowel symptoms, mental health, sleep dysfunction, erectile function and urological pain significantly differed across the clusters., Conclusions: We identified 4 data derived clusters among men seeking care for lower urinary tract symptoms. The clusters differed from traditional diagnostic categories. Further subtype refinement will be done to incorporate clinical data and nonurinary patient reported outcomes.

Purpose: Self-reported measurement tools often provide a recall period, eg "In the past 7 days…" For lower urinary tract symptoms the concordance of end of day (daily) reports with 7 and 30-day recalled reports is unknown to our knowledge. We evaluated how accurately 7 or 30-day recall questions capture lower urinary tract symptoms., Materials and Methods: The 261 female and 254 male participants were recruited from a total of 6 United States tertiary care sites. We evaluated 18 items representing 7 symptoms covering storage, voiding and post-micturition symptoms. Item responses on the daily forms were averaged for a 7 or a 30-day period and compared to the corresponding 7 or 30-day recall version of the item. Analyses were item and gender specific. Within person concordance was assessed using the Pearson correlation. Bias (systematic overreporting or underreporting) was calculated as the difference between the recalled item and the averaged daily item score, and reported as a percent of the item scale., Results: All correlations exceeded 0.60. Correlations between averaged daily reports and recalled reports ranged from 0.72 to 0.89 for 7 days and from 0.71 to 0.91 for 30 days among women, and from 0.68 to 0.90 and 0.68 to 0.95, respectively, among men. Most items did not show systematic bias and the median percent bias did not exceed 10% for any item. However, bias exceeding ±10% for some items was observed in a subset of individuals., Conclusions: Recalled reports during the 7 and 30 days tracked well with averaged daily reports for men and women. Systematic bias was minimal, suggesting that 7 and 30-day recall periods for self-reported lower urinary tract symptoms are reasonable.

Purpose: Some patients continue to have bothersome lower urinary tract symptoms despite treatment. We examined characteristics associated with bother from lower urinary tract symptoms in a prospective cohort., Materials and Methods: In this 1-year prospective, observational cohort study we obtained data on patients with lower urinary tract symptoms who were seeking care at a total of 6 tertiary care centers in the United States. Participants answered the AUA-SI (American Urological Association Symptom Index) global urinary bother question at study entry and 12 months later. Multilevel logistic and linear regression was used to identify factors associated with worsening bother and bother at 12 months, respectively., Results: Of the 756 participants 121 (16%) had worsened lower urinary tract symptom bother during the study period. When adjusted for other variables, worsened lower urinary tract symptom bother was more likely among men who were nonwhite (OR 1.79, 95% CI 0.94-3.40) or who had diabetes (OR 1.68, 95% CI 0.86-3.27) and among women with diabetes (OR 1.77, 95% CI 0.85-3.67), prior treatment of lower urinary tract symptoms (OR 2.58, 95% CI 1.22-5.46) or a higher depression level (OR 1.29, 95% CI 1.10-1.52). Baseline factors associated with more severe bother at 12 months in men included more severe bother at baseline, nonwhite race, worse urinary frequency and incontinence, and higher levels of stress (p <0.05). Among women more severe bother at baseline, urinary urgency and frequency, and worse physical function were associated with more severe bother at 12 months., Conclusions: Urinary symptom severity at baseline, race, depression and psychological stress were associated with the bother of lower urinary tract symptoms in a prospective cohort of men and women treated at tertiary care facilities. These findings may inform the clinical care of patients with bothersome lower urinary tract symptoms and direct providers to better prognosticate for patients with challenging lower urinary tract symptoms cases.

Purpose: Women with lower urinary tract symptoms are often diagnosed based on a predefined symptom complex or a predominant symptom. There are many limitations to this paradigm as often patients present with multiple urinary symptoms which do not perfectly fit the preestablished diagnoses. We used cluster analysis to identify novel, symptom based subtypes of women with lower urinary tract symptoms., Materials and Methods: We analyzed baseline urinary symptom questionnaire data obtained from 545 care seeking female participants enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Observational Cohort Study. Symptoms were measured with the LUTS (lower urinary tract symptoms) Tool and the AUA SI (American Urological Association Symptom Index), and analyzed using a probability based consensus clustering algorithm., Results: Four clusters were identified. The 138 women in cluster F1 did not report incontinence but experienced post-void dribbling, frequency and voiding symptoms. The 80 women in cluster F2 reported urgency incontinence as well as urgency and frequency but minimal voiding symptoms or stress incontinence. Cluster F3 included 244 women who reported all types of incontinence, urgency, frequency and mild voiding symptoms. The 83 women in cluster F4 reported all lower urinary tract symptoms at uniformly high levels. All but 2 of 44 LUTS Tool and 8 AUA SI questions significantly differed between at least 2 clusters (p <0.05). All clusters contained at least 1 member from each conventional group, including continence, and stress, urgency, mixed and other incontinence., Conclusions: Women seeking care for lower urinary tract symptoms cluster into 4 distinct symptom groups which differ from conventional clinical diagnostic groups. Further validation is needed to determine whether management improves using this new classification., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We examined how mental health measures, sleep and physical function are associated with the presence and type of urinary incontinence and severity in women seeking treatment for lower urinary tract symptoms., Materials and Methods: This baseline cross-sectional analysis was performed in treatment seeking women with lower urinary tract symptoms. All participants completed the LUTS (Lower Urinary Tract Symptoms) Tool (Pfizer, New York, New York), which was used to classify women based on urinary incontinence symptoms and measure severity. The PROMIS (Patient-Reported Outcomes Measurement Information System) questionnaire for depression, anxiety, sleep disturbance and physical function, the PSS (Perceived Stress Scale) and the IPAQ-SF (International Physical Activity Questionnaire Short Form) were administered. Multivariable regression modeling was done to assess associations with urinary symptom presence, type and severity., Results: We studied 510 women with a mean ± SD age of 56 ± 14 years. Of the women 82% were Caucasian, 47% were obese and 14% reported diabetes. Urinary incontinence was reported by 420 women (82.4%), including stress urinary incontinence in 70, urgency urinary incontinence in 85, mixed urinary incontinence in 240 and other urinary incontinence in 25. On adjusted analyses there was no difference in any mental health, sleep or physical function measure based on the presence vs the absence of urinary incontinence. Among women with urinary incontinence PROMIS anxiety and sleep disturbance scores were higher in those with mixed urinary incontinence than stress urinary incontinence. Increasing urinary incontinence severity was associated with higher PROMIS depression and anxiety scores, and higher PSS scores. However, higher urinary incontinence severity was not associated with a difference in sleep or physical function., Conclusions: Among treatment seeking women with lower urinary tract symptoms, increasing urinary incontinence severity rather than the presence or type of urinary incontinence was associated with increased depression, anxiety and stress., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Male urinary incontinence is thought to be infrequent. We sought to describe the prevalence of urinary incontinence in a male treatment seeking cohort enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network)., Materials and Methods: Study inclusion and exclusion criteria, including men with prostate cancer or neurogenic bladder, were previously reported. LURN participants prospectively completed questionnaires regarding lower urinary tract symptoms and other clinical variables. Men were grouped based on incontinence type, including 1) no urinary incontinence, 2) post-void dribbling only and 3) urinary incontinence. Comparisons were made using ANOVA and multivariable regression., Results: Of the 477 men 24% reported no urinary incontinence, 44% reported post-void dribbling only and 32% reported urinary incontinence. African American men and those with sleep apnea were more likely to be in the urinary incontinence group than in the no urinary incontinence group (OR 3.2, p = 0.02 and OR 2.73, p = 0.003, respectively). Urinary incontinence was associated with significantly higher bother compared to men without leakage (p <0.001). Compared to men without urinary incontinence and men with only post-void dribbling those with urinary incontinence were significantly more likely to report higher scores (more severe symptoms) on the PROMIS (Patient-Reported Outcomes Measurement Information System) questionnaires regarding bowel issues, depression and anxiety than men without urinary incontinence (p <0.01)., Conclusions: Urinary incontinence is common among treatment seeking men. This is concerning because the guideline recommended questionnaires to assess male lower urinary tract symptoms do not query for urinary incontinence. Thus, clinicians may be missing an opportunity to intervene and improve patient care. This provides a substantial rationale for a new or updated symptom questionnaire which provides a more comprehensive symptom assessment., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We described and compared the frequency and type of lower urinary tract symptoms reported by men and women at the time that they were recruited from urology and urogynecology clinics into the Symptoms of Lower Urinary Tract Dysfunction Research Network multicenter, prospective, observational cohort study., Materials and Methods: At 6 research sites treatment seeking men and women were enrolled who reported any lower urinary tract symptoms at a frequency more than rarely during the last month on the LUTS (Lower Urinary Tract Symptoms) Tool. At baseline the study participants underwent a standardized clinical evaluation and completed validated questionnaires. Urological tests were performed, including pelvic/rectal examination, post-void residual urine measurement and urinalysis., Results: A total of 545 women and 519 men were enrolled in the study. Mean ± SD age was 58.8 ± 14.1 years. At baseline nocturia, frequency and a sensation of incomplete emptying were similar in men and women but men experienced more voiding symptoms (90% vs 85%, p = 0.007) and women reported more urgency (85% vs 66%, p <0.001). Women also reported more of any type of urinary incontinence than men (82% vs 51% p <0.001), which was mixed incontinence in 57%. Only 1% of men reported stress incontinence but they had other urinary incontinence, including post-void dribbling in 44% and urgency incontinence in 46%. Older participants had higher odds of reporting symptoms of nocturia and urgency., Conclusions: In this large, treatment seeking cohort of men and women lower urinary tract symptoms varied widely by gender and age. Men reported more voiding symptoms and nonstress or urgency urinary incontinence while women reported more incontinence overall and urgency. Older participants had greater odds of urgency and nocturia., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Severe hemorrhagic cystitis is a major complication in the pediatric population undergoing hematopoietic stem cell transplantation. Percutaneous nephrostomy tube drainage as a treatment for severe hemorrhagic cystitis has rarely been investigated. We examined children undergoing hematopoietic stem cell transplantation for risk factors associated with severe hemorrhagic cystitis, as well as our experience with percutaneous nephrostomy tube placement as an adjunctive management strategy., Materials and Methods: Using prospectively collected data from the Blood and Marrow Transplant Database at the University of Minnesota, we reviewed 40 pediatric patients with severe hemorrhagic cystitis from 1996 to 2010. Specific treatment for each patient was administered at the discretion of the attending physician and generally included bladder irrigation before bladder fulguration or percutaneous nephrostomy tube placement. A percutaneous nephrostomy tube was placed in 11 patients due to the intractable nature of the hemorrhagic cystitis., Results: Of the 11 patients who underwent percutaneous nephrostomy tube drainage 5 (45%) had improvement of the hemorrhagic cystitis within 30 days and the same number had long-term resolution. Among the patients with long-term resolution hemorrhagic cystitis resolved an average of 12.4 days after percutaneous nephrostomy tube placement, and the tubes were removed an average of 8.8 weeks after placement. Through September 2011 mortality among patients with percutaneous nephrostomy tubes was 55% (6 of 11 patients), which was identical to the overall mortality in the severe hemorrhagic cystitis group (22 of 40). No death could be directly attributed to hemorrhagic cystitis or percutaneous nephrostomy tube placement., Conclusions: Placement of percutaneous nephrostomy tubes for treatment of severe hemorrhagic cystitis results in long-term improvement in intractable hemorrhagic cystitis, and is a safe and viable option for the majority of patients., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)