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Purpose: We developed prediction models for severe pain and urinary symptoms after ureteroscopy with ureteral stent placement., Materials and Methods: The development cohort included 424 adults and adolescents enrolled in the multicenter STENTS prospective cohort study who underwent ureteroscopy with stent placement for urinary stones. The validation cohort was an independent prospective cohort of 115 adults. The outcomes were severe pain intensity and pain interference, measured by Patient-Reported Outcomes Measurement Information System, and severe urinary symptoms, measured by the Ureteral Stent Symptom Questionnaire. The top quartile of symptoms on postoperative days 1 and 3 were defined as severe. Generalized estimating equation models were used to predict severe symptoms on postoperative days 1, 3, 5, and 7 to 9 in the development cohort and severe pain interference on days 1 and 7 in the validation cohort., Results: Female sex, younger age, higher BMI, baseline pain interference, number of chronic pain conditions, renal stone location, and history of anxiety predicted severe pain. In the development cohort, the C-statistics were 0.83 (95% CI 0.80-0.85) for severe pain interference and 0.82 (95% CI 0.79-0.84) for severe pain intensity. A model in which baseline urinary symptoms replaced pain interference had excellent discrimination for severe urinary symptoms (C-statistic 0.83; 95% CI 0.81-0.85). In the validation cohort, the C-statistic was 0.7 for severe pain interference (95% CI 0.54-0.78)., Conclusions: Preoperative characteristics accurately predicted severe pain and urinary symptoms after ureteroscopy with stent placement. On further validation, these models could guide clinical decisions to improve surgical outcomes.

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: 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: The STudy to Enhance uNderstanding of sTent-associated Symptoms sought to identify risk factors for pain and urinary symptoms, as well as how these symptoms interfere with daily activities after ureteroscopy for stone treatment., Materials and Methods: This prospective observational cohort study enrolled patients aged ≥12 years undergoing ureteroscopy with ureteral stent for stone treatment at 4 clinical centers. Participants reported symptoms at baseline; on postoperative days 1, 3, 5; at stent removal; and day 30 post-stent removal. Outcomes of pain intensity, pain interference, urinary symptoms, and bother were captured with multiple instruments. Multivariable analyses using mixed-effects linear regression models were identified characteristics associated with increased stent-associated symptoms., Results: A total of 424 participants were enrolled. Mean age was 49 years (SD 17); 47% were female. Participants experienced a marked increase in stent-associated symptoms on postoperative day 1. While pain intensity decreased ∼50% from postoperative day 1 to postoperative day 5, interference due to pain remained persistently elevated. In multivariable analysis, older age was associated with lower pain intensity ( P = .004). Having chronic pain conditions ( P < .001), prior severe stent pain ( P = .021), and depressive symptoms at baseline ( P < .001) were each associated with higher pain intensity. Neither sex, stone location, ureteral access sheath use, nor stent characteristics were drivers of stent-associated symptoms., Conclusions: In this multicenter cohort, interference persisted even as pain intensity decreased. Patient factors (eg, age, depression) rather than surgical factors were associated with symptom intensity. These findings provide a foundation for patient-centered care and highlight potential targets for efforts to mitigate the burden of stent-associated 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: Urinary incontinence is frequently underreported and underdiagnosed in the clinical setting. We analyzed 12 years of data from a large, nationally representative sample of women in the United States to assess the prevalence, severity, and daily impact of urinary incontinence and its subtypes at the population level., Materials and Methods: We analyzed data from 15,003 women aged ≥20 years who participated in the 2005-2016 National Health and Nutrition Examination Survey. We estimated the prevalence of urinary incontinence in the prior year, overall and by subtype (stress, urgency or mixed). Among women with urinary incontinence, we additionally assessed symptom severity using the validated 4-level Incontinence Severity Index, as well as impact on daily activities., Results: The 2005-2016 prevalence of any urinary incontinence was 53%; 16% of women had mixed urinary incontinence, 26% had stress only and 10% had urgency only. While urgency urinary incontinence and mixed urinary incontinence were highest among women aged ≥60 years, stress urinary incontinence was highest among women aged 40-59 years. NonHispanic Black women had higher prevalence of urgency urinary incontinence and lower prevalence of stress urinary incontinence compared to other racial/ethnic groups. Of women with urinary incontinence, 30% reported moderate or severe symptoms, which were more common among older than younger women. In addition, 24% of women with urinary incontinence reported that the condition affected their daily activities., Conclusions: Our study demonstrates a high prevalence of urinary incontinence among a nationally representative population of women in the United States, with many reporting that urinary incontinence affected their daily activities. Age and racial/ethnic trends varied by urinary incontinence subtype.

Purpose: The objective of this study was to examine national trends in the surgical management of urinary incontinence in women in the United States from 2004 to 2013., Materials and Methods: We analyzed the CDM (Optum® de-identified Clinformatics® Data Mart) for women 18 to 64 years old and the CMS (Centers for Medicare and Medicaid Services) Medicare 5% Sample for women 65 years old or older. We created annual cross-sectional cohorts and assessed trends in the annual prevalence of urinary incontinence related surgical procedures overall and by age, race/ethnicity and geographic region., Results: We observed a decline in the percent of women with urinary incontinence who underwent surgical treatment according to the CMS (from 4.7% in 2004 to 2.7% in 2013) and the CDM (from 12.5% in 2004 to 9.1% in 2013). This trend persisted independently of age, race/ethnicity and geographic region. Slings were the most common procedure but started to decline in 2011, ultimately decreasing by about 50% during the study period. Compared to other groups the prevalence of urinary incontinence related surgical procedures, including slings, was highest among women 35 to 54 years old and White women, and lowest among women residing in the Northeast. These sociodemographic patterns persisted with time. During the study period injection procedures remained stable, sacral neuromodulation increased slightly but remained uncommon and suspension decreased to nearly 0% of all anti-incontinence procedures., Conclusions: Surgical management of female urinary incontinence experienced several shifts from 2004 to 2013, including a decline in sling procedures. Age, racial/ethnic and regional differences in treatment persisted with time. Improved understanding of the drivers of these trends may help direct future development of treatments of pelvic floor disorders.

Purpose: Our current understanding of recent trends in the management of lower urinary tract symptoms associated with benign prostatic hyperplasia is incomplete, particularly in younger men. The 2018 Urologic Diseases in America Project attempted to fill this gap by analyzing multiple large administrative claims databases which include men of all ages and permit longitudinal followup. To our knowledge we report these findings for the first time in the scientific literature., Materials and Methods: The 2 data sources used in this study included the de-identified Optum® Clinformatics® Data Mart database for men 40 to 64 years old and the Medicare 5% Sample for men 65 years old or older. To assess trends in lower urinary tract symptoms/benign prostatic hyperplasia related medication prescriptions and surgical procedures from 2004 to 2013 we created annual cross-sectional cohorts and a longitudinal cohort of patients with incident lower urinary tract symptoms/benign prostatic hyperplasia and 5 years of followup., Results: The use of medications related to lower urinary tract symptoms/benign prostatic hyperplasia increased with age, particularly among men 40 to 60 years old. While medication use increased with time, surgical procedures decreased. Increasing age correlated with a higher rate of surgical procedures in the longitudinal cohort. Younger men were more likely to elect treatments of lower urinary tract symptoms/benign prostatic hyperplasia which reportedly optimize sexual function., Conclusions: Medication use increased and surgery decreased during the study period. Treatment approaches to lower urinary tract symptoms/benign prostatic hyperplasia varied greatly by patient age. While the minority of men in the fifth and sixth decades of life required treatment, a sharp increase in treatment use was seen between these decades. Younger men were more likely to elect less invasive surgical options. Future studies of lower urinary tract symptoms/benign prostatic hyperplasia should focus on age specific treatment selection.

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: Lower urinary tract symptoms are prevalent and burdensome, yet methods to enhance diagnosis and appropriately guide therapies are lacking. We systematically reviewed the literature for human studies of biomarkers associated with lower urinary tract symptoms., Materials and Methods: PubMed®, EMBASE® and Web of Science® were searched from inception to February 13, 2018. Articles were included if they were in English, performed in benign urological populations without neurological disorders or interstitial cystitis/bladder pain syndrome, and assessed a biomarker's association with or ability to predict specific lower urinary tract symptoms or urological conditions. Bioinformatic pathway analyses were conducted to determine whether individual biomarkers associated with symptoms are present in unifying pathways., Results: Of 6,150 citations identified 125 met the inclusion criteria. Most studies (93.6%) assessed biomarkers at 1 time point and were cross-sectional in nature. Few studies adjusted for potentially confounding clinical variables or assessed biomarkers in an individual over time. No individual biomarkers are currently validated as diagnostic tools for lower urinary tract symptoms. Compared to controls, pathway analyses identified multiple immune response pathways that were enriched in overactive bladder syndrome and cell migration/cytoskeleton remodeling pathways that were enriched in female stress incontinence., Conclusions: Major deficiencies in the existing biomarker literature include poor reproducibility of laboratory data, unclear classification of patients with lower urinary tract symptoms and lack of adjustment for clinical covariates. Despite these limitations we identified multiple putative pathways in which panels of biological markers need further research.

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: To improve the potential for finding clinically important subtypes of patients with lower urinary tract symptoms we developed the CASUS (Comprehensive Assessment of Self-reported Urinary Symptoms). We used it to present data on the experiences of lower urinary tract symptoms in treatment seeking women and men from a prospective observational cohort., Materials and Methods: We created an initial list of lower urinary tract symptoms that were confirmed in 22 qualitative interviews with providers, and 88 qualitative interviews with care seeking and noncare seeking women and men with lower urinary tract symptoms. Items from extant measures were adopted and revised, and new items were developed. All items were evaluated for understanding in 64 cognitive interviews. Items were administered to a prospective cohort of female and male patients with lower urinary tract symptoms who were seeking care. Analyses were done to describe item response distributions and correlations among item responses separately for women and men., Results: A total of 444 males and 372 females provided responses to the CASUS. Several sets of items showed different relationships for women compared to men. In particular the associations between sensation related items and incontinence related items were generally positive among females but often negative among males., Conclusions: After using an intensive development process the CASUS addresses a wide range of lower urinary tract symptoms. It should help identify clinically important subtypes of patients. Further, item collection can provide the foundation for shorter measures for use in the clinic and as trial end points.

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: The primary objective of this study was to evaluate reasons for seeking care among men and women with lower urinary tract symptoms., Materials and Methods: Participants were recruited from urology and urogynecology clinics, and the community. The sample was enriched with persons expected to have abnormal or diminished bladder sensations (eg participants with lower back surgery and participants 65 years old or older). Interviews were performed in person beginning with an open-ended assessment of urinary symptoms and associated bother followed by more directed questions, including reasons for seeking or not seeking treatment. We also examined the relationship between symptom frequency and bother using the LUTS (Lower Urinary Tract Symptoms) Tool., Results: A total of 88 participants, including 38 men and 50 women, with a mean ± SD age of 52.2 ± 14.3 years provided information about urinary symptoms, including a range of quality of life consequences and coping behaviors. They sought treatment mostly because of new, continuing or bothersome symptoms. Factors associated with not seeking treatment included low symptom severity and concerns about the costs vs the benefits of treatment (eg side effects of medication). Symptom frequency and bother were associated with each other across symptoms assessed by the LUTS Tool., Conclusions: In this large qualitative study we obtained useful insights into the impact of lower urinary tract symptoms from the perspective of the person with the symptoms. Removing barriers and misconceptions about the treatment of lower urinary tract symptoms may increase the number of people who seek clinical care and improve the clinical course of men and women who experience lower urinary tract symptoms., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Diet, fluid intake and caffeine, alcohol and tobacco use may have effects on lower urinary tract symptoms. Constructive changes in these modifiable nonurological factors are suggested to improve lower urinary tract symptoms. To better understand the relationship between nonurological factors and lower urinary tract symptoms, we performed a systematic literature review to examine, grade and summarize reported associations between lower urinary tract symptoms and diet, fluid intake and caffeine, tobacco and alcohol use., Materials and Methods: We performed PubMed® searches for eligible articles providing evidence on associations between 1 or more nonurological factors and lower urinary tract symptoms. A modified Oxford scale was used to grade the evidence., Results: We reviewed 111 articles addressing diet (28 studies), fluid intake (21) and caffeine (21), alcohol (26) and tobacco use (44). The evidence grade was generally low (6% level 1, 24% level 2, 11% level 3 and 59% level 4). Fluid intake and caffeine use were associated with urinary frequency and urgency in men and women. Modest alcohol use was associated with decreased likelihood of benign prostatic hyperplasia diagnosis and reduced lower urinary tract symptoms in men. Associations between lower urinary tract symptoms and ingestion of certain foods and tobacco were inconsistent., Conclusions: Evidence of associations between lower urinary tract symptoms and diet, fluid intake and caffeine, alcohol and tobacco use is sparse and mostly observational. However, there is evidence of associations between increased fluid and caffeine intake and urinary frequency/urgency, and between modest alcohol intake and decreased benign prostatic hyperplasia diagnosis and lower urinary tract symptoms. Given the importance of these nonurological factors in daily life, and their perceived impact on lower urinary tract symptoms, higher quality evidence is needed., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Lower urinary tract symptoms are common in the United States population, leading to significant economic, quality of life and public health issues. The burden will increase as the population ages, and risk factors for lower urinary tract symptoms, including diabetes and obesity, remain highly prevalent. Improving clinical management and establishing the knowledge base to prevent lower urinary tract symptoms will require a comprehensive research approach that examines factors beyond the lower urinary tract. While the study of extra-lower urinary tract factors has increased recently, current urological research does not systematically account for the broad set of potential contributing factors spanning biological, behavioral, psychological/executive function and sociocultural factors. A comprehensive assessment of potential contributors to risk, treatment response and progression is necessary to reduce the burden of this condition in the United States., Materials and Methods: We considered challenges to continuing the predominantly lower urinary tract dysfunction centric approach that has dominated previous research of lower urinary tract symptoms., Results: We developed a new, comprehensive framework for urology research that includes a broader set of potential factors contributing to lower urinary tract symptoms. This framework aims to broaden research to consider a comprehensive set of potential contributing factors and to engage a broad range of researchers in the investigation of as many extra-lower urinary tract factors as possible, with the goal of improving clinical care and prevention., Conclusions: We propose a new framework for future urology research, which should help to reduce the medical and economic burden of lower urinary tract symptoms in the United States population., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To address gaps in understanding and treating lower urinary tract symptoms, the NIDDK created the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN). The goals of LURN are to work collaboratively to 1) identify and explain the important subtypes of lower urinary tract symptoms; 2) improve the measurement of patient experiences of lower urinary tract symptoms; 3) disseminate novel findings to researchers, clinicians and patients; and 4) generate data, research tools and biological samples for future studies., Materials and Methods: As a first step in understanding subtypes of lower urinary tract symptoms, LURN will focus on disorders of urinary sensation (eg urgency) and their causes. These are being examined with respect to patient experience, organism or systemic factors, genitourinary organs and tissues, and cellular/molecular factors. This is being achieved via an observational cohort study that is currently enrolling patients with lower urinary tract symptoms (target number 1,000) and that will extensively characterize patients with lower urinary tract symptoms. Future studies embedded within the observational cohort study will focus on neuroimaging and sensory testing, biomarkers and organ based factors. To advance the science of measurement of lower urinary tract symptoms, LURN is also developing and evaluating a comprehensive set of self-report questions to provide more granular assessments of lower urinary tract symptoms., Results: LURN has taken its first steps by developing a framework for studying lower urinary tract symptom subtypes., Conclusions: In developing this framework, LURN is choosing an initial domain on which to focus (sensory experiences), and creating and executing protocols designed to improve measurement of self-reported symptoms and identify patient subtypes., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We examine the cross-sectional associations between baseline characteristics and sexual function and the longitudinal associations between change in lower urinary tract symptoms and change in sexual function among men with benign prostatic hyperplasia., Materials and Methods: We studied lower urinary tract symptoms assessed by the AUA-SI and sexual function determined by the BMSFI in men enrolled in the MTOPS study. The cross-sectional cohort included 2,916 men who completed the BMSFI at baseline. The longitudinal cohort included 672 men who were randomized to placebo and had completed the BMSFI at baseline and at least once during a 4-year followup. Multiple adjusted linear modeling for each domain of the BMSFI was performed to assess associations of sexual function with lower urinary tract symptoms., Results: After adjustment for baseline demographic and clinical characteristics, increased age, less education, obesity and severe lower urinary tract symptoms were each significantly associated with poorer sexual drive, erectile function, ejaculatory function, sexual problem assessment and overall satisfaction in the cross-sectional cohort. However, none of these baseline characteristics predicted change in sexual function in the longitudinal cohort. Decline in sexual function in all sexual function domains associated with worsening of lower urinary tract symptoms in this group was small., Conclusions: Increased age, less education, obesity and more severe lower urinary tract symptoms were individually associated cross-sectionally, but not longitudinally, with poorer sexual function in men with lower urinary tract symptoms/benign prostatic hyperplasia. The decline in sexual function associated with worsening of lower urinary tract symptoms in men assigned to placebo was small., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We examined the effects of doxazosin, finasteride and combined therapy in men with lower urinary tract symptoms associated with benign prostatic hyperplasia on sexual function, as assessed by the Brief Male Sexual Function Inventory during 4 years., Materials and Methods: The MTOPS (Medical Therapy of Prostatic Symptoms) study was a multicenter, randomized, double-blind, placebo controlled clinical trial with a primary outcome of time to benign prostatic hyperplasia progression. Change in sexual function was a secondary outcome. We analyzed the records of 2,783 men enrolled in the study who completed the inventory at baseline and at least once during followup., Results: In men enrolled in MTOPS sexual function decreased with time. Men assigned to finasteride and combined therapy experienced overall statistically significant but slight worsening of ejaculatory function compared with men on placebo. Men assigned to combined therapy also experienced significant worsening in erectile function and sexual problem assessment. There was no significant difference in changes in any inventory domain in men assigned to doxazosin alone compared to placebo., Conclusions: This study significantly extends understanding of the effects of long-term treatment with these drugs on sexual function in men with lower urinary tract symptoms associated with benign prostatic hyperplasia. Treatment with finasteride or combined therapy was associated with worsening sexual function while treatment with doxazosin alone was associated with minimal negative impact, if any. Physicians should discuss with their patients the possible long-term effects of these drugs for lower urinary tract symptoms associated with benign prostatic hyperplasia on sexual function., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We examined the effects of doxazosin, finasteride and combination therapy among men with benign prostatic hyperplasia on quality of life assessed with MOS-SF-36 (Medical Outcomes Study Short-Form 36) and 2 disease specific instruments (BII, benign prostatic hyperplasia Impact Index and I-PSS-QoL, International Prostate Symptom Score-QoL) during 4 years., Materials and Methods: The MTOPS (Medical Therapy of Prostatic Symptoms) study was a multicenter, randomized, double-blind, placebo controlled clinical trial with a primary outcome of time to benign prostatic hyperplasia progression. Change in quality of life was a secondary outcome. A total of 2,872 men enrolled in the MTOPS study who had 3 baseline quality of life measures and at least 1 followup measure by any of the quality of life instruments were analyzed., Results: Compared with men assigned to placebo, men assigned to doxazosin and combination experienced a statistically significant improvement in the BII at year 4. Men assigned to each of the drug groups also experienced a significant improvement in the I-PSS-QoL compared with those assigned to placebo. Considering longitudinal changes during 4 years, a significant improvement in BII and I-PSS-QoL scores was observed in men assigned to the drug groups compared with those assigned to placebo. However, there were no significant differences for the MOS-SF-36 subscales and summary scores when drug groups were compared with the placebo group., Conclusions: The quality of life of men treated with doxazosin, finasteride, and the drugs combined generally improved when assessed with the BII and the I-PSS-QoL compared with those treated with placebo. Quality of life did not show improvement when measured by the MOS-SF-36., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Transurethral bladder tumor resection is associated with imperfect clinical staging and incomplete tumor removal. Transurethral prostate resection may be complicated by inadvertent damage to the urinary sphincter, bladder neck and trigone. We performed a multicenter pilot and feasibility study of a novel working element for resectoscopes designed to improve the efficacy and safety of transurethral endoscopic surgery., Materials and Methods: An innovative working element for resectoscopes was developed to convert the standard in/out linear/axial movement at the handgrip into a side-to-side, bidirectional, lateral rotating motion. The device is compatible with current optical technology and conventional electrocautery generators, and it has been granted marketing approval. It consists of variably sized cutting loops designed for transurethral resection of bladder tumors and the prostate. To date 80 patients with bladder cancer (38) or benign prostatic hyperplasia (42) have undergone surgery with this instrument at our 3 clinical sites., Results: No safety concerns were evident. When used during transurethral bladder tumor resection, lateral resection at the base of the tumor enabled accurate depth of penetration into the bladder wall, which may decrease the risk of bladder perforation and improve pathological assessment of tumor invasion. During transurethral prostate resection this novel tool facilitated dissection of adenoma adjacent to the verumontanum and prostatovesical junction, which may decrease the risk of sphincteric damage and bladder neck injury., Conclusions: A novel resectoscope is currently under prospective clinical investigation to establish its surgical and pathological efficacy, ease of use and side effect profile. Current data suggest that the learning curve is mild, its use is safe and it provides distinct advantages when used for transurethral resection of bladder tumors and the prostate.

Purpose: We investigated the immunohistochemical localization of metallothionein (MT) in renal cell carcinoma and determined the potential role of MT expression as a possible prognostic variable for tumor proliferation and progression., Materials and Methods: Tumor tissue blocks from 70 patients with renal cell carcinoma who underwent radical or partial nephrectomy were investigated. Mean followup plus or minus standard error was 36 +/- 3 months. Immunohistochemical testing was performed by the avidin-streptavidin method using a monoclonal mouse antiMT antibody. MT staining intensity in samples was evaluated semiquantitatively. The subcellular distribution of MT was also determined. Staining characteristics were compared with the clinicopathological results., Results: MT immunostaining was found in 39 of 70 tumors (55.7%) and subcellulary MT was localized in the cytoplasm, nucleus and cell membrane. The survival of patients with MT immunostaining was significantly worse than that of those with MT negative results (p = 0.02). A significant relationship of higher tumor grade and MT staining intensity was observed in grades I and III (p = 0.01), and grades II and III (p = 0.02) tumors. No association was found of MT expression and pathological stage. Sarcomatoid tumors showed significantly higher MT expression than clear cell, papillary, granular or chromophobe tumors (p = 0.02, 0.001, 0.01 and 0.01, respectively). MT expression was not an independent prognostic variable., Conclusions: MT over expression seems to be associated with malignant behavior and poor prognosis in renal cell carcinoma. Therefore, MT expression may be considered a useful marker of less differentiated and more aggressive renal cell carcinoma.

Purpose: Penile erection is a complex neurovascular phenomenon that takes place with the active contribution of arterial and sinusoidal structures. However, some authors claim that larger veins including the deep dorsal veins that produce contractions, might be involved in the physiology of erection. This study was designed to clarify the contractile properties of deep dorsal penile veins (DDPV)., Materials and Methods: The effect of serotonin (5-HT), noradrenaline (NA), adenosine triphosphate (ATP) and acethylcholine (Ach) on the isolated DDPVs of 16 impotent men, 9 with veno-occlusive dysfunction and 7 without venous leakage, and 5 potent men (controls) who underwent radical prostatectomy, were examined in vitro., Results: Although NA, ATP and Ach had no effect, 5-HT produced concentration-dependent contractions. Emax and pEC50 of 5-HT were 411 +/- 10 mg., 5.92 +/- 0.25; 1020 +/- 260 mg., 5.83 +/- 0.24 and 160 +/- 40 mg., 6.4 +/- 0.22 in controls and patients who had venous leakage and no venous leakage, respectively. Samples of controls were contracted only with 5-HT2 agonist, DOI (pEC50 = 5.63 +/- 0.02), and these contractions were antagonized with 5-HT2 antagonist ketanserin. On the other hand, both DOI (pEC50 = 6.30 +/- 0.77) and 5-HT1 agonist, 5-CT (pEC50 = 6.23 +/- 0.21) produced venoconstriction in patients with veno-occlusive dysfunction., Conclusions: The present findings suggest that 5-HT receptor functions in the DDPVs are of 5-HT2 subtype in potent men and the altered response to 5-HT in patients with veno-occlusive disease may play a role in the pathophysiology of impotence.

Purpose: Although extracorporeal shock wave lithotripsy (ESWL) is known to cause pathologic changes in various organs, little is known about its effects on the ureter, the target organ in ESWL of ureteral stones in situ. In this study, we sought to determine the short-term effects of ESWL on the ureter., Materials and Methods: Left lower ureteral segments of 21 rabbits were removed to serve as the control group and 2000 shocks were applied to the right lower ureters. Groups of 7 rabbits were sacrificed 1, 3 and 5 days after shock wave exposure. While histomorphological alterations were examined under light and transmission electron microscopy, contractility of all ureters was determined in organ baths., Results: The epithelial cells disclosed no change after shock wave application. Histologically the muscular layer was the most affected part of the ureter. There was interstitial and intracellular edema on light microscopy and marked chromatin and mitochondrial changes at the subcellular level. The adventitial layer was also edematous. These changes were prominent on days 1 and 3 and returned to normal on day 5. The contractility of the ureters on day 1 was significantly reduced (p < 0.05). However, the contractility of the samples on days 3 and 5 were not significantly different from controls., Conclusion: Our findings demonstrate that electromagnetic shock waves produce reversible morphological and functional changes in rabbit ureteric muscle.