Lower Urinary Tract Dysfunction Research Research Articles

Impact of Sleep Disturbance, Physical Function, Depression and Anxiety on Male Lower Urinary Tract Symptoms: Results from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).

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. 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. 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. 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.

Survey of lower urinary tract symptoms in United States women using the new lower urinary tract dysfunction research Network-Symptom Index 29 (LURN-SI-29) and a national research registry.

An online bladder health survey was administered to national registry volunteers to: (1) determine the feasibility of using ResearchMatch for studying lower urinary tract symptoms (LUTS); (2) pilot the new, comprehensive Lower Urinary Tract Dysfunction Research Network Symptom Index-29 (LURN-SI-29) and determine its ability to detect known associations with LUTS; and (3) explore novel areas of bladder health in community-based women. A cross-sectional web-based survey was administered to a random sample of ResearchMatch adult female, transgender and non-binary volunteers. Participant demographics, health characteristics, the LURN-SI-29, and LUTS-related experiences were collected. A total of 1725 ReseachMatch volunteers with a mean age of 44.0 years completed the study and were eligible for the analysis. Participants were primarily white, cisgendered, highly educated, nulliparous, and premenopausal. The median LURN-SI-29 score was 17 (interquartile range: 11-26). More than half the sample reported urinary urgency (71.0%), nocturia (65.7%), and stress incontinence (52.3%) a "few times" or more in the last 7 days. Approximately half reported sensation of incomplete bladder emptying (49.6%) with one-third reporting urgency incontinence (37.6%); notably, 52.6% of respondents reported being at least "somewhat" bothered by LUTS. LURN-SI-29 scores increased with age, body mass index, decrements in self-reported health, medical comorbidity, parity, menopausal status, and urinary symptom bother, providing evidence of convergent validity. LURN-SI-29 scores varied by race and education, with the lowest scores in Asian and highly educated women. Overall, the prevalence and spectrum of LUTS in an online research registry of women volunteers were high and comparable to other population-based samples. The new LURN-SI-29 demonstrated its ability to detect expected associations with demographic and health characteristics in a nonclinical population.

Turkish validation and reliability of the symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index-29 (LURN SI-29) questionnaire in patients with lower urinary tract symptoms.

To evaluate the validity and reliability of the Turkish version of the Symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index-29 (LURN SI-29). Patients with lower urinary tract symptoms (LUTS) were included in a single-center study between January and April 2021. Patients' demographics, such as age, sex, and level of education, were recorded. The Turkish version of the LURN SI-29 and the International Prostate Symptom Score (IPSS) were administered to all patients, and the Urogenital Distress Inventory (UDI-6) was additionally administered to female patients. Construct validity was evaluated by confirmatory factor analysis. Concurrent validity was evaluated with correlations to similar measures. Internal consistency (Cronbach's alpha) and split-half reliability analyses were used to establish the scale's reliability. A total of 295 participants, 35.3% females and 64.7% males, were included in the final analysis. The mean age was 56.4 ± 11.7 years. The median total LURN SI-29 scores were 38.0 (26-50) and 26.0 (18-43) for female and male patients, respectively. The LURN SI-29 scale showed a high correlation with IPSS and UDI-6 scales (r = .758, p < .001; r = .774, p < .001, respectively) in concurrent validity analysis. Cronbach's alpha coefficient of the scale and all subscales were greater than 0.70 for both female and male patients. This measurement tool can potentially be used to evaluate LUTS in Turkish women and men. Further studies should be performed to reveal the clinical usefulness of this scale.

Experimental Pain and Auditory Sensitivity in Overactive Bladder Syndrome: A Symptoms of the Lower Urinary Tract Dysfunction Research Network (LURN) Study.

The objective of this study was to investigate the presence of nonbladder sensory abnormalities in participants with overactive bladder syndrome (OAB). 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. 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. 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.

Relationship of symptom severity and bother in individuals seeking care for lower urinary tract symptoms.

Bother attributed to lower urinary tract symptoms (LUTS) drives care-seeking and treatment aggressiveness. The longitudinal relationship of LUTS severity and bother in a care-seeking cohort, however, is not well understood. We aim to conduct a longitudinal evaluation of LUTS severity and bother and identify characteristics of patients with discordant LUTS bother relative to severity. Men and women with LUTS seeking care at six US tertiary care centers enrolled in the symptoms of lower urinary tract dysfunction research network study. Patients reporting at least one urinary symptom based on the LUTS Tool were prospectively enrolled from June 2015 to January 2017. Correlations were used to assess the relationship between LUTS severity and bother. Discordance scores (ie, the difference between bother and severity) were used to classify patients with high and low bother. Patients were classified as having high or low bother phenotypes if scores were one standard deviation above or below zero, respectively. Repeated measures multinomial logistic regression evaluated characteristics associated with high and low bother phenotypes. LUTS severity and bother were at least moderately correlated for all symptom items and highly correlated for 13 out of 21 items. Correlations were highest for urgency, and lowest for daytime frequency and urinary incontinence. Odds of being in high bother phenotype were lowest at 3 and 12 months (3 months vs baseline odds ratio [OR] = 0.71, 95% confidence ninterval [CI] = 0.54-0.94; 12 months vs baseline OR = 0.66, 95% CI = 0.48-0.91), and highest for those who endorsed all urgency questions (OR = 3.65, 95% CI = 2.17-6.13). Odds of being in the low bother phenotype were lowest for patients who endorsed all urgency items (OR = 0.33, 95% CI = 0.26-0.42), and all frequency items (OR = 0.68, 95% CI = 0.53-0.88). LUTS severity and bother correlate highly and measurement of both in clinical practice is likely redundant. There are patient factors associated with discordance which may justify additional evaluation.

Patient demographic and psychosocial characteristics associated with 30-day recall of self-reported lower urinary tract symptoms.

Measurement of self-reported lower urinary tract symptoms (LUTS) typically uses a recall period, for example, "In the past 30 days…." Compared to averaged daily reports, 30-day recall is generally unbiased, but recall bias varies by item. We examined the associations between personal characteristics (eg, age, symptom bother) and 30-day recall of LUTS using items from the Symptoms of Lower Urinary Tract Dysfunction Research Network Comprehensive Assessment of Self-reported Urinary Symptoms questionnaire. Participants (127 women and 127 men) were recruited from 6 US tertiary care sites. They completed daily assessments for 30 days and a 30-day recall assessment at the end of the study month. For each of the 18 tested items, representing 10 LUTS, the average of the participant's daily responses was modeled as a function of their 30-day recall, the personal characteristic, and the interaction between the 30-day recall and the characteristic in separate general linear regression models, adjusted for sex. Nine items representing 7 LUTS exhibited under- or overreporting (recall bias) for at least 25% of participants. Bias was associated with personal characteristics for six LUTS. Underreporting of incontinence was associated with older age, lower anxiety, and negative affect; overreporting of other LUTS was associated with, symptom bother, symptom variability, anxiety, and depression. We identified under- or overreporting that was associated with personal characteristics for six common LUTS. Some cues (eg, less bother and lower anxiety) were related to recall bias in an unexpected direction. Thus, providers should exercise caution when making judgments about the accuracy of a patient's symptom recall based on patient demographic and psychosocial characteristics.

Prevalence, subtypes, and correlates of nocturia in the symptoms of Lower Urinary Tract Dysfunction Research Network cohort.

We determined the prevalence, severity, and correlates of nocturia in a large clinical cohort of patients. Patients presenting with lower urinary tract symptoms (LUTS) completed 3-day bladder diaries. Nocturia was quantified based on the mean number of nighttime voids documented over the 3 days. Nocturia subtypes (global polyuria, nocturnal polyuria [NP], reduced global bladder capacity, and reduced nocturnal bladder capacity) were assessed. Bother due to nocturia was measured by the LUTS Tool. Sleep quality was assessed with the Patient-Reported Outcomes Measurement Information System Sleep Scale. Multivariable multinomial regression was used to explore patient characteristics associated with nocturia. In 502 participants with analyzable diaries (285 men and 217 women), the mean number of nocturia episodes over 3 days was 0 in 103 (20.5%), >0 to <1 in 151 (20.1%), 1 to <2 in 165 (32.9%), and ≥2 in 83 (16.5%). Sixty-seven percent of the participants with nocturia ≥1 reported significant bother from their nocturia. NP was the most common nocturia subtype and was present in 17% of those with nocturia = 0, 40% of those with nocturia >0 to <1, 65% of those with nocturia 1 to <2%, and 77% with nocturia 2+. Higher degrees of nocturia were associated with male sex, greater sleep disturbance, and a higher likelihood of exhibiting multiple nocturia subtypes. Nocturia ≥1 occurred in 49% of LUTS patients and caused significant bother in the majority of them. The most common subtype was NP, but a substantial proportion of patients exhibited additional characteristics.

Longitudinal changes in symptom-based female and male LUTS clusters.

Lower urinary tract symptoms (LUTS) are diverse in type and variable in severity. We examined symptom change within the Symptoms of the Lower Urinary Tract Dysfunction Research Network (LURN) Observational Cohort study identified clusters over time and tested associations with treatments received. Patient-reported LUTS and treatment data were collected at multiple time points between baseline and 12 months from the LURN Observational Cohort study. LUTS severity scores were calculated to summarize changes in symptom reporting over time in previously identified LURN clusters. Repeated measures linear regression models tested adjusted associations between cluster membership and severity scores. Four-hundred seventeen men and 396 women were classified into improved, unchanged, and worsened symptoms between baseline and 12 months (men: 44.1%, 40.5%, and 15.3%; women: 55.8%, 33.1%, 11.1%, respectively). Improvement in LUTS severity scores varied by cluster (estimated adjusted mean change from baseline range: -.04 change in standard deviations of severity scores (ΔSD) to -.67 ΔSD). Prostate surgery was associated with improved severity scores (-.63 ΔSD) in men, while stress incontinence surgery was associated with improved severity scores (-.88 ΔSD) in women. Symptom improvement varied by cluster indicating response to therapy differs amongst subtypes of patients with LUTS. The differential improvement of patients in clusters suggests mechanistic differences between clusters and may aid in selecting more targeted treatments in the future.

A New Brief Clinical Assessment of Lower Urinary Tract Symptoms for Women and Men: LURN SI-10.

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. 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. 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). 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.

Are three-day voiding diaries feasible and reliable? Results from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) cohort.

The aims of this study were to assess the completeness of voiding diaries in a research context and to correlate diary data with patient-reported questionnaires. Men and women enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) were given a 3-day voiding and fluid-intake diary to fill-out. Diaries were assessed for completeness and intake-output imbalances. They were assigned to one of four categories based on a percentage of missing data and fluid imbalance: no diary submitted, unusable (>40% missing void or intake volumes, or unphysiological fluid imbalance), usable but not complete, and complete. A total of 1064 participants were enrolled and 85% (n = 902) returned the bladder diary. Of the diaries returned, 94% (n = 845) had data on three separate days, 87% (n = 786) had no missing intake volumes, 61% (n = 547) had no missing voided volumes, and 70% (n = 635) had a fluid imbalance within 3 L across the 3-day time period, resulting in 50% (n = 448) of participants with 100% complete diaries. Younger age was associated with a higher likelihood of not submitting a diary, or submitting an unusable diary. Women had a higher likelihood of submitting an unusable diary or a usable but incomplete diary. Overall, 50% of LURN participants returned voiding diaries with perfectly complete data. Incomplete data for voided volumes was the most common deficiency. There was only a moderate correlation between diary data and questionnaire responses, indicating that diaries are a source of unique information.

A new outcome measure for LUTS: Symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index-29 (LURN SI-29) questionnaire.

To develop a representative, self-report assessment of lower urinary tract symptoms (LUTS) for men and women, the symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index-29 (LURN SI-29). Women and men seeking treatment for LUTS at one of six academic medical centers in the US were assessed at baseline, 3-month and 12-month intervals. Twelve-month data on 78 LURN SI-29 items were analyzed among 353 women and 420 men using exploratory factor analysis (EFA), with factor structure confirmed using confirmatory factor analysis (CFA). Internal consistency, reliability, and validity of the five developed scales were evaluated by assessing correlations with the American Urological Association Symptom Index (AUA-SI), the genitourinary pain index (GUPI), and the Pelvic Floor Distress Inventory-20 (PFDI-20), and by examining expected sex differences in scores. EFA results (n = 150 women; 150 men) produced an interpretable eight-factor solution, with three of the factors comprised of dichotomous items addressing LUTS-associated sensations. The remaining five factors, confirmed with CFA in an independent sample of 473 participants, produced five scales: incontinence, urgency, voiding difficulty, bladder pain, and nocturia. Subscales and total LURN SI-29 scores were correlated as expected with AUA-SI, GUPI, and PFDI-20. LURN SI-29 scores also performed as expected in differentiating men from women based upon clinically expected differences, with men reporting more voiding difficulties and nocturia, and women reporting more urgency and incontinence. The LURN SI-29 questionnaire has the potential to improve research and clinical outcome measurement for both men and women with LUTS.

The Distribution of Post-Void Residual Volumes in People Seeking Care in the Symptoms of Lower Urinary Tract Dysfunction Network Observational Cohort Study With Comparison to Asymptomatic Populations

To describe the distribution of post-void residual (PVR) volumes across patients with and without lower urinary tract symptoms (LUTS) and examine relationships between self-reported voiding symptoms, storage symptoms, and PVR. PVR and demographic data were obtained from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) observational cohort study. Self-reported symptoms were collected using the American Urological Association Symptom Index and the LUTS Tool. PVR values were obtained from 2 other cohorts: living kidney donors with unknown LUTS from the Renal and Lung Living Donors Evaluation Study (RELIVE), and continent women in the Establishing the Prevalence of Incontinence (EPI) study, a population-based study of racial differences in urinary incontinence prevalence. Across the 3 studies, median PVRs were similar: 26 mL in LURN (n = 880, range 0-932 mL), 20 mL in EPI (n = 166, range 0-400 mL), and 14 mL in RELIVE (n = 191, range 0-352 mL). In LURN, males had 3.6 times higher odds of having PVR > 200 mL (95% CI = 1.72-7.48). In RELIVE, median PVR was significantly higher for males (20 mL vs 0 mL, P= .004). Among women, only the intermittency severity rating was associated with a probability of an elevated PVR. Among men, incomplete emptying and burning severity rating were associated with a higher odds of elevated PVR, but urgency severity ratings were associated with lower odds of elevated PVR. Care-seeking patients have PVRs similar to those in people with unknown history of LUTS (RELIVE) and without self-reported LUTS (EPI). Although PVR was correlated with voiding symptoms, the mean differences only explain ∼2% of the variance.

A Novel Proteomics Approach to Identify Serum and Urinary Biomarkers and Pathways that Associate with Lower Urinary Tract Symptoms in Men and Women: Pilot Results of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Study

ObjectivesTo assess the feasibility of a novel proteomics approach to identify biomarkers associated with lower urinary tract symptoms (LUTS) within serum and urine, because many clinical factors contribute to LUTS in men and women. These factors confound clinicians’ abilities to reliably evaluate and treat LUTS. Previous studies identified candidate LUTS biomarkers, but none are clinically utilized. MethodsEighteen male and 18 female symptoms of lower urinary tract dysfunction research network (LURN) observational cohort study participants with LUTS (measured on the LUTS Tool questionnaire) were randomly selected. Twelve male and 12 female controls with minimal or no LUTS were recruited and matched for clinico-demographic characteristics. The SomaScan Assay (SomaLogic) was used to measure the abundance of 1305 proteins contained within urine and serum. Statistical analyses were performed to evaluate reproducibility of assays, compare protein abundances, and estimate effect size. ResultsSomaScan assay results were more reproducible in serum than in urine. Within serum, there were many more differentially abundant proteins between cases and controls in males than in females. An enrichment/pathway analysis of the affected proteins in male and female subjects demonstrated that the enriched Gene Ontology processes were related to prostate morphogenesis in men and growth and inflammation in women. ConclusionThe pilot study results support that the etiology and pathophysiologic mechanisms underlying LUTS may be sex-specific. While further studies involving larger numbers of subjects are warranted, our results support the feasibility of a novel proteomic approach to identify biomarkers for diagnostic classification of LUTS.

Relationship Between Central Obesity, General Obesity, Overactive Bladder Syndrome and Urinary Incontinence Among Male and Female Patients Seeking Care for Their Lower Urinary Tract Symptoms

ObjectivesTo describe the relationship between metabolic factors and lower urinary tract symptoms, overactive bladder syndrome (OAB) and urinary incontinence (UI). MethodsAdult male and female patients who presented to a clinician from the symptoms of lower urinary tract dysfunction research network were recruited. Urinary symptoms (presence of OAB, any UI, stress UI (SUI), urgency UI (UUI), urgency, frequency, and nocturia) were assessed with the lower urinary tract symptoms tool. Metabolic factors assessed included central obesity (waist circumference, using the Adult Treatment Panel III, the International Diabetes Federation thresholds, and waist circumference as a continuous variable), general obesity (body mass index as dichotomous or continuous variables), diabetes mellitus, hypertension, and dyslipidemia. Multivariable logistic regression was used to test for associations. Results920 participants were studied. In multivariable analyses, central obesity (per 10 cm larger waist) was associated with higher odds of UI in both sexes (odds ratio [OR] = 1.16, P = .008), SUI in females (OR = 1.27, P = .008), UUI in both sexes (OR = 1.24, P = .001), OAB in females (OR = 1.248, P = .003), as well as frequency and nocturia. General obesity (5-unit increase in body mass index) was associated with UI, UUI, urgency and frequency in both sexes, and with SUI and OAB in females. We did not find associations between central or general obesity and OAB in males. Dyslipidemia was associated with nocturia ≥2. ConclusionIn patients, central and general obesity were key metabolic factors associated with UI in both males and females, and with OAB in females but not in males. The association between dyslipidemia and nocturia ≥2 needs further research.

The LURN Research Network Neuroimaging and Sensory Testing (NIST) Study: Design, protocols, and operations

The Neuroimaging and Sensory Testing (NIST) Study of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is a cross-sectional, case-control study designed to investigate whether disrupted brain connectivity and sensory processing are associated with abnormal lower urinary tract symptoms (LUTS) in patients with overactive bladder syndrome (OAB). The NIST Study tests the hypotheses that patients with urinary urgency will demonstrate: (1) abnormal functional and structural connectivity of brain regions involved in urinary sensation on magnetic resonance imaging (MRI), and (2) hypersensitivity to painful (pressure) and non-painful (auditory) sensory stimuli on quantitative sensory testing (QST), compared to controls. Male and female adults (18 years or older) who present at one of the six participating LURN clinical centers for clinical care of their LUTS, with symptoms of urinary urgency with or without urgency urinary incontinence, are eligible to participate. The NIST Study is the largest MRI and QST study of its kind, yielding a neuroimaging and sensory testing dataset unprecedented in OAB research. Advanced multi-modal techniques are used to understand brain functional and structural connectivity, including gray matter volume, and sensory function. Unlike previous MRI studies which involved invasive catheterization and repeated cycles of non-physiologic bladder filling and emptying via a catheter, we use a water ingestion protocol to mimic more physiological bladder filling through natural diuresis. Furthermore, these data will be used in concert with other phenotyping data to improve our understanding of clinically meaningful subtypes of patients with LUTS in order to improve patient care and management outcomes.

Symptom Based Clustering of Women in the LURN Observational Cohort Study

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. 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. 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. 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.

Symptom Based Clustering of Men in the LURN Observational Cohort Study.

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. 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. 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. 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.

Prevalence and Characteristics of Urinary Incontinence in a Treatment Seeking Male Prospective Cohort: Results from the LURN Study

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). 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. 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). 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.

Baseline Lower Urinary Tract Symptoms in Patients Enrolled in LURN: A Prospective, Observational Cohort Study

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. 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. 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. 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.

Symptoms of Lower Urinary Tract Dysfunction Research Network

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. As a first step in understanding subtypes of lower urinary tract symptoms, LURN will focus on disorders of urinary sensation (egurgency) and their causes. These are being examined with respect to patient experience, organism or systemic factors, genitourinary organs and tissues, andcellular/molecular factors. This is being achieved via an observational cohortstudy 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. LURN has taken its first steps by developing a framework for studying lower urinary tract symptom subtypes. 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.