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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: 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 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: The clinician treating patients with neurogenic lower urinary tract dysfunction (NLUTD) needs to balance a variety of factors when making treatment decisions. In addition to the patient's urologic symptoms and urodynamic findings, other issues that may influence management options of the lower urinary tract include cognition, hand function, type of neurologic disease, mobility, bowel function/management, and social and caregiver support. This Guideline allows the clinician to understand the options available to treat patients, understand the findings that can be seen in NLUTD, and appreciate which options are best for each individual patient. This allows for decisions to be made with the patient, in a shared decision-making manner, such that the patient's quality of life can be optimized with respect to their bladder management., Materials and Methods: A comprehensive search for studies assessing patients undergoing evaluation, surveillance, management, or follow-up for NLUTD was conducted from January 2001 through October 2017 and was rerun in February 2021 to capture newer literature. The primary search returned 20,496 unique citations. Following a title and abstract screen, full texts were obtained for 3,036 studies. During full-text review, studies were primarily excluded for not meeting the PICO criteria. One hundred eight-four primary literature studies met the inclusion criteria and were included in the evidence base., Results: This guideline was developed to inform clinicians on the proper evaluation, diagnosis, and risk stratification of adult patients with NLUTD and the non-surgical and surgical treatment options available. Additional statements on urinary tract infection and autonomic dysreflexia were developed to guide the clinician., Conclusions: NLUTD patients may undergo non-surgical and surgical treatment options depending on their level of risk, symptoms, and urodynamic findings. Appropriate follow-up, primarily based on their risk stratification, must be maintained after treatment.

Purpose: The clinician treating patients with neurogenic lower urinary tract dysfunction (NLUTD) needs to balance a variety of factors when making treatment decisions. In addition to the patient's urologic symptoms and urodynamic findings, other issues that may influence management options of the lower urinary tract include cognition, hand function, type of neurologic disease, mobility, bowel function/management, and social and caregiver support. This Guideline allows the clinician to understand the options available to treat patients, understand the findings that can be seen in NLUTD, and appreciate which options are best for each individual patient. This allows for decisions to be made with the patient, in a shared decision-making manner, such that the patient's quality of life can be optimized with respect to their bladder management., Materials and Methods: A comprehensive search for studies assessing patients undergoing evaluation, surveillance, management, or follow-up for NLUTD was conducted from January 2001 through October 2017 and was rerun in February 2021 to capture newer literature. The primary search returned 20,496 unique citations. Following a title and abstract screen, full texts were obtained for 3,036 studies. During full-text review, studies were primarily excluded for not meeting the PICO criteria. One hundred eight-four primary literature studies met the inclusion criteria and were included in the evidence base., Results: This guideline was developed to inform clinicians on the proper evaluation, diagnosis, and risk stratification of patients with NLUTD and the non-surgical and surgical treatment options available. Additional statements on urinary tract infection and autonomic dysreflexia were developed to guide the clinician. This Guideline is for adult patients with NLUTD and pediatric NLUTD will not be discussed., Conclusions: NLUTD patients should be risk-stratified as either low-, moderate-, high-, or unknown-risk. After diagnosis and stratification, patients should be monitored according to their level of risk at regular intervals. Patients who experience new or worsening signs and symptoms should be reevaluated and risk stratification should be repeated.

Introduction: An interprofessional consultation (eConsult) is an asynchronous form of telehealth whereby a primary care provider requests electronic consultation with a specialist in place of an in-person consultation. While eConsults have been successfully implemented in many medical specialties, their use in the practice of urology is relatively unknown., Methods: We included data from four academic institutions: University of Michigan, University of California -San Francisco, University of Washington, and Montefiore Medical Center. We included every urological eConsult performed at each institution from the launch of their respective programs through August 2019. We considered an eConsult "converted" when the participating urologist recommended a full in-person evaluation. We report eConsult conversion rate, response time, completion time, and diagnosis categories., Results: A total of 462 urological eConsults were requested. Of these, 36% were converted to a traditional in-person visit. Among resolved eConsults, with data on provider response time available (n=119),53.8% of eConsults were addressed in less than 1 day; 28.6% in 1 day; 8.4% in 2 days; 3.4% in 3 days; 3.4% in 4 days; 1.7% in 5 days; and 0.8% in ≥6 days. Among resolved eConsults, with data on provider completion time available (n=283), 50.2% were completed in 1-10 minutes; 46.7% in 11-20 minutes; 2.8% in 21-30 minutes; and less than 1% in ≥31 minutes., Discussion: Our study suggests that eConsults are an effective avenue for urologists to provide recommendations for many common non-surgical urological conditions and thus avoid a traditional in-person for low-complexity situations. Further investigation into the impact of eConsults on healthcare costs and access to urological care are necessary., Competing Interests: DECLARATION OF CONFLICTING INTERESTS: The Authors declare that there is no conflict of interest.

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: 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: 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: Although many factors have been proposed to trigger symptom exacerbations (flares) in patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, few studies have investigated these factors empirically. Therefore, we embedded a case-crossover study in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain longitudinal study to evaluate a range of patient reported triggers., Materials and Methods: We assessed exposure to proposed triggers, including diet, physical activities, sedentary behaviors, stress, sexual activities, infection-like symptoms and allergies, by questionnaire a maximum of 3 times when participants reported flares and at 3 randomly selected times. We compared participant preflare to nonflare exposures by conditional logistic regression., Results: In our full analytical sample of 292 participants only 2 factors, including recent sexual activity (OR 1.44, 95% CI 1.06-1.96) and urinary tract infection symptoms (OR 3.39, 95% CI 2.02-5.68), which may overlap with those of flares, were associated with flare onset. On subanalyses restricted to flares with specific suspected triggers additional positive associations were observed for some factors such as certain dietary factors, abdominal muscle exercises, and vaginal infection-like symptoms and fever, but not for other factors (eg stress)., Conclusions: Except for sexual activity our findings suggest that patient reported triggers may be individual or group specific, or they may not contribute to flares. These findings suggest caution in following rigid, global flare prevention strategies and support additional research to develop evidence-based strategies., (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: 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.)

Introduction: Prevention of catheter associated urinary tract infection relies on timely catheter removal and care of indwelling catheters. Educational and quality improvement initiatives to prevent catheter associated urinary tract infection should address the basics of urinary catheter placement and management. Internal medicine residents are an appropriate target for these efforts and they may lack formal training in these issues. We developed a resident driven orientation session that covers basic Foley catheter management principles called the TIPS (Troubleshooting, Indications and Practice Sessions) program., Methods: Urology residents at our institution were queried on common consultations for urinary catheter related issues. The incoming intern internal medicine class at our institution completed a pre-TIPS survey that evaluated their baseline urological experience and knowledge. A 1-hour didactic session led by urology residents was followed by hands-on directed practice with mannequins. The web based survey was repeated 1 month later., Results: Of the total of 60 residents 54 (90%) completed the initial survey. In medical school 38 of 54 residents (70%) had never rotated in urology. Upon repeating the survey at 1 month the response rate was 34 of 60 residents (57%). The proportion of residents confident in their ability to troubleshoot catheter problems increased from 50% to 88% (p <0.05). Knowledge of indications, clot retention and proper catheter technique also improved (p <0.05)., Conclusions: A focused educational session about common urological catheter management scenarios resulted in improved internal medicine resident confidence in catheter troubleshooting and knowledge of basic urinary catheter placement indications. These educational sessions may be a method to improve nonurology resident education and awareness of common urological issues.

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: Urological chronic pelvic pain syndromes have refractory bladder or pelvic pain as the dominant symptom. This has been attributed to changes in the central nervous system caused by a chronic barrage of noxious stimuli. We developed what is to our knowledge a novel challenge protocol that induced bladder distention in study participants to reproduce pain and urinary symptoms. We tested to see whether it could discriminate between persons with urological chronic pelvic pain syndrome-like symptoms and asymptomatic controls., Materials and Methods: We recruited 10 female twin pairs who were discordant for urological chronic pelvic pain syndrome-like symptoms. Before scanning each twin urinated to completion and then consumed 500 cc water. Each twin was scanned with our resting state functional magnetic resonance imaging protocol immediately and approximately 50 minutes after consumption. Time series were extracted from the right and left periaqueductal gray, and the right and left amygdala subregions. We performed the repeated measures 2-sample t-test to assess differences in connectivity between symptomatic and asymptomatic twins before and after bladder distention., Results: Group by condition interaction effects were found from the periaqueductal gray to the right cerebellum VIIIa, the amygdala, the right premotor cortex/supplementary motor area and the insular cortex, and between the amygdala and the frontal pole/medial orbital frontal cortex, the hypothalamus, the insular cortex, the thalamus and the anterior cingulate cortex., Conclusions: These findings demonstrate that our noninvasive bladder distention protocol can detect differences in the processing of urinary sensation between twins discordant for lower urinary tract pain., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Several chronic pain conditions may be distinguished by condition specific brain anatomical and functional abnormalities on imaging, which are suggestive of underlying disease processes. We present what is to our knowledge the first characterization of interstitial cystitis/bladder pain syndrome associated white matter (axonal) abnormalities based on multicenter neuroimaging from the MAPP Research Network., Materials and Methods: We assessed 34 women with interstitial cystitis/bladder pain syndrome and 32 healthy controls using questionnaires on pain, mood and daily function. White matter microstructure was evaluated by diffusion tensor imaging to model directional water flow along axons or fractional anisotropy. Regions correlating with clinical parameters were further examined for gender and syndrome dependence., Results: Women with interstitial cystitis/bladder pain syndrome showed numerous white matter abnormalities that correlated with pain severity, urinary symptoms and impaired quality of life. Interstitial cystitis/bladder pain syndrome was characterized by decreased fractional anisotropy in aspects of the right anterior thalamic radiation, the left forceps major and the right longitudinal fasciculus. Increased fractional anisotropy was detected in the right superior and bilateral inferior longitudinal fasciculi., Conclusions: To our knowledge we report the first characterization of brain white matter abnormalities in women with interstitial cystitis/bladder pain syndrome. Regional decreases and increases in white matter integrity across multiple axonal tracts were associated with symptom severity. Given that white matter abnormalities closely correlated with hallmark symptoms of interstitial cystitis/bladder pain syndrome, including bladder pain and urinary symptoms, brain anatomical alterations suggest that there are neuropathological contributions to chronic urological pelvic pain., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The pathophysiology of interstitial cystitis/painful bladder syndrome remains incompletely understood but is thought to involve central disturbance in the processing of pain and viscerosensory signals. We identified differences in brain activity and connectivity between female patients with interstitial cystitis/painful bladder syndrome and healthy controls to advance clinical phenotyping and treatment efforts for interstitial cystitis/painful bladder syndrome., Materials and Methods: We examined oscillation dynamics of intrinsic brain activity in a large sample of well phenotyped female patients with interstitial cystitis/painful bladder syndrome and female healthy controls. Data were collected during 10-minute resting functional magnetic resonance imaging as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network project. The blood oxygen level dependent signal was transformed to the frequency domain. Relative power was calculated for multiple frequency bands., Results: Results demonstrated altered frequency distributions in viscerosensory (post insula), somatosensory (postcentral gyrus) and motor regions (anterior paracentral lobule, and medial and ventral supplementary motor areas) in patients with interstitial cystitis/painful bladder syndrome. Also, the anterior paracentral lobule, and medial and ventral supplementary motor areas showed increased functional connectivity to the midbrain (red nucleus) and cerebellum. This increased functional connectivity was greatest in patients who reported pain during bladder filling., Conclusions: Findings suggest that women with interstitial cystitis/painful bladder syndrome have a sensorimotor component to the pathological condition involving an alteration in intrinsic oscillations and connectivity in a cortico-cerebellar network previously associated with bladder function., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: We reviewed the significance and achievements of female urologists and urological researchers who have impacted the field of urology., Methods: We reviewed the past and current status of female urologists and researchers in urological investigation., Results: Since 1962, the year that the first woman was board certified as a urologist, the number of women working in urological practice and urological research has steadily increased. As of January 2014 there are 350 female board certified urologists and in tandem a progressive increase in female researchers engaged in urological investigation. Indeed, slightly more than a quarter of urology residents today are women and the match rate is equivalent for men and women seeking a residency slot. Women are beginning to assume leadership positions in academic urology and research environments, working in all areas of the field., Conclusions: As the number of women urologists and female scientists in urological investigation increased in the last 50 years, their contributions significantly advanced the practice of urology and our understanding of the previously unrecognized causes of urological disease.

Purpose: We performed this study to identify the source of complexes recorded during corpus cavernosum electromyography., Materials and Methods: A total of 10 healthy male volunteers 19 to 54 years old (mean age 36) with normal erectile function, participated in the study. A Porti electrodiagnostic system (TMS International, Enschede, The Netherlands) connected to a notebook computer recorded low frequency corpus cavernosum electromyography complexes via penile surface electrodes in 3 phases. In phase 1 baseline corpus cavernosum electromyography was recorded for 30 minutes. In phase 2 penile skin block was performed followed by 30 minutes of corpus cavernosum electromyography recording. Phase 3 consisted of intracavernous block followed by corpus cavernosum electromyography recording for 30 minutes. During all 3 phases startling auditory stimuli and median nerve stimulation were used at random intervals to evoke a sympathetic nervous system response. A suprapubic electrode was used as a control to record sympathetic electrodermal activity., Results: In phase 1 all subjects had spontaneous and evoked corpus cavernosum complexes. The penile skin block used in phase 2 did not affect the presence of these complexes, which remained present in all subjects. During phase 3 no spontaneous or evoked corpus cavernosum complexes were recorded in any subjects, indicating that the intracavernous block eliminated the corporally generated signal. All subjects in all 3 phases demonstrated a sympathetic electrodermal response in the suprapubic electrode in response to evoking stimuli., Conclusions: This study confirms the penile cavernous tissue, and not the penile skin or surrounding tissue, as the origin of the corpus cavernosum electromyography complex. Further refinement of this technique may render it useful in the evaluation of neurogenic and myogenic erectile dysfunction., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated the efficacy and tolerability of mycophenolate mofetil in patients with treatment refractory interstitial cystitis/painful bladder syndrome., Materials and Methods: A total of 210 patients with interstitial cystitis/painful bladder syndrome were to be randomized into a multicenter, placebo controlled trial using a 2:1 randomization. Participants in whom at least 3 interstitial cystitis/painful bladder syndrome specific treatments had failed and who had at least moderately severe symptoms were enrolled in a 12-week treatment study. The primary study end point was the global response assessment. Secondary end points were general and disease specific symptom questionnaires, and voiding diaries., Results: Only 58 subjects were randomized before a black box warning regarding mycophenolate mofetil safety was issued by the manufacturer in October 2007. The trial was halted, and interim analysis was performed and presented to an independent data and safety monitoring board. Six of the 39 subjects (15%) randomized at study cessation were considered responders for mycophenolate mofetil compared to 3 of 19 controls (16%, p=0.67). Secondary outcome measures reflected more improvement in controls., Conclusions: In a randomized, placebo controlled trial that was prematurely halted mycophenolate mofetil showed efficacy similar to that of placebo to treat symptoms of refractory interstitial cystitis/painful bladder syndrome. The results of this limited study cannot be used to confirm or refute the hypothesis that immunosuppressive therapy may be beneficial to at least a subgroup of patients with interstitial cystitis/painful bladder syndrome. Despite study termination lessons can be gleaned to inform future investigations., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We characterized and compared the impact of clinical phenotypic associations between interstitial cystitis/painful bladder syndrome and controls in relation to potentially related conditions, particularly irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome., Materials and Methods: Female patients with interstitial cystitis/painful bladder syndrome and controls with no interstitial cystitis/painful bladder syndrome completed a biopsychosocial phenotyping questionnaire battery which included demographics/history form, self-reported history of associated conditions, and 10 validated questionnaires focused on symptoms, suffering/coping and behavioral/social factors., Results: Questionnaires were completed by 205 patients with interstitial cystitis/painful bladder syndrome and 117 controls matched for age. Prevalence of self-reported associated condition diagnosis in interstitial cystitis/painful bladder syndrome vs controls was irritable bowel syndrome 38.6% vs 5.2%, fibromyalgia 17.7% vs 2.6% and chronic fatigue syndrome 9.5% vs 1.7% (all p <0.001). In the interstitial cystitis/painful bladder syndrome cohort 50.3% reported no other associated condition, 24.4% had interstitial cystitis/painful bladder syndrome + irritable bowel syndrome only, 2.5% had interstitial cystitis/painful bladder syndrome + fibromyalgia only, 1.5% had interstitial cystitis/painful bladder syndrome + chronic fatigue syndrome only, while 20.2% had multiple associated conditions. As the number of associated conditions increased (ie localized, regional, systemic), pain, stress, depression and sleep disturbance increased while social support, sexual functioning and quality of life deteriorated. Anxiety and catastrophizing remained increased in all groups. Symptom duration was associated with this apparent phenotypic progression., Conclusions: Irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome are more prevalent in patients with interstitial cystitis/painful bladder syndrome than in asymptomatic control subjects, and result in significant impact. There are at least 3 distinct clinical phenotypes based on identification of overlapping syndrome patterns. A suggestion that remains to be proven with longitudinal studies is that there may be progression over time from an organ centric to a regional and finally to a systemic pain syndrome with progression of symptom severity, and deterioration of cognitive and psychosocial parameters., (Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Amitriptyline is frequently used to treat patients with interstitial cystitis/painful bladder syndrome. The evidence to support this practice is derived mainly from a small, single site clinical trial and case reports., Materials and Methods: We conducted a multicenter, randomized, double-blind, placebo controlled clinical trial of amitriptyline in subjects with interstitial cystitis/painful bladder syndrome who were naïve to therapy. Study participants in both treatment arms received a standardized education and behavioral modification program. The drug dose was increased during a 6-week period from 10 up to 75 mg once daily. The primary outcome was a patient reported global response assessment of symptom improvement evaluated after 12 weeks of treatment., Results: A total of 271 subjects were randomized and 231 (85%) provided a global response assessment at 12 weeks of followup. Study participants were primarily women (83%) and white (74%), with a median age of 38 years. In an intent to treat analysis (271) the rate of response of subjects reporting moderate or marked improvement from baseline in the amitriptyline and placebo groups was 55% and 45%, respectively (p = 0.12). Of the subgroup of subjects (207) who achieved a drug dose of at least 50 mg, a significantly higher response rate was observed in the amitriptyline group (66%) compared to placebo (47%) (p = 0.01)., Conclusions: When all randomized subjects were considered, amitriptyline plus an education and behavioral modification program did not significantly improve symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome. However, amitriptyline may be beneficial in persons who can achieve a daily dose of 50 mg or greater, although this subgroup comparison was not specified in advance., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We characterized and compared psychosocial phenotypes in a female interstitial cystitis/painful bladder syndrome cohort and an age matched cohort without that diagnosis., Materials and Methods: Female patients with interstitial cystitis/painful bladder syndrome and controls without the condition completed a psychosocial phenotyping questionnaire battery, including a demographics/history form and validated questionnaires focused on a range of presenting symptoms, psychosocial parameters and quality of life. Specific measures included interstitial cystitis symptom and problem index, McGill Pain Questionnaire, Medical Outcomes Study Sleep Scale, Center for Epidemiological Studies Depression Scale, State-Trait Anxiety Inventory, Pain Catastrophizing Scale, Female Sexual Functioning Index and Multidimensional Scale of Perceived Social Support and Medical Outcomes Study Short Form-12 quality of life. Direct comparisons and correlations were made to establish group differences and the strength of associations for psychosocial parameters in patients with interstitial cystitis/painful bladder syndrome., Results: Questionnaires completed by 207 patients with interstitial cystitis/painful bladder syndrome were compared to those of 117 controls matched for age, partner status and education. Compared to controls patients reported significantly more pain (total, sensory and affective), worse physical quality of life, increased sleep dysfunction, depression, catastrophizing, anxiety, stress and moderately more sexual/social function problems. These suffering, coping and social parameters correlated with the degree of general pain but stress, anxiety, depression and catastrophizing further correlated with IC specific symptoms and strongly with decreased quality of life. Pain was strongly associated with physical quality of life, while depression, catastrophizing and stress, and to a lesser extent social support were associated with poor mental quality of life., Conclusions: Patients with interstitial cystitis/painful bladder syndrome have significant cognitive and psychosocial alterations compared to controls.

Purpose: We present normative data for evoked cavernous activity, an electrodiagnostic test that evaluates the autonomic innervation of the corpora cavernosa., Materials and Methods: We enrolled 37 healthy, sexually active and potent men for the study. Each subject completed an International Index of Erectile Function questionnaire, and underwent simultaneous evoked cavernous activity and hand and foot sympathetic skin response testing. The sympathetic skin response tests were performed as autonomic controls., Results: A total of 36 men had discernible evoked cavernous activity and sympathetic skin responses. The mean International Index of Erectile Function erectile domain score was 27. Evoked cavernous activity is a low frequency wave that is morphologically and temporally similar in both corpora. The amplitudes of the responses were highly variable. The latencies, although variable, always occurred after the hand sympathetic skin response. There was no change in the quality or the latency of the evoked cavernous activity with age., Conclusions: Evoked cavernous activity is measurable in healthy, potent men in a wide range of ages. Similar to other evoked responses of the autonomic nervous system, the measured waveform is highly variable but its presence is consistent. The association between evoked cavernous activity and erectile function is to be determined.

Purpose: We review the myriad contributions to urological science by neurologist and engineer, William E. Bradley., Materials and Methods: Remembrances and personal interviews were collated for this article., Results: Doctor Bradley was a pioneer in neurourology. He described a neurophysiological paradigm for micturition, devised urodynamic and electrophysiological techniques, and contributed to the development of genitourinary prosthetic devices., Conclusions: Doctor Bradley made notable and groundbreaking contributions to urology, many of which are still in use today.

Purpose: We investigated the role of the autonomic nervous system in the chronic pelvic pain syndrome by studying blood pressure changes, power spectral analysis of heart rate variability, and hand and foot sympathetic skin responses in men with the chronic pelvic pain syndrome and healthy controls., Materials and Methods: We recruited 22 men with the chronic pelvic pain syndrome and 20 controls. The subjects underwent 5-minute resting and standing blood pressure readings as well as electrocardiogram recordings. Heart rate variability was evaluated using the low frequency (sympathetic) and high frequency (parasympathetic) components of power spectral analysis. We recorded sympathetic skin responses with surface electrodes placed on the dorsal and ventral sides of both hands and feet, measuring amplitude and latency., Results: Mean blood pressure readings for supine and standing were higher in the chronic pelvic pain syndrome group. Between group comparisons revealed no differences in low or high power spectra for supine or standing positions. When subjects were taken to standing from the supine position, mean low frequency power increased in the controls and decreased in the chronic pelvic pain syndrome group. High frequency power, a reflection of parasympathetic activity, decreased significantly in the control group while the decrease was not statistically significant in the chronic pelvic pain syndrome group. There was no difference between the 2 groups for hand and foot sympathetic skin response latency and amplitudes., Conclusions: The heart rate variability and blood pressure changes suggest altered autonomic nervous system responses in men with the chronic pelvic pain syndrome. Sympathetic skin response findings were not conclusive. Heart rate variability and blood pressure findings provide a basis for therapeutic manipulation of the autonomic nervous system for management of the chronic pelvic pain syndrome.

Purpose: Female sexual dysfunction is a common disorder but there are few objective measures of female genital function. We present a novel technique to record electrical activity of the female genital erectile tissue., Materials and Method: We placed concentric needle electrodes in the right clitoral crus and the bulb of 22 healthy women. Following spontaneous activity recording we stimulated the median nerve to activate the sympathetic nervous system. We simultaneously measured evoked activity in the clitoris and bulb, and hand sympathetic skin responses (SSRs)., Results: Spontaneous electrical activity of the clitoris and bulb was present in 13 subjects. A total of 21 subjects had evoked activity in the bulb, while 18 had evoked activity in the clitoris. All subjects had hand SSRs. Evoked genital response latencies were similar to hand SSR latency (p > 0.05). Evoked electrical activity was recordable in the clitoris and bulb but it was more easily performed in the bulb., Conclusions: Evoked electrical activity is more consistently obtained than spontaneous activity. These tests represent possible objective measures of female genital autonomic innervation, which may have relevance to female sexual function.

Purpose: Intravesical potassium chloride has been reported to cause pain in patients with interstitial cystitis and male chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS). We performed the potassium chloride sensitivity test (PST) in subjects with CP/CPPS and healthy men without pelvic pain., Materials and Methods: We recruited 40 men with CP/CPPS and 63 healthy men. The National Institutes of Health CPPS symptom index was used to measure the severity of symptoms. We instilled 100 ml physiological saline (NaCl 0.9%) intravesically. The bladder was emptied and 100 ml potassium chloride solution (KCl 40 mEq) were instilled. The subjects were asked to score urgency (0 to 10) and pain (0 to 10) sensations after each instillation. A positive PST was defined by 5 different cut-off points as the difference in score between KCl and NaCl instillations. Logistic regression analyses and area under the receiver operating characteristics curve were used to determine the predictive power of PST in CP/CPPS., Results: There was no difference in pain and urgency scores between the men with CP/CPPS and controls (p >0.05 for each). Men with CP/CPPS had higher pain and urgency scores with KCl than with NaCl (p = 0.011 and 0.033, respectively). The rates of positive PST were 50% and 36.5% in the CP/CPPS and control groups, respectively (p = 0.160). There was no significant correlation of potassium chloride sensitivity scores with National Institutes of Health symptom scores (p >0.05 for each). The sensitivity, specificity, and positive predictive and negative predictive values of PST were 50%, 63.5%, 46.5% and 66.7%, respectively., Conclusions: Although there was a significant increase in pain and urgency scores following KCl instillation in patients with CP/CPPS, these scores and the rate of positive PST were not statistically different from those of healthy subjects. Thus, PST does not have a good predictive value in the diagnosis of CP/CPPS.

Purpose: Male chronic pelvic pain syndrome (CPPS) is a chronic and debilitating symptom complex, and inconsistent outcomes of antibiotic and anti-inflammatory treatments have created an interest in investigating the neurological mechanisms of CPPS pain. Because chronic pelvic pain likely results in hyperexcitability of dorsal horn neurons, ie central sensitization, thermal algometry may be useful in the assessment of CPPS. We evaluated men with and without CPPS to determine if there were differences between the 2 groups in their responses to noxious heat stimuli., Materials and Methods: We recruited 66 healthy men without CPPS and 36 men with a history of CPPS for the study. Mean age of CPPS subjects was 43.1 years (range 18 to 62) and mean age of controls was 35.1 (range 21 to 61). All subjects with pain completed a National Institutes of Health-Chronic Prostatitis Symptom Index. We conducted thermal sensory tests with a small thermode programmed to deliver 2 series of 4 rapid bursts of noxious heat stimuli to the perineum and the anterior thigh. The subjects reported sensation on a computerized visual analog scale (COVAS) with a manual sliding lever. The average peak COVAS values and time to peak values from thigh and perineum of each series of thermal bursts were compared between CPPS and controls., Results: The mean pain score on questionnaires was 9.7 (4 or greater indicating significant pain), mean urinary score was 4.7 (range 0 to 10) and mean quality of life impact score was 7.3 (range 3 to 13). Compared to controls men with CPPS reported higher mean peak COVAS values in the perineum. There was no difference between groups in the peak COVAS value on the thigh., Conclusions: Men with CPPS have altered heat sensation/pain sensitization in the perineum compared to controls. This finding is another that supports the resemblance of CPPS to other chronic pain syndromes and may help explain why CPPS is often refractory to treatment. Further investigations into male CPPS should focus on the mechanisms inducing and maintaining pain in an effort to treat this condition effectively.

Purpose: We used contrast enhanced magnetic resonance imaging (MRI) of the female genital organs to describe normal anatomy and differences between premenopausal and postmenopausal women., Materials and Methods: A total of 12 healthy premenopausal and 9 healthy postmenopausal women underwent MRI. A 1.5 Tesla system with phased array coils anterior and posterior to the pelvis was used to produce T1-weighted images before and after intravenous administration of MS-325 (Epix Medical, Cambridge, Massachusetts), a new gadolinium based blood pool contrast agent. Select structural dimensions were measured for reference., Results: The clitoris and vestibular bulbs were well delineated on T1-weighted post-contrast images. The clitoral unit formed a brightly enhancing, wishbone-shaped structure lying just anterior to the inverted V of the bulbs, which surrounded the urethra and vagina. The urethral complex had a target-like appearance with layers that were discernible on T1 post-contrast images. The urethra, vagina and rectum formed a distinct complex within uniformly enhancing soft tissue. The vagina was well visualized in premenopausal subjects but without distinguishable mucosal rugae or clearly separate layers in postmenopausal subjects. Postmenopausal subjects were also observed to have smaller labia minora width, vestibular bulb width, vaginal width and wall thickness, and cervical diameter. Pelvic and genital structures were not well visualized on T1 noncontrast images., Conclusions: To our knowledge we describe detailed female genital anatomy for the first time using MRI with MS-325 contrast medium. The clitoris, vestibular bulbs, labia majora and minora, urethra, vagina, cervix and rectum are well visualized on T1 post-contrast images. The observed genital anatomy on MRI was consistent with descriptions in current anatomical texts. Differences in the female genitalia between premenopausal and postmenopausal women were discernible on MRI. These data are important for future studies using MRI for evaluating anatomical anomalies, postoperative changes and female sexual function.