Véronique Keppenne

Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity.

PURPOSE We assessed the efficacy, safety and effects on quality of life of onabotulinumtoxinA in patients with neurogenic detrusor overactivity. MATERIALS AND METHODS In this 52-week, international, multicenter, double-blind, randomized, placebo controlled trial 416 patients with neurogenic detrusor overactivity and urinary incontinence (14 or more episodes per week) resulting from multiple sclerosis (227) and spinal cord injury (189) were treated with intradetrusor injections of onabotulinumtoxinA (200 or 300 U) or placebo. The primary end point was the change from baseline in the mean number of urinary incontinence episodes per week at week 6. Maximum cystometric capacity, maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life total score were secondary end points. Adverse events were monitored. RESULTS OnabotulinumtoxinA at a dose of 200 U in 135 patients and 300 U in 132 decreased mean urinary incontinence at week 6 by 21 and 23 episodes per week, respectively, vs 9 episodes per week in 149 on placebo (each dose p<0.001). Also, maximum cystometric capacity, maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life score were significantly improved over values in the placebo group (each dose p<0.001). Median time to patient re-treatment request was greater for onabotulinumtoxinA 200 and 300 U than for placebo (256 and 254 days, respectively, vs 92). The most common adverse events were urinary tract infection and urinary retention. Of patients who did not catheterize at baseline 10% on placebo, 35% on 200 U and 42% on 300 U initiated catheterization due to urinary retention. CONCLUSIONS OnabotulinumtoxinA significantly improved neurogenic detrusor overactivity symptoms vs placebo. Clean intermittent catheterization initiation due to urinary retention appeared to increase in a dose dependent fashion. No clinically relevant benefit in efficacy or duration was identified for the 300 U dose over the 200 U dose.

Banking and distribution of large cryopreserved arterial homografts in Brussels: Assessment of 4 years of activity by the European Homograft Bank (EHB) with reference to implantation results in reconstruction of infected infrarenal arterial prostheses and mycotic aneurysms

In 1991 European Homograft Bank (EHB) initiated a program of cryopreservation and distribution of large arteries to meet a new demand for quality-controlled arterial homo grafts of various sizes. From May 1991 to June 1995, 308 arteries have been registered from 136 donors: 122 brain death cases and 14 cadavers (mean age 34 years, male/female ratio 1.52/1); 263 arteries were cryopreserved (113 aortas, 64 aortic bifur cations, and 86 femoral); 19 were discarded for atherosclerosis (6.7%); 10 batches of arteries were partially or totally discarded because of persistent contamination and further eight batches for positive or doubtful viral serology. One hundred patients were treated in nine European centers with one (N = 69) or more EHB homografts. Indications were: infected prosthesis 70 (17 with aortoenteric fistula); mycotic aneurysm 19 (four ascending aortas, two with bronchial fistula); neoplastic infiltration of subrenal aorta one; extracardiac reconstructions/shunts 10. (continued on next page) (Abstract continued) Results from homograft reconstructions in infected prosthesis or mycotic aneurysm were available in 90 patients. There were 19 early deaths and 24 early complications, three were directly graft-related and included a fatal case of homograft rupture. Sixty- seven vascular cases were followed up from 1 month onward (mean: 16 months): 50 were uneventful; there were nine late deaths, of which two resulted from graft-related digestive hemorrhage; there were eight cases of late complications; three arteries were partly explanted as a result of focal thrombosis. Four patients were lost to follow-up. In the cases of aortoenteric fistula, however, the results were disappointing with only five late survivors of the 16 treated patients. Finally, these results show that cryopreserved arteries seem to perform as well in the midterm as the fresh ones. Both the banking activity of cryopreserved homografts and the short- to mid-term performances of the implants in cases of prosthetic or native arterial infection are very satisfactory, provided no aortoenteric fistula is present. Cryopreserved arteries can also be used for extracardiac shunts and reconstructions.

Late rupture of a saphenous vein aortorenal graft

It is well known that aortorenal venous grafts can dilate, whereas actual rupture has not been reported. However, rupture of aortocoronary vein grafts has been reported. Dilations at this site are relatively less common, but such bypass grafting procedures are much more commonly performed, so the potential for rupture of dilated vein grafts is apparent. We report the first known rupture of a dilated aortorenal vein graft.

Pathologie du sphincter urinaire chez ľhomme

La symptomatologie liee a la pathologie du sphincter urinaire chez ľhomme se presente sous deux formes: ľincontinence urinaire et la dysurie.

Efficacy and safety of onabotulinumtoxin A 100U for treatment of urinary incontinence due to neurogenic detrusor overactivity in non-catheterising multiple sclerosis patients

OBJECTIFS We evaluated the efficacy/safety of onabotulinumtoxin A 100U versus placebo for treatment of urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO) in non-catheterising multiple sclerosis (MS) patients inadequately managed by≥1 anticholinergic. MéTHODES: A multicentre, double-blind study randomised patients 1:1 to onabotulinumtoxin A 100U (n=66) or placebo (n=78). Assessments (week 6 primary endpoint) included change from baseline in UI episodes (UIE)/day (primary endpoint), maximum cystometric capacity (MCC), maximum detrusor pressure (MDP) during first involuntary detrusor contraction (IDC), incontinence-quality of life (I-QOL) total summary score, and proportions of patients achieving 100% UIE reduction. Median duration of effect (DOE), initiation of clean intermittent catheterisation (CIC), and adverse events (AEs) were also assessed. RéSULTATS: Baseline characteristics were similar between groups. The mean baseline EDSS score was 4.7. Onabotulinumtoxin A 100U significantly improved UIE (-3.3 vs-1.1; P<.001), MCC (+127.2 vs-1.8mL; P<.001), and MDP during first IDC (-19.6 vs 3.7cm H2O; P<.01) versus placebo. Significantly greater proportions of onabotulinumtoxin A treated patients achieved 100% UIE reduction versus placebo (53.0% vs 10.3%; P<.001). I-QOL improvements were significantly greater with onabotulinumtoxin A versus placebo (40.4 vs 9.9; P<.001). DOE was 11.9 versus 2.9 months, respectively (P<.001). Discontinuations due to AEs/lack of efficacy were low (1.4%/2.1%). Most common AEs were UTI, elevated residual urine volume, and urinary retention. CIC rates were 15.2% for onabotulinumtoxinA 100U and 2.6% for placebo. Previous studies demonstrated CIC rates of 31.4% for onabotulinumtoxinA 200U and 4.5% for placebo in MS patients not catheterising at baseline1. CONCLUSION In non-catheterising MS patients with UI, onabotulinumtoxin A 100U resulted in significant and clinically-meaningful improvements in UI, MCC, MDP at first IDC, and QOL versus placebo and was well-tolerated.