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Purpose: We evaluated whether combination therapy with transcutaneous electrical nerve stimulation and oxybutynin results in a superior treatment response compared to either therapy alone in children with urge incontinence., Materials and Methods: In this placebo controlled study 66 children with a mean ± SD age of 7.3 ± 1.6 years who were diagnosed with urge incontinence were randomized to 3 treatment groups. Group 1 consisted of 22 children undergoing transcutaneous electrical nerve stimulation plus active oxybutynin administration. Group 2 included 21 children undergoing active transcutaneous electrical nerve stimulation plus placebo oxybutynin administration. Group 3 consisted of 23 children undergoing active oxybutynin administration plus placebo transcutaneous electrical nerve stimulation. The children received active or placebo transcutaneous electrical nerve stimulation over the sacral S2 to S3 outflow for 2 hours daily in combination with 5 mg active or placebo oxybutynin twice daily. The intervention period was 10 weeks. Primary outcome was number of wet days weekly. Secondary outcomes were severity of incontinence, frequency, maximum voided volume over expected bladder capacity for age, average voided volume over expected bladder capacity for age and visual analogue scale score., Results: Combination therapy was superior to oxybutynin monotherapy, with an 83% greater chance of treatment response (p = 0.05). Combination therapy was also significantly more effective than transcutaneous electrical nerve stimulation monotherapy regarding reduced number of wet days weekly (mean difference -2.28, CI -4.06 to -0.49), severity of incontinence (-3.11, CI -5.98 to -0.23) and daily voiding frequency (-2.82, CI -4.48 to -1.17)., Conclusions: Transcutaneous electrical nerve stimulation in combination with oxybutynin for childhood urge incontinence was superior to monotherapy consisting of transcutaneous electrical nerve stimulation or oxybutynin, although the latter only reached borderline statistical significance. Furthermore, transcutaneous electrical nerve stimulation was associated with a decreased risk of oxybutynin induced post-void residual urine greater than 20 ml., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated bladder reservoir function in children with monosymptomatic nocturnal enuresis with and without response to desmopressin, and assessed the importance of first morning voiding when defining maximum voided volume., Materials and Methods: A total of 238 patients 5 to 15 years old with monosymptomatic nocturnal enuresis completed 2 weeks of enuresis recordings and 4 days of frequency-volume charts. Of the patients 186 completed subsequent home recordings during titration with desmopressin. Maximum voided volumes with and without the first morning void were calculated. Desmopressin response was defined as greater than 50% reduction in wet nights. Maximum voided volume with and without first morning voiding was evaluated as a prognostic factor for desmopressin response., Results: Mean ± SD maximum voided volume without first morning void was comparable between desmopressin responders and nonresponders (230.5 ± 69.3 ml and 219.0 ± 84.8 ml, respectively, p = 0.391). Inclusion of the first morning void demonstrated responders to have significantly larger values than nonresponders (mean ± SD 296.0 ± 94.0 ml vs 233.5 ± 90.0 ml, p <0.001). When first morning void was included, desmopressin response was seen in 40% of patients with voided volumes of 65% expected volume for age vs 10% of patients with volumes less than 65% expected volume for age., Conclusions: Maximum voided volume can be used as a predictor of desmopressin response only if first morning voids are taken into consideration. All patients with monosymptomatic nocturnal enuresis should receive clear instructions to include this measure when completing frequency-volume charts., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated the effect of timer watch treatment in addition to standard urotherapy in children with overactive bladder and daytime urinary incontinence., Materials and Methods: A total of 60 children with daytime urge incontinence were included in the study. Following a 4-week run-in period of standard urotherapy children were randomized to 12 weeks of standard urotherapy with or without a timer watch. Incontinence episodes were registered and 48-hour bladder diaries were obtained before randomization, and at weeks 1, 11 and 12. Long-term response was evaluated at 7 months., Results: Two children became continent during the run-in period. Before intervention children in the timer group were slightly more wet than children in the standard urotherapy group (median 7 [IQR 25% to 75% 6 to 7] vs 6 [3 to 7] wet days per week, p <0.05). Following 12 weeks of standard urotherapy children randomized to timer assisted urotherapy had significantly fewer wet days per week (median 2, IQR 25% to 75% 0 to 5) vs those undergoing standard urotherapy alone (5, 2.75 to 6.75, p <0.01). In the timer group 18 children (60%) achieved a greater than 50% decrease in incontinence episodes, compared to only 5 (18%) treated without timer assistance. Nine patients (30%) in the timer group and no child in the standard urotherapy group achieved complete daytime continence. The timer increased compliance with the timed voiding regimen. At 7 months of followup 60% of children in the timer group were still continent in the daytime., Conclusions: A programmable timer watch significantly improves the effect of standard urotherapy. When using the timer watch as a supplement to standard urotherapy 60% of the children obtained complete and sustainable daytime continence., (Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We determined normal, age related reference data regarding maximum voided volume and nocturnal urine production using the same methodology as in clinical practice., Materials and Methods: A total of 62 girls and 86 boys without enuresis (mean +/- SD age 9.64 +/- 2.63 years, range 3 to 15) completed 4 days (2 weekends) of frequency-volume charts and 14 days of home recording of nocturnal urine production. From these recordings maximum voided volume with and without first morning void was derived for each subject. Also, average nocturnal urine volume with and without nocturia was calculated. Percentiles were produced by dividing the population into 1-year age groups., Results: Based on 2,836 daytime voids and 1,977 overnight recordings, maximum voided volume and nocturnal urine volume showed a significant linear relationship with age but not with gender. Maximum voided volume with first morning void was significantly higher than without (403 +/- 137 ml vs 281 +/- 112 ml, p <0.0001) and the 50th percentile line of maximum voided volume with first morning void was 80 to 100 ml higher than Koff's formula (30 x [age + 1] ml). Conversely the 50th percentile of maximum voided volume without first morning void was almost identical to Koff's formula. Regarding nocturnal measurements, nocturia was noted on 128 nights (6.5%) and nocturnal urine volume on nights with nocturia was significantly higher than on nights without nocturia (365 +/- 160 ml vs 248 +/- 75 ml, respectively, p <0.0001). The 97.5th nocturnal urine volume percentile line of healthy children deviated markedly from the current International Children's Continence Society definition of nocturnal polyuria, especially at low and high ages., Conclusions: We demonstrate clearly that the universally used formula 30 x (age + 1) ml is indeed valid for a population of healthy Danish children but only if the first morning void is disregarded. Furthermore, we question the validity of the current International Children's Continence Society formula for nocturnal polyuria (nocturnal urine volume greater than 130% of maximum voided volume for age), and instead we propose the formula, nocturnal urine volume greater than 20 x (age + 9) ml., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We describe prolonged rectal manometry used to characterize rectal motor activity patterns and possible rectum-bladder interaction during defecation and micturition in children with nonneuropathic overactive bladder., Materials and Methods: We evaluated 10 children with a mean +/- SD age of 9.7 +/- 1.3 years with overactive bladder who underwent urodynamics and 24-hour rectal manometric recording. All records were analyzed visually. Rectal contractions were defined as pressure runs exceeding 5 cm H(2)O and lasting longer than 5 seconds., Results: Three rectal motility patterns were noted in all children, including 1) slow tonic pressure waves with a frequency of 3 to 12 per hour, b) rectal motor complexes with a frequency of 3 to 10 per minute and c) single contractions 10 to 30 seconds in duration. The median nocturnal duration of rectal motor complexes was longer than that during the day (16.3 minutes, range 10.8 to 18.8 vs 11.0, range 8.9 to 12.6, p <0.05). As a percent of time, median total contraction time was greater at night than during the day (51.9%, range 42.6% to 56.9% vs 30.6%, range 19.4% to 49.3%, p <0.05). Characteristic rectal activity was seen during defecation and voiding but no bladder-rectum interaction was detected., Conclusions: We identified 3 rectal motility patterns in all children with overactive bladder. Like the upper gastrointestinal tract, the rectum shows some periodic motor activity, which is more frequent at night. No association was observed between bladder and rectal activity during micturition and defecation.

Purpose: We studied the effect of transcutaneous electrical nerve stimulation in children with overactive bladder and treatment refractory daytime urinary incontinence., Materials and Methods: We recruited 27 children 5 to 14 years old with daytime urge incontinence refractory to timer assisted standard urotherapy and anticholinergics who had normal urinalysis, and unremarkable urinary tract ultrasound and physical examination. Study exclusion criteria were bladder underactivity, lower urinary tract obstruction, ongoing defecation disorders, lower urinary tract surgery and previous transcutaneous electrical nerve stimulation. After a 2-week run-in of standard urotherapy the children underwent natural fill ambulatory urodynamics to confirm detrusor overactivity. Subsequently they were randomly allocated to 4 weeks of 2 hours of daily active or placebo S2-S3 transcutaneous electrical nerve stimulation. The severity of incontinence and urgency, and 48-hour bladder diaries were recorded before randomization and during intervention week 4. Children withdrew from anticholinergics throughout the study period., Results: Two children were excluded from randomization due to urodynamic signs of lower urinary tract obstruction. After 4 weeks of intervention 8 children (61%) in the active group showed a significant decrease in incontinence severity but this occurred in only 2 (17%) in the sham treated group (p <0.05). The active group had a significantly greater decrease in daily incontinence episodes compared to the sham treated group (p <0.01). Transcutaneous electrical nerve stimulation did not alter maximal and average voided volumes., Conclusions: Sacral transcutaneous electrical nerve stimulation seems superior to placebo for refractory daytime incontinence in children with overactive bladder. This effect does not seem to be a consequence of improved bladder reservoir function.

Purpose: Daytime voiding frequency is an important criterion in the classification of childhood incontinence. The aim of this study was to assess the relative impact of diuresis and bladder capacity on voiding frequency., Materials and Methods: We analyzed data from 570 children 4 to 15 years old (median age 8.3 +/- 2.0 years) treated for urinary incontinence at a secondary referral center, and 87 healthy controls. Based on frequency-volume charts, daytime voiding frequency, age adjusted maximum voided volume, daytime diuresis and fluid intake were calculated. Children were classified according to voiding frequency into 3 groups-decreased (fewer than 3 voids daily), normal (3 to 7) and increased voiding frequency (more than 7)., Results: A total of 219 children had monosymptomatic enuresis, while 351 children presented with daytime symptoms. In children with daytime symptoms we found a significant difference between voiding frequency groups regarding daytime diuresis (decreased voiding frequency 12.3 +/- 4.1 ml/kg, normal 18.7 +/- 6.0 ml/kg, increased 31.1 +/- 9.8 ml/kg, p <0.001). In contrast, maximum voided volume observed/expected bladder capacity for age did not differ significantly between normal and increased frequency groups (72% +/- 25% vs 74% +/- 23%), compared to patients with decreased voiding frequency (89% +/- 30%, p <0.01). Also, in healthy children we found a positive correlation between voiding frequency and daytime diuresis, whereas maximum voided volume observed/expected bladder capacity for age did not correlate with voiding frequency. Furthermore, we observed a significant positive correlation between fluid intake and diuresis (r = 0.53, p <0.001)., Conclusions: In healthy controls and children with incontinence daytime voiding frequency depends mainly on diuresis, and seems less influenced by bladder capacity. Diuresis should be taken into consideration when evaluating voiding frequency from frequency-volume charts in children.

Purpose: We tested whether transverse rectal diameter measured by ultrasound could identify rectal impaction, investigated whether transverse diameter is enlarged in constipated children compared to healthy children and evaluated transverse diameter during treatment of constipation., Materials and Methods: A total of 51 children 4 to 12 years old were included in the study. Of the children 27 (mean age 7.0 +/- 1.8 years) had been diagnosed with chronic constipation by Rome III criteria and 24 (9.1 +/- 2.7 years) were healthy controls. All patients underwent a thorough medical history and physical examination, including digital rectal examination and measurement of rectal diameter by transabdominal ultrasound. Constipated children underwent repeat investigations after 4 weeks of laxative treatment., Results: Average rectal diameter of children with negative digital rectal examination was 21 +/- 4.2 mm (mean +/- SD), leading to the approximation that a value greater than 29.4 mm (mean +/- 2 SD) indicates rectal impaction. All children with rectal impaction identified by digital examination had a rectal diameter larger than 29.4 mm. Moreover, constipated children had a significantly larger rectal diameter (42.1 +/- 15.4 mm) than healthy children (21.4 +/- 6.0 mm, p <0.001). After 4 weeks of laxative treatment constipated children had a significant reduction in rectal diameter (mean 26.9 +/- 5.6 mm, p <0.001)., Conclusions: Transverse rectal diameter seems to be a valuable tool to identify rectal impaction and may replace digital rectal examination. Constipated children have a significantly larger rectal diameter compared to healthy children, and when constipation is treated the diameter is reduced significantly.

Purpose: We sought to evaluate the combination of the enuresis alarm and desmopressin in treating children with enuresis., Materials and Methods: A retrospective analysis was performed on data from 423 children treated at our clinics with the enuresis alarm during the years 2000 to 2004. Frequency volume charts and desmopressin titration facilitated characterization of the participants using the current International Children's Continence Society standardization. Children were treated with the enuresis alarm as monotherapy before the addition of desmopressin, which commenced after 6 weeks in patients exhibiting inadequate response to alarm or after 2 weeks in patients experiencing multiple enuretic episodes per night or showing no indication of improvement., Results: Of the initial population 315 children (74%) were treated only with alarm, of whom 290 became dry. A total of 108 children (26%) were treated with a combination of alarm and desmopressin, with 80 being cured. Children dry on alarm therapy were not different from those needing the addition of desmopressin in terms of demographics. Children dry on desmopressin plus alarm had higher average nocturnal urine production on wet nights (303 +/- 12 ml compared to 269 +/- 5 ml, p <0.001). Maximum voided volume before treatment corrected for age was not different between children dry on alarm and those dry on combination therapy (0.84 +/- 0.02 compared to 0.86 +/- 0.05, not significant)., Conclusions: Children needing the addition of desmopressin have a higher nocturnal urine production on wet nights but do not seem to differ in terms of bladder reservoir function characteristics.

Purpose: We investigated bladder reservoir function in children with monosymptomatic nocturnal enuresis and in healthy controls., Materials and Methods: A total of 18 children with monosymptomatic nocturnal enuresis and 119 controls who were 7 to 13 years old were recruited. Children completed frequency volume charts and measurements of nocturnal urine production. Mean diuresis in the period preceding each voiding was calculated. Those with enuresis were grouped according to bladder capacity and hospitalized for 4 nights, including a baseline night and 3 with an oral water load. Enuresis volumes and post-void residual volume were estimated, allowing the calculation of bladder volume at the time of enuresis., Results: Nine children with monosymptomatic nocturnal enuresis were characterized as having normal bladder capacity and 9 had decreased bladder capacity. We found large intra-individual variability in daytime voided volume in all 3 groups of participants. Children with enuresis and small bladder capacity generally voided with volumes close to maximal voided volume. A total of 93 enuresis episodes were recorded. Large intra-individual variability was seen in bladder volume at enuresis and it was lower than maximal voided volume in more than 50% of episodes. Variability in bladder volume at enuresis was greatest in the patient group with decreased bladder capacity. We found a significant correlation between diuresis and bladder capacity in all groups during the day and night., Conclusions: There is a great intra-individual diurnal variability in voided volume in children with enuresis and in healthy children. Enuresis seems to occur at bladder volumes that are smaller and larger than the maximal voided volume obtained from voiding charts.

Purpose: We investigated the role of urinary Ca excretion in monosymptomatic nocturnal enuresis, and defined normality and intra-individual variability in Ca excretion in healthy children., Materials and Methods: We included 46 Danish children with desmopressin resistant nocturnal enuresis and 96 healthy controls. We performed fractional urine collections at home during 2 days in controls or during hospitalization in children with enuresis. Urine volume, osmolality, and Ca and creatinine measurements were performed and Ca-to-creatinine ratios were calculated and compared between groups. Based on nocturnal urine output children with enuresis were characterized as having polyuria (nocturnal urine volume greater than 130% of expected bladder capacity) or not having polyuria., Results: We did not find any differences in controls compared with children with enuresis who did not and did have nocturnal polyuria in daytime Ca excretion (mean +/- SE 0.121 +/- 0.012, 0.078 +/- 0.014 and 0.095 +/- 0.020 mg/mg creatinine), nighttime Ca excretion (0.115 +/- 0.011, 0.092 +/- 0.019 and 0.139 +/- 0.029 mg/mg creatinine) or 24-hour Ca excretion (0.118 +/- 0.011, 0.083 +/- 0.014 and 0.106 +/- 0.020 mg/mg creatinine, respectively). Urinary Ca excretion was not influenced by patient age, sex or body weight and, furthermore, we did not find evidence of diurnal variation. However, we observed considerable intra-individual variability in diurnal, nocturnal and total 24-hour urinary Ca-to-creatinine ratios., Conclusions: These observations contradict several previous reports and speculations on a role of Ca in the pathogenesis of nocturnal enuresis.

Purpose: In adults and adolescents the transition from day to night is followed by a pronounced decrease in diuresis, as well as reduction in the amount of osmotically active substances excreted. We investigate the circadian variations in urine production in healthy children 3 to 14 years old., Materials and Methods: A total of 92 children completed urine collections in 2 consecutive days to be analyzed for electrolytes, urea, creatinine, osmolality, vasopressin and prostaglandin E2., Results: We found a marked reduction in urine output during the night (43.41 +/- 18.53 to 25.69 +/- 12.71 ml per hour) accompanied by a decrease in the amount of electrolytes excreted (sodium 4.44 +/- 2.09 to 2.66 +/- 1.55 mmol per hour and potassium 2.38 +/-0.96 to 0.90 +/- 0.54 mmol per hour). Age and gender did not influence the observed circadian rhythm in the quantity and quality of urine production. Urinary excretion of vasopressin did not seem to reflect the circadian variations previously described for the plasma levels of the hormone. Prostaglandin E2 showed a clear circadian variation with a 30% decrease at night (32.2 +/- 19.0 to 22.0 +/- 12.6 ng/mmol creatinine)., Conclusions: Healthy children exhibit pronounced circadian variations in the amount and composition of urine output with a decrease in nocturnal diuresis and excretion of osmotically active solutes. In the age range of 3 to 14 years neither age nor gender seems to affect this rhythm. Vasopressin-to-prostaglandin E2 excretion ratio appears to be of importance for regulation of urine production.

Purpose: We investigate the nature of enuresis episodes in monosymptomatic nocturnal enuresis using a fluid provocation model., Materials and Methods: The study included 18 children 7 to 13 years old with monosymptomatic nocturnal enuresis. Based on basal home recordings patients were subgrouped into those with a normal nocturnal urine output and those with nocturnal polyuria (mean nocturnal urine production on wet nights exceeding 130% of functional bladder capacity, normal functional bladder capacity for age provided). Children were admitted to the hospital for 4 consecutive nights. After an adaptation night all children received orally 25 ml/kg water, 30 minutes before bedtime on the remaining 3 nights. A cordless alarm device enabled registration of enuretic episodes from another room and diapers allowed the measurement of enuresis volumes. Post-void residual volumes were measured by ultrasound. Pelvic floor electromyography was continuously recorded throughout the night, and its association to bladder emptying was investigated., Results: A total of 95 enuresis and 14 nocturia episodes were recorded. Significantly more enuresis episodes were registered on nights with oral fluid load, whereas no increase in number of nocturia episodes was seen. Of the enuresis episodes 46 were associated with incomplete bladder emptying (post-void residual volume greater than 10% of total bladder volume at time of enuresis). No difference between patient groups regarding post-void residual volume was seen. Abnormal bursts of electromyography activity were associated with incomplete micturitions., Conclusions: Enuresis nocturna episodes in polyuric and nonpolyuric patients are frequently incomplete micturitions. The present findings question the definition of nocturnal enuresis episode as normal complete voiding.