A double-blind,randomized, placebo-controlled clinical trial evaluating the safety and efficacy of autologous muscle derived cells in female subjects with stress urinary incontinence

Purpose

The purpose of the study was to assess safety and efficacy of autologous muscle derived cells for urinary sphincter repair (AMDC-USR) in female subjects with predominant stress urinary incontinence.

Methods

A randomized, double-blind, multicenter trial examined intra-sphincteric injection of 150?×?10⁶ AMDC-USR versus placebo in female subjects with stress or stress predominant, mixed urinary incontinence. AMDC-USR products were generated from vastus lateralis needle biopsies. Subjects were randomized 2:1 to receive AMDC-USR or placebo and 1:1 to receive 1 or 2 treatments (6 months after the first). Primary outcome was composite of ≥?50% reduction in stress incontinence episode frequency (IEF), 24-h or in-office pad weight tests at 12 months. Other outcome data included validated subject-recorded questionnaires. Subjects randomized to placebo could elect to receive open-label AMDC-USR treatment after 12 months. Subject follow-up was up to 2 years.

Results

AMDC-USR was safe and well-tolerated with no product-related serious adverse events or discontinuations due to adverse events. Interim analysis revealed an unexpectedly high placebo response rate (90%) using the composite primary outcome which prevented assessment of treatment effect as designed and thus enrollment was halted at 61% of planned subjects. Post hoc analyses suggested that more stringent endpoints lowered placebo response rates and revealed a possible treatment effect.

Conclusions

Although the primary efficacy finding was inconclusive, these results inform future trial design of AMDC-USR to identify clinically meaningful efficacy endpoints based on IEF reduction, understanding of placebo response rate, and refinement of subject selection criteria to more appropriately align with AMDC-USR’s proposed mechanism of action.

     

Kunstfehler. Ärzterecht

Ohne Zusammenfassung     

Association study of the G-protein β3 subunit C825T polymorphism with disease progression in patients with bladder cancer

The T-allele in the GNB3 C825T polymorphism has been associated with increased cell migration, a prerequisite for metastasis. In this study we investigated a potential association of the C825T-allele status and disease progression in patients with transitional cell carcinoma of the bladder (TCC). Genotyping of the GNB3 C825T polymorphism was performed in 389 patients with transitional cell carcinoma of the bladder and in 104 control subjects and clinical follow-up was worked up in 339 patients. Genotype distribution in 389 patients with bladder cancer was comparable to genotype distribution of the control group. There was no association of GNB3 C825T genotype with tumor stage or grade, but follow-up analysis in the subgroup of non-smokers revealed a shorter time to metastasis in 825T-allele carriers compared to individuals homozygous CC. The genotype of the GNB3 C825T polymorphism appears to influence the biological behavior of tumor disease in non-smoking TCC patients. This work was supported by a grant of the Deutsche Forschungsgemeinschaft     

Praxismarketing

The urological practice setting in Germany has changed tremendously over the last years. Group practices with two or more urologists working together are becoming more and more popular. At the same time, marketing has become essential even for urologists. To evaluate the patient flow to our group practice, we asked all new patients to fill out a questionnaire (n=2112). We also evaluated the efficacy of our recall system. The analysis showed that patients were 18–93 years old (mean 57 years), 68% being male and 32% female. The largest age group consisted of 41–50-year-olds. The most important reasons for choosing our practice were recommendations by general practitioners in 38%, recommendations by specialists in 11%, and recommendations by friends and relatives in 27%. Five percent of the patients chose the practice because of the Internet home page and 10% because of entries in various phone books. Three percent of the patients came because of newspaper articles about the practice owners, and <1% had attended patient presentations. The Internet was used mainly by 31–40-year-old patients. Our recall system showed an efficacy of 59%. In summary, a good reputation in the medical society as well as in the neighbourhood is still the best advertising for a urological practice. Phone books are increasingly becoming less important, and the Internet is increasingly attractive to the younger population. Recall systems can also be useful for urological practices.     

An Integrated Therapy Concept for Reduction of Postoperative Complications After Resection of a Panniculus Morbidus

Background  

Panniculus morbidus is characterized by an edematous, painful hanging abdominal mass, due to laxity and redundancy of the abdominal skin in morbid obesity, particularly after massive weight loss. Panniculectomy, by wedge resection, is a salvage procedure with high satisfaction rates though associated with high complication rates. Here we investigated the effects of perioperative complex decongestive physical therapy (CDP) on outcome and complication rates.