Interstitial Cystitis Symptom Research Articles

The MAPP research network: design, patient characterization and operations.

BackgroundThe “Multidisciplinary Approach to the Study of Chronic Pelvic Pain” (MAPP) Research Network was established by the NIDDK to better understand the pathophysiology of urologic chronic pelvic pain syndromes (UCPPS), to inform future clinical trials and improve clinical care. The evolution, organization, and scientific scope of the MAPP Research Network, and the unique approach of the network’s central study and common data elements are described.MethodsThe primary scientific protocol for the Trans-MAPP Epidemiology/Phenotyping (EP) Study comprises a multi-site, longitudinal observational study, including bi-weekly internet-based symptom assessments, following a comprehensive in-clinic deep-phenotyping array of urological symptoms, non-urological symptoms and psychosocial factors to evaluate men and women with UCPPS. Healthy controls, matched on sex and age, as well as “positive” controls meeting the non-urologic associated syndromes (NUAS) criteria for one or more of the target conditions of Fibromyalgia (FM), Chronic Fatigue Syndrome (CFS) or Irritable Bowel Syndrome (IBS), were also evaluated. Additional, complementary studies addressing diverse hypotheses are integrated into the Trans-MAPP EP Study to provide a systemic characterization of study participants, including biomarker discovery studies of infectious agents, quantitative sensory testing, and structural and resting state neuroimaging and functional neurobiology studies. A highly novel effort to develop and assess clinically relevant animal models of UCPPS was also undertaken to allow improved translation between clinical and mechanistic studies. Recruitment into the central study occurred at six Discovery Sites in the United States, resulting in a total of 1,039 enrolled participants, exceeding the original targets. The biospecimen collection rate at baseline visits reached nearly 100%, and 279 participants underwent common neuroimaging through a standardized protocol. An extended follow-up study for 161 of the UCPPS participants is ongoing.DiscussionThe MAPP Research Network represents a novel, comprehensive approach to the study of UCPPS, as well as other concomitant NUAS. Findings are expected to provide significant advances in understanding UCPPS pathophysiology that will ultimately inform future clinical trials and lead to improvements in patient care. Furthermore, the structure and methodologies developed by the MAPP Network provide the foundation upon which future studies of other urologic or non-urologic disorders can be based.Trial registrationClinicalTrials.gov identifier: NCT01098279 “Chronic Pelvic Pain Study of Individuals with Diagnoses or Symptoms of Interstitial Cystitis and/or Chronic Prostatitis (MAPP-EP)”. http://clinicaltrials.gov/show/NCT01098279

Examination of the Significant Placebo Effect in the Treatment of Interstitial Cystitis/Bladder Pain Syndrome

To examine the significant "placebo effect" in a randomized, double-blind, placebo-controlled interstitial cystitis/bladder pain syndrome trial. Randomized clinical trials are the reference standard for therapeutic impact assessment. However, proving efficacy of treatments for interstitial cystitis/bladder pain syndrome with rigorous placebo-controlled trials is difficult due to a significant effect of the placebo intervention. Interstitial cystitis/bladder pain syndrome patients were randomized to receive subcutaneous adalimumab or subcutaneous placebo every 2 weeks for 12 weeks and outcome measures were assessed. Of the 43 patients, 21 received adalimumab and 22 received placebo. Of the patients who received placebo, there was a statistically significant improvement demonstrated in the O'Leary-Sant Interstitial Cystitis Symptom and Problem Indexes of -8.1 (95% confidence interval [CI], 3.0-13.2), Interstitial Cystitis Symptom Index of -3.7 (95% CI, 0.9-6.5), Interstitial Cystitis Problem Index of -4.4 (95% CI, 2.0-6.8), and Pelvic Pain, Urgency, Frequency scale of -6.9 (95% CI, 2.8-11.0) at week 12 compared with baseline. Most of the significantly improved placebo patients felt their improvement was because they were more conscientious about following physician advice and feeling less stress while in the study. Patients with moderate to severe interstitial cystitis/bladder pain syndrome had significant improvement after receiving only advice and support. This intervention is risk free and inexpensive. Physicians should review standard advice with all interstitial cystitis/bladder pain syndrome patients before starting medical therapy.

Symptom persistence in a community cohort of women with interstitial cystitis/bladder pain syndrome (IC/BPS): 3-, 6-, 9-, and 12-month follow-up from the RICE cohort.

The persistence of interstitial cystitis/bladder pain syndrome (IC/BPS) symptoms has been described in women seeking medical care. The purpose of this study was to determine whether symptoms persist among a population-based sample of women. A probability sample of US women was identified through a two-stage telephone screening process using the Research and Development (RAND) Interstitial Cystitis Epidemiology (RICE) high-sensitivity case definition. A randomly selected subgroup (n = 508) was enrolled in a longitudinal study and interviewed about their symptoms at baseline, 3, 6, 9, and 12 months. Bivariate and multivariate linear regression analyses determined predictors of persistence of symptoms over the four waves. A total of 436 women with a mean age of 47.5 years responding to all waves were included in the analysis. Forty-one percent met the RICE high-sensitivity case definition at baseline and in all four waves; an additional 21 % met the definition at baseline and in three waves. Women with a college degree (+12 % vs. no college, p = 0.02) and who were younger (-5 % per decade of age, p < 0.01) had higher chances of symptom persistence at each wave. Scoring one standard deviation higher on the continuity of symptoms and the O'Leary-Sant Interstitial Cystitis Symptom index increased the chances of symptom persistence by 4 % and 2 %, respectively (both p < 0.01). The majority of women demonstrated symptom persistence across at least three of four waves over 12 months. These women tended to be younger, college-educated, and to have reported a history of greater continuity of symptoms and higher severity of symptoms at baseline.

Efficacy of Daily Low-dose Sildenafil for Treating Interstitial Cystitis: Results of a Randomized, Double-blind, Placebo-controlled Trial—Treatment of Interstitial Cystitis/Painful Bladder Syndrome With Low-dose Sildenafil

To evaluate the efficacy of daily low-dose sildenafil for the treatment of nonulcer interstitial cystitis (IC) in women. Forty-eight women with a clinical diagnosis of IC from 3 medical centers were randomly assigned to treatment with daily low-dose sildenafil (25 mg, n=24) or placebo (n=24) for 3 months. The O'Leary-Sant IC symptom and problem indices, visual analog scale scores, and a micturition diary with the interval of micturition, the frequency of nocturia, and urgency episodes were recorded before treatment, every 2 weeks after the treatment until 3 months. Patient Overall Rating of Improvement in Symptoms was assessed and regarded as effective when the value was above 50%. The IC symptom and problem indices scores and urodynamic index were significantly improved in sildenafil treatment group as compared with placebo group and baselines at week 4, 6, 8, 10, and 12, as well as 3 months after treatment (P<.05). Urodynamic index including first desire to void, strong desire to void, and maximum cystometric capacity was significantly improved in sildenafil treatment group at week 12 and at 3 months after treatment (P<.05). The efficiency of treatment reached 62.5%. However, no significant change of the visual analog scale values was observed between 2 groups except at week 12 in the sildenafil treatment group (P<.05). All adverse events were mild to moderate and transient. Daily low-dose sildenafil is an easy, well-tolerated, and effective treatment for IC in women.

Phenotype-directed Management of Interstitial Cystitis/Bladder Pain Syndrome

To assess a flexible therapeutic strategy for patients referred to a specialized interstitial cystitis/bladder pain syndrome (IC/BPS) clinic using an individualized phenotype-directed treatment plan based on clinically based urinary, psychosocial, organ-specific, infection, neurologic or nonbladder, and tenderness of pelvic floor (UPOINT) categorization, instead of the traditional algorithmic stepwise approach. Consecutive patients referred to a specialized tertiary IC/BPS clinic with at least 1 follow-up posttreatment visit were categorized according to their UPOINT status and treated according to previously published individualized phenotype-based treatment plan. Patients were assessed at baseline and up to 2 years with validated symptom scores (interstitial cystitis symptom score [ICSI]; and pain urgency frequency questionnaire) as well as pain and voiding assessments. Follow-up visit data were available for 93 patients (mean age, 45.2 years; median age, 44 years; mean ICSI, 13.2±3.6). Patients reported a median of 4 UPOINT domains (mean, 3.7±0.94) with the following distribution: U=100%; P=31.2%; O=97.8%; I=45.2%; N=39.8%; and T=55.9%. The mean decrease in ICSI was 3.4 points. Significant clinical improvement (>30% decrease in ICSI) was observed in 46.2% compared with initial baseline visit. Pain urgency frequency, and pain and urgency scoring changes were comparable. No correlation between severity of symptoms and number of domains and ICSI decrease was observed. Almost 50% of patients referred to a tertiary IC/BPS clinic, regardless of the complexity or severity of condition, experienced clinically significant improvement using an individualized phenotype-directed therapeutic approach.

Persistent Genital Arousal in Women With Pelvic and Genital Pain

ObjectivePersistent genital arousal disorder (PGAD) has been identified as a condition of often unprovoked genital arousal associated with a significant level of distress. PGAD is not well understood, and no definitive cause has been determined. The aim of this study was to gain a better understanding of the disorder and to seek commonalities between cases of PGAD encountered in a chronic pain management clinic. MethodWe reviewed a cohort of 15 women with PGAD who presented to a chronic non-cancer pain clinic in a large urban tertiary teaching hospital that provides pelvic and genital pain management. We conducted a series of interviews to examine medical history, history of presenting illness, and management. Descriptive statistics were used to examine the data. ResultsFindings were largely consistent with previous research on PGAD regarding symptomatology and aggravating and alleviating factors. Symptoms of genital pain, depression, and interstitial cystitis were found in over one half of the patients in this cohort. Previous antidepressant use, restless legs syndrome, and pudendal neuralgia were found in a number of cases. Pelvic varices and Tarlov cysts have been previously identified as possible contributors to PGAD, but these were not a common finding in our cohort. ConclusionFurther research is needed to build on the current understanding of PGAD. Patients should be asked about persistent arousal as part of a sexual and reproductive history, especially in the case of common comorbidities.

Mechanisms of pain from urinary tract infection.

The pain response to urinary tract infection is largely uncharacterized, but the symptomatic response to urinary tract infection contrasts with the lack of pain response among individuals with asymptomatic bacteriuria. Quantifying pelvic pain in a murine urinary tract infection model, uropathogenic Escerichia coli induces transient pelvic pain, whereas an asymptomatic bacteriuria E. coli isolate causes no pain, thus recapitulating the spectrum of clinical responses to intravesical E. coli. These differential pain responses are not correlated with bladder colonization or inflammation, but instead are intrinsic to E. coli lipopolysaccharide and dependent on the lipopolysaccharide receptor, TLR4. Epidemiological data suggest a link between interstitial cystitis and a history of urinary tract infection, so it was evaluated whether repetitive uropathogenic E. coli instillation would result in chronic pain through central sensitization. Although repeated infection with wild type uropathogenic E. coli results in only transient episodes of acute pain, a uropathogenic E. coli mutant lacking O-antigen causes chronic, post-urinary tract infection pelvic pain. Similarly, a K-12 E. coli strain lacking O-antigen induces chronic pain that persisted long after bacterial clearance, and expressing O-antigen nullified the pain phenotype. Spinal cords isolated from mice with post-urinary tract infection chronic pain showed deficits in short-term depression consistent with central sensitization. Deleting O-antigen gene complex from a uropathogenic E. coli strain and subsequent heterologous expression of O-antigen gene clusters shows that a single bacterial isolate can exhibit pain phenotypes ranging from a null phenotype, an acute pain phenotype, to a chronic pain phenotype. Post-urinary tract infection chronic pain is also associated with voiding dysfunction and anxious/depressive behavior. These effects are also mediated by TRPV1 at the level of pain establishment and CCR2 at the level of pain maintenance. Together, these findings show that transient infection with E. coli might result in chronic visceral pain with the hallmarks of neuropathic pain. This pattern of behaviors mimics the spectrum of interstitial cystitis symptoms, thus supporting the possibility of an infectious etiology of interstitial cystitis.

Efficacy and safety of augmentation ileocystoplasty combined with supratrigonal cystectomy for the treatment of refractory bladder pain syndrome/interstitial cystitis with Hunner's lesion.

To evaluate the efficacy and safety of augmentation ileocystoplasty with supratrigonal cystectomy for the treatment of refractory bladder pain syndrome/interstitial cystitis patients with Hunner's lesion. Of 45 patients who underwent augmentation ileocystoplasty with supratrigonal cystectomy between July 2006 and June 2012, 40 patients (33 women, 7 men) were included in the analysis. Primary outcome was the change in the O'Leary-Sant interstitial cystitis symptoms/problem index from baseline to 1, 3 and 6 months. Changes in pain, urgency, frequency, functional bladder capacity and maximal cystometric capacity were also assessed. Intraoperative and postoperative complications were evaluated. Median preoperative symptom duration was 5.0 years (range 3.0-6.0 years). Pain decreased significantly after surgery (8.3 vs. 1.3, P < 0.001). Functional bladder capacity and maximal cystometric capacity increased, whereas frequency, urgency and nocturia decreased significantly after surgery (all P < 0.001). At 6 months, significant improvements in the interstitial cystitis symptom index (17.8 vs. 9.9, P < 0.001) and interstitial cystitis problem index (14.6 vs. 6.5, P < 0.001) compared with baseline were noted. Seven patients developed vesicoureteral reflux and seven patients had acute pyelonephritis that resolved with antibiotic treatment. Five patients required clean intermittent self-catheterization. None of the preoperative factors were significant predictors of treatment failure. Augmentation ileocystoplasty with supratrigonal cystecomy decreased pain and frequency, and increased bladder capacity significantly. There were no severe complications related to surgery during follow up. Augmentation ileocystoplasty with supratrigonal cystectomy is therefore an appropriate final treatment strategy for refractory bladder pain syndrome/interstitial cystitis patients with Hunner's lesion.

MP2-18 DEVELOPMENT AND IMPLEMENTATION OF A VALIDATED ELECTRONIC MEDICAL RECORD EXTRACTION PROCESS TO DETERMINE ADHERENCE WITH THE AUA CLINICAL PRACTICE GUIDELINES ON LUTS/BPH

INTRODUCTION AND OBJECTIVES: The validated Interstitial Cystitis Symptom and Problem Index (ICSI-PI) reliably measures symptoms and associated bother in patients with interstitial cystitis. We evaluated whether the ICSI-PI reliably measures overactive bladder (OAB) symptoms in patients with OAB with/without incontinence (OAB wet/dry). METHODS: Adults in our prospective observational neuromodulation study were evaluated. Inclusion criteria were OAB wet/dry and staged lead and generator implant. Subjects completed the ICSI-PI and Overactive Bladder Questionnaire-short form (OAB-q) at baseline and 3, 6, and 12 months post implant. The ICSI-PI is comprised of a symptom index (IC-SI) and bother index (IC-PI) which assess voiding symptoms and pain. The OAB-q contains symptom severity (SS) and health related quality of life (HRQOL) scales. Descriptive statistics were performed for sample characteristics. At each time point, IC-SI and OAB-q SS responses, and IC-PI and OAB-q HRQOL responses were compared with Spearman’s Correlations in patients that completed both measures. RESULTS: Of 215 patients (mean age 65.1 14.2 years), 80% were female, 94% were caucasian, 67.4% had attended at least some college, 24.5% had an income >$70,000/year, and 84% had OAB wet. As shown in the table below, at each time point there was a strong correlation between IC-SI and OAB-q SS scores. Additionally, IC-PI and OAB-q QOL scores were strongly negatively correlated indicating that higher symptom bother negatively impacted HRQOL. CONCLUSIONS: Even though pain is not a component of the OAB syndrome, the ICSI-PI appears to reliably measure voiding symptoms and bother in patients with OAB.

MP2-17 DOES THE INTERSTITIAL CYSTITIS SYMPTOM AND PROBLEM INDEX RELIABLY MEASURE OVERACTIVE BLADDER SYMPTOMS?

INTRODUCTION AND OBJECTIVES: The validated Interstitial Cystitis Symptom and Problem Index (ICSI-PI) reliably measures symptoms and associated bother in patients with interstitial cystitis. We evaluated whether the ICSI-PI reliably measures overactive bladder (OAB) symptoms in patients with OAB with/without incontinence (OAB wet/dry). METHODS: Adults in our prospective observational neuromodulation study were evaluated. Inclusion criteria were OAB wet/dry and staged lead and generator implant. Subjects completed the ICSI-PI and Overactive Bladder Questionnaire-short form (OAB-q) at baseline and 3, 6, and 12 months post implant. The ICSI-PI is comprised of a symptom index (IC-SI) and bother index (IC-PI) which assess voiding symptoms and pain. The OAB-q contains symptom severity (SS) and health related quality of life (HRQOL) scales. Descriptive statistics were performed for sample characteristics. At each time point, IC-SI and OAB-q SS responses, and IC-PI and OAB-q HRQOL responses were compared with Spearman’s Correlations in patients that completed both measures. RESULTS: Of 215 patients (mean age 65.1 14.2 years), 80% were female, 94% were caucasian, 67.4% had attended at least some college, 24.5% had an income >$70,000/year, and 84% had OAB wet. As shown in the table below, at each time point there was a strong correlation between IC-SI and OAB-q SS scores. Additionally, IC-PI and OAB-q QOL scores were strongly negatively correlated indicating that higher symptom bother negatively impacted HRQOL. CONCLUSIONS: Even though pain is not a component of the OAB syndrome, the ICSI-PI appears to reliably measure voiding symptoms and bother in patients with OAB.

PD9-10 PROSPECTIVE LONG-TERM FOLLOW-UP STUDY OF PATIENTS WITH REFRACTORY INTERSTITIAL CYSTITIS TREATED WITH CYCLOSPORINE A

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Interstitial Cystitis1 Apr 2014PD9-10 PROSPECTIVE LONG-TERM FOLLOW-UP STUDY OF PATIENTS WITH REFRACTORY INTERSTITIAL CYSTITIS TREATED WITH CYCLOSPORINE A Jamil Chade, Daher Chade, Antonio M. Lucon, Homero Bruschini, and Miguel Srougi Jamil ChadeJamil Chade More articles by this author , Daher ChadeDaher Chade More articles by this author , Antonio M. LuconAntonio M. Lucon More articles by this author , Homero BruschiniHomero Bruschini More articles by this author , and Miguel SrougiMiguel Srougi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.792AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Interstitial Cystitis (IC) is a challenging disease of the urinary bladder. Although several different types of medical treatment have been used, none of them has been significantly successful and therefore a standard of care is still debatable. We sought to analyze the impact of a 5-year therapy of cyclosporine A (CYA) on clinical and urodynamic findings for interstitial cystitis METHODS Two male and 43 female patients who fulfilled the NIDDKD (National Institute for Diabetes and Digestive and Kidney Diseases) criteria for the diagnosis of IC were included in this study. Diagnosis was confirmed by cystoscopic examination, biopsy of the bladder, urodynamic evaluation and voiding diary. The symptoms were measured using O'Leary-Sant interstitial cystitis symptoms index (ICSI) and problem index (ICPI) before and after the proposed treatment. Quality of life (QoL) was assessed by AUA QoL index. All patients had been treated with at least 2 other drugs previously, unsuccessfully. After signing the informed consent, they received 1.5 mg/kg of cyclosporine A, twice a day, for 5 years. The patients were evaluated for the symptoms (ICSI) and by urodynamics before, during and after treatment. RESULTS All patients had ICSI of 36 and ICPI above 8 prior to treatment. The mean ICSI score decreased from 36 to 21.6 at 6 months, and to 8.4 at 5 years (p<0.001) of treatment. Mean initial filling sensation increased from 103mL before receiving CYA to 170mL after treatment (p<0.001). Mean bladder capacity prior to CYA was 207mL and 318mL after treatment (p<0.001). Mean AUA QoL index went from 4.8 to 1.3 with CYA use. All 45 patients had ICPI above 8 before treatment, but only 22% of patients remained in this group after CYA. All the patients had biochemical analysis before and after the treatment, and no significant abnormalities were found for liver and renal function. CONCLUSIONS Long term Cyclosporine A therapy is an effective alternative treatment for refractory IC. Our data suggest beneficial results and clinically significant improvement, despite failure to multiple previous treatments. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e215 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Jamil Chade More articles by this author Daher Chade More articles by this author Antonio M. Lucon More articles by this author Homero Bruschini More articles by this author Miguel Srougi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Effect of Sacral Neuromodulation on Outcome Measures and Urine Chemokines in Interstitial Cystitis/Painful Bladder Syndrome Patients.

Sacral neuromodulation (SNM) may improve interstitial cystitis/painful bladder syndrome (IC/BPS) symptoms of urinary frequency, urgency and perhaps even pain, but objective measures of improvement are lacking. We evaluated the potential for urinary chemokines to serve as measures of treatment response over time to SNM. Women with IC/BPS undergoing SNM consented for this study. Three-day bladder/pain diaries were collected at baseline and validated Interstitial Cystitis Symptom Problem Index (ICSPI) scores and mid-stream urine specimens were collected at baseline and at 24 weeks after successful implant. Collected urine was screened for infection by dipstick and analyzed for chemokines by luminex xMAP analysis. At baseline (n = 16), urine levels of CXCL-1 positively correlated with pain score (r = 0.63, P = 0.009), urgency (r = 0.61, P = 0.01), ICSPI (r = 0.43, P = 0.09) and daily voids (r = 0.44, P = 0.08). ICSPI and pain scores also positively correlated with sIL-1ra (r = 0.50, P = 0.04) and monocyte chemotactic protein-1 (MCP-1) or CCL2 positively correlated with daily voids (r = 0.45, P = 0.07) only. At 24 weeks, the median ICSPI index fell from 28 to 15 (n = 7, P = 0.008). Urine levels of sIL-1ra (633.8 ± 188.2 vs. 149.9 ± 41.62 pg/mL) and MCP-1 (448.3 ± 11.6 vs. 176.9 ± 46.16 pg/mL) and CCL5 (20.78 ± 4.09 vs. 11.21 ± 4.12 pg/mL) were also significantly reduced at the follow-up relative to baseline values (P = 0.04). Multivariable analysis of data revealed that sIL-1ra and MCP-1 together explained the majority of variance in data. Levels of CXCL-1, CXCL-10, interleukin (IL)-8, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) were also reduced at 24 weeks, but differences were not significant. Concomitant decrease in urine levels of chemokines especially MCP-1 was associated with treatment response of SNM. These results support the role of chemokines as downstream effectors of neuromodulation response and could serve as potential non-invasive measures of treatment response. NCT01739946.

Risk factors for interstitial cystitis/painful bladder syndrome in patients with lower urinary tract symptoms presenting for urologic care

To identify the risk factors in interstitial cystitis/painful bladder syndrome (IC/PBS) patients with lower urinary tract symptoms (LUTS) without urinary tract infection or benign prostate hyperplasia in China. A total of 954 outpatients with LUTS presenting for care to urology clinics at 8 hospitals throughout China from November 20, 2008 to August 24, 2012 were surveyed with a standardized questionnaire and validated outcome measures. The definitions for IC/PBS based on the O'Leary-Sant interstitial cystitis symptom and problem indices were used. The possible risk factors was analyzed with the Fisher's exact and Pearson chi-square tests. And multivariate predictive models were developed with binary Logistic regression methods. There were 491 females and 463 males. And 44.7% (427/954) met the criteria for IC/PBS. There was significant gender difference (51.7% (254/491) vs 37.4% (173/463), P < 0.05) . After adjusting for confounding factors, bladder pain was significantly associated with stimulatory foods (OR: 81.16, 95%CI: 11.50-590.00, P = 0.001) and anorectal disease (OR: 54.90, 95%CI: 9.52-401.00, P = 0.001) in females. Caffeine beverage intake (OR: 4.29, 95%CI: 1.86-9.86, P = 0.001) was the only modifiable association according to multivariate analysis of males. Stimulatory foods, anorectal disease and caffeine beverages are potential risk factors for IC/PBS.Further studies are necessary to determine their roles in the pathogenesis of this disorder.

EP-1369: PDRNs intravesical instillations reduces symptoms of interstitial radiation-induced cystitis

EP-1369: PDRNs intravesical instillations reduces symptoms of interstitial radiation-induced cystitis

Pretreatment features to influence effectiveness of intravesical hyaluronic Acid instillation in refractory interstitial cystitis/painful bladder syndrome.

PurposeTo determine the efficacy of intravesical hyaluronic acid (HA) instillation in treating patients with refractory interstitial cystitis/painful bladder syndrome (IC/PBS) and to identify any related factors that influence its therapeutic effect.MethodsThirty-three female IC/PBS patients who demonstrated poor or unsatisfactory responses to previous treatments between December 2010 and October 2012 were enrolled. Despite previous treatments, the enrolled patients had visual analogue scale (VAS) pain scores ≥4 and total scores (symptom and bother scores) ≥13 on the pelvic pain and urgency/frequency (PUF) questionnaire and ≥12 on the O'Leary-Sant interstitial cystitis symptoms index (ICSI)/problems index (ICPI). All patients received once weekly intravesical instillations of 40-mg HA diluted in 50-mL saline for 4 weeks. The efficacy of the HA instillation was evaluated by comparing the mean changes in the scores of the VAS and questionnaires from baseline to 4 weeks after treatment. Improvement was defined as a ≥2 decrease in the VAS. Moreover, we investigated the effects of the presence of Hunner's ulcer and previous treatment modalities on the therapeutic outcome of HA instillation.ResultsThe mean age was 57.0±1.8 years (range, 28-75 years). The VAS score significantly decreased from baseline to 4 weeks after treatment (-2.5, P<0.001). The mean changes in the PUF, ICSI, and ICPI from baseline to 4 weeks after the treatment were -3.8 (P<0.001), -2.3 (P<0.001), and -2.7 (P<0.001), respectively. Twenty patients (61%) showed improvements. Previous treatment modalities did not affect the efficacy of HA instillation and the presence of Hunner's ulcer was unrelated to outcomes. No complications were observed.ConclusionsThese results show that intravesical HA instillation is an effective and safe treatment for patients with refractory IC/PBS. Previous treatment modalities and presence of Hunner's ulcer do not affect the efficacy of HA instillation.

Efficiency of O'Leary-Sant symptom index and problem index in the diagnosis of interstitial cystitis

To evaluate the efficiency of O'Leary-Sant problem index and symptom index (OPSI) in the diagnosis of interstitial cystitis (IC). A total of 82 patients, initially diagnosed as IC, with urinary frequency, urgency and pain on pubic area during bladder filling phase from January 2008 to March 2013 were enrolled.OPSI was used to evaluate their symptoms. They were eventually divided into IC and non-IC groups according to the clinical diagnosis. The scores of OPSI, interstitial cystitis problem index (ICPI) and interstitial cystitis symptom index (ICSI) were compared between two groups. And the ROC curve was plotted to screen the diagnostic specificity and sensitivity. Among them, 58 were diagnosed with IC and the rest with non-IC. The average score of OPSI for groups IC and non-IC were 24.7 ± 6.9 and 23.2 ± 7.8 respectively (P = 0.403). And the ICPI score for two groups were 11.7 ± 3.2 and 10.2 ± 3.7 (P = 0.070) and the ICSI score 13.0 ± 4.0 and 13.1 ± 4.3 (P = 0.975) respectively.No significant differences existed between two groups. If an OPSI score of 12 or greater for diagnosing IC, the sensitivity was 98% and specificity 8%. Because of a high sensitivity, OPSI was a useful indicator for screening IC patients from others.In the ROC curve, acreage under curve for OPSI, ICPI, ICSI were 0.548 ± 0.071, 0.622 ± 0.069 and 0.492 ± 0.070 respectively. These three indices were not good indicators for diagnosing IC. The O'Leary-Sant symptom index and problem index has a high sensitivity but a low specificity in the diagnosis of IC. Therefore it should not be used to differentiate interstitial cystitis. A cutoff OPSI value of 12 may be used for differentiation.

High-dose tranilast administration to rats creates interstitial cystitis-like symptoms with increased vascular permeability

AimWe investigated whether the high-dose administration of tranilast could be used to create an animal model of interstitial cystitis (IC). Then, we used this model to assess the relationship between IC and changes in the vascular permeability of the bladder. Main methodsFemale rats were divided into the following 4 groups: a control group, a tranilast group, a carbazochrome group and a combination (tranilast+carbazochrome) group. Continuous cystometry, bladder distension, and the Evans blue dye extravasation test were performed 4weeks after drug administration. Locomotor activity, the plasma TGF-β1 level, and collagen fibers in the bladder wall were also examined in the control and tranilast groups. Key findingsThe interval between bladder contractions was shorter and the leakage of Evans blue dye into the bladder wall was greater in the tranilast group than in the control group. Glomerulations of the bladder wall after bladder distention and thinning of the collagen fiber layer in the bladder were observed in the tranilast group. Locomotor activity in darkness and the plasma TGF-β1 level were both lower in the tranilast group than in the control group. In the combination group, the leakage of Evans blue dye was greater than in the control group; however, it was less prominent than in the tranilast group. SignificanceThese results suggest that high-dose administration of tranilast to rats can create an IC-like rat model and that an increase in the vascular permeability of the bladder wall may be one cause of IC symptoms.

Consequences of Interstitial Cystitis/Bladder Pain Symptoms on Women's Work Participation and Income: Results from a National Household Sample

We describe differences in work participation and income by bladder symptom impact and comorbidities among women with interstitial cystitis/bladder pain syndrome. Cross-sectional data from 2,767 respondents younger than 65 years identified with interstitial cystitis/bladder pain syndrome symptoms were analyzed. The data were taken from the RAND Interstitial Cystitis Epidemiology (RICE) survey, and included retrospective self-reports of interstitial cystitis/bladder pain syndrome impact, severity, years since onset, related comorbidities (depressive symptomatology, number of conditions), work participation and income, and personal characteristics. Multiple regressions predicted 5 current work outcomes of works now, kept from working by pain, missed work days, days worked when bothered by symptoms and real income change since symptom onset. Controlling for work status at symptom onset and personal characteristics, greater bladder symptom impact predicted a greater likelihood of not now working, kept more days from working by pain, missed more work days and working more days with symptoms. More depressive symptomatology and greater number of comorbidities predicted reduced work participation. Women experienced no growth in real income since symptom onset. Measures of symptom severity were not associated with any of the economic outcomes. Greater interstitial cystitis/bladder pain syndrome symptom impact, depressive symptomatology and count of comorbidities (but not symptom severity) were each associated with less work participation and leveling of women's long-term earnings. Management of bladder symptom impact on nonwork related activities and depressive symptomatology may improve women's work outcomes.

A Randomized, Double-Blind, Placebo Controlled Trial of Adalimumab for Interstitial Cystitis/Bladder Pain Syndrome

The efficacy of adalimumab for the treatment of interstitial cystitis/bladder pain syndrome was investigated in a phase III, randomized, double-blind, placebo controlled, proof of concept study. Patients with interstitial cystitis/bladder pain syndrome were randomized to receive a loading dose of 80 mg subcutaneous adalimumab followed by 40 mg every 2 weeks or subcutaneous placebo for 12 weeks, and outcome measures were assessed. The incidence of adverse events was also assessed. Of a total of 43 patients 21 received adalimumab and 22 received placebo. Of the patients who received adalimumab, there was a statistically significant improvement demonstrated in the O'Leary-Sant Interstitial Cystitis Symptom and Problem Indexes (p = 0.0002), Interstitial Cystitis Symptom Index (p = 0.0011), Interstitial Cystitis Problem Index (p = 0.0002), and Pelvic Pain, Urgency, Frequency Symptom Scale (p = 0.0017) at 12 weeks compared to baseline. At 12 weeks 11 of 21 (53%) patients in the adalimumab group had a 50% or greater improvement in global response assessment (p ≤ 0.0001). There was not a statistically significant improvement in any outcome measure in patients receiving adalimumab compared to placebo. There were no significant adverse events. Adalimumab treatment resulted in a statistically significant improvement in outcome measures compared to baseline in patients with moderate to severe interstitial cystitis/bladder pain syndrome. Adalimumab failed to demonstrate positive proof of concept compared to placebo due to a significant placebo effect.

Combined intravesical sodium hyaluronate/chondroitin sulfate therapy for interstitial cystitis/bladder pain syndrome: a prospective study

The aim of this study was to verify the efficacy and safety of intravesical treatment combining sodium hyaluronate (HA) and chondroitin sulfate (CS) in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Between February 2010 and May 2011, 20 consecutive women with IC/BPS were treated with intravesical instillations containing sodium HA (1.6%; 800 mg/50 ml) and sodium CS (2%; 1 g/50 ml) weekly for the first month, biweekly for the second month, and then monthly for at least 3 months. Before and after treatment, all patients filled in the Interstitial Cystitis Symptom Index and Problem Index (ICSI/ICPI), the Patient Health Questionnaire 9 and the Pelvic Pain and Urgency/Frequency Patient Symptom Scale (PUF). Treatment efficacy was assessed by comparing the pre- and post-treatment mean scores of the three questionnaires using Student's t test (p value <0.05 was considered significant). Statistically significant mean decreases in ICSI (from 13.0 to 9.3; p = 0.0003), ICPI (from 11.35 to 8.85; p = 0.0078) and PUF (from 20.0 to 15.75; p = 0.0007) questionnaire scores were seen. No cases of side effects or complications were observed. The mean follow up was 5 months. Despite the limitations of this study, the outcomes confirmed the role of combination therapy with HA and CS as a safe and effective option for the treatment of IC/BPS. Further randomized controlled studies with a higher number of patients and a longer follow-up period are needed to confirm these results.