Dana Creanga

Sexual function and satisfaction in heterosexual couples when men are administered sildenafil citrate (Viagra®) for erectile dysfunction: a multicentre, randomised, double‐blind, placebo‐controlled trial

Objective  To investigate the effect of improvement in erectile dysfunction (ED) on sexual function and satisfaction measures in heterosexual couples in which the woman reports that sexual intercourse is unsatisfactory at least half of the time.

A meta-analysis of the placebo response in antimuscarinic drug trials for overactive bladder

BackgroundThe purpose of this analysis was to characterize the placebo response in antimuscarinic drug trials for OAB, based on changes in commonly-used efficacy endpoints.MethodsPlacebo arm data for incontinence episodes, micturitions, voided volume and study characteristics were extracted from randomized placebo controlled antimuscarinic drug trials in OAB, from studies identified in a prior meta-analysis, and from a systematic review of more recently published studies. Relationships between variables were examined using linear regression, and changes in endpoints were analyzed by a meta-analysis approach. The effect of placebo arm size and magnitude of placebo response on probability of successful study outcome was analyzed using an ANOVA model.ResultsChanges in the placebo arms for all 3 endpoints were substantial and statistically significant, and highly heterogeneous. There were significant associations between baseline and change scores for some but not all of the endpoints. More recent studies tended to have more subjects than earlier studies, and there were positive associations between probability of achieving statistically significant results and size of the placebo arm. The magnitude of changes in placebo arms did not appear to influence the likelihood of the study to be statistically significant.ConclusionThis analysis confirms earlier observation that the placebo response in OAB trials is substantial and highly heterogeneous. There are multiple potential reasons for this; however, these could not be explored in this analysis of study-level data. Two approaches may be used in clinical trials to manage high placebo effect: recruitment of 1) greater numbers of patients and/or 2) more severely affected patients; however, only the former approach is associated with increased probability of successful study outcome.

Acute Nonarteritic Anterior Ischemic Optic Neuropathy and Exposure to Phosphodiesterase Type 5 Inhibitors

INTRODUCTION Nonarteritic anterior ischemic optic neuropathy (NAION), a rare visual disorder, has been reported in men using phosphodiesterase type 5 inhibitors (PDE5i) for erectile dysfunction. AIM We examined whether intermittent use of PDE5i is associated with acute NAION onset within approximately five half-lives following drug ingestion. METHODS One hundred two ophthalmology centers in the United States and Europe identified potential cases of NAION. An expert adjudication committee conducted a blind review of the records of those with recent PDE5i use to classify cases as Definite, Possible, or not NAION. Subjects provided information on PDEi use via telephone interview. Each NAION cases PDE5i exposure immediately prior to onset was compared against his recent patterns of use in an observational case-crossover design. A sample size of 40 cases with intermittent PDE5i exposure in the 30 days prior to NAION onset was needed to detect an odds ratio (OR) of 3.0 with 80% power. MAIN OUTCOME MEASURES The daily relative risk for acute NAION on days within five half-lives of PDE5i use vs. other days was estimated via an OR obtained from conditional logistic regression. RESULTS Among 43 Definite NAION cases with PDE5i exposure in the prior 30 days, the OR was 2.15 (95% confidence interval [CI]: 1.06, 4.34). When 21 Possible NAION cases were included (n = 64), the OR was 2.36 (95% CI: 1.33, 4.19). CONCLUSIONS We found an approximately twofold increased risk of acute NAION within five half-lives of PDE5i use compared with use in a more prior time period. Bias from inaccurate recall of exposure was unlikely to have substantially affected the results. Based on our results, we estimate that weekly use of PDE5i adds three NAION cases per 100,000 men 50 years and older annually.

Efficacy of fesoterodine compared with extended-release tolterodine in men and women with overactive bladder

To assess the efficacy of fesoterodine 8 mg vs extended‐release (ER) tolterodine 4 mg for overactive bladder (OAB) symptoms in terms of patient‐reported outcomes in women and in men.

Efficacy and tolerability of fesoterodine versus tolterodine in older and younger subjects with overactive bladder: A post hoc, pooled analysis from two placebo-controlled trials†‡

To assess the efficacy and tolerability of fesoterodine 8 mg versus tolterodine extended release (ER) 4 mg in subjects with overactive bladder (OAB) stratified by age (<65, 65–74, and ≥75 years).

Improvement in erection hardness and intercourse success with first dose of sildenafil citrate 100 mg

Purpose To determine, in men with erectile dysfunction (ED), the extent of improvement in erection hardness and in the rate of successful sexual intercourse (SSI) during the final intercourse attempt using sildenafil 50 mg compared with the subsequent initial attempt after a dose increase to 100 mg. Patients and methods This post hoc analysis used data from two randomized, double-blind, placebo-controlled studies of flexible-dose sildenafil for the treatment of men with ED, who were given sildenafil 50 mg or matching placebo, to be taken as needed before sexual intercourse. After 2 weeks, those with no tolerability concerns were titrated up to 100 mg, forming the subgroup of this analysis. The main outcome measures were event log data, including an Erection Hardness Score (EHS) and a question on SSI (“Did your erection last long enough for you to have successful sexual intercourse?”), for each attempt at sexual intercourse, analyzed by study and treatment group (sildenafil or placebo). Statistical comparisons were conducted by using the Fisher’s exact test. Results In both studies, the sildenafil group had a larger proportion of EHS4 (completely hard and fully rigid) erections (P < 0.001) and SSI (P < 0.005) compared with the placebo group, both before and after the dose increase. Between the final 50 mg sildenafil dose and the initial 100 mg sildenafil dose, the outcomes improved and significantly so in the larger study. Conclusion The improved efficacy with sildenafil 100 mg versus 50 mg, which occurs rapidly, suggests that patients should be encouraged to use 100 mg if they are unable to achieve completely hard and fully rigid erections or SSI with the 50 mg dose.