Solifenacin appears effective and well tolerated in patients with symptomatic idiopathic detrusor overactivity in a placebo- and tolterodine-controlled phase 2 dose-finding study

OBJECTIVES: To evaluate the dose-response relationship and safety/tolerability of solifenacin succinate (YM905) in the treatment of overactive bladder (OAB), and to compare its efficacy and safety/tolerability with tolterodine 2 mg twice daily. PATIENTS AND METHODS: This multicentre study included a 2-week single-blind placebo run-in, a 4-week double-blind placebo-controlled active treatment phase, and a 2-week follow-up. Men and women with an OAB and urodynamic evidence of detrusor overactivity were randomized to placebo or solifenacin 2.5, 5, 10 or 20 mg once daily, or tolterodine 2 mg twice daily. RESULTS: Of 265 patients enrolled, 225 were randomized and 192 completed the study. Solifenacin 5, 10 and 20 mg produced statistically significant (P < 0.05) improvements in voids/24 h vs placebo, whereas tolterodine did not; the mean change with tolterodine was between those with solifenacin 2.5 and 5 mg. The outcome was similar for the mean change from baseline to endpoint in mean volume voided/void. For incontinence and urgency episodes/24 h the solifenacin dose groups showed numerically superior changes vs placebo; the mean effects with tolterodine were generally smaller than with solifenacin. Most of the efficacy effect of solifenacin was evident at 2 weeks. Quality-of-life outcomes supported the efficacy results. Solifenacin 5 and 10 mg were well tolerated; there were no serious treatment-related adverse events. The incidence of dry mouth was 14% for solifenacin 5 and 10 mg, 2.6% for placebo and 24% for tolterodine. CONCLUSION: In this study, the 5- and 10-mg doses of solifenacin appeared to be the most clinically effective for treating OAB, considering the balance between efficacy, quality of life and tolerability. From the results of this study solifenacin 5 and 10 mg were selected for further evaluation in large-scale phase 3 studies.     

EAU Guidelines on Assessment and Nonsurgical Management of Urinary Incontinence

Context

The previous European Association of Urology (EAU) guidelines on urinary incontinence comprised a summary of sections of the 2009 International Consultation on Incontinence. A decision was made in 2010 to rewrite these guidelines based on an independent systematic review carried out by the EAU guidelines panel, using a sustainable methodology.

Objective

We present a short version of the full guidelines on assessment, diagnosis, and nonsurgical treatment of urinary incontinence, with the aim of increasing their dissemination.

Evidence acquisition

Evidence appraisal included a pragmatic review of existing systematic reviews and independent new literature searches, based on Population, Intervention, Comparator, Outcome questions. Appraisal of papers was carried out by an international panel of experts, who also collaborated on a series of consensus discussions, to develop concise structured evidence summaries and action-based recommendations using a modified Oxford system.

Evidence summary

The full version of the guidelines is available online (http://www.uroweb.org/guidelines/online-guidelines/). The guidelines include algorithms that refer the reader back to the supporting evidence, and they are more immediately useable in daily clinical practice.

Conclusions

These new guidelines present an up-to-date summary of the available evidence, together with clear clinical algorithms and action-based recommendations based on the best available evidence. Where such evidence does not exist, they present a consensus of expert opinion.     

Volumetric MR-guided high-intensity focused ultrasound versus uterine artery embolisation for treatment of symptomatic uterine fibroids: comparison of symptom improvement and reintervention rates

Purpose

To compare the effectiveness of magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) with that of uterine artery embolisation (UAE) for treatment of uterine fibroids.

Methods

Between January 2010 and January 2013, 51 women with symptomatic uterine fibroids underwent MR-HIFU. Follow-up and MR imaging were compared to 68 women treated with UAE, who fulfilled eligibility criteria for MR-HIFU – e.g., size (≤ 12 cm) and number (≤ 5) of fibroids. We compared median symptom severity (tSSS), total health-realted quality of life (HRQoL) scores, and reintervention rates. The adjusted effect on symptom relief and HRQoL improvement was calculated using multivariable linear regression. Cox regression was applied to calculate the adjusted risk of reintervention between both treatments.

Results

Median tSSS improved significantly from baseline to three-month follow-up (P?P?P?P?=?0.002) times higher risk of reintervention within 12 months (18/51 vs. 3/68).

Conclusion

Both MR-HIFU and UAE result in significant symptom relief related to uterine fibroids. However, MR-HIFU is associated with a higher risk of reintervention.

Key Points

? This study compared outcomes between volumetric MR-HIFU and UAE for uterine fibroids. ? Both MR-HIFU and UAE result in significant symptom relief and quality of life improvement. ? UAE had a stronger positive effect on the clinical outcomes. ? Reintervention rate after MR-HIFU ablation was significantly higher than after UAE.     

Transforming growth factor-β (TGF-β) activity in urine of patients with glomerulonephritis is related to their renal functional and structural changes

SUMMARY: Transforming growth factor-β (TGF-β) has been considered the principal cytokine involved in the pathogenesis of renal fibrosis. In the present study, we evaluated TGF-β activity in occasional samples from 22 normal individuals and 29 patients (11 with focal glomerulosclerosis, 11 with membranous nephropathy, five with Berger disease, one with type I membranoproliferative glomerulonephritis and one with postinfectious glomerulonephritis) using a CCL-64 mink lung cell growth inhibition assay.
A significantly increased urinary TGF-β activity (reported in relation to urine creatinine, Ucreat, and median) was observed in patients with glomerulonephritis compared with normal individuals ( P <0.01). the patients with Berger disease [median (Md) = 9.96/10 μg Ucreat.], membranous glomerulonephritis (Md = 7.23/10 μg Ucreat.) and focal glomerulosclerosis (Md = 16.6/10 μg Ucreat.) showed higher urinary TGF-β than normal individuals (Md = 1.09/10 μg Ucreat.) ( P <0.01). We found a positive correlation between the TGF-β activity in the urine of these patients and the incidence of segmental glomerulosclerosis ( r = 0.45, P <0.05) and their plasma creatinine levels ( r = 0.87, P <0.01). A negative correlation was observed between the TGF-β activity in the urine of these patients and their creatinine clearance ( r =−0.75, P <0.01).
Our data suggest that measurement of urinary TGF-β activity could be a useful non-invasive procedure for the evaluation of renal TGF-β production, permitting the assessment of prognosis and the evaluation of therapeutic efficacy in patients with renal disease.     

Low incidence of acute urinary retention in the general male population: the triumph project

OBJECTIVE: To describe the incidence of acute urinary retention (AUR) in the general male population and in a population of men newly diagnosed with lower urinary tract symptoms suggestive of BPH (LUTS/BPH). METHODS: We performed a retrospective cohort study in the Integrated Primary Care Information (IPCI) database, a GP research database in The Netherlands, during the period 1995-2000. All males, > or =45 years, without a history of AUR or radical cystectomy were included in the study. In addition, we followed a sub-cohort of men, newly diagnosed with LUTS/BPH. AUR was defined as the sudden inability to urinate, requiring catheterization. RESULTS: Amongst 56,958 males with a mean follow-up of 2.8 years, 344 AUR cases occurred (incidence rate 2.2/1000 man-years) of whom more than 40% were precipitated. AUR was the first symptom of LUTS/BPH in 73 (49%) of the 149 AUR cases that occurred in men newly diagnosed with LUTS/BPH. The risk of AUR was 11-fold higher in patients newly diagnosed with LUTS/BPH (RR 11.5; 95%CI: 8.4-15.6) with an overall incidence rate of 18.3/1000 man-years (95%CI: 14.5-22.8). CONCLUSIONS: The incidence rate of AUR is low in the general population but substantial in a population of men newly diagnosed with LUTS/BPH. The incidence rate increases with age and AUR is precipitated in approximately 40% of all cases. Within the LUTS/BPH cohort, AUR is the first presenting symptom of BPH in 50% of all AUR cases.     

Role of Percutaneous Glue Treatment After Persisting Leak After Laparoscopic Sleeve Gastrectomy

Background

Over the years, many treatment modes have been attempted for gastrocutaneous fistula (GCF) after laparoscopic sleeve gastrectomy (LSG). Minimally invasive techniques for GCF treatment include stent placement and radiological percutaneous glue treatment (GT).

Material and Method

Ten patients underwent a radiological acrylate mixed with contrast medium GT combined or not with other treatment strategies such as relaparoscopy, ultrasound, or computerized tomography scan (CT scan)-guided drain and endoscopic stent placement.

Results

Ten patients (mean age 47.1 years, range 64–29) were treated by percutaneous injection of glue after LSG leak. Body mass index (BMI) was 42.2 kg/m²?±?6.7 at the time of LSG surgery. Mean time between LSG and leak diagnosis was 12 days (range 4–31 days). GT was only effective when performed after endoscopic stent placement (80 % resolution). With this regimen, five patients required a laparoscopic Roux limb placement. All fistulas eventually healed a mean of 75 days (range 29–293 days) after GCF diagnosis.

Conclusions

Percutaneous glue treatment alone does not seem to provide adequate results. Stenting previous to the glue treatment allows for better results.

     

Stent placement for renal arterial stenosis: where do we stand? A meta-analysis

PURPOSE: To perform a meta-analysis of renal arterial stent placement in comparison with renal percutaneous transluminal angioplasty (PTA) in patients with renal arterial stenosis. MATERIALS AND METHODS: Studies dealing with renal arterial stent placement (14 articles; 678 patients) and renal PTA (10 articles; 644 patients) published up to August 1998 were selected. A random-effects model was used to pool the data. RESULTS: Renal arterial stent placement proved highly successful, with an initial adequate performance in 98% and major complications in 11%. The overall cure rate for hypertension was 20%, whereas hypertension was improved in 49%. Renal function improved in 30% and stabilized in 38% of patients. The restenosis rate at follow-up of 6-29 months was 17%. Stent placement had a higher technical success rate and a lower restenosis rate than did renal PTA (98% vs 77% and 17% vs 26%, respectively; P <.001). The complication rate was not different between the two treatments. The cure rate for hypertension was higher and the improvement rate for renal function was lower after stent placement than after renal PTA (20% vs 10% and 30% vs 38%, respectively; P <.001). CONCLUSION: Renal arterial stent placement is technically superior and clinically comparable to renal PTA alone.