The bacterial microbiota of Hunner lesion interstitial cystitis/bladder pain syndrome.

OBJECTIVE: To undertake the first comprehensive evaluation of the urinary microbiota associated with Hunner lesion (HL) interstitial cystitis/bladder pain syndrome (IC/BPS). Despite no previous identification of a distinct IC/BPS microbial urotype, HL IC/BPS, an inflammatory subtype of IC/BPS, was hypothesized most likely to be associated with a specific bacterial species or microbial pattern. PARTICIPANTS AND METHODS: The bacterial microbiota of midstream urine specimens from HL IC/BPS and age- and gender-matched IC/BPS patients without HL (non-HL IC/BPS) were examined using the pan-bacterial domain clinical-level molecular diagnostic Pacific Biosciences full-length 16S gene sequencing protocol, informatics pipeline and database. We characterized the differential presence, abundances, and diversity of species, as well as gender-specific differences between and among HL and non-HL IC/BPS patients. RESULTS: A total of 59 patients with IC/BPS were enrolled (29 HL, 30 non-HL; 43 women, 16 men) from a single centre and the microbiota in midstream urine specimens was available for comparison. The species abundance differentiation between the HL and non-HL groups (12 species) was not significantly different after Bonferroni adjustments for multiple comparisons. Similarly, the nine differentiating species noted between female HL and non-HL patients were not significantly different after similar statistical correction. However, four species abundances (out of the 10 species differences identified prior to correction) remained significantly different between male HL and non-HL subjects: Negativicoccus succinivorans, Porphyromonas somerae, Mobiluncus curtisii and Corynebacterium renale. Shannon diversity metrics showed significantly higher diversity among HL male patients than HL female patients (P = 0.045), but no significant diversity differences between HL and non-HL patients overall. CONCLUSIONS: We were not able to identify a unique pathogenic urinary microbiota that differentiates all HL from all non-HL IC/BPS. It is likely that the male-specific differences resulted from colonization/contamination remote from the bladder. We were not able to show that bacteria play an important role in patients with HL IC/BPS.

Depression and Coping Behaviors Are Key Factors in Understanding Pain in Interstitial Cystitis/Bladder Pain Syndrome.

BACKGROUND: Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a urologic chronic pelvic pain syndrome with suboptimal treatment outcomes. Catastrophizing is an empirically supported risk factor for greater IC/BPS pain. AIMS: In this study, a moderated multiple mediation model is tested in which several additional psychosocial risk factors (depression, illness and wellness-focused behavioral coping strategies) are proposed as mediators or moderators in the existing relationship between catastrophizing and IC/BPS pain. DESIGN: The present questionnaire study employed a cross-sectional design. SETTINGS AND PARTICIPANTS: Female patients with an IC/BPS diagnosis (n = 341) were recruited at tertiary care sites. METHODS: Participants completed questionnaires assessing pain, catastrophizing, behavioral coping strategies, and depressive symptoms. Aggregate factor scores were calculated following exploratory factor analyses. RESULTS: It was found that patients with a greater tendency to catastrophize were more likely to engage in illness-focused coping strategies, which contributed to the reporting of greater sensory and affective pain. Furthermore, this mediating effect of illness-focused coping on affective pain was more likely to occur in those patients reporting greater depressive symptoms. CONCLUSIONS: Illness-focused behavioral coping is an important mechanism between maladaptive pain cognition and aspects of patient pain, with patients reporting greater depressive symptoms at increased risk for elevated pain. Patient management techniques, including screening for catastrophizing, coping, and depression, are recommended to enrich IC/BPS management.

Clinical Phenotyping Does Not Differentiate Hunner Lesion Subtype of Interstitial Cystitis/Bladder Pain Syndrome: A Relook at the Role of Cystoscopy.

PURPOSE: Identifying Hunner lesions in patients with interstitial cystitis/bladder pain syndrome presents an opportunity for objective classification into Hunner lesion interstitial cystitis/bladder pain syndrome (classic interstitial cystitis) and nonHunner lesion bladder pain syndrome. While currently the former diagnosis requires cystoscopy, limited data suggest that these subtypes can be distinguished without endoscopy based on the degree of bladder focused centricity and the infrequent association with generalized pain conditions. MATERIALS AND METHODS: Patients in a prospective, single center database of interstitial cystitis/bladder pain syndrome who had documented cystoscopic findings were categorized with Hunner lesion interstitial cystitis/bladder pain syndrome or nonHunner lesion bladder pain syndrome. Demographics, pain and symptom scores, voiding symptoms, irritable bowel syndrome and clinical UPOINT (urinary, psychosocial, organ specific, infection, neurological and tenderness) scoring were comparatively analyzed. RESULTS: We reviewed the records of 469 patients, including 359 with documented local anesthetic cystoscopic findings, 44 (12.3%) with Hunner lesion interstitial cystitis/bladder pain syndrome and 315 (87.7%) with nonHunner bladder pain syndrome. Patients with Hunner lesions were older (p = 0.004) and had greater urinary frequency (p = 0.013), more nocturia (p = 0.0004) and higher ICSI (Interstitial Cystitis Symptom Index) scores (p = 0.017). Hunner lesion prevalence was significantly lower in those younger than 50 years vs those 50 years old or older (7.8% vs 14.9%, p = 0.0095). There was no difference in the number of UPOINT phenotype domains reported, overall UPOINT scores or the prevalence of irritable bowel syndrome between the groups. CONCLUSIONS: A subtype of interstitial cystitis with Hunner lesions has worse bladder centric symptoms but did not show a distinct bladder centric phenotype. Given the management implications of distinguishing classic interstitial cystitis from nonHunner lesion bladder pain syndrome, we recommend cystoscopy with local anesthesia in patients diagnosed with interstitial cystitis/bladder pain syndrome.

MV140 sublingual vaccine reduces recurrent urinary tract infection in women Results from the first North American clinical experience study.

INTRODUCTION: This is the first North American clinical evidence for MV140, a novel bacterial sublingual vaccine, developed for prevention of recurrent urinary tract infection (UTI) in women. METHODS: Female subjects with ≥3 documented UTIs/year underwent three-month vaccination treatment, nine-month efficacy period, and optional three-month followup (total 15 months). Primary outcome was no clinically diagnosed UTI following vaccination (UTI-free rate). Secondary outcomes included absolute, mean, and median overall reduction in UTI compared to pre-vaccination, quality of life, global response assessment, patient satisfaction, microbiology, and safety. RESULTS: Sixty-seven subjects (mean age 56 years, range 18-80) were enrolled; 64 completed the vaccination period and at least one post-vaccination assessment. Prior to vaccination, subjects reported a mean 6.8 UTIs/year. The UTI-free rate for the nine-month efficacy period was 40.6%. Compared to the infection rate in the year prior to vaccination, the reduction was 75.3% for the nine-month efficacy period post-vaccination. At 12-month followup, 80.3% reported that they were moderately/markedly improved; 58.1% were mostly satisfied, pleased, or delighted, while mean quality of life score improved by 1.5 points. Fourteen of the adverse events in nine subjects were potentially related to the vaccine - all mild and resolved by three months. None of the 13 serious adverse events were related to vaccine. CONCLUSIONS: This first-in-North-America, prospective case series with the sublingual vaccine, MV140, adds further clinical evidence to its safety and effectiveness in reducing recurrent UTIs in women.

Mirabegron as adjuvant treatment for patients with interstitial cystitis/bladder pain syndrome.

INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) patients represent a heterogeneous group with pain and urinary storage symptoms and varying responses to current treatment options. The novel beta-3 agonist, mirabegron, has been shown to improve storage symptoms of patients with bladder overactivity; however, its effect on symptoms in the IC/BPS population has yet to be studied. METHODS: Patients diagnosed at a single IC centre with IC/BPS undergoing standard therapy were treated with additional daily mirabegron 25 mg and seen in followup post-treatment. Patients completed the Interstitial Cystitis Symptom Index and Problem Index (ICSI/ICPI), and the Pelvic Pain and Urgency/Frequency Patient Symptom Scale (PUF) prior to and following mirabegron treatment. Global (NRS) and symptom-specific outcomes were assessed by comparing the pre- and post-treatment mean scores using tailed-t test (p<0.05 considered statistically significant). RESULTS: A total of 23 patients were available for review pre- and post-mirabegron treatment. There was no significant difference in ICSI (p=0.448), ICPI (p=0.352), or PUF (p=0.869) pre- and post-treatment. Analysis of symptom-specific outcomes show statistically significant improvements in urgency (p=0.048); however, no statistically significant improvements in frequency (p=0.951) or pain (p=0.952) were observed with mirabegron therapy. CONCLUSIONS: IC/BPS patients treated with mirabegron had improvement of urinary urgency, but no significant benefit in terms of pain or urinary frequency. This data suggests that mirabegron's role in the IC/BPS patient should be that of adjuvant treatment to ameliorate urgency.

Early experience with topical meloxicam and lidocaine combination for the treatment of vulvodynia.

INTRODUCTION: We report our early clinical observations on the use of topical meloxicam and lidocaine gel for patients with vulvodynia. METHODS: This is an early experience in participants with a history of vulvodynia evaluated and treated at the Queen's University Pelvic and Bladder Pain Clinic. Combination meloxicam 0.3% and lidocaine 5% were provided to the participants and they were instructed to apply 5 cc to the vulvar area twice daily. Standardized assessment was conducted for each participant before the start of the topical therapy and again at one week, and included Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), and pain scoring (Likert) for vulvar pain, in addition to a subjective global assessment after a week of treatment. RESULTS: Of the eight participants, six had a subjective improvement in their symptoms with the use of the combination gel. They reported between one- and four-point reductions on the Likert pain scale and mild to moderate improvement of symptoms. Common side effects reported were burning and stinging. CONCLUSIONS: The results from this early experience are promising for a potentially effective topical treatment for vulvodynia.

The Interstitial Cystitis/Bladder Pain Syndrome Clinical Picture: A Perspective from Patient Life Experience.

INTRODUCTION: We hypothesize that optimal management of interstitial cystitis/bladder pain syndrome requires more personalized data than obtained with symptom questionnaires and standard urological assessment. We used a qualitative approach to develop a best evidence series of questions to explore the total clinical picture in the patient with interstitial cystitis/bladder pain syndrome. METHODS: The methodology of this project included preliminary focus groups, individual patient interviews, content development and validity analyses to develop a series of questions of value to patients with interstitial cystitis/bladder pain syndrome. A new convenience sample of patients with this syndrome completed the series of questions exploring not only pain and urination symptoms, but also other biopsychosocial parameters noted to be of relevance to these patients. RESULTS: Content of final series of questions addressed pain, urination symptoms, flares and the 10 most important domains impacted by interstitial cystitis/bladder pain syndrome. Further questions addressed thoughts or feelings, attitudes and suicidal ideation. A series of questions addressed how patients cope with and manage their condition. A total of 32 patients with interstitial cystitis/bladder pain syndrome completed the finalized series of questions. Bladder pain and urination symptoms were primary concerns of patients but other domains related to associated nonurological conditions (poor sleep/persistent fatigue, irritable bowel syndrome-like symptoms, low back and general muscle pain, interference/impact [eg sleep, diet, travel, activities, sexual functioning], positive and negative beliefs/attitudes, and coping mechanisms) make up the total clinical picture for each patient. CONCLUSIONS: The biopsychosocial information provided by our patients will better inform the health care professional on how to develop personalized treatment strategies and also individualized patient directed outcomes independent of bladder pain and urination symptoms.