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Pediatric Urology
Urological Survey PEDIATRIC UROLOGY Efficacy, Tolerability and Safety of Propiverine Hydrochloride in Children and Adolescents With Congenital or Traumatic Neurogenic Detrusor Overactivity—A Retrospective Study U. Grigoleit, G. Murtz, S. Laschke, M. Schuldt, M. Goepel, G. Kramer and M. Stohrer, Department of Urology, Berufsgenossenschaftliche Unfallklinik Murnau, Murnau, Germany Eur Urol 2006; 49: 1114 –1121. Objectives: Anticholinergic treatment combined with intermittent catheterisation is the cornerstone of the conservative treatment strategy in children with neurogenic detrusor overactivity, which in most cases is due to congenital causes. Efficacy, tolerability and safety of propiverine hydrochloride were evaluated retrospectively in these children. Methods: At four specialized outpatient clinics, all children’s records were scrutinized for first-line propiverine hydrochloride treatment, or second- or third-line treatment after failure of a non-selective alpha-blocker (phenoxybenzamine) and/or other anticholinergics (oxybutynin, trospium chloride). The primary efficacy outcomes were urodynamic parameters, with clinical symptoms as secondary outcomes. Statistical analysis was performed by paired t-tests (significance level p ⬍ 0.05). Results: Altogether 74 children and adolescents (40 boys, 34 girls; age range 11 months–19 years) were treated with propiverine hydrochloride (average duration 2 years and approximately 4 months; individual dose range 5–75 mg). The primary efficacy outcome parameters improved significantly: maximum cystometric capacity 161.2 [standard deviation (SD) 97.3] to 252.2 ml (SD 117.2), p ⬍ 0.001; maximum detrusor pressure 43.8 (SD 39.2) to 27.1 cm H(2)O (SD 26.4), p ⫽ 0.002; bladder compliance 7.6 (SD 6.4) to 17.0 ml/cm H(2)O (SD 16.2), p ⬍ 0.001. Phasic detrusor overactivity was abolished by 63%; incontinence resolved by 54%. One patient spontaneously reported a typical anticholinergic adverse event, which resolved after dose reduction. No safety concerns were documented. Conclusions: Propiverine hydrochloride is effective in neurogenic detrusor overactivity in children and adolescents, even in some of those cases unresponsive to other anticholinergics. The low incidence rate (⬍1.5%) of adverse events evidences a favourable risk-benefit profile of propiverine hydrochloride, considering in particular the total documented treatment and surveillance period of 171 patient years and nine months.
Urodynamic Effects of Propiverine Hydrochloride in Children With Neurogenic Detrusor Overactivity: A Prospective Analysis H. Schulte-Baukloh, G. Murtz, T. Henne, T. Michael, K. Miller and H. H. Knispel, Department of Urology, St. Hedwig Hospital, Teaching Hospital of University Hospital Charite, Berlin, Germany BJU Int 2006; 97: 355–358. Objectives: To evaluate prospectively the efficacy and tolerability of propiverine for treating neurogenic detrusor overactivity (NDO) in children. Patients and Methods: Twenty children (mean age 8.9 years; median 5.6) with NDO due to an upper motor neurone lesion were enrolled (17 had myelomeningocele). In the urodynamic examination, reflex volume (RV), maximum detrusor pressure (MDP), maximum cystometric bladder capacity (MCBC) and bladder compliance (BC) before and after a twice-daily propiverine hydrochloride regimen were determined. The urodynamic follow-up was after 3– 6 months. Incontinence was assessed by an incontinence score. Results: The mean (sem) RV increased from 103.8 (21.3) to 174.5 (33.7) mL (P ⬍ 0.005), MDP decreased from 52.5 (7.9) to 40.1 (6.2) cm H(2)O (P ⬍ 0.05), MCBC increased from 166 (28.8) to 231.9 (34.8) mL (P ⬍ 0.005), and BC improved from 11.2 (2.8) to 30.6 (9.7) mL/cm H(2)O (P ⬍ 0.01), with propiverine treatment. The incontinence score (scale 0 –3) improved from 2.4 (0.2) to 1.6 (0.3) (P ⬍ 0.05). Propiverine was well tolerated, although some children were given higher doses than recommended. Conclusions: Propiverine hydrochloride is effective and well tolerated in the treatment of children with NDO. Because of its dual mode of action, it is well tolerated even in children who need higher doses. 0022-5347/07/1772-0732/0 THE JOURNAL OF UROLOGY® Copyright © 2007 by AMERICAN UROLOGICAL ASSOCIATION
732
Vol. 177, 732-733, February 2007 Printed in U.S.A. DOI:10.1016/j.juro.2006.10.104
PEDIATRIC UROLOGY
733
Propiverine hydrochloride is a preferable alternative to oxybutynin, the anticholinergic most frequently used in children with NDO to date. Editorial Comment: Propiverine is an antimuscarinic and calcium channel blocking drug currently licensed in the United Kingdom and Europe. The retrospective study by Grigoleit et al shows that propiverine was effective as either primary or secondary therapy in treatment periods of more than 5 years. Propiverine improved maximum cystometric capacity, maximum detrusor pressure and bladder compliance. Maximum cystometric capacity increased from an average of 161 to 252 cc, bladder compliance increased from 7.6 to 17 cc/cm and maximum detrusor pressure was reduced from 43.8 to 27.1 cm. Although patients were not specifically asked about side effects, only 1 of 74 reported dizziness and visual disturbance at a dose of 0.09 mg/kg. Similar efficacy was reported by Schulte-Baukloh et al, with reported side effects of 10%. Two mothers in this study described difficulties with their children concentrating in school. Propiverine is not currently available in the United States. Should it become available in the future, it may be of value in children who do not tolerate oxybutynin or in whom oxybutynin results in only moderate success. At this time there is no evidence from prospective trials to suggest that propiverine is superior to oxybutynin dosing that is titrated to maximize efficacy and reduce side effects in the treated child. Douglas A. Canning, M.D.
Breastfeeding During Infancy May Protect Against Bed-Wetting During Childhood J. G. Barone, R. Ramasamy, A. Farkas, E. Lerner, E. Creenan, D. Salmon, J. Tranchell and D. Schneider, Department of Urology, Robert Wood Johnson Medical School, New Brunswick, New Jersey Pediatrics 2006; 118: 254 –259. Objective: Our goal was to test the hypothesis that children who exhibit bed-wetting during childhood were less likely to be breastfed during infancy compared with normal controls. Methods: A case-control study was conducted in a pediatric continence center and a general pediatric practice. Cases (n ⫽ 55) were recruited from the continence center and defined as children 5 to 13 years of age who experienced lifetime involuntary voiding of urine during nighttime sleep at least 2 times a week in the absence of defects of the central nervous system or urinary tract. Age- and gender-matched controls (n ⫽ 117) who did not exhibit bedwetting were enrolled from a general pediatric practice. Infant feeding practices were measured as breastfeeding (yes/no) and, for those who were breastfeed, by the duration of breastfeeding and the time of formula supplementation. Results: Among the case subjects, 45.5% were breastfed, whereas among the controls 81.2% were breastfed. The controls reported higher household incomes than the case subjects, and their mean family size (number of children) was slightly lower. After adjusting for race, income, and family size, the odds ratio was 0.283, indicating that case subjects were significantly less likely than controls to be breastfeed. Among all the study subjects who were breastfed, controls were breastfed for a significantly longer period than case subjects (an average of 3 months longer). Although breastfed controls were less likely to be supplemented with formula than breastfed case subjects, this difference was not statistically significant. Conclusions: Breastfeeding longer than 3 months may protect against bed-wetting during childhood. Breast milk supplemented with formula did not make a difference in the rate of enuresis. Editorial Comment: This is a case-control study in which girls and boys 5 to 13 years old with a history of monosymptomatic nocturnal enuresis at least twice weekly were compared to a control group who did not wet the bed. Parents were sent a questionnaire that assayed for birth, gender, race/ethnicity, number of children in the household, socioeconomic variables and family history of bedwetting. Breastfeeding history was measured by 2 variables, a dichotomous yes/no variable and duration of breastfeeding in months. The children with nocturnal enuresis were breastfed for an average of 3 months less than boys and girls who were dry. This is an interesting study, perhaps the first suggesting a potential protective role that breastfeeding may have on bedwetting. It appears that breastfeeding must continue beyond 4 months for it to have a significant beneficial effect. Previous studies have suggested an advantage in neurodevelopment in children who are breastfed.1 I agree with the authors. If findings consistent with these results are found in prospective cohort studies, it is possible that “breastfeeding may be viewed as the first true preventive approach toward bedwetting.” Douglas A. Canning, M.D. 1. Vestergaard M, Obel C, Henriksen TB, Sorensen HT, Skajaa E and Ostergaard J: Duration of breastfeeding and developmental milestones during the latter half of infancy. Acta Paediatr 1999; 88: 1327.
Urodynamic Effects of Propiverine Hydrochloride in Children With Neurogenic Detrusor Overactivity: A Prospective Analysis H. Schulte-Baukloh, G. Murtz, T. Henne, T. Michael, K. Miller and H. H. Knispel, Department of Urology, St. Hedwig Hospital, Teaching Hospital of University Hospital Charite, Berlin, Germany BJU Int 2006; 97: 355–358. Objectives: To evaluate prospectively the efficacy and tolerability of propiverine for treating neurogenic detrusor overactivity (NDO) in children. Patients and Methods: Twenty children (mean age 8.9 years; median 5.6) with NDO due to an upper motor neurone lesion were enrolled (17 had myelomeningocele). In the urodynamic examination, reflex volume (RV), maximum detrusor pressure (MDP), maximum cystometric bladder capacity (MCBC) and bladder compliance (BC) before and after a twice-daily propiverine hydrochloride regimen were determined. The urodynamic follow-up was after 3– 6 months. Incontinence was assessed by an incontinence score. Results: The mean (sem) RV increased from 103.8 (21.3) to 174.5 (33.7) mL (P ⬍ 0.005), MDP decreased from 52.5 (7.9) to 40.1 (6.2) cm H(2)O (P ⬍ 0.05), MCBC increased from 166 (28.8) to 231.9 (34.8) mL (P ⬍ 0.005), and BC improved from 11.2 (2.8) to 30.6 (9.7) mL/cm H(2)O (P ⬍ 0.01), with propiverine treatment. The incontinence score (scale 0 –3) improved from 2.4 (0.2) to 1.6 (0.3) (P ⬍ 0.05). Propiverine was well tolerated, although some children were given higher doses than recommended. Conclusions: Propiverine hydrochloride is effective and well tolerated in the treatment of children with NDO. Because of its dual mode of action, it is well tolerated even in children who need higher doses. 0022-5347/07/1772-0732/0 THE JOURNAL OF UROLOGY® Copyright © 2007 by AMERICAN UROLOGICAL ASSOCIATION
732
Vol. 177, 732-733, February 2007 Printed in U.S.A. DOI:10.1016/j.juro.2006.10.104
PEDIATRIC UROLOGY
733
Propiverine hydrochloride is a preferable alternative to oxybutynin, the anticholinergic most frequently used in children with NDO to date. Editorial Comment: Propiverine is an antimuscarinic and calcium channel blocking drug currently licensed in the United Kingdom and Europe. The retrospective study by Grigoleit et al shows that propiverine was effective as either primary or secondary therapy in treatment periods of more than 5 years. Propiverine improved maximum cystometric capacity, maximum detrusor pressure and bladder compliance. Maximum cystometric capacity increased from an average of 161 to 252 cc, bladder compliance increased from 7.6 to 17 cc/cm and maximum detrusor pressure was reduced from 43.8 to 27.1 cm. Although patients were not specifically asked about side effects, only 1 of 74 reported dizziness and visual disturbance at a dose of 0.09 mg/kg. Similar efficacy was reported by Schulte-Baukloh et al, with reported side effects of 10%. Two mothers in this study described difficulties with their children concentrating in school. Propiverine is not currently available in the United States. Should it become available in the future, it may be of value in children who do not tolerate oxybutynin or in whom oxybutynin results in only moderate success. At this time there is no evidence from prospective trials to suggest that propiverine is superior to oxybutynin dosing that is titrated to maximize efficacy and reduce side effects in the treated child. Douglas A. Canning, M.D.
Breastfeeding During Infancy May Protect Against Bed-Wetting During Childhood J. G. Barone, R. Ramasamy, A. Farkas, E. Lerner, E. Creenan, D. Salmon, J. Tranchell and D. Schneider, Department of Urology, Robert Wood Johnson Medical School, New Brunswick, New Jersey Pediatrics 2006; 118: 254 –259. Objective: Our goal was to test the hypothesis that children who exhibit bed-wetting during childhood were less likely to be breastfed during infancy compared with normal controls. Methods: A case-control study was conducted in a pediatric continence center and a general pediatric practice. Cases (n ⫽ 55) were recruited from the continence center and defined as children 5 to 13 years of age who experienced lifetime involuntary voiding of urine during nighttime sleep at least 2 times a week in the absence of defects of the central nervous system or urinary tract. Age- and gender-matched controls (n ⫽ 117) who did not exhibit bedwetting were enrolled from a general pediatric practice. Infant feeding practices were measured as breastfeeding (yes/no) and, for those who were breastfeed, by the duration of breastfeeding and the time of formula supplementation. Results: Among the case subjects, 45.5% were breastfed, whereas among the controls 81.2% were breastfed. The controls reported higher household incomes than the case subjects, and their mean family size (number of children) was slightly lower. After adjusting for race, income, and family size, the odds ratio was 0.283, indicating that case subjects were significantly less likely than controls to be breastfeed. Among all the study subjects who were breastfed, controls were breastfed for a significantly longer period than case subjects (an average of 3 months longer). Although breastfed controls were less likely to be supplemented with formula than breastfed case subjects, this difference was not statistically significant. Conclusions: Breastfeeding longer than 3 months may protect against bed-wetting during childhood. Breast milk supplemented with formula did not make a difference in the rate of enuresis. Editorial Comment: This is a case-control study in which girls and boys 5 to 13 years old with a history of monosymptomatic nocturnal enuresis at least twice weekly were compared to a control group who did not wet the bed. Parents were sent a questionnaire that assayed for birth, gender, race/ethnicity, number of children in the household, socioeconomic variables and family history of bedwetting. Breastfeeding history was measured by 2 variables, a dichotomous yes/no variable and duration of breastfeeding in months. The children with nocturnal enuresis were breastfed for an average of 3 months less than boys and girls who were dry. This is an interesting study, perhaps the first suggesting a potential protective role that breastfeeding may have on bedwetting. It appears that breastfeeding must continue beyond 4 months for it to have a significant beneficial effect. Previous studies have suggested an advantage in neurodevelopment in children who are breastfed.1 I agree with the authors. If findings consistent with these results are found in prospective cohort studies, it is possible that “breastfeeding may be viewed as the first true preventive approach toward bedwetting.” Douglas A. Canning, M.D. 1. Vestergaard M, Obel C, Henriksen TB, Sorensen HT, Skajaa E and Ostergaard J: Duration of breastfeeding and developmental milestones during the latter half of infancy. Acta Paediatr 1999; 88: 1327.