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Purpose: Although many factors have been proposed to trigger symptom exacerbations (flares) in patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, few studies have investigated these factors empirically. Therefore, we embedded a case-crossover study in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain longitudinal study to evaluate a range of patient reported triggers., Materials and Methods: We assessed exposure to proposed triggers, including diet, physical activities, sedentary behaviors, stress, sexual activities, infection-like symptoms and allergies, by questionnaire a maximum of 3 times when participants reported flares and at 3 randomly selected times. We compared participant preflare to nonflare exposures by conditional logistic regression., Results: In our full analytical sample of 292 participants only 2 factors, including recent sexual activity (OR 1.44, 95% CI 1.06-1.96) and urinary tract infection symptoms (OR 3.39, 95% CI 2.02-5.68), which may overlap with those of flares, were associated with flare onset. On subanalyses restricted to flares with specific suspected triggers additional positive associations were observed for some factors such as certain dietary factors, abdominal muscle exercises, and vaginal infection-like symptoms and fever, but not for other factors (eg stress)., Conclusions: Except for sexual activity our findings suggest that patient reported triggers may be individual or group specific, or they may not contribute to flares. These findings suggest caution in following rigid, global flare prevention strategies and support additional research to develop evidence-based strategies., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to create symptom indexes, that is scores derived from questionnaires to accurately and efficiently measure symptoms of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively referred to as urological chronic pelvic pain syndromes. We created these indexes empirically by investigating the structure of symptoms using exploratory factor analysis., Materials and Methods: As part of the MAPP (Multi-Disciplinary Approach to the Study of Chronic Pelvic Pain) Research Network 424 participants completed questionnaires, including GUPI (Genitourinary Pain Index), ICSI (Interstitial Cystitis Symptom Index) and ICPI (Interstitial Cystitis Problem Index). Individual items from questionnaires about bladder and pain symptoms were evaluated by principal component and exploratory factor analyses to identify indexes with fewer questions to comprehensively quantify symptom severity. Additional analyses included correlating symptom indexes with symptoms of depression, which is a known comorbidity of patients with pelvic pain., Results and Conclusions: Exploratory factor analyses suggested that the 2 factors pain severity and urinary severity provided the best psychometric description of items in GUPI, ICSI and ICPI. These factors were used to create 2 symptom indexes for pain and urinary symptoms. Pain, but not urinary symptoms, was associated with symptoms of depression on multiple regression analysis, suggesting that these symptoms may impact patients with urological chronic pelvic pain syndromes differently (B ± SE for pain severity = 0.24 ± 0.04, 95% CI 0.16-0.32, β = 0.32, p <0.001). Our results suggest that pain and urinary symptoms should be assessed separately rather than combined into 1 total score. Total scores that combine the separate factors of pain and urinary symptoms into 1 score may be limited for clinical and research purposes., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The clinical features of the interstitial cystitis/bladder pain syndrome are similar to those of the chronic prostatitis/chronic pelvic pain syndrome. However, to our knowledge no studies have directly compared the characteristics of these syndromes in men and women., Materials and Methods: The MAPP Research Network recruited 191 men and 233 women with IC/BPS or CP/CPPS. Baseline data included demographics, Interstitial Cystitis Symptom Index and Problem Index scores; Genitourinary Pain Index score; American Urological Association Symptom Index score; Likert scales to assess urinary urgency, frequency, pain and overall symptom severity; and a single question about the most bothersome pelvic symptom., Results: After adjustment for age, income and symptom duration, measures of pain severity were similar across genders. Mean scores for the ICSI, ICPI and AUASI were significantly higher in women than in men, reflecting more bladder focused symptoms in women. The most bothersome single symptom in men as well as in women was pain in the pubic/bladder area (men 34%, women 58%). The characteristics of the men and women in the MAPP cohort were similar to those reported in other research cohorts for IC/BPS and CP/CPPS., Conclusions: Our findings indicate that pain severity is similar for both genders and that bladder focused symptoms (urgency, suprapubic pain, frequency) are more common in women. However, a substantial proportion of men also reported these types of bladder symptoms., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes., Materials and Methods: We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods., Results: There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03)., Conclusions: We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome., Materials and Methods: A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical centers in North America. We recruited women with interstitial cystitis/painful bladder syndrome with demonstrable pelvic floor tenderness on physical examination and a limitation of no more than 3 years' symptom duration. The primary outcome was the proportion of responders defined as moderately improved or markedly improved in overall symptoms compared to baseline on a 7-point global response assessment scale. Secondary outcomes included ratings for pain, urgency and frequency, the O'Leary-Sant IC Symptom and Problem Index, and reports of adverse events. We compared response rates between treatment arms using the exact conditional version of the Mantel-Haenszel test to control for clustering by clinical center. For secondary efficacy outcomes cross-sectional descriptive statistics and changes from baseline were calculated., Results: A total of 81 women randomized to the 2 treatment groups had similar symptoms at baseline. The global response assessment response rate was 26% in the global therapeutic massage group and 59% in the myofascial physical therapy group (p=0.0012). Pain, urgency and frequency ratings, and O'Leary-Sant IC Symptom and Problem Index decreased in both groups during followup, and were not significantly different between the groups. Pain was the most common adverse event, occurring at similar rates in both groups. No serious adverse events were reported., Conclusions: A significantly higher proportion of women with interstitial cystitis/painful bladder syndrome responded to treatment with myofascial physical therapy than to global therapeutic massage. Myofascial physical therapy may be a beneficial therapy in women with this syndrome., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

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

Objectives: To describe the practice patterns among primary care physicians' (PCPs) managing patients with symptoms suggestive of interstitial cystitis/painful bladder syndrome (IC/PBS)., Methods: We developed a clinical vignette describing a woman with typical IC/PBS symptoms to elicit questions about etiology, management strategies, and familiarity with this syndrome. We mailed the questionnaire to 556 PCPs, including academicians and community physicians, in Boston, Los Angeles, and Chicago., Results: We received 290 completed questionnaires (response rate, 52%). Nineteen percent of respondents reported they had "never" seen a patient like the one described in the vignette. Two-thirds of respondents correctly identified the hallmark symptom of IC/PBS (bladder pain/pressure). Regarding etiology, 90% correctly indicated that IC/PBS was a noninfectious disease, 76% correctly reported that it was not caused by a sexually transmitted infection, and 61% correctly indicated that it was not caused by a psychiatric illness. Common treatments included antibiotics and nonsteroidal anti-inflammatory agents. Referrals were often made to a specialist., Conclusions: Although most PCPs indicate familiarity with IC/PBS, they manage the condition infrequently. They also appear to have significant knowledge deficits about the clinical characteristics of IC/PBS, and they indicate variable practice patterns in the diagnosis and treatment of the condition. Educational efforts directed at PCPs will likely improve the care of patients with IC/PBS., (Copyright 2010 Elsevier Inc. All rights reserved.)

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

Purpose: The etiology of painful bladder syndrome is currently unknown. We investigated the relationship between medical factors and symptoms suggestive of painful bladder syndrome in a population based random sample., Materials and Methods: Data were collected from the Boston Area Community Health Survey, an epidemiological study conducted from 2002 to 2005 in a racially and ethnically diverse population (30 to 79 years old) from Boston, Massachusetts. The operational definition of painful bladder syndrome was symptom based. Those reporting pain increasing as the bladder fills and/or pain relieved by urination (fairly often/usually/almost always) for 3+ months were considered to have symptoms suggestive of painful bladder syndrome. We used multivariate logistic regression to estimate odds ratios and 95% confidence intervals (adjusted for demographics, anthropometric and other factors) for the association of comorbidities, surgery and medication use with painful bladder syndrome symptoms., Results: The prevalence of painful bladder syndrome symptoms was 1.3% in men and 2.6% in women. In men only depression was associated in a multivariate model (OR 4.96; 95% CI 1.65, 14.92). In women associations were observed for depression (OR 3.35; 95% CI 1.93, 5.81), history of urinary tract infections (OR 2.17; 95% CI 1.49, 4.96), chronic yeast infections (OR 3.11; 95% CI 1.29, 7.51), hysterectomy (OR 2.82; 95% CI 1.20, 6.62), calcium channel blockers (OR 4.59; 95% CI 2.71, 9.72) and cardiac glycosides (OR 10.28; 95% CI 1.46, 72.35), while thyroid medications and statins were inversely associated (OR 0.13; 95% CI 0.03, 0.47 and OR 0.24; 95% CI 0.08, 0.76; respectively)., Conclusions: Gynecologic factors and certain medications may be associated with the painful bladder syndrome in women. Our results for medications suggest potentially modifiable risk factors.

Purpose: We estimated the prevalence of symptoms suggestive of painful bladder syndrome defined as pain increasing as the bladder fills and/or pain relieved by urination for at least 3 months, and its association with sociodemographics (gender, age, race/ethnicity and socioeconomic status), lifestyle (smoking, alcohol consumption, physical activity) and psychosocial variables (sexual, physical, emotional abuse experienced as a child or as an adult, worry, trouble paying for basics, depression)., Materials and Methods: The data used come from the Boston Area Community Health Survey, an epidemiological study of 5,506 randomly selected adults 30 to 79 years old of 3 race/ethnic groups (black, Hispanic, white)., Results: The overall prevalence of symptoms suggestive of painful bladder syndrome was 2% (1.3% in men and 2.6% in women) with increased prevalence in middle-aged adults and those of lower socioeconomic status. Symptoms suggestive of painful bladder syndrome were more common in those who experienced abuse, in those who were worried about someone close to them and in those who were having trouble paying for basics. This pattern held even after adjusting for depression., Conclusions: Painful bladder syndrome is associated with a number of lifestyle and psychosocial correlates. This suggests that the treatment of patients with painful bladder syndrome (physical symptoms) may benefit from a multifaceted approach of combining medical, psychological and cognitive treatment.

Purpose: We evaluated the longer term response in patients with interstitial cystitis who initially responded to intravesical bacillus Calmette-Guerin or placebo in a randomized clinical trial., Materials and Methods: Patients with interstitial cystitis who responded positively to treatment with bacillus Calmette-Guerin or placebo after 34 weeks of followup in a double-blind clinical trial were followed for an additional 34 weeks in an observational study to assess response durability. Outcomes at 68 weeks included a patient reported global response assessment, 24-hour voiding diary, and pain, urgency and validated interstitial cystitis symptom indexes., Results: Of responders to bacillus Calmette-Guerin or placebo in the clinical trial 38 continued extended followup in the observational study. A total of 12 (75%) responders who received placebo and 19 (86%) who received bacillus Calmette-Guerin considered themselves to remain moderately or markedly improved at week 68. Improved symptom outcomes were also generally maintained during followup in the 2 groups., Conclusions: Most patients who respond to therapy with intravesical bacillus Calmette-Guerin or placebo maintain improved symptoms for up to 68 weeks after the initiation of therapy. However, initial response rates are low and placebo responders demonstrated essentially the same durability of response as bacillus Calmette-Guerin responders. These results argue against the routine use of bacillus Calmette-Guerin in this patient group.

We measured candidate urine biomarkers and bladder cell DNA cytometry in interstitial cystitis (IC) patients randomized to receive intravesical Bacillus Calmette Guerin (BCG) or placebo in a multicenter trial. Participants received 6 weekly instillations and were followed for 34 weeks. Urine was collected at baseline, prior to fourth treatment, and at study end. Antiproliferative factor (APF) activity was determined by 3H-thymidine incorporation assay; heparin-binding epidermal growth factor-like growth factor (HB-EGF) and epidermal growth factor-like growth factor (EGF) levels were determined by ELISA. Cellular DNA content was measured by image analysis to determine the mean hyperdiploid fraction (HDF) of the urine cell pellet. Associations between marker levels, and treatment or symptoms, were examined. Baseline APF positivity rate and mean levels of the other biomarkers were similar to previous smaller studies. During the week 34 follow-up, mean HDF decreased (P = 0.0003) and HB-EGF increased (P < 0.0001); both correlated weakly with decreased urgency. There was no difference in any biomarker between symptom responders and non-responders, but the percentage of responders was low and not significantly different for BCG versus placebo. APF positivity, decreased HB-EGF, increased EGF, and increased HDF were confirmed at baseline in IC patients. Changes in HDF and HB-EGF levels correlated weakly with changes in urgency, but the low BCG response rate prevented identification of additional associations between biomarker changes and treatment or symptoms.

Purpose: We evaluated safety and efficacy outcomes in a case series of subjects who received open label intravesical bacillus Calmette-Guerin after failing to respond to bacillus Calmette-Guerin or intravesical placebo in a randomized clinical trial., Materials and Methods: Subjects who met National Institutes of Health-National Institute of Diabetes and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency were initially randomized to 6 weekly intravesical instillations of bacillus Calmette-Guerin or placebo and followed for a total of 34 weeks. At 34 weeks subjects who reported that they had not responded to treatment were offered treatment with open label bacillus Calmette-Guerin, using the same course of treatment and followup. Outcomes included a patient reported global response assessment, a 24-hour voiding diary, pain, urgency, validated interstitial cystitis symptom indexes and adverse events., Results: A total of 156 subjects elected open label bacillus Calmette-Guerin, of whom 18 (12%) withdrew during the open label series. The response rate based on the global response assessment was 18% and it was identical between those initially randomized to placebo (first course of bacillus Calmette-Guerin in the open label series) and those initially randomized to bacillus Calmette-Guerin (second course). Small improvements were observed for most secondary efficacy outcomes. Most participants reported at least 1 adverse event, primarily pain, genitourinary symptoms and gastrointestinal disturbances. However, there was no difference in adverse events between those who received the first course of bacillus Calmette-Guerin in this series compared to those who received 2 courses., Conclusions: The low response rate for bacillus Calmette-Guerin in this open label case series further argues against the routine use of bacillus Calmette-Guerin as treatment for interstitial cystitis.

Purpose: Interstitial cystitis significantly negatively impacts quality of life. The demographic and clinical factors associated with decreased quality of life in these patients have not been well studied., Materials and Methods: Women with moderate/severe interstitial cystitis enrolled in a clinical trial of intravesical bacillus Calmette-Guerin were studied. Demographic data and responses to questionnaires were evaluated at baseline, including the O'Leary-Sant Interstitial Cystitis Symptom Index and Problem Index, University of Wisconsin Interstitial Cystitis Inventory, Medical Outcomes Study sexual functioning scale, and the physical composite and mental composite scales of the Medical Outcomes Study Short Form Health Status Survey. Three composite indexes were constructed (from the O'Leary-Sant Interstitial Cystitis Symptom Index, O'Leary-Sant Interstitial Cystitis Problem Index, pain/urgency Likert scales and 24-hour voiding diary) to document the severity, frequency and bother of pain, urinary urgency and frequency (frequency composite index). Linear and multivariate regression models were used to examine predictors of the physical composite and mental composite scales of the Medical Outcomes Study Short Form Health Status Survey. Medical Outcomes Study sexual functioning scale data were available for 163 of the 217 women in the trial., Results: Physical composite scale (median 36) and mental composite scale (median 42) were lower than the standard population value of 50. Multivariate models showed that employment, pain composite index and Medical Outcomes Study sexual functioning scale (all p<0.001) predicted physical composite scale, while only Medical Outcomes Study sexual functioning scale (p<0.001) remained a strong predictor of mental composite scale., Conclusions: Sexual functioning, employment and pain issues predict mental and physical quality of life. In particular, this study identifies sexual functioning as a primary predictor of mental quality of life in women with long-standing interstitial cystitis. It is suggested that sexual functioning may be a salient therapeutic target in the multifaceted treatment of patients with interstitial cystitis.

Purpose: The prevalence of painful bladder symptoms is poorly defined, especially in racial and ethnic minority groups. We estimated the prevalence of painful bladder symptoms in a community based sample, assessed symptom variation by age, gender, race/ethnicity and socioeconomic status, and estimated their impact on quality of life., Materials and Methods: A population based cross-sectional survey of individuals was done in the Boston area using a multistage stratified cluster sample. A 2-hour in person interview performed by a bilingual interviewer was done, generally in the home of the subject. The research design was for equal numbers of subjects in each of 24 design cells, as defined by age (30 to 39, 40 to 49, 50 to 59 and 60 to 79 years), gender and race/ethnicity (black, Hispanic and white). The sample of 5,506 subjects was recruited from April 2002 through June 2005. Multiple definitions of painful bladder symptoms were used based on consensus statements, research definitions and published articles. The effect of gender, age, race/ethnicity and socioeconomic status on symptom prevalence was assessed., Results: The prevalence of painful bladder syndrome symptoms was 0.83% to 2.71% in women and 0.25% to 1.22% in men depending on the definition used. Multivariate analyses revealed that symptoms were significantly more common in women, middle-aged individuals (40 to 59 years old) and lower socioeconomic status groups. For most definitions there were no variations by race or ethnicity. The presence of symptoms was associated with a significant adverse impact on quality of life., Conclusions: Painful bladder symptoms are more common than suggested by coded physician diagnoses. Although most bladder pain research cohorts have included predominantly white women, these population based findings indicate no racial/ethnic disparity and limited gender disparity in the prevalence of painful bladder symptoms. This suggests that the burden of painful bladder syndrome may be greater in nonwhite individuals and men than previously suspected.

Objectives: To evaluate the responsiveness of composite scales to change over time in a clinical trial of patients with interstitial cystitis (IC). The measurement of symptoms in IC includes the O'Leary-Sant Symptom and Problem Indexes and the University of Wisconsin Interstitial Cystitis Inventory and scales that measure the individual symptom domains of pain/discomfort, urgency, and voiding frequency., Methods: The data were derived from a randomized clinical trial conducted by the Interstitial Cystitis Clinical Trials Group. Participants met the National Institutes of Health-National Institute for Diabetes, and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency. The primary endpoint was a patient-reported global response assessment (GRA) at 24 weeks. Secondary endpoints included the three composite indexes, pain/discomfort and urgency, and 24-hour frequency. Responsiveness was assessed by comparing symptom score changes against response categories defined by the GRA., Results: Of the 121 subjects in the original trial, 94 with complete data were included. All three composite indexes were sensitive to subject improvement over time as measured by the GRA. A 1.2-point change in the O'Leary-Sant indexes and a 3.1-point change in the Wisconsin IC inventory corresponded to a one-category change in the GRA. Individual symptoms were also responsive. The correlation was high among the changes in the six outcome measures., Conclusions: The three composite symptom scales are responsive to change over time in patients with IC. These indexes provide important insight into symptom changes and are recommended as secondary endpoints in future clinical trials of IC. Additional endpoints addressing individual symptom domains should also be considered to aid in the evaluation of effect mechanisms.

Purpose: We compared intravesical bacillus Calmette-Guerin (BCG) to placebo instillations in patients with treatment refractory interstitial cystitis (IC)., Materials and Methods: Subjects who met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC, and reported at least moderate pain and frequency for a minimum of 6 months before study entry, were randomized to 6 weekly double-blinded intravesical instillations of either BCG or placebo, and then followed for a total of 34 weeks. The primary outcome was a patient reported global response assessment at week 34, supplemented with medications for IC during weeks 31 to 34. Secondary outcomes included a 24-hour voiding diary, pain, urgency, validated IC symptom indexes and adverse events. The target sample size was 260 participants, designed to detect a difference in response rates between placebo and BCG of 30% and 50%, respectively., Results: A total of 265 participants were randomized and 17 (6%) patients withdrew from study. The response rates for the primary outcome were 12% for placebo and 21% for BCG (p = 0.062). Small improvements were observed for all secondary outcomes, some more so with BCG, but these differences were of borderline statistical significance. Although a large number of adverse events were reported in the BCG arm, there was no statistically significant difference between the treatment arms in overall adverse event rates., Conclusions: Although the BCG safety profile was acceptable, the response rate for the primary outcome was low. Effective medical treatment for patients with moderate to severe interstitial cystitis remains elusive.

Very few epidemiologic studies of interstitial cystitis (IC) have been published over the past 5 years. One population-based study focused only on women and suggested that the prevalence of the IC symptom complex in the United States is much higher than previously reported. Future epidemiologic studies of IC must overcome major obstacles to obtain more accurate population-based estimates. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) criteria used to assist in identifying patients with IC have proven to be cumbersome and too restrictive. Other obstacles include (1) the relative infrequency of the condition; (2) the long duration between development of symptoms and diagnosis; and (3) the perception that the disorder occurs predominantly in white women. Evidence suggests men with the IC symptom complex are often misdiagnosed by physicians and identified as having chronic prostatitis (also called the chronic pelvic pain syndrome) or benign prostatic hyperplasia. Children who present with the IC symptom complex are often thought to have voiding dysfunction. We propose that the more inclusive, less restrictive term chronic pelvic pain of the bladder (CPPB) be used in future epidemiologic studies of persons with the characteristic IC symptoms of urinary frequency, urgency, and pain. Early studies of chronic pelvic pain in general suggest that it is most common in women, of unknown etiology, and, in many patients, is associated with urinary bladder symptoms. It is necessary to develop case definitions for CPPB to accurately identify those patients with symptoms currently identified as IC.

The purpose of this study was to investigate associations between bladder biopsy features and urinary symptoms for patients enrolled in the Interstitial Cystitis Database (ICDB) Study. Bladder biopsies were obtained during baseline screening in the ICDB Study and were evaluated for histopathologic features. Multivariable models for nighttime voiding frequency, urinary urgency, and pain were developed, incorporating biopsy features from the most diseased area of the bladder as predictors, adjusting for significant clinical factors, and clinical center variation. Among 204 interstitial cystitis (IC) patients providing biopsy specimens, cystoscopic pathology findings were not statistically associated (P >0.1) with primary IC symptoms, although the presence of Hunner's ulcer (n = 12) was suggestive of increased urinary frequency. Within a multivariable predictive model for nighttime voiding frequency, adjusting for age and minimum volume per void, 4 pathology features were noted: (1) mast cell count in lamina propria on tryptase stain; (2) complete loss of urothelium; (3) granulation tissue in lamina propria; and (4) vascular density in lamina propria on factor VIII (F8) stain were statistically significant (P <0.01). Similarly, in a multivariable model for urinary urgency, minimum volume, and percentage of submucosal granulation tissue remained statistically significant (P <0.01). Finally, the percentage of mucosa denuded of urothelium and the percentage of submucosal hemorrhage remained highly associated (P <0.01) with pain in a multivariable predictive model. The fact that the presence or severity of glomerulations was not selected for any of these predictive models suggests that cystoscopic findings of glomerulations are not predictive of IC symptoms. Furthermore, these results suggest an important role for certain pathologic features in the predictive modeling of IC symptoms.

Objectives: To evaluate the frequency and types of treatments reported at baseline in women who entered the Interstitial Cystitis Data Base (ICDB) cohort study., Methods: From 1993 to 1997, 581 women were enrolled and followed in the ICDB. All treatments reported at study entry, including those prescribed for interstitial cystitis (IC) and concomitant medications, were reviewed. The number and types of treatments were evaluated with respect to baseline factors such as prior diagnosis of IC and symptom severity., Results: One hundred five (18%) women were receiving no therapy at baseline. Single-mode therapy was reported by 195 (34%) women, and a combination of two treatments was reported by 119 (21%) women. Three or more treatments were reported in 162 (28%) women. A total of 183 different types of therapies were recorded. The five most commonly used therapies for IC symptoms were cystoscopy and hydrodistention, amitriptyline, phenazopyridine, special diet, and intravesical heparin. Because most patients entered the ICDB before the approval of oral pentosan polysulfate sodium (PPS), only 6% of women reported oral PPS use at baseline. There were statistically significant associations between the number and types of treatments and clinical center, a prior diagnosis of IC, and symptom severity., Conclusions: The diversity of IC therapies underscores the lack of understanding about the treatment of this syndrome. Further research in IC is essential to develop and to evaluate rational therapies and treatment algorithms. These algorithms should be "evidence based" and should be revised as the underlying etiology and pathophysiology of IC is delineated.

Purpose: We present baseline characteristics and longitudinal profiles of symptoms in the Interstitial Cystitis Data Base study, a prospective cohort study of patients with interstitial cystitis., Materials and Methods: A total of 637 eligible patients were entered into the study and followed for symptoms of pain, urgency and urinary frequency. Median followup was 31 months., Results: More than 90% of patients were white women with a median age of 43 years. Using the overall pain-urgency-frequency score 7% of participants presented with mild, 44% with moderate and 49% with severe symptoms. Severe urgency in 41% of cases and severe 24-hour frequency in 41% were more common than severe pain in 29%. Of the patients 51% reported nighttime frequency of 2 or more voids. Median duration of interstitial cystitis symptoms was 8 years and 68% of participants were previously diagnosed with the condition. The 36% of patients who withdrew from study or were lost to followup were more likely to have had more severe symptoms at baseline. Patterns of change with time suggest initial symptom improvement due to regression to the mean, and an intervention effect associated with the increased followup and care of cohort participants. Although all symptoms fluctuated, there was no evidence of significant long-term change in overall disease severity., Conclusions: Our observations support the clinical observation that interstitial cystitis is a chronic disease and no current treatments have a significant impact on symptoms with time. These results provide a foundation for the design and performance of future clinical trials in interstitial cystitis using these end points in a similar patient population.