Effect of surgical approach on erectile function recovery following bilateral nerve-sparing radical prostatectomy: an evaluation utilising data from a randomised, double-blind, double-dummy multicentre trial of tadalafil vs placebo.

OBJECTIVES: To report pre-specified and exploratory results on the effect of different surgical approaches on erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) obtained from the multicentre, randomised, double-blind, double-dummy REACTT trial of tadalafil (once a day [OaD] or on-demand [pro-re-nata, PRN]) vs placebo. PATIENTS AND METHODS: Patients aged <68 years with normal preoperative EF who underwent nsRP for localised prostate cancer (Gleason ≤7, prostate-specific antigen [PSA] <10 ng/mL) were randomised after nsRP 1:1:1 to 9-month double-blind treatment with tadalafil 5 mg OaD, tadalafil 20 mg PRN, or placebo, followed by 6-week drug-free washout, and 3-month open-label OaD treatment (all patients). Recovery of EF was defined as an International Index of Erectile Function (IIEF)-EF domain score of ≥22 and normal orgasmic function was defined based on IIEF Question 10. Both parameters were analysed at the end of washout using logistic regression including terms for treatment, country, visit, visit-by-treatment interaction, age group, nerve-sparing score (perfect = 2, non-perfect >2), and surgical approach (open surgery, robot-assisted laparoscopy, conventional laparoscopy, other). Time to EF recovery was analysed post hoc with a Cox proportional-hazards model including terms for treatment, age-group, country, surgical approach and surgery-by-treatment interaction. RESULTS: Of 422 patients treated, 189 underwent open surgery, 115 robot-assisted laparoscopy, 88 conventional laparoscopy and 30 surgery classified as 'other'. The odds of achieving EF recovery at the end of drug-free washout were about twice as high for the robot-assisted laparoscopy group compared with the open surgery group (odds ratio 2.42; 95% confidence interval [CI] 1.24, 4.72; P = 0.029). Patients who underwent robot-assisted laparoscopy were significantly more likely to recover during double-blind treatment compared with patients who underwent open surgery (hazard ratio 1.92; 95% CI 1.17, 3.15; P = 0.010). No favourable effect of conventional laparoscopy compared with open surgery could be seen. CONCLUSION: These results may provide further insights into the role of surgery on EF recovery after nsRP. However, the trial was not designed for these analyses and further prospective studies are needed.

Patient characteristics impacting health state index scores, measured by the EQ-5D of females with stress urinary incontinence symptoms.

OBJECTIVE: To describe the characteristics of women seeking treatment for symptoms of stress urinary incontinence (SUI) and to investigate the association of SUI symptoms with generic health-related quality of life (HRQoL) as measured by the EuroQol (EQ-5D) instrument. METHODS: The Stress Urinary Incontinence Treatment (SUIT) study was a 12-month observational study in four European countries that evaluated the cost-effectiveness of duloxetine compared with other forms of nonsurgical intervention in the treatment of the symptoms of SUI. Four hundred thirty-one physicians observed women seeking treatment for their SUI, and recorded the care provided and the outcomes of that care at enrollment and at 3, 6 and 12 months afterward The impact of SUI on baseline HRQoL as expressed by the EQ-5D index score was assessed by linear and logistic regression. RESULTS: Three thousand seven hundred sixty-two women were enrolled into SUIT, with the largest patient group from Germany. Overall, the majority of women were postmenopausal, had a mean age of 58.0 years, were not current smokers, and tended to be overweight (mean body mass index [BMI]=27.7 kg/m2), with at least one comorbidity. The health state index scores were significantly and independently influenced by the presence of comorbidity(ies) affecting quality of life, total number of stress and urge incontinence episodes, urinary incontinence subtype, comorbidity(ies) affecting incontinence, BMI, socioeconomic status, educational status, age, and country. CONCLUSION: This article describes the characteristics of patients at the SUIT enrollment visit, and demonstrates that the number of incontinence episodes has a significant impact on the EQ-5D index score.

Patient reported outcomes tools in an observational study of female stress urinary incontinence.

AIMS: To determine which patient characteristics, incontinence and non-incontinence related, are associated with the symptom severity scores of the Urogenital Distress Inventory (UDI) and the International Consultation on Incontinence Questionnaire Urinary Incontinence (ICIQ-UI); and to determine the association of both patient characteristics and symptom severity scores with quality-of-life scores of the Incontinence Impact Questionnaire (IIQ) and the Incontinence-Quality of Life (I-QOL) questionnaire. METHODS: Women presenting with stress urinary incontinence (SUI) symptoms in primary and secondary care entered the Stress Urinary Incontinence Treatment Study (SUIT), an observational study evaluating the cost-effectiveness of duloxetine compared to other non-surgical treatments for SUI. At enrollment patients completed the UDI-6, the short form ICIQ-UI, the IIQ-7 and the I-QOL. Multivariate linear regressions were performed with the UDI-6, ICIQ-UI SF, IIQ-7, and I-QOL as outcomes. RESULTS: The total number of incontinence episodes is the most significant explanatory variable of the two symptom questionnaire scores, but the UDI-6 score also reflects the type of incontinence. The variability of the condition-specific quality-of-life questionnaires is primarily explained by the symptom severity questionnaire scores. Although there is a high intercorrelation, both these symptom questionnaires independently contributed significantly to the IIQ-7 and I-QOL total scores. CONCLUSIONS: The UDI-6 and ICIQ-UI SF can be regarded as scientifically sound symptom questionnaires in UI evaluation; but they have differences. Since the UDI-6 and ICIQ-UI SF independently contribute to the quality-of-life scores, this suggests that in incontinence research symptom questionnaires should not focus only on incontinence, but on a broader range of urogenital symptoms.

Long-term efficacy of duloxetine in women with stress urinary incontinence.

OBJECTIVE: To assess the maintenance of efficacy of duloxetine beyond 3 months, using data from several long-term, open-label studies, as the efficacy of duloxetine 40-mg twice daily for treating women with stress urinary incontinence (SUI) for up to 3 months has been established in several randomized, placebo-controlled clinical trials. PATIENTS AND METHODS: Data from 1424 patients (Cohort A) enrolled in three 12-week, placebo-controlled clinical trials and their uncontrolled, open-label extensions, and in one uncontrolled, open-label study, were used to assess long-term continuation rates and continued efficacy based on responses to the validated Patient Global Impression of Improvement (PGI-I) scale for up to 30 months. Data from another 2758 patients (Cohort B) enrolled in an additional placebo-controlled study and its open-label extension were used to assess PGI-I ratings, reductions in incontinence episode frequency (IEF) recorded on urinary diaries, and the relationship between PGI-I ratings and reductions in IEF for up to 72 weeks. RESULTS: In Cohort A, the duloxetine continuation rate at 1 year was 42.5%. At 12, 24 and 30 months, most (83%, 83% and 88%, respectively) patients in Cohort A who continued treatment rated their incontinence in one of the three 'better since starting treatment' PGI-I categories. Both the median IEF reductions (50-77%) and the PGI-I 'better' ratings (70-88% of patients) remained fairly consistent over 72 weeks in Cohort B. Finally, IEF reductions increased with increasing PGI-I ratings (approximately 46% for 'a little better', 75% for 'much better' and 95% for 'very much better') over the first year of treatment. CONCLUSION: The benefits of duloxetine were maintained in patients who continued treatment for up to 30 months. However, these favourable results need to be interpreted cautiously, as many patients discontinued treatment and those with better responses are more likely to continue taking medication.

Short- and long-term efficacy and safety of duloxetine in women with predominant stress urinary incontinence.

OBJECTIVE: To evaluate short- and long-term safety and efficacy of duloxetine in women with predominant stress urinary incontinence (SUI). RESEARCH DESIGN AND METHODS: The study was a 6-week, double-blind, randomised, parallel, placebo-controlled study followed by an uncontrolled open-label extension (OLE) run in 342 study centres in 16 European countries. Women with predominant SUI were randomly assigned to placebo (n = 1380) or duloxetine 40 mg twice daily (n = 1378) for 6 weeks. Completers of the acute phase were enrolled in the OLE, which had a minimum duration of 6 weeks and ended, based on the approval status of duloxetine in the participating country. MAIN OUTCOME MEASURES: The primary outcome measure was the change in incontinence episode frequency (IEF) over 6 weeks. Secondary outcome measures were the long-term maintenance of effect on IEF and Patient Global Impression of Improvement (PGI-I), the short- and long-term impact on quality of life using the King's Health Questionnaire (KHQ), and the long-term safety of duloxetine. RESULTS: After 6 weeks, the decrease in weekly IEF was significantly greater with duloxetine treatment compared to placebo (-50.0 vs. -29.9%; p < 0.001). The percentage of responders (defined as > or =50% decrease in IEF) was significantly higher with duloxetine treatment than with placebo (50.6 vs. 31.2%; p < 0.001). Duloxetine treatment was associated with improvements in weekly pad use (-31.4%), PGI-I ratings (63.6%), and KHQ score (-6.25) compared to placebo (-12.5%, 48.5% and -3.13, respectively, all p < 0.001). Treatment-emergent adverse events were significantly more common during duloxetine treatment (48.3%) than placebo (33.3%), (p < 0.001). Of the 2290 patients continuing into the OLE, 1165 (42.2%) completed the available duration, and 592 (21.5%) discontinued because of an adverse event (percentages relative to total randomised patients). Long-term efficacy in the OLE was assessed over a 72-week period and was maintained over that time. However, the results should be interpreted within the context that better responding patients are more likely to remain on duloxetine, while patients responding poorly are more likely to discontinue over time. CONCLUSIONS: Duloxetine seems to be an efficacious treatment with an acceptable safety profile for women with SUI. Achieved improvement is maintained over the longer term in those women who remain on therapy.

Long-term results of plaque thinning with carbide burs, small incisions and venous grafting for correcting complex penile curvature in Peyronie's disease: poor results of an "ideal" approach.

PURPOSE: We evaluated the long-term results of plaque thinning by carbide burs, small transverse incisions and venous grafting for correcting complex penile curvature in patients with Peyronie's disease. MATERIALS AND METHODS: A total of 13 patients with Peyronie's disease and complex penile curvature received plaque thinning by carbide burs equipped with a fraise, small plaque incision and venous grafting. All patients were available for long-term followup at a mean of 29 months. Preoperatively the mean dorsal curvature angle was 73 degrees with an additional malrotation in 4 patients. Followup consisted of a standardized interview and 3-dimensional photo documentation during erection. RESULTS: Although penile straightening was achieved intraoperatively, dorsal curvature (mean 35 degrees) recurred in 8 men, of whom 3 noticed this deterioration after a longer period. Penile shortening (mean 3.3 cm.) occurred in 7 patients, and decreased rigidity during intercourse occurred in 4. CONCLUSIONS: Hypothetically, a combined technique of thinning, incision and grafting seems to be an ideal surgical approach for correction of complex penile curvatures in Peyronie's disease without plaque excision. Although the penis had been completely straightened intraoperatively, severe dorsal curvatures recurred and significant penile shortening became obvious in more than half of the patients. Manipulation of the plaque may be associated with activation of the disease, with all of the risks of recurrence and deterioration. Due to the poor results of the thinning procedures, we stopped using this surgical approach and now prefer a combination of small incisions and grafting only.