Response to fesoterodine in patients with an overactive bladder and urgency urinary incontinence is independent of the urodynamic finding of detrusor overactivity

Study Type – Therapy (RCT)
Level of Evidence 1b

OBJECTIVE

To determine whether the presence of detrusor overactivity (DO) in patients with overactive bladder (OAB) and urgency urinary incontinence (UUI) is a predictor of the response to treatment with fesoterodine.

PATIENTS AND METHODS

This phase 2 randomized, multicentre, placebo‐controlled trial consisted of a 1‐week placebo run‐in phase followed by an 8‐week double‐blind period. Eligible for the study were men and women aged 18–78 years with symptoms or signs of OAB with UUI; they were stratified into two balanced strata depending on the outcome of a baseline urodynamic assessment. By using this particular study design it was possible to investigate whether there were differences between the strata. The primary endpoint was the change from baseline to week 8 in mean voids/24 h. Secondary endpoints were the changes in UUI episodes/week, and for those patients with DO at baseline, the mean changes in volume at first involuntary contraction associated with a feeling of urgency, first desire to void, and strong desire to void, and change in maximum cystometric capacity. Because there were few patients the secondary analyses were considered exploratory.

RESULTS

Overall, there were linear dose‐response relationships for placebo and the fesoterodine groups for the reduction in the number of voids/24 h and UUI episodes/week. Compared with the placebo group, the least squares mean changes from baseline to week 8 in both variables were significantly improved in patients receiving fesoterodine 4 mg (P = 0.045 and 0.040, respectively), 8 mg (P < 0.001 for both), and 12 mg (P < 0.001 for both). There were no significant differences in treatment responses, as measured by both variables between patients with and without DO. For patients with DO, the mean volume at the first desire to void improved in all fesoterodine treatment groups and worsened in the placebo group.

CONCLUSIONS

Regardless of the presence of DO, the response to fesoterodine treatment was dose‐proportional and associated with significant improvements in OAB symptoms, indicating that the response to OAB pharmacotherapy in patients with UUI was independent of the urodynamic diagnosis of DO.     

Preventing depression after stroke

Mental health prevention research is an emerging and intriguing field. Preventing mental disorders is attractive as successful prevention, as it could potentially avert both emotional suffering and illness related morbidity and mortality. Several studies have looked at preventing post-stroke depression, a common complication of stroke. In this review article, we will first provide a conceptual overview of mental health prevention research. Then, we will discuss recent research supporting the prevention of depression after stroke and the likely positive effect successful prevention may have on non-psychiatric outcomes.     

Effect of oral contraceptives on plasma glucose, insulin, and glucagon levels

Effects of oral contraceptive agents (mestranol and norethindrone) on carbohydrate metabolism were evaluated in a group of 18 healthy young women. Plasma glucose, insulin, and glucagon responses were evaluated after a glucose load (oral and intravenous) and an amino acid challenge (oral and intravenous). The oral glucose tolerance was normal and was unaltered by the use of oral contraceptive agents. However, following intravenous administration of glucose, plasma glucose levels were slightly but significantly elevated when subjects were using oral contraceptives. Plasma insulin concentrations were slightly but significantly higher than control values in response to oral and intravenous administration of glucose while subjects were using oral contraceptives. Plasma glucagon concentrations in response to oral and intravenous glucose were similar whether the subjects were using oral contraceptive agents or not. No significant differences from control values were observed after oral and intravenous amino acid challenges when subjects were using oral contraceptive agents. Mild elevations of glucose and insulin without any significant change in glucagon concentrations suggest that glucagon levels do not play a major role in the development of insulin resistance seen in some patients using oral contraceptive agents.     

Trospium chloride: the European experience

The primary pharmacological therapy for overactive bladder syndrome is muscarinic receptor antagonists. Muscarinic receptor blockade is effective in decreasing the symptoms of urinary urgency and urgency incontinence, but can be associated with troublesome complications, such as dry mouth, blurred vision, constipation and CNS side effects. Trospium chloride, an antimuscarinic medication, has been available in Europe for > 20 years and has recently been approved by the FDA for the treatment of overactive bladder. Trospium chloride is a quaternary amine that is minimally metabolised, not highly protein bound and, importantly, has not been demonstrated to cross the unaltered blood-brain barrier in healthy volunteers. Some characteristics of this unique antimuscarinic agent and the European experience with trospium chloride are reviewed in this article.     

Once-daily, extended-release formulations of antimuscarinic agents in the treatment of overactive bladder: a review

Overactive bladder (OAB) is a chronic condition that often requires long-term treatment to maintain control of symptoms. A range of therapeutic options are available; however, antimuscarinic agents form the mainstay of treatment. Of these agents, tolterodine and oxybutynin are the most widely used. It is well documented that the immediate-release (IR) formulations of these agents have equivalent efficacy in relieving OAB symptoms. However, tolterodine demonstrates a more favorable tolerability profile, particularly in terms of the frequency and severity of dry mouth. Due to the development of novel drug delivery systems, extended-release (ER) formulations of both oxybutynin and tolterodine are now available, permitting once-daily dosing. The convenience of once-daily dosing of antimuscarinic agents would be expected to improve patient compliance and further relieve the symptoms of OAB. Clinical studies with the ER formulations of tolterodine and oxybutynin demonstrate potential clinical advantages over their respective IR forms in terms of either efficacy or tolerability or both, although the therapeutic index of tolterodine ER appears to show a greater advantage over its IR counterpart compared with oxybutynin ER and its IR form. Importantly, the two ER agents have not been compared directly in a head-to-head clinical study. Overall, available clinical data suggest that the newly developed ER formulation of tolterodine represents a significant therapeutic advancement in the treatment of OAB.     

Organizational ethics: it's your move

As market forces have continued to push healthcare systems toward greater efficiency and lower costs, providers have begun asking for help in balancing ethical concerns. Several organizations are responding by establishing programs to provide guidelines for ethical decisionmaking. Health System Leader talked with these pioneers about their progress, the thinking that went into establishing these programs, and their recommendations for others beginning to tackle this need.