Iltamiocel Autologous Cell Therapy for the Treatment of Female Stress Urinary Incontinence: A Double-Blind, Randomized, Stratified, Placebo-Controlled Trial.

AIMS: This study aimed to determine the efficacy and safety of iltamiocel investigational autologous muscle cell therapy in females with stress urinary incontinence (SUI). METHODS: Adult females were randomized 2:1 to iltamiocel (150 × 106 cells) or placebo and stratified by severity and prior SUI surgery. The primary objective was efficacy based on the frequency of stress incontinence episodes (SIE) recorded in a 3-day diary at 12 months posttreatment. After 12 months, placebo participants could elect to receive open-label iltamiocel. Efficacy and safety analyses were performed using all patients as treated populations. RESULTS: The study enrolled 311 patients, 297 were randomized to either iltamiocel (n = 199) or placebo (n = 98). Of the 295 participants that completed 12 months blinded follow-up, the proportion achieving the primary endpoint of ≥ 50% SIE reduction was not statistically different between treatment groups (52% vs. 53.6%; p = 0.798). A significantly greater proportion of iltamiocel participants in the prior SUI surgery stratum group achieved ≥ 75% SIE reduction compared with placebo, (40% vs. 16%; p = 0.037). Treatment response was maintained at 24 months in 78.4% and 64.9% of iltamiocel participants who achieved ≥ 50% and ≥ 75% SIE reduction, respectively, at Month 12. Adverse events related to the treatment were reported in 19 (9.5%) iltamiocel participants and 6 (6.1%) placebo participants. CONCLUSION: The study did not meet its primary endpoint however, iltamiocel cell therapy is safe and may be ideally suited to female patients who have undergone prior surgery for SUI. Additional study in this group of patients with high unmet medical needs is warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01893138; EudraCT number: 2014-002919-41.

Six-Month Results of Selective Bladder Denervation in Women with Refractory Overactive Bladder.

PURPOSE: We report 6-month efficacy and safety outcomes of selective bladder denervation in women with refractory overactive bladder. MATERIALS AND METHODS: Women with refractory overactive bladder and urgency urinary incontinence were enrolled in 2 prospective feasibility studies with the same entry criteria. They underwent selective bladder denervation of the subtrigonal region containing afferent sensory nerves. Patients were followed for 6 months and assessed for adverse events, overactive bladder symptoms and health related quality of life measures. RESULTS: In the 35 women with a mean age of 66 years who were enrolled in the study all selective bladder denervation procedures were completed successfully. During 6 months of followup the symptom improvement based on 3-day bladder diaries was 59% for urgency urinary incontinence (p <0.001), 59% for urinary incontinence (p <0.001), 39% for urgency (p <0.001), 9% for urinary frequency (p = 0.01) and 27% for the total urgency and frequency score (p <0.001). Most of this treatment benefit was realized in the first month. The rate of clinical success, defined as a 50% or greater reduction in urgency urinary incontinence, was 70%, treatment benefit was reported in 75% of patients and the dry/cure rate was 27%. Statistically significant improvements during 6 months were identified on the symptom bother and health related quality of life scales on the OAB-q (Overactive Bladder Questionnaire) and on all KHQ (King's Health Questionnaire) domains except general health perception. Device or procedure related adverse events were reported in 6 patients (17%). CONCLUSIONS: Pooled results of 2 prospective feasibility studies suggest that selective bladder denervation is a promising minimally invasive treatment option in women with refractory overactive bladder.

The prevalence of urinary incontinence in American Indian women from a South Dakota tribe.

INTRODUCTION AND HYPOTHESIS: The purpose of this pilot study was to evaluate the prevalence and associated risk factors for urinary incontinence in a Northern Plains tribe of American Indian women. METHODS: The Urogenital Distress Inventory-Short Form was used to assess urinary incontinence in a sample of American Indian women from one tribe. This was a cross-sectional convenience sampling of 234 eligible participants. Participant's ages ranged from 18 to 80 years. Stata/Se 9.1 software was used in statistical analysis. RESULTS: The overall prevalence of urinary stress incontinence was 15.4%, urgency incontinence 2.14%, and mixed incontinence 20.5%. Both stress and urgency incontinence was found to be low in this sample population. CONCLUSIONS: A reduced prevalence of stress and urgency incontinence is seen in our sample. Our study group showed a high prevalence of known risk factors associated with urinary incontinence. We intend to extend our study for further understanding of this patient population.

Pulsed-field fingerprinting of vaginal group B streptococcus in pregnancy.

OBJECTIVE: There is more to be learned about the epidemiology of group B beta-hemolytic streptococci infections in pregnancy. In this study, we investigated the discriminating capabilities of pulsed-field gel electrophoresis of group B streptococci strains from pregnant patients and mother/infant pairs of patients compared with serotyping. METHODS: Forty-two vaginal strains of group B streptococci cultured from pregnant patients in the third trimester and strains from 20 mother/infant pairs with documented newborn group B streptococci infection were studied. Isolates were serotyped by the Lancefield capillary precipitin method and molecularly characterized by counterclamped homogeneous electrical field pulsed-field gel electrophoresis with rarely cutting restriction enzymes. RESULTS: Nine of the 13 serotypes of group B streptococci identified thus far in the scientific literature (Ia, Ia/c, Ib, Ib/c, II, IIc, III, V, and NT/c) were represented among the 62 isolates. Among the 42 maternal isolates, eight serotypes were represented, and among the 20 mother/infant isolates, six serotypes were represented. Serotypes of mother/infant isolates matched in nine of the ten pairs. Restriction endonuclease profiles, or digests, from the 42 maternal isolates resulted in 25 unique profiles that were arranged into five major groups based on the overall relatedness. Each group was comprised of one predominant serotype. The 20 mother/infant paired isolates displayed nine unique restriction endonuclease profiles and nine of the ten paired isolates showed indistinguishable restriction endonuclease profiles between mother and infant. CONCLUSION: Deoxyribonucleic acid profiling using pulsed-field gel electrophoresis is more discriminating of group B streptococci strains than serotyping because of the different yet closely related patterns within each restriction endonuclease profile group that are linked to one specific serotype. Pulsed-field gel electrophoresis can refine our epidemiologic studies of group B streptococci transmission and acquisition.