Efficacy and safety of two administration modes of an intra-detrusor injection of 750 units dysport® (abobotulinumtoxinA) in patients suffering from refractory neurogenic detrusor overactivity (NDO): A randomised placebo-controlled phase IIa study.

AIMS: Assess the efficacy and safety of abobotulinumtoxinA (Dysport®) in adult patients with neurogenic detrusor overactivity (NDO). METHODS: This Phase IIa, international, multicentre, double-blind, randomised, placebo controlled, pilot study enrolled 47 patients with NDO and urinary incontinence resulting from spinal cord injury (SCI) or multiple sclerosis (MS). Patients were treated with 15 intra-detrusor injections of Dysport 750 U or the equivalent placebo (n = 16 and 7) or 30 injections of Dysport 750 U or the equivalent placebo (n = 17 and 7). Primary endpoint was change from baseline in mean number of daily incontinence episode frequency (IEF) at day 84. Secondary endpoints included change from baseline in urodynamic parameters and quality of life (QOL). A safety assessment was also conducted. RESULTS: Adjusted mean changes from baseline in IEF were -3.2 (-76%) and -1.7 (-15%) for 15 injections Dysport and placebo groups, respectively, (P = 0.1103) and -3.2 (-88%) and -2.6 (-73%) for 30 injections Dysport and placebo groups, respectively, (P = 0.0686). Statistically significant improvements in maximum cystometric capacity, maximum detrusor pressure and volume at first contraction were reported in the Dysport groups compared with placebo (P < 0.05). Improvements in QOL were reported. Three muscle weakness episodes were reported as serious adverse events in two tetraplegic and one paraplegic patient, all in the 15 injections Dysport group. CONCLUSIONS: Both 15 and 30 injections administration modes of Dysport decreased daily IEF and resulted in significant improvements in urodynamic parameters in NDO patients with MS or SCI. Reduction to 15 injection sites did not appear to be associated with any impact on efficacy. Neurourol. Urodynam. 36:457-462, 2017. © 2016 Wiley Periodicals, Inc.

Libertas: a phase II placebo-controlled study of NRL001 in patients with faecal incontinence showed an unexpected and sustained placebo response.

PURPOSE: Faecal incontinence (FI) is distressing, significantly reduces quality of life (QoL) and has few pharmacological treatments. The α1-adrenoceptor agonist NRL001 (1R,2S-methoxamine hydrochloride) improves anal sphincter tone. NRL001 efficacy was evaluated by changes in Wexner scores at week 4 vs. baseline in NRL001-treated patients compared with placebo. Impact of NRL001 on QoL and safety were also assessed. METHODS: Four hundred sixty-six patients received NRL001 (5, 7.5 or 10 mg) or placebo as suppository, once daily over 8 weeks. Wexner score, Vaizey score and QoL were analysed at baseline, week 4 and week 8. FI episodes and adverse events were recorded in diaries. RESULTS: At week 4, mean reductions in Wexner scores were -3.0, -2.6, -2.6 and -2.4 for NRL001 5, 7.5, 10 mg and placebo, respectively. All reduced further by week 8. As placebo responses also improved, there was no significant treatment effect at week 4 (p = 0.6867) or week 8 (p = 0.5005). FI episode frequency improved for all patients, but not significantly compared with placebo (week 4: p = 0.2619, week 8: p = 0.5278). All patients' QoL improved, but not significantly for all parameters (p > 0.05) except depression/self-perception at week 4 (p = 0.0102) and week 8 (p = 0.0069), compared with placebo. Most adverse events were mild and judged probably or possibly related to NRL001. CONCLUSIONS: All groups demonstrated improvement in efficacy and QoL compared with baseline. NRL001 was well-tolerated without serious safety concerns. Despite the improvement in all groups, there was no statistically significant treatment effect, underlining the importance of relating results to a placebo arm.

The effect of electroacupuncture applied to women with stress urinary incontinence on urinary incontinence severity and symptoms: Systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Stress Urinary Incontinence is a condition that impairs the quality of life in women and randomized controlled trials of electroacupuncture for stress urinary incontinence have been conducted. OBJECTIVE: The aim of this systematic review and meta-analysis was to examine the effect of electroacupuncture on the severity and symptoms of urinary incontinence in women with stress urinary incontinence. METHODS: Literature searches were conducted in PubMed, CINAHL, Scopus and Science Citation Index until November 2023. This study was based on the recommendations of the Cochrane guidelines. Data were analyzed using the Review Manager computer program (Version 5.4). The methodological quality of the studies was assessed using the RoB-2 tool. RESULTS: The analysis included 888 women with stress urinary incontinence and three studies. In women with stress urinary incontinence, electroacupuncture intervention improved urinary incontinence severity and quality of life (MD: -2.37, 95% CI: -3.29 to 1.45, Z = 5.07, p < 0.001), urinary leakage (SMD: -0.79, 95% CI: -1.02 to -0.55, Z = 6.60, p = 0.001) and incontinence episode frequency (SMD: -2.24, 95% CI: -4.17 to -0.32, Z = 2.29, p < 0.02). CONCLUSION: In women with stress urinary incontinence, electroacupuncture intervention decreased the severity of urinary incontinence and improved the quality of life. Symptoms related to urinary incontinence were found to decrease urinary leakage and incontinence episode frequency. The studies included in the analysis were determined to be low-risk studies in quality assessment.

Characteristics of rapid cycling in 1261 bipolar disorder patients.

BACKGROUND: Rapid-cycling (RC; ≥ 4 episodes/year) in bipolar disorder (BD) has been recognized since the 1970s and associated with inferior treatment response. However, associations of single years of RC with overall cycling rate, long-term morbidity, and diagnostic subtypes are not clear. RESULTS: We compared descriptive and clinical characteristics in 1261 BD patients with/without RC, based on history and prospective follow-up for several years. RC in any previous year was identified in 9.36% of BD subjects (3.74% in BD1, 15.2% BD2), and somewhat more among women than men. RC-BD subjects had 3.21-fold greater average prospective annual rates of recurrence but not hospitalizations, had less difference in %-time-ill, received more mood-stabilizing treatments, and had greater suicidal risk, lacked familial psychiatric illnesses, had more cyclothymic temperament, were more likely to be married, had more siblings and children, experienced early sexual abuse, but were less likely to abuse drugs (not alcohol) or smoke. In multivariable regression modeling, older age, mood-switching with antidepressants, and BD2 > BD1 diagnosis, as well as more episodes/year were independently associated with RC. Notably, prospective mean recurrence rates were below 4/year in 79.5% of previously RC patients, and below 2/year in 48.1%. CONCLUSIONS: Lifetime risk of RC in BD was 9.36%, more likely in women, with older age, and in BD2 > BD1. With RC, recurrence rates were much higher, especially for depression with less effect on %-time ill, suggesting shorter episodes. Variable associations with unfavorable outcomes and prospective recurrence rates well below 4/year in most previously RC patients indicate that RC was not a sustained characteristic and probably was associated with use of antidepressants.