An exploratory, placebo-controlled, dose–response study of the efficacy and safety of onabotulinumtoxinA in spinal cord injury patients with urinary incontinence due to neurogenic detrusor overactivity

Purpose

To explore the dose response to onabotulinumtoxinA 50, 100, and 200 U in patients with spinal cord injury (SCI) with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO).

Methods

Patients (N = 73) with SCI (level T1 or lower) with NDO and UI (≥14 UI episodes/week) received 30 intradetrusor injections of onabotulinumtoxinA (50 U [n = 19], 100 U [n = 21], or 200 U [n = 17]) or placebo (n = 16) via cystoscopy, avoiding the trigone. Changes from baseline in UI episodes/week, volume voided/micturition, maximum cystometric capacity, and maximum detrusor pressure (MDP) during first involuntary detrusor contraction (IDC) were evaluated. Adverse events (AEs) were assessed.

Results

A significant linear dose response for UI episodes/week was identified at weeks 18, 30, 36, 42, and 54 (P < 0.05) with a similar trend (P = 0.092) at week 6 (primary time point). A significant linear dose response was observed in volume/void at all post-treatment time points up to week 54 (P < 0.05) and in MDP during first IDC at week 6 (P = 0.034). The proportion of patients who achieved continence at week 6 was highest in the 200 U group. Duration of effect was longest with the 200 U dose, compared with other treatment groups. The AEs were comparable across groups; urinary tract infection was the most common AE across all treatment groups.

Conclusions

In this exploratory dose–response study of SCI patients with UI due to NDO, onabotulinumtoxinA 200 U was the most effective dose. The AE profile was comparable across all groups.     

Joint hypermobility, obstetrical outcomes, and pelvic floor disorders

Introduction and hypothesis

Benign joint hypermobility syndrome may be a risk factor for pelvic floor disorders. It is unknown whether hypermobility impacts the progress of childbirth, a known risk factor for pelvic floor disorders. Our objective was to investigate the association between joint hypermobility syndrome, obstetrical outcomes, and pelvic floor disorders. Our hypotheses were: (1) women with joint hypermobility are less likely to experience operative delivery and prolonged second-stage labor; and (2) pelvic floor disorders are associated with benign hypermobility syndrome, controlling for obstetrical history.

Methods

Joint hypermobility was measured in 587 parous women (participants in a longitudinal cohort study of pelvic floor disorders after childbirth). Their obstetrical histories were obtained from review of hospital records. Pelvic floor disorders were assessed using validated questionnaires and a structured examination for prolapse. Joint hypermobility and pelvic floor disorders were evaluated at enrollment (5–10 years after first delivery). We compared obstetrical outcomes and pelvic floor disorders between women with and without joint hypermobility, defined as a Beighton score ≥4.

Results

Hypermobility was diagnosed in 46 women (7.8 %) and was associated with decreased odds of cesarean after complete cervical dilation or operative vaginal delivery [odds ratio (OR)?=?0.51; 95 % confidence interval (CI):0.27–0.95]. Anal sphincter laceration was unlikely to occur in women with hypermobility (OR?=?0.19; 95 % CI 0.04–0.80). However, hypermobility was not associated with any pelvic floor disorder considered.

Conclusions

Benign joint hypermobility syndrome may facilitate spontaneous vaginal birth but does not appear to be a risk factor for pelvic floor disorders in the first decade after childbirth.     

Metabolic effects of sleeve gastrectomy in female rat model of diet-induced obesity

BackgroundAlthough women disproportionately undergo bariatric surgery, the rodent models investigating the mechanisms of bariatric surgery have been limited to males. Female rodent models can also potentially allow us to understand the effects of surgical intervention on future generations of offspring. Sleeve gastrectomy is an attractive weight loss procedure for reproductive-age female patients because it avoids the malabsorption associated with intestinal bypass. We sought to evaluate the effect of sleeve gastrectomy on young female rats with diet-induced obesity at the University of California, Los Angeles, David Geffen School of Medicine.MethodsSprague-Dawley female rats were fed a 60% high-fat diet. At 12 weeks of age, the rats underwent either sleeve gastrectomy or sham surgery. The rats were killed 4 weeks after surgery. A chemistry panel was performed, and the serum adipokines and gut hormones were assayed. The homeostasis model assessment score was calculated. The liver histologic findings were graded for steatosis. The 2-sample t test was used to compare the results between the 2 groups.ResultsSleeve gastrectomy was associated with significant weight loss (5% ± 6% versus ?4% ± 6%; P < .001), lower leptin levels (1.3 ± 1.2 versus 3.5 ± 2.3 ng/mL; P < .01), and higher adiponectin levels (.43 ± .19 versus .17 ± .14 ng/mL; P < .004) compared with the sham-operated rats. No significant differences were found in the fasting ghrelin levels. Furthermore, we did not observe evidence of insulin resistance or steatohepatitis after 11 weeks of high-fat diet. Despite these limitations, additional gender-specific studies are warranted given that most bariatric surgeries are performed in women.ConclusionSleeve gastrectomy appears to result in weight loss and improvements in adiponectin and leptin by way of mechanisms independent of ghrelin levels in a female model of diet-induced obesity.