Geneviève Nadeau

Validity and reproducibility of an interviewer-administered food frequency questionnaire for healthy French-Canadian men and women

ObjectiveTo evaluate the validity (study 1) and the reproducibility (study 2) of an interviewer-administered food frequency questionnaire (FFQ).MethodThe FFQ was designed at Laval University and contains 91 items and 33 subquestions. Study 1: The FFQ was compared against a 3-day food record (2 week-days and 1 weekend-day), at week 0, 6 and 12 of a nutritional intervention. Study 2: In order to evaluate the reproducibility of the FFQ, 2 registered dietitians administered the FFQ 4-weeks apart among subjects who were not part of the nutritional intervention.ResultsStudy 1: Mean values for intake of most nutrients assessed by the FFQ and by the 3-day food record were not statistically different. Energy-adjusted correlation coefficients for major macronutrients ranged from 0.36 for proteins to 0.60 for carbohydrates (p ≤ 0.01). Agreement analysis revealed that on average, 35% of the subjects were classified in the same quartile when nutrients were assessed by either the 3-day food record or the FFQ. Study 2: Significant associations were observed between dietary measurements derived from the two FFQs administered 4 weeks apart. Correlation coefficients for the reproducibility of macronutrients ranged from 0.66 for carbohydrates to 0.83 for lipids after energy adjustment. On average, 46% of the subjects were classified in the same quartile when nutrient intakes were assessed by either FFQ.ConclusionThese data indicated that the FFQ developed has a good validity and is reproducible.

SRD5A polymorphisms and biochemical failure after radical prostatectomy.

BACKGROUND The relationship between inherited germ-line variations in the 5α-reductase pathways of androgen biosynthesis and the risk of biochemical recurrence (BCR) after radical prostatectomy (RP) remains an unexplored area. OBJECTIVE To determine the link between germ-line variations in the steroid-5α-reductase, α-polypeptide 1 (SRD5A1) and steroid-5α-reductase, α-polypeptide 2 (SRD5A2) genes and BCR. DESIGN, SETTINGS, AND PARTICIPANTS We studied retrospectively two independent cohorts composed of 526 white (25% BCR) and 320 Asian men (36% BCR) with pathologically organ-confined prostate cancer who had a median follow-up of 88.8 and 30.8 mo after surgery, respectively. MEASUREMENTS Patients were genotyped for 19 haplotype-tagging single nucleotide polymorphisms (htSNPs) in SRD5A1 and SRD5A2 genes, and their prognostic significance on prostate-specific antigen recurrence was assessed using Kaplan-Meier analysis and the Cox regression model. RESULTS AND LIMITATIONS After adjusting for all clinicopathologic risk factors, four SNPs (rs2208532, rs12470143, rs523349, and rs4952197) were associated with BCR in both whites and Asians. The strongest effect was conferred by the SRD5A2 V89L nonsynonymous SNP (rs523349C) with a hazard ratio (HR) of 2.87 (95% confidence interval [CI], 2.07-4.00; p = 4 × 10⁻¹⁰; 48% BCR). In addition, in whites, the combination of two SNPs, rs518673T in SRD5A1 and rs12470143A in SRD5A2, was associated with a reduced BCR rate for carriers of three or four alleles (HR: 0.37; 95% CI, 0.19-0.71; p=0.003;16% BCR) compared with noncarriers (38% BCR), whereas the SRD5A2 rs12470143A was significant in Asians (HR: 0.46; 95% CI, 0.28-0.73; p=0.001). Limitations of our study include few events of androgen-deprivation resistance or cancer-specific death. CONCLUSIONS Our study is the first to show positive associations of several SRD5A1 and SRD5A2 variations as independent predictors of BCR after RP.

Prospective Open Label Study of Solifenacin for Overactive Bladder in Children

PURPOSE We evaluated the effect of solifenacin for urinary incontinence in children with overactive/neurogenic bladder refractory to oxybutynin or tolterodine. MATERIALS AND METHODS Pediatric patients presenting with refractory overactive bladder with incontinence were offered the opportunity to enter a prospective, open label protocol using adjusted dose regimens of 1.25 to 10 mg solifenacin. Study inclusion criteria were absent correctable neurological anomalies on magnetic resonance imaging, failure of symptoms to improve on intensive behavioral and medical (oxybutynin or tolterodine) therapy, and/or significant side effects of those agents. Followup consisted of a voiding diary, post-void residual urine measurement, urine culture, ultrasound and urodynamics. Families were questioned about continence, side effects, compliance, behavior change and quality of life. The primary end point was efficacy for continence and secondary end points were tolerability and safety. RESULTS Enrolled in the study were 42 girls and 30 boys. Of the patients 27 with neurogenic bladder, of whom 11 were on clean intermittent catheterization, and 45 with overactive bladder completed a minimum 3-month followup. Patients were on solifenacin a mean of 15.6 months. Mean age at study initiation was 9.0 years. Mean ± SD urodynamic capacity improved from 146 ± 64 to 311 ± 123 ml and uninhibited contractions decreased from 70 ± 29 to 20 ± 19 cm H(2)O (p <0.01). Continence improved in all patients, including 24 who were dry, and 42 and 6 who were significantly and moderately improved, respectively. Of the patients 50 reported no side effects while 15 had mild and 3 had moderate side effects. Four patients withdrew from the protocol due to intolerable side effects. Four patients had significant post-void residual urine (greater than 20 ml). CONCLUSIONS In children with overactive bladder refractory to oxybutynin or tolterodine solifenacin is an effective alternative to improve symptoms. Tolerability was acceptable and the adjusted dose regimen appeared safe.

Prospective Pilot Study of Mirabegron in Pediatric Patients with Overactive Bladder

BACKGROUND Antimuscarinics are the pharmacologic mainstay of overactive bladder (OAB) management, but side effects limit their use. Mirabegron, a new molecule with a distinct mechanism of action (β3-adrenoreceptor agonist), was recently approved as monotherapy for idiopathic OAB in adults but has not been studied in the pediatric population. OBJECTIVE To evaluate the efficacy and safety of mirabegron to treat urinary incontinence in children with idiopathic OAB who were refractory to and/or intolerant of antimuscarinics. DESIGN, SETTING, AND PARTICIPANTS A prospective off-label study using mirabegron was conducted. Pediatric patients without symptom improvement under behavioral and medical therapies and/or with significant side effects with at least two different antimuscarinic agents were recruited. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Our primary outcome was better reported efficacy than with the use of prior anticholinergic medication. Secondary end points were tolerability, safety, and satisfaction. Efficacy and tolerability were assessed with voiding diaries, postvoid residuals, urine cultures, electrocardiogram, and vital signs. Families were questioned for continence, side effects, compliance, and Patient Perception of Bladder Condition (PPBC) questionnaire. The Wilcoxon rank sum test and Wilcoxon signed rank test were used for statistical analysis. RESULTS AND LIMITATIONS A total of 58 patients were recruited at a median age of 10.1 yr and were on mirabegron for a median of 11.5 mo. Median bladder capacity improved from 150ml to 200ml (p<0.001). Continence improved in 52 of 58, with 13 being completely dry. Median PPBC improved from 4.0 to 2.0 (p<0.001). Eight patients reported mild or moderate side effects. Absence of a placebo group is a limitation of the study. CONCLUSIONS Mirabegron, a novel first-in-class therapy, appeared as a safe and effective alternative for children with idiopathic OAB refractory to antimuscarinics. PATIENT SUMMARY We evaluated the efficacy and safety of mirabegron to treat incontinence in pediatric patients. Continence, median voided volumes, and quality of life were improved after the introduction of mirabegron, and few side effects were reported.

Long-term use of solifenacin in pediatric patients with overactive bladder: Extension of a prospective open-label study.

INTRODUCTION We evaluate the efficacy and safety of solifenacin to treat incontinence in children with non-neurogenic (DO) or neurogenic detrusor overactivity (NDO) refractory to oxybutinin or tolterodine. METHODS We updated and extended our previously published non-randomized uncontrolled study on open-label use of adjusted-dose regimens of solifenacin (1.25-10 mg) in children with refractory incontinence. The follow-up included voiding diaries, post-void residuals, urine cultures, ultrasounds and urodynamic studies. Clinical data were updated as of September 2012. Subjective improvement was assessed with the Patient Perception of Bladder Condition (PPBC) scale. The primary end point was efficacy toward continence and secondary end points were tolerability and safety. RESULTS Overall, 244 patients (112 girls, 132 boys) were enrolled; 53 with NDO and 191 with DO. Minimal follow-up was 5 months, the mean duration of treatment was 21.0 months and the mean age at initiation was 9.2 years. Urodynamic capacity improved from 145 ± 76 mL to 339 ± 152 mL and the amplitude of uninhibited contractions decreased from 66 ± 26 to 20 ± 20 cmH2O (p < 0.0001). The overall success rate is 91%, and more specifically 94% for non-neurogenic and 79% for neurogenic, which is significantly different (p = 0.013). Twenty-three patients discontinued treatment for unsatisfactory clinical response or bothersome side effects. No side effects were reported by 175 patients, mild by 46, moderate by 9, and 14 withdrew due to their side effects. Ten patients developed post-void residuals of ≥20 mL. CONCLUSION Although higher in the non-neurogenic group, high subjective and objective success rates were maintained over a longer follow-up with an adjusted-dose regimen of solifenacin to treat pediatric NDO or DO refractory to oxybutynin or tolterodine. Moreover, we found acceptable tolerability and safety profiles.

Modified Scrotal (Bianchi) Mid Raphe Single Incision Orchiopexy for Low Palpable Undescended Testis: Early Outcomes

PURPOSE We compared the results of low transscrotal mid raphe orchiopexy, high scrotal incision (Bianchi) and conventional inguinal approach in patients with palpable undescended testes. MATERIALS AND METHODS Orchiopexies performed between January 2003 and September 2009 with a minimum 3-month followup were included. Low scrotal incision (group 1) and high scrotal incision (group 2) were compared to the traditional inguinal 2-incision technique (group 3). We retrospectively reviewed operative time, success as defined by mid or lower scrotal position of the testis, and complications at 12 weeks and 1 year postoperatively. RESULTS A total of 286 orchiopexies were performed in 214 patients with palpable undescended testes. Group 1 included 81 patients with 125 undescended testes. Group 2 consisted of 44 patients with 60 undescended testes. Group 3 included 89 patients with 101 undescended testes. Postoperatively the testes were located in a good position within the scrotum in 99% of patients in group 1, 98% in group 2 and 100% in group 3. Mean±SD operative time for unilateral undescended testes was significantly shorter for low transscrotal compared to inguinal orchiopexy (28±10 vs 37±12 minutes, p<0.0001) but equivalent to a high scrotal incision (27±10 minutes, p=0.59). For all 160 children followed for 1 year no long-term atrophy or secondary reascent was observed. CONCLUSIONS Low transscrotal mid raphe orchiopexy appears to be an excellent alternative to high scrotal incision or standard inguinal orchiopexy for low palpable undescended testes, especially bilateral cases.

Effect of a nutritional intervention promoting the Mediterranean food pattern on electrophoretic characteristics of low-density lipoprotein particles in healthy women from the Québec City metropolitan area.

The objective of the present study was to evaluate the effect of a nutritional intervention promoting the Mediterranean food pattern in free-living conditions on LDL electrophoretic characteristics in a group of seventy-one healthy women, aged between 30 and 65 years. The 12-week nutritional intervention consisted of two courses on nutrition and seven individual sessions with a dietitian. The first course provided information on the Mediterranean food pattern and the second was a cooking lesson. LDL peak particle diameter (LDL-PPD) and cholesterol levels in small (LDL-cholesterol<255 A) and large LDL fractions (LDL-cholesterol>260 A) were obtained by 2-16 % polyacrylamide gel electrophoresis of whole plasma. The sample was divided on the basis of baseline LDL-PPD using tertiles of the distribution (258.4 A and 260.0 A). Among the total sample of women, no significant change in LDL-PPD was observed in response to the nutritional intervention. However, subjects who at baseline were in the first tertile of the LDL-PPD distribution (<258.4 A) showed a significant increase in LDL-PPD and in the proportion of LDL %>260 A in response to the 12-week nutritional intervention (P<0.05). In contrast, LDL-PPD decreased significantly (P=0.007) among women with large LDL particles at baseline (LDL-PPD >260 A) while the proportion of LDL %<255 A and of LDL %>260 A remained unchanged. To conclude, changes in the food pattern, in response to a nutritional intervention promoting the Mediterranean food pattern, were accompanied by beneficial modifications in LDL electrophoretic characteristics in women who were characterised at baseline by smaller LDL particles.

Double anticholinergic therapy for refractory neurogenic and non-neurogenic detrusor overactivity in children: Long-term results of a prospective open-label study

INTRODUCTION In this study, we optimize pharmacotherapy in children who failed anticholinergic monotherapy by simultaneous administration of 2 anticholinergics (oxybutynin and/or tolterodine and/or solifenacin). METHODS This report is an update of our previously published study on double anticholinergic regimen in children with refractory incontinence due to neurogenic (NDO) and non-neurogenic (DO) detrusor overactivity. Patients with an insufficient response (clinically/urodynamically) to an optimized dose of a single anticholinergic (oxybutynin or tolterodine) received a second anticholinergic (tolterodine or solifenacin), in addition to the pre-existing medication. The primary end-point was efficacy (continence) and the secondary end-points were tolerability and safety. The Patient Perception of Bladder Condition (PPBC) scale was used to rate subjective improvement of patients. RESULTS In total, 56 patients with DO (n = 31) or NDO (n = 25) were enrolled at a mean age of 11.4 ± 3.5 years and were followed for a minimum of 3 months. The duration of double treatment was 36 ± 23 months. Our results found that 23 patients became dry, 18 improved significantly and 15 improved moderately. Urodynamic capacity improved from 158 ± 87 mL to 359 ± 148 mL and maximal pressure of contractions decreased from 76 ± 24 to 22 ± 22 cmH2O (p < 0.0001). The overall success rate was 82%, since 10 patients discontinued treatment for unsatisfactory clinical response or bothersome side effects. No side effects were reported by 28 patients, mild side effects by 20, moderate side effects by 8; 2 patients withdrew from the study due to their side effects. Of the 35 patients who voided spontaneously, 8 developed post-void residuals (>20%). CONCLUSIONS With a larger cohort and prospective follow-up, we reiterated that double anticholinergic regimen in children with DO or NDO refractory to anticholinergic monotherapy is a feasible and efficient approach.

Dual Therapy for Refractory Overactive Bladder in Children: A Prospective Open-Label Study

Purpose: Mirabegron (&bgr;3 adrenoreceptor agonist) is a new molecule with a mechanism of action distinct from antimuscarinics. Combination therapy with solifenacin was recently studied in an adult population. We evaluated the efficacy and safety of mirabegron as add‐on therapy to treat urinary incontinence in children with idiopathic overactive bladder refractory/intolerant to antimuscarinics. Materials and Methods: A prospective off‐label study using add‐on regimens of mirabegron was conducted in pediatric patients presenting with no symptom improvement while undergoing intensive behavioral and medical therapies and/or significant side effects while undergoing antimuscarinic dose escalation. Our primary outcome was better reported efficacy than with the use of prior antimuscarinic monotherapy. Secondary end points were tolerability, safety and satisfaction. Efficacy and tolerability were assessed based on voiding diaries, post‐void residuals, urine cultures, electrocardiograms and vital signs. Families were questioned regarding continence, side effects and compliance. Wilcoxon signed‐rank test was used for statistical analysis. Results: A total of 35 patients were recruited at a median age of 10.3 years and were administered add‐on mirabegron for a median of 16.4 months. Median bladder capacity improved from 50% to 74% expected bladder capacity (p <0.001). Continence improved in all patients, with 12 being completely dry. Post‐void residual was increased in 2 patients and 1 urinary tract infection was reported. Seven patients reported mild or moderate side effects, with 2 withdrawals because of side effects (1 patient) and post‐void residual (1). Conclusions: Add‐on mirabegron appears to be a safe alternative for children with refractory overactive bladder. Dual therapy is well tolerated and adjusted dose regimen appears safe in this first pediatric study.

Learning curve for TIP urethroplasty: A single-surgeon experience

INTRODUCTION We evaluate the influence of surgeon experience and other clinical factors on the success of primary hypospadias repair, using the tubularized incised plate urethroplasty (TIPU) technique. METHODS We retrospectively reviewed pediatric cases of primary hypospadias repair performed by a single pediatric urologist (soon after his fellowship training) using TIPU between July 2002 and January 2011. The surgical techniques (including the fact that the procedure was an outpatient one) were the same for each patient. The overall complication rate (CR) was analyzed for the following factors: patient age, use of a stent, meatal position, and surgeon experience. All significant covariates on univariate analysis or with a clinical relevance were entered into a multivariable logistic regression model. A non-linear model was created to estimate the change in the CR over the years. RESULTS Pediatric patients (median age 1.4 years old) presenting with distal (n = 251), midshaft (n = 22) or proximal (n = 30) hypospadias and with a minimum 6-week follow-up (median 13 months) were included. Most patients (87%) had a urethral stent postoperatively (mean duration 9.8 days). In total, 96 patients had 133 complications: 27 meatal stenosis, 25 meatal coronal migrations, 22 urethrocutaneous fistulas and 59 other complications. Of these, 53 patients underwent a second operation. On multivariate analysis, the only factor increasing the CR was a non-distal meatus. The non-linear model demonstrated a significant learning curve with a decreasing CR over the years. The limitations of this study are its retrospective nature and lack of long-term follow-up. CONCLUSIONS When using TIPU, the CR significantly increases as the meatal position gets more proximal; the learning curve stabilizes after about 50 to 75 cases.