Naturalistic Bladder Filling Reveals Subtypes in Overactive Bladder Syndrome That Differentially Engages Urinary Urgency-Related Brain Circuits: Results From the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).

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.

Structural Changes in Brain White Matter Tracts Associated With Overactive Bladder Revealed by Diffusion Tensor Magnetic Resonance Imaging: Findings From a Symptoms of Lower Urinary Tract Dysfunction Research Network Cross-Sectional Case-Control Study.

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.

Living Donor Decision-Making and the Complex Interplay of Finances and Other Motivators, Barriers, and Facilitators.

INTRODUCTION: The decision to become a living donor requires consideration of a complex, interactive array of factors that could be targeted for clinical, policy, and educational interventions. Our objective was to assess how financial barriers interact with motivators, other barriers, and facilitators during this process. METHODS: Data were obtained from a public survey assessing motivators, barriers, and facilitators of living donation. We used multivariable logistic regression and consensus k-means clustering to assess interactions between financial concerns and other considerations in the decision-making process. RESULTS: Among 1592 respondents, the average age was 43; 74% were female and 14% and 6% identified as Hispanic and Black, respectively. Among employed respondents (72%), 40% indicated that they would not be able to donate without lost wage reimbursement. Stronger agreement with worries about expenses and dependent care challenges was associated with not being able to donate without lost wage reimbursement (OR = 1.2, 95% CI = 1.0-1.3; OR = 1.2, 95% CI = 1.1-1.3, respectively). Four respondent clusters were identified. Cluster 1 had strong motivators and facilitators with minimal barriers. Cluster 2 had barriers related to health concerns, nervousness, and dependent care. Clusters 3 and 4 had financial barriers. Cluster 3 also had anxiety related to surgery and dependent care. CONCLUSIONS: Financial barriers interact primarily with health and dependent care concerns when considering living organ donation. Targeted interventions to reduce financial barriers and improve provider communication regarding donation-related risks are needed.

Phenotyping of Urinary Urgency Patients Without Urgency Incontinence, and Their Comparison to Urgency Incontinence Patients: Findings From the LURN Study.

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

Age of Onset and Disease Course in Biopsy-Proven Minimal Change Disease: An Analysis From the Cure Glomerulonephropathy Network.

RATIONALE & OBJECTIVE: Adolescent- and adult-onset minimal change disease (MCD) may have a clinical course distinct from childhood-onset disease. We characterized the course of children and adults with MCD in the Cure Glomerulonephropathy Network (CureGN) and assessed predictors of rituximab response. STUDY DESIGN: Prospective, multicenter, observational study. STUDY PARTICIPANTS: CureGN participants with proven MCD on biopsy. EXPOSURE: Age at disease onset, initiation of renin-angiotensin-aldosterone system (RAAS) blockade, and immunosuppression including rituximab during the study period. OUTCOME: Relapse and remission, change in estimated glomerular filtration rate (eGFR), and kidney failure. ANALYTICAL APPROACH: Remission and relapse probabilities were estimated using Kaplan-Meier curves and gap time recurrent event models. Linear regression models were used for the outcome of change in eGFR. Cox proportional hazards models were used to estimate the association between rituximab administration and remission. RESULTS: The study included 304 childhood- (≤12 years old), 49 adolescent- (13-17 years old), and 201 adult- (≥18 years) onset participants with 2.7-3.2 years of follow-up after enrollment. Children had a longer time to biopsy (238 vs 23 and 36 days in adolescent- and adult-onset participants, respectively; P<0.001) and were more likely to have received therapy before biopsy. Children were more likely to be treated with immunosuppression but not RAAS blockade. The rate of relapse was higher in childhood- versus adult-onset participants (HR, 1.69 [95% CI, 1.29-2.21]). The probability of remission was also higher in childhood-onset disease (HR, 1.33 [95%CI, 1.02-1.72]). In all groups eGFR loss was minimal. Children were more likely to remit after rituximab than those with adolescent- or adult-onset disease (adjusted HR, 2.1; P=0.003). Across all groups, glucocorticoid sensitivity was associated with a greater likelihood of achieving complete remission after rituximab (adjusted HR, 2.62; P=0.002). LIMITATIONS: CureGN was limited to biopsy-proven disease. Comparisons of childhood to nonchildhood cases of MCD may be subject to selection bias, given that childhood cases who undergo a biopsy may be limited to patients who are least responsive to initial therapy. CONCLUSIONS: Among patients with MCD who underwent kidney biopsy, there were differences in the course (relapse and remission) of childhood-onset compared with adolescent- and adult-onset disease, as well as rituximab response. PLAIN-LANGUAGE SUMMARY: Minimal change disease is a biopsy diagnosis for nephrotic syndrome. It is diagnosed in childhood, adolescence, or adulthood. Patients and clinicians often have questions about what to expect in the disease course and how to plan therapies. We analyzed a group of patients followed longitudinally as part of the Cure Glomerulonephropathy Network (CureGN) and describe the differences in disease (relapse and remission) based on the age of onset. We also analyzed rituximab response. We found that those with childhood-onset disease had a higher rate of relapse but also have a higher probability of reaching remission when compared with adolescent- or adult-onset disease. Children and all steroid-responsive patients are more likely to achieve remission after rituximab.

Racial and Ethnic Disparities in Acute Care Utilization Among Patients With Glomerular Disease.

RATIONALE & OBJECTIVE: The effects of race, ethnicity, socioeconomic status (SES), and disease severity on acute care utilization in patients with glomerular disease are unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 1,456 adults and 768 children with biopsy-proven glomerular disease enrolled in the Cure Glomerulonephropathy (CureGN) cohort. EXPOSURE: Race and ethnicity as a participant-reported social factor. OUTCOME: Acute care utilization defined as hospitalizations or emergency department visits. ANALYTICAL APPROACH: Multivariable recurrent event proportional rate models were used to estimate associations between race and ethnicity and acute care utilization. RESULTS: Black or Hispanic participants had lower SES and more severe glomerular disease than White or Asian participants. Acute care utilization rates were 45.6, 29.5, 25.8, and 19.2 per 100 person-years in Black, Hispanic, White, and Asian adults, respectively, and 55.8, 42.5, 40.8, and 13.0, respectively, for children. Compared with the White race (reference group), Black race was significantly associated with acute care utilization in adults (rate ratio [RR], 1.76 [95% CI, 1.37-2.27]), although this finding was attenuated after multivariable adjustment (RR, 1.31 [95% CI, 1.03-1.68]). Black race was not significantly associated with acute care utilization in children; Asian race was significantly associated with lower acute care utilization in children (RR, 0.32 [95% CI 0.14-0.70]); no significant associations between Hispanic ethnicity and acute care utilization were identified. LIMITATIONS: We used proxies for SES and lacked direct information on income, household unemployment, or disability. CONCLUSIONS: Significant differences in acute care utilization rates were observed across racial and ethnic groups in persons with prevalent glomerular disease, although many of these difference were explained by differences in SES and disease severity. Measures to combat socioeconomic disadvantage in Black patients and to more effectively prevent and treat glomerular disease are needed to reduce disparities in acute care utilization, improve patient wellbeing, and reduce health care costs.

Treatment patterns in women with urinary urgency and/or urgency urinary incontinence in the symptoms of Lower Urinary Tract Dysfunction Research Network Observational Cohort Study.

BACKGROUND: Limited epidemiological data exist describing how patients engage with various treatments for overactive bladder (OAB). To improve care for patients with OAB, it is essential to gain a better understanding of how patients interface with OAB treatments longitudinally, that is, how often patients change treatments and the pattern of this treatment change in terms of escalation and de-escalation. OBJECTIVES: To describe treatment patterns for women with bothersome urinary urgency (UU) and/or urgency urinary incontinence (UUI) presenting to specialty care over 1 year. STUDY DESIGN: The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) study enrolled adult women with bothersome UU and/or UUI seeking care for lower urinary tract symptoms (LUTS) between January 2015 and September 2016. An ordinal logistic regression model was fitted to describe the probabilities of escalating or de-escalating level of treatment during 1-year follow-up. RESULTS: Among 349 women, 281 reported UUI and 68 reported UU at baseline. At the end of 1 year of treatment by a urologist or urogynecologist, the highest level of treatment received by participants was 5% expectant management, 36% behavioral treatments (BT), 26% physical therapy (PT), 26% OAB medications, 1% percutaneous tibial nerve stimulation, 3% intradetrusor onabotulinum toxin A injection, and 3% sacral neuromodulation. Participants using BT or PT at baseline were more likely to be de-escalated to no treatment than participants on OAB medications at baseline, who tended to stay on medications. Predictors of the highest level of treatment included starting level of treatment, hypertension, UUI severity, stress urinary incontinence, and anticholinergic burden score. CONCLUSIONS: Treatment patterns for UU and UUI are diverse. Even for patients with significant bother from OAB presenting to specialty clinics, further treatment often only involves conservative or medical therapies. This study highlights the need for improved treatment algorithms to escalate patients with persistent symptoms, or to adjust care in those who have been unsuccessfully treated.

Total fluid intake, caffeine, and other bladder irritant avoidance among adults having urinary urgency with and without urgency incontinence: The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).

INTRODUCTION: Caffeine has long been vilified as a cause for urinary urgency incontinence (UUI) along with other potential bladder irritants such as carbonation, alcohol, and acidic juices. The objective of this study was to assess the fluid intake behavior of people with urgency, UUI, and those with lower urinary tract symptoms (LUTS) without UUI or urgency to assess if they avoided certain potential bladder irritants or had different fluid intake. We hypothesized that patients with UUI would avoid caffeine as a self-management method more so than these other two groups. METHODS: Treatment-seeking men and women with LUTS in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Observational Cohort study completed a baseline 3-day voiding and intake diary. "Complete" diaries had 3 days of data and no missing intake or voided volumes. Beverages with any caffeine, alcohol, carbonation, or acidic juice were identified and the total volume was recorded as well as the type of beverage containing caffeine to calculate the daily caffeine dose. RESULTS: Four hundred and ninety-one participants (277 men and 214 women) with a median age of 63 had complete diaries. Urinary urgency was more prevalent in women than men (79% vs. 55%, p < 0.0001) as was UUI (84% vs. 47%, p < 0.0001). Total fluid intake over 3 days was lower among the urgency group versus the nonurgency group (median [interquartile range] 5.2 [4.0-6.8] L vs. 5.7 [4.3-7.0] L, p = 0.028) and the UUI group compared to the urgency without incontinence group were less likely to consume alcohol (26% vs. 37%, p = 0.04). After adjusting for sex, BMI, age, and total intake volume, UUI participants had 54% lower odds of consuming any caffeine (odds ratio = 0.46, 95% confidence interval = 0.22-0.96, p = 0.04) than those without incontinence, but among those that did consume caffeine, no difference in the volume of caffeinated beverages or milligrams of caffeine consumed was detected between those with UUI and those with urgency without incontinence. No difference in carbonation or acidic juice intake was detected between groups. CONCLUSIONS: Individuals with urgency consume a lower volume of fluid than those without urgency. UUI participants more often abstain from caffeine, but among those that consume caffeine, the dose is similar to those without UUI. One explanation for these results is that only a subset of individuals with urgency or UUI are caffeine sensitive.

Natural history of lower urinary tract symptoms in treatment-seeking women with pelvic organ prolapse; the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).

BACKGROUND: The association of pelvic organ prolapse with overactive bladder and other lower urinary tract symptoms, and the natural history of those symptoms are not well characterized. Previous cross-sectional studies demonstrated conflicting relationships between prolapse and lower urinary tract symptoms. OBJECTIVE: This study primarily aimed to determine the baseline association between lower urinary tract symptoms and prolapse and to assess longitudinal differences in symptoms over 12 months in women with and without prolapse. Secondary aims were to explore associations between lower urinary tract symptoms and prolapse treatment. We hypothesized that: (1) prolapse is associated with the presence of lower urinary tract symptoms, (2) lower urinary tract symptoms are stable over time in patients with and without prolapse, and (3) prolapse treatment is associated with lower urinary tract symptom improvement. STUDY DESIGN: Women enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network Observational Cohort Study with adequate 12-month follow-up data were included. Prolapse and lower urinary tract symptom treatment during follow-up was guided by standard of care. Outcome measures included the Lower Urinary Tract Symptoms Tool total severity score (in addition to overactive bladder, obstructive, and stress urinary incontinence subscales) and Urogenital Distress Inventory-6 Short Form. Prolapse (yes or no) was defined primarily when Pelvic Organ Prolapse Quantification System points Ba, C or Bp were >0 (beyond the hymen). Mixed-effects models with random effects for patient slopes and intercepts were fitted for each lower urinary tract symptom outcome and prolapse predictor, adjusted for other covariates. The study had >90% power to detect differences as small as 0.4 standard deviation for less prevalent group comparisons (eg, prolapse vs not). RESULTS: A total of 371 women were analyzed, including 313 (84%) with no prolapse and 58 (16%) with prolapse. Women with prolapse were older (64.6±8.8 vs 55.3±14.1 years; P<.001) and more likely to have prolapse surgery (28% vs 1%; P<.001) and pessary treatment (26% vs 4%; P<.001) during the study. Average baseline Lower Urinary Tract Symptoms Tool total severity scores were lower (fewer symptoms) for participants with prolapse compared with those without (38.9±14.0 vs 43.2±14.0; P=.036), but there were no differences in average scores between prolapse groups for other scales. For all urinary outcomes, average scores were significantly lower (improved) at 3 and 12 months compared with baseline (all P<.05). In mixed-effects models, there were no statistically significant interactions between pelvic organ prolapse measurement and visit and time-dependent prolapse treatment groups (P>.05 for all regression interaction coefficients). The Lower Urinary Tract Symptoms Tool obstructive severity score had a statistically significant positive association with Pelvic Organ Prolapse Quantification System Ba, Bp, and point of maximum vaginal descent. The Lower Urinary Tract Symptoms Tool total severity scale had a statistically significant negative association with Pelvic Organ Prolapse Quantification System Ba and point of maximum vaginal descent. No other associations between prolapse and lower urinary tract symptoms were significant (P>.05 for all regression coefficients). Symptom differences between prolapse groups were small: all regression coefficients (interpretable as additive percentage change in each score) were between -5 and 5 (standard deviation of outcomes ranged from 14.0-32.4). CONCLUSION: Among treatment-seeking women with urinary symptoms, obstructive symptoms were positively associated with prolapse, and overall lower urinary tract symptom severity was negatively associated with prolapse. Lower Urinary Tract Symptoms Tool scores improved over 12 months regardless of prolapse status, including in those with treated prolapse, untreated prolapse, and without prolapse.

Comparing clinical bladder diaries and recalled patient reports for measuring lower urinary tract symptoms in the symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).

PURPOSE: Bladder diaries are a key source of information about lower urinary tract symptoms (LUTS); however, many patients do not complete them as instructed. Questionnaire-based patient-reported outcome measures (PROMs) are another option for reporting LUTS but may have recall bias. We assessed the strength of the associations between PROMs and a 3-day bladder diary. MATERIALS AND METHODS: Symptomatic adults from 6 tertiary care sites completed a 3-day paper bladder diary and 3-, 7-, and 30-day electronic PROMs. We assessed the linear associations between mapped pairs of diary variables and responses to PROM items using biserial and polyserial correlation coefficients with 95% confidence intervals. RESULTS: Of 290 enrolled participants, 175 (60%) completed the bladder diary as instructed and at least one corresponding PROM. Linear associations were strongest between the diary and 3-day recall of daytime frequency (r = 0.75) and nighttime frequency (r = 0.69), followed by voids with urgency sensations (r = 0.62), and an item reporting any incontinence (r = 0.56). Linear associations between bladder diary and specific incontinence variables (e.g., stress, urgency) were low to negligible (ranging from r = 0.16-0.39). Linear associations were consistent across the 3-, 7-, and 30-day recall periods. CONCLUSIONS: Missing and unusable bladder diary data were common, highlighting the patient burden associated with this method of data collection. A questionnaire-based PROM is a reasonable alternative to a diary for reporting voiding frequency and may offer an easier option for reporting some symptoms.

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

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Can 7 or 30-Day Recall Questions Capture Self-Reported Lower Urinary Tract Symptoms Accurately?

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

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

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.

Patient Characteristics Associated with More Bother from Lower Urinary Tract Symptoms.

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.

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

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Mental Health, Sleep and Physical Function in Treatment Seeking Women with Urinary Incontinence.

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