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.

Ecological momentary assessment of pelvic pain and urinary urgency variability in urologic chronic pelvic pain syndrome and their association with illness impact and quality of life: Findings from the multidisciplinary approach to the study of chronic pelvic pain symptom patterns study.

PURPOSE: This study tested the hypothesis that ecological momentary assessment (EMA) of pelvic pain (PP) and urinary urgency (UU) would reveal unique Urologic Chronic Pelvic Pain Syndrome (UCPPS) phenotypes that would be associated with disease specific quality of life (QOL) and illness impact metrics (IIM). MATERIALS AND METHODS: A previously validated smart phone app (M-app) was provided to willing Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) participants. M-app notifications were sent 4-times daily for 14 days inquiring about PP and UU severity. A clustering algorithm that accounted for variance placed participants into PP and UU variability? clusters. Associations between clusters and QOL and IIM were then determined. RESULTS: A total of 204 participants enrolled in the M-app study (64% female). M-app compliance was high (median 63% of surveys). Cluster analysis revealed k = 3 (high, low, none) PP clusters and k = 2 (high, low) UU clusters. When adjusting for baseline pain severity, high PP variability, but not UU variability, was strongly associated with QOL and IIM; specifically worse mood, worse sleep and higher anxiety. UU and PP clusters were associated with each other (p < 0.0001), but a large percentage (33%) of patients with high PP variability had low UU variability. CONCLUSIONS: PP variability is an independent predictor of worse QOL and more severe IIM in UCPPS participants after controlling for baseline pain severity and UU. These findings suggest alternative pain indices, such as pain variability and unpredictability, may be useful adjuncts to traditional measures of worst and average pain when assessing UCPPS treatment responses.

Early and recent exposure to adversity, TLR-4 stimulated inflammation, and diurnal cortisol in women with interstitial cystitis/bladder pain syndrome: A MAPP research network study.

Both early (ELA) and recent life adversity (RLA) have been linked with chronic pain conditions and persistent alterations of neuroendocrine and inflammatory responses. Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic urologic disorder characterized by bladder and/or pelvic pain, and excessive urinary frequency and/or urgency. IC/BPS has been associated with high levels of ELA as well as a distinct inflammatory signature. However, associations between ELA and RLA with inflammatory mechanisms in IC/BPS that might underlie the link between adversity and symptoms have not been examined. Here we investigated ELA and RLA in women with IC/BPS as potential risk factors for inflammatory processes and hypothalamic-pituitaryadrenal (HPA) abnormalities using data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. Women with IC/BPS and healthy controls (n = 154 and 32, respectively) completed surveys, collected salivary cortisol at awakening and bedtime for 3 days, and gave a blood sample which was analyzed for 7 LPS-stimulated cytokines and chemokines (IL-6, TNFα, IL-1ß, MIP1α, MCP1, IL-8, and IL-10). Two cytokine/chemokine composites were identified using principal components analysis. Patients with greater exposure to RLA or cumulative ELA and RLA of at least moderate severity showed elevated levels of a composite of all cytokines, adjusting for age, body mass index, and study site. Furthermore, there was a trending relationship between ELA and the pro-inflammatory composite score. Nocturnal cortisol and cortisol slope were not associated with ELA, RLA, or inflammation. The present findings support the importance of adverse events in IC/BPS via a biological mechanism and suggest that ELA and RLA should be assessed as risk factors for inflammation as part of a clinical workup for IC/BPS.

Overexpression of HIF1α in Hunner Lesions of Interstitial Cystitis: Pathophysiological Implications.

PURPOSE: The aim of our study was to elucidate biological changes in Hunner lesions, which underlie the pathophysiology of Hunner-type interstitial cystitis, by characterizing their whole transcriptome and immunopathological profiles. MATERIALS AND METHODS: Paired bladder mucosal biopsies, 1 sample each from the Hunner lesion and nonlesion area, were obtained from 25 patients with Hunner-type interstitial cystitis. The samples were subjected to whole-transcriptome profiling; immunohistochemical quantification of CD3, CD4, CD8, CD20, CD138, mast cell tryptase, cytokeratin and HIF1α; and quantitative polymerase chain reaction for IFN-α, IFN-ß, IFN-γ, TNF, TGF-ß1, HIF1α, IL-2, IL-4, IL-6, IL-10 and IL-12A. The results were compared between the lesion and nonlesion areas. RESULTS: RNA sequencing identified 109 differentially expressed genes and 30 significantly enriched biological pathways in Hunner lesions. Up-regulated pathways (24) included HIF1α signaling pathway, PI3K-Akt signaling pathway, RAS signaling pathway and MAPK signaling pathway. By contrast, down-regulated pathways (6) included basal cell carcinoma and protein digestion and absorption. The mRNA levels of HIF1α, IFN-γ and IL-2, and the HIF1α protein level were significantly higher in lesion areas. Otherwise, there were no significant differences between the lesion and nonlesion samples in terms of mRNA levels of inflammatory cytokines or histological features such as lymphoplasmacytic and mast cell infiltration, epithelial denudation and CD4/CD8 T-lymphocyte ratio. CONCLUSIONS: Our findings demonstrate significant overexpression of HIF1α and up-regulation of its related biological pathways in Hunner lesions. The results indicate that ischemia, in conjunction with inflammation, plays a pathophysiological role in this subtype of interstitial cystitis/bladder pain syndrome, particularly in Hunner lesions.

Flares and their impact among male urologic chronic pelvic pain syndrome patients: An in-depth qualitative analysis in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

INTRODUCTION: There has been a sparse exploration of the lived experience of men with urologic chronic pelvic pain syndrome (UCPPS), and none with the goal of Investigating the experience of "flares" as part of this chronic pain syndrome in men. METHODS: We conducted three focus groups of male UCPPS patients at two sites of the MAPP Research Network (n = 16 total participants) to explore the full spectrum of flares and their impact on men's lives. RESULTS: Flare experiences were common and specific symptom components varied widely. Men reported nonpelvic symptoms (e.g., diarrhea), and variability in symptom intensity (mild to severe), duration (minutes to days), and frequency of flares. Flares episodes, and the threat of flares, were disruptive to their lives, social roles, and relationships. Distinct long-term impacts were reported, such as decreased sexual activity, decreased travel, and potential loss of employment or career. The themes included social isolation and the need for a sense of control and understanding over their unpredictable symptoms. CONCLUSIONS: Given their negative impact, future research with men and UCPPS should focus on approaches to prevent flares, and should consider a multimodal approach to reducing the frequency, severity, and/or duration. Quality of life may be improved by providing men with a sense of control over their symptoms and offering them multimodal treatment options, consistent with the recommendations for further research for women with UCPPS.

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.

Daily symptom associations for urinary urgency and anxiety, depression and stress in women with overactive bladder.

INTRODUCTION AND HYPOTHESIS: Women with overactive bladder (OAB) report psychological distress, anxiety and depression, but short-term associations between these symptoms are poorly studied. Our objectives were to study daily associations between OAB symptoms and psychological symptoms and test whether these associations were stable when reassessed after 3 months. We hypothesized that OAB symptoms are positively associated with anxiety and depression symptoms over a short-term (daily) basis. METHODS: Female patients with OAB [bothersome urgency and/or urgency urinary incontinence (UUI)] assessed OAB and mood symptoms at baseline and 3 months using a 3-day bladder diary and visual analog scale (VAS) ratings (0-100 mm) for anxiety, depression and stress. Daily OAB and mood symptom associations were tested using Spearman correlations. Generalized estimating equation (GEE) models tested associations between daily urgency scores and each psychological rating adjusting for covariates, time and a time-symptom interaction term. RESULTS: Participants (n = 69) had mean (SD) age 63.3 (13.4) years. Baseline diary outcomes [median (IQR)/day] included day voids 8 (7-11), nocturia 0 (0-1), UUI episodes 1 (0-3) and urgency score 1.75 (1-2.25). Anxiety and depression diagnoses (dx) and treatment (tx) were common (anxiety dx 30.4%, tx 21.7%; depression dx 47.8%, tx 37.7%), but daily anxiety, depression and stress ratings were low [median (IQR) mm 10 (3-35), 5 (1-16), and 16 (4-39), respectively]. Daily urgency scores correlated with anxiety (r = 0.30-0.40, days 1-3, p ≤ 0.01 for all), depression (r = 0.24-0.35, p ≤ 0.05 all) and stress (r = 0.27-0.34, p ≤ 0.03 all). GEE models indicated no significant change in these associations between baseline and 3 months, and OAB treatment did not impact the associations. CONCLUSIONS: Urgency scores were positively associated with same-day ratings of anxiety, depression and stress in OAB patients.

Autoimmunity to urothelial antigen causes bladder inflammation, pelvic pain, and voiding dysfunction: a novel animal model for Hunner-type interstitial cystitis.

Recent evidence revealed that Hunner-type interstitial cystitis (HIC) is a robust inflammatory disease potentially associated with enhanced immune responses and histologically characterized by epithelial denudation and lymphoplasmacytic infiltration with frequent clonal expansion of infiltrating B cells. To date, few animal models that reproduce the histological and clinical correlates of HIC have yet been established. In the present study, we aimed to develop a novel animal model for HIC via autoimmunity to the bladder urothelium using the transgenic mouse model (URO-OVA) that expresses the membrane form of the model antigen ovalbumin (OVA) as a self-antigen on the bladder urothelium. OVA-specific lymphocytes (splenocytes) were generated by immunization of C57BL/6 mice with OVA protein and injected intravenously into URO-OVA mice. The splenocytes from OVA-immunized C57BL/6 mice showed increased interferon (IFN)-γ production in response to OVA stimulation in vitro. URO-OVA mice adoptively transferred with OVA-primed splenocytes developed cystitis exhibiting histological chronic inflammatory changes such as remarkable mononuclear cell infiltration predominantly composed of T and B lymphocytes, increased vascularity, and mucosal hyperemia in the bladder at days 7-28 with a peak at day 21 tested. No systemic inflammation was found in cystitis-induced URO-OVA mice, nor was any inflammation found in wild-type C57BL/6 mice adoptively transferred with OVA-primed splenocytes. Along with bladder inflammation, URO-OVA mice demonstrated significantly increased pelvic nociceptive responses, voiding dysfunction, and upregulated mRNA expression levels for IFN-γ, tumor necrosis factor-α (TNF-α), and substance P precursor in the bladder. This model reproduces the histological and clinical features of human HIC, providing a novel model for HIC research.

Overactive bladder phenotypes: development and preliminary data.

INTRODUCTION: The purpose of this study is to develop overactive bladder (OAB) phenotypes that can be used to develop diagnostic and treatment pathways and offer clues to the underlying etiologies of patients with OAB. MATERIALS AND METHODS: This is a retrospective, multicenter study of patients with lower urinary tract symptoms (LUTS). Evaluation included a 24-hour bladder diary (24HBD), the lower urinary tract symptoms score (LUTSS) questionnaire, uroflowmetry (Q), and post-void residual urine (PVR) measurement. Patients completed the 24HBD and LUTSS on a smartphone application or paper. Those with an OAB symptom sub-score (OABSS) ≥ 8 were included. An expert panel developed a phenotype classification system based on variables considered to be important for treatment. RESULTS: The following variables were selected for inclusion in the phenotype modeling: 24-hour voided volume (24HV), maximum voided volume (MVV), Qmax and PVR. Subjects were divided into three phenotypes based on the 24HV: polyuria (24HV > 2.5 L), normal (24 HV 1-2.5 L), and oliguria (24HV < 1 L). Each phenotype was subdivided based on MVV, Qmax & PVR, resulting in 18 sub-types. Five hundred thirty-three patients, 348 men and 185 women, completed the LUTSS and 24HBD. OAB was present in 399 (75%) - 261 men and 138 women. The prevalence of the primary phenotypes was polyuria (25%), normal (63%), and oliguria (11%). CONCLUSIONS: Classification of OAB variants into phenotypes based on 24HV, MVV, Qmax, and PVR provides the substrate for further research into the diagnosis, etiology, treatment outcomes and development of granular diagnostic and treatment algorithms.

The Multidisciplinary Approach to The Study of Chronic Pelvic Pain (MAPP) Research Network*: Design and implementation of the Symptom Patterns Study (SPS).

AIMS: The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network initiated a second observational cohort study-the Symptom Patterns Study (SPS)-to further investigate the underlying pathophysiology of Urologic Chronic Pelvic Pain Syndrome (UCPPS) and to discover factors associated with longitudinal symptom changes and responses to treatments. METHODS: This multisite cohort study of males and females with UCPPS features a run-in period of four weekly web-based symptom assessments before a baseline visit, followed by quarterly assessments up to 36 months. Controls were also recruited and assessed at baseline and 6 months. Extensive clinical data assessing urological symptoms, nonurological pain, chronic overlapping pain syndromes, and psychosocial factors were collected. Diverse biospecimens for biomarker and microbiome studies, quantitative sensory testing (QST) data under multiple stimuli, and structural and functional neuroimaging scans were obtained under a standardized protocol. RESULTS: Recruitment was initiated (July 2015) and completed (February 2019) at six discovery sites. A total of 620 males and females with UCPPS and 73 Controls were enrolled, including 83 UCPPS participants who re-enrolled from the first MAPP Network cohort study (2009-2012). Baseline neuroimaging scans, QST measures, and biospecimens were obtained on 578 UCPPS participants. The longitudinal follow-up of the cohort is ongoing. CONCLUSIONS: This comprehensive characterization of a large UCPPS cohort with extended follow-up greatly expands upon earlier MAPP Network studies and provides unprecedented opportunities to increase our understanding of UCPPS pathophysiology, factors associated with symptom change, clinically relevant patient phenotypes, and novel targets for future interventions.

Cystitis-induced bladder pain is Toll-like receptor 4 dependent in a transgenic autoimmune cystitis murine model: a MAPP Research Network animal study.

Altered Toll-like receptor (TLR)4 activation has been identified in several chronic pain conditions but has not been well studied in interstitial cystitis/bladder pain syndrome (IC/BPS). Our previously published human studies indicated that patients with IC/BPS present altered systemic TLR4-mediated inflammatory responses, which were significantly correlated with reported pain severity. In the present study, we sought to determine whether altered TLR4 activation plays a role in pelvic/bladder pain seen in patients with IC/BPS using our validated IC/BPS-like transgenic autoimmune cystitis model (URO-OVA). URO-OVA mice developed responses consistent with pelvic and bladder pain after cystitis induction, which was associated with increased splenocyte production of TLR4-mediated proinflammatory cytokines IL-1ß, IL-6, and TNF-α. Increased spinal expression of mRNAs for proinflammatory cytokines IL-6 and TNF-α, glial activation markers CD11b and glial fibrillary acidic protein, and endogenous TLR4 ligand high mobility group box 1 was also observed after cystitis induction. Compared with URO-OVA mice, TLR4-deficient URO-OVA mice developed significantly reduced nociceptive responses, although similar bladder inflammation and voiding dysfunction, after cystitis induction. Intravenous administration of TAK-242 (a TLR4-selective antagonist) significantly attenuated nociceptive responses in cystitis-induced URO-OVA mice, which was associated with reduced splenocyte production of TLR4-mediated IL-1ß, IL-6, and TNF-α as well as reduced spinal expression of mRNAs for IL-6, TNF-α, CD11b, glial fibrillary acidic protein, and high mobility group box 1. Our results indicate that altered TLR4 activation plays a critical role in bladder nociception independent of inflammation and voiding dysfunction in the URO-OVA model, providing a potential mechanistic insight and therapeutic target for IC/BPS pain.

Histopathology of Anterior Urethral Strictures: Toward a Better Understanding of Stricture Pathophysiology.

PURPOSE: Histopathology can provide insights into disease mechanisms but to date it has been poorly described for urethral stricture. The purpose of this study was to comprehensively describe histopathological findings of stricture specimens obtained at the time of anterior urethroplasty. MATERIALS AND METHODS: All pathological specimens of men who underwent anterior urethroplasty of urethral stricture disease from 2010 to 2017 at a single institution were rereviewed by a single blinded pathologist directed to rule out lichen sclerosus and then describe inflammatory cell type and severity when present. Cohorts comprising strictures with no inflammation, minimal to mild inflammation or moderate to severe inflammation were developed and stricture, patient and surgical outcome characteristics were compared. RESULTS: Histopathology slides from 100 anterior urethroplasty cases were reviewed. Two or more lichen sclerosus characteristics were present in 21% of specimens and 44% of specimens showed chronic inflammation, which was minimal in 20%, mild in 39%, moderate in 39% and severe in 2%. Lymphocytes in 86% of specimens and plasma cells in 12% were the predominant cell types. Patients with inflammatory stricture reported worse overall health. Inflammation was largely absent from isolated bulbomembranous strictures (9%) and more common in lichen sclerosus strictures (100%). The 11% overall failure rate was not affected by the presence (7%) or absence (14%) of inflammation. CONCLUSIONS: Chronic inflammation is prevalent in a significant percent of urethral stricture disease specimens. Associations with worse overall health suggest systemic mediators. Absent inflammation in bulbomembranous strictures suggests a unique pathophysiology in this region. The presence of inflammation did not affect surgical outcomes at mid-term followup.

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

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.

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.

Reasons for Seeking Clinical Care for Lower Urinary Tract Symptoms: A Mixed Methods Study.

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

A Case-Crossover Study of Urological Chronic Pelvic Pain Syndrome Flare Triggers in the MAPP Research Network.

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.

Bowel function, sexual function, and symptoms of pelvic organ prolapse in women with and without urinary incontinence.

AIMS: Bowel symptoms, pelvic organ prolapse, and sexual dysfunction are common, but their frequency among women with lower urinary tract symptoms (LUTS) has not been well described. Our aims were to describe pelvic floor symptoms among women with and without urinary incontinence (UI) and among subtypes of UI. METHODS: Women with LUTS seeking care at six U.S. tertiary care centers enrolled in prospective cohort study were studied. At baseline, participants completed the Pelvic Floor Distress Inventory (PFDI-20), Pelvic Organ Prolapse/Incontinence Sexual Questionnaire (PISQ-IR), and PROMIS GI Diarrhea, Constipation, and Fecal Incontinence Scales. RESULTS: Mean age among the 510 women was 56.4 ± 14.4 years. Women who reported UI (n = 420) had more diarrhea and constipation symptoms (mean scores 49.5 vs 46.2 [P = 0.01] and 51.9 vs 48.4 [P < 0.01], respectively) at baseline. Among sexually active women, mean PISQ-IR subscale scores were lower among those with UI (condition specific: 89.8 vs 96.7, P < 0.01; condition impact: 79.8 vs 92.5, P < 0.01). Women with mixed urinary incontinence (MUI) (n = 240) reported more prolapse symptoms, fecal incontinence, and worse sexual function compared to those with stress urinary incontinence (SUI) and urgency urinary incontinence (UUI). CONCLUSIONS: Women presenting with LUTS with UI reported significantly worse constipation, diarrhea, fecal incontinence, and sexual function compared to women without UI. In women with UI, sexual function and pelvic organ prolapse (POP) symptoms were worse in those with MUI compared to SUI and UUI.

Evidence of the Impact of Diet, Fluid Intake, Caffeine, Alcohol and Tobacco on Lower Urinary Tract Symptoms: A Systematic Review.

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.