Development of a Novel Prediction Tool for Response to First-Line Treatments of Monosymptomatic Nocturnal Enuresis-A Randomized, Controlled International Multicenter Study (DRYCHILD).

PURPOSE: Nocturnal urine volume and bladder reservoir function are key pathogenic factors behind monosymptomatic nocturnal enuresis (MNE). We investigated the predictive value of these together with other demographic and clinical variables for response to first-line treatments in children with MNE. MATERIALS AND METHODS: A randomized, controlled, international multicenter study was conducted in 324 treatment-naïve children (6-14 years) with primary MNE. The children were randomized to treatment with or without prior consideration of voiding diaries. In the group where treatment choice was based on voiding diaries, children with nocturnal polyuria and normal maximum voided volume (MVV) received desmopressin (dDAVP) treatment and children with reduced MVV and no nocturnal polyuria received an enuresis alarm. In the other group, treatment with dDAVP or alarm was randomly allocated. RESULTS: A total of 281 children (72% males) were qualified for statistical analysis. The change of responding to treatment was 21% higher in children where treatment was individualized compared to children where treatment was randomly selected (RR = 1.21 (1.02-1.45), P = .032). In children with reduced MVV and no nocturnal polyuria (35% of all children), individualized treatment was associated with a 46% improvement in response compared to random treatment selection (RR = 1.46 (1.14-1.87), P = .003). Furthermore, we developed a clinically relevant prediction model for response to dDAVP treatment (ROC 0.85). CONCLUSIONS: The present study demonstrates that treatment selection based on voiding diaries improve response to first line treatment, particularly in specific subtypes. Information from voiding diaries together with clinical and demographic information provides the basis for predicting response.

Discontinuing absorbent pants in children with bedwetting: a randomized controlled trial.

The objective of this study is to examine the effect of discontinuing wearing protective garments (absorbent pyjama pants - APP) in children with severe childhood nocturnal enuresis (NE). The study employs a multicenter, parallel, randomized controlled trial. Following a 4-week run-in period, participants were randomly allocated in a 2:1 group allocation to discontinue or continue using APP. The research was conducted across seven European pediatric incontinence centers. The study included treatment-naïve children aged 4-8 years with severe (7/7 wet nights per week) mono-symptomatic NE, who had used nighttime protection for at least 6 months prior to the study. The study consisted of a 4-week run-in period (± 7 days), where all children slept wearing APP (DryNites®). At week 4 (± 7 days), if meeting randomization criteria (7/7 wet nights during the last week of run-in), participants were randomized to continue to sleep in APP or to discontinue their use for a further 4 weeks, with the option of another 4 weeks in the extension period. The primary outcome was the difference between groups of wet nights during the last week of intervention. Quality of life (QoL) and sleep were secondary endpoints. In total, 105 children (43 girls and 62 boys, mean age 5.6 years [SD 1.13]) were randomized (no-pants group n = 70, pants group n = 35). Fifteen children (21%) in the no-pants group discontinued early due to stress related to the intervention. Children in the no-pants group experienced fewer wet nights compared to the pants group during the last week (difference 2.3 nights, 95% CI 1.54-3.08; p < 0.0001). In the no-pants group, 20% responded to the intervention, of whom 13% had a full response. Clinical improvement was detected within 2 weeks. Sleep and QoL were reported as negatively affected by APP discontinuation in the extension period but not in the core period.    Conclusion: A ~ 10% complete resolution rate was associated with discontinuing APP. While statistically significant, the clinical relevance is debatable, and the intervention should be tried only if the family is motivated. Response was detectable within 2 weeks. Discontinuing APP for 4-8 weeks was reported to negatively affect QoL and sleep quality. No severe side effects were seen.Trial registration: Clinicaltrials.gov Identifier: NCT04620356; date registered: September 23, 2020. Registered under the name: "Effect of Use of DryNites Absorbent Pyjama Pants on the Rate of Spontaneous Resolution of Paediatric Nocturnal Enuresis (NE)."

The genetics of incontinence: A scoping review.

The genetic causes underlying incontinence in both children and adults have begun to be unravelled during the last decades. The aim of this scoping review is to synthesize current knowledge on the genetics of childhood and adult urinary and faecal incontinence, identify similarities between different incontinence subgroups, and identify knowledge gaps to aid future research. PRISMA-ScR was used, and 76 studies were included. Early epidemiological family and twin studies suggest high heritability of incontinence. Linkage studies provide evidence for the existence of rare genetic variants; however, these variants have not been identified. Later candidate gene association studies and recent genome-wide association studies provide the first preliminary evidence that common risk variants also play a role. The genetics of incontinence in children and adults has predominantly been studied separately, but this review identifies for the first time the endothelin system as a potential common pathophysiological pathway. Overall, these findings strengthen the hypothesis that genetic variants play a prominent role in the pathogenesis of incontinence. Future research should include hypothesis-free studies of rare and common variants in large well-characterized cohorts with incontinence. Studies should include different age groups and ethnicities and both sexes to fully reveal the genetics of incontinence.

The effect of methylphenidate for giggle incontinence in children.

INTRODUCTION: Giggle incontinence (GI) is a rare form of urinary incontinence that occurs during or immediately after laughing due to involuntary and complete bladder emptying. Few studies in the literature report that methylphenidate can be effective in treatment of this condition. OBJECTIVE: The aim of this study is to characterize children with GI and evaluate their response to methylphenidate, as well as describe treatment duration, dosage of methylphenidate, relapse rates after discontinuation of medication, and side effects. METHODS: Medical records and 48-h frequency-volume charts from children treated with methylphenidate for GI in the period January 2011-July 2021 were retrospectively analyzed. RESULTS: Eighteen children were diagnosed with GI and fulfilled inclusion criteria. Fifteen patients were included in analysis, as 3 out of 18 children decided not to take the methylphenidate that was prescribed. In total, 14 out of the 15 GI patients treated with methylphenidate experienced clinical effect. All patients included in the study had methylphenidate prescribed in a dose range of 5-20 mg daily. Treatment duration ranged from 30 to 1001 days, with a median of 152 days (IQR 114, 243.5). Ten children experienced complete response and two of those reported symptom relapse after discontinuation of the methylphenidate. Only mild and short-lasting side effects were reported by two patients. DISCUSSION: Our study demonstrates that methylphenidate is an effective treatment in children diagnosed with GI. Side effects are mild and uncommon.

The role of renal circadian biorhythms in lifelong LUTS.

INTRODUCTION: This article delves into the intricate relationship between kidney function, diuresis, and lower urinary tract symptoms (LUTS) throughout the transitions of the human lifespan. It explores circadian regulation of urine production, maturation of renal function from birth to adulthood, and effects of aging on kidney function and LUTS. The complex connections between these factors are highlighted, offering insights into potential interventions and personalized management strategies. METHODS: An international panel of seven experts engaged in online discussions, focusing on kidney function, diuresis, and LUTS throughout life. This manuscript summarizes expert insights, literature reviews, and findings presented during a webinar and subsequent discussions. RESULTS: Renal function undergoes significant maturation from birth to adulthood, with changes in glomerular filtration rate, diuresis, and tubular function. A circadian rhythm in urine production is established during childhood. Adolescents and young adults can experience persistent enuresis due to lifestyle factors, comorbidities, and complex physiological changes. In older adults, age-related alterations in kidney function disrupt the circadian rhythm of diuresis, contributing to nocturnal polyuria and LUTS. CONCLUSION: The interplay between kidney function, diuresis, and LUTS is crucial in understanding lifelong urinary health. Bridging the gap between pediatric and adult care is essential to address enuresis in adolescents and young adults effectively. For older adults, recognizing the impact of aging on renal function and fluid balance is vital in managing nocturia. This holistic approach provides a foundation for developing innovative interventions and personalized treatments to enhance quality of life for individuals with LUTS across all stages of life.

Differences in the urinary metabolome and proteome between wet and dry nights in children with monosymptomatic nocturnal enuresis and nocturnal polyuria.

BACKGROUND: Nocturnal enuresis (NE) is a common disease with multiple pathogenic mechanisms. This study aimed to compare levels of metabolites and proteins between wet and dry nights in urine samples from children with monosymptomatic NE (MNE). METHODS: Ten boys with MNE and nocturnal polyuria (age: 7.6 ± 1.3 years) collected their total nighttime urine production during a wet and a dry night. Untargeted metabolomics and proteomics were performed on the urine samples by liquid chromatography coupled with high-mass accuracy tandem mass spectrometry (LC-MS/MS). RESULTS: On wet nights, we found reduced urine osmolality (P = 0.025) and increased excretion of urinary potassium and sodium by a factor of, respectively, 2.1 (P = 0.038) and 1.9 (P = 0.19) compared with dry nights. LC-MS identified 59 metabolites and 84 proteins with significantly different levels between wet and dry nights (fold change (FC) < 0.67 or > 1.5, P < 0.05). Some compounds were validated by different methodologies. During wet nights, levels of compounds related to oxidative stress and blood pressure, including adrenalin, were increased. We found reduced levels of aquaporin-2 on wet nights. The FCs in the 59 metabolites were positively correlated to the FCs in the same metabolites identified in urine samples obtained during the evening preceding wet and dry nights. CONCLUSIONS: Oxidative stress, which in the literature has been associated with nocturia and disturbances in sleep, might be increased during wet nights in children with MNE. We further found evidence of increased sympathetic activity. The mechanisms related to having wet nights in children with MNE seem complex, and both free water and solute handling appear to be important. A higher resolution version of the Graphical abstract is available as Supplementary information.

Functional constipation as a risk factor for pyelonephritis and recurrent urinary tract infection in children.

AIM: Acute pyelonephritis is one of the most common bacterial infections in childhood. This potentially serious condition can lead to renal scarring, loss of kidney function and hypertension. The aim of this study was to identify risk factors associated with pyelonephritis in children without kidney or urinary tract abnormalities. METHODS: Medical records of children aged 4-18 diagnosed with 1st time pyelonephritis from 2016 to 2021 were retrospectively analysed. Children with abnormal kidney ultrasound were excluded. In addition to demographic data, information on bladder and bowel function was extracted together with habits of fluid intake. RESULTS: A total of 105 patients were diagnosed with 1st time pyelonephritis. Of these, 47% were diagnosed with constipation according to the Rome IV criteria within a mean follow-up period of 167 days after their pyelonephritis, which is markedly higher than the estimated prevalence of constipation in the background population. Constipation was positively associated with recurrent urinary tract infection (p = 0.01). CONCLUSION: Constipation is associated with pyelonephritis and recurrent urinary tract infection in children (primarily girls) 4-18 years of age without evident kidney or urinary tract abnormalities. We recommend systematic evaluation of bowel and bladder function after 1st time pyelonephritis in all children >4 years.

Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study.

BACKGROUND: Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. METHODS: Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN). RESULTS: A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs -0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate-standard deviation score < -2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting. CONCLUSIONS: Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.

Transcutaneous electrical nerve stimulation as add-on therapy in children receiving anticholinergics and/or mirabegron for refractory daytime urinary incontinence: A retrospective cohort study.

AIMS: To investigate if children with daytime urinary incontinence (DUI) and overactive bladder (OAB) refractory to standard urotherapy and medicinal treatment, would experience improvement in symptoms after add-on treatment with transcutaneous electrical nerve stimulation (TENS). METHODS: Children were retrospectively enrolled from tertiary referral centers at Aarhus and Aalborg University Hospitals. All data were retrieved from the patients' journals. All children were prescribed TENS as an add-on treatment to the highest-tolerable dose of medicinal treatment in a standardized regime of 2 h a day for around 3 months. Primary endpoints were the number of wet days per week (WDPW) and incontinence episodes per day. Effect of treatment was defined as greater or equal to 50% reduction in the frequency of DUI episodes. Secondary endpoints were to establish predictive factors for the effect of treatment using logistic regression. RESULTS: Seventy-six children diagnosed with DUI and OAB refractory to treatment with standard urotherapy and pharmacological treatment, at the age of 5-16 years were included from February 2017 to February 2020. A reduction in WDPW (from 6.31 [5.86-6.61] to 4.27 [3.45-4.90], p < 0.05) and incontinence episodes per day (from 2.45 [1.98-2.91] to 1.43 [1.07-1.80], p < 0.05) was observed. Twelve patients became completely dry. At 6 months follow-up, seven of the 12 complete responders had relapsed while five remained dry. A history of constipation before TENS was a predictor of poor treatment response (p = 0.016). CONCLUSIONS: TENS as add-on to anticholinergic treatment seems effective in a number of children with treatment-refractory DUI.

Pitfalls in Diagnosing Urinary Tract Infection in Children below the Age of 2: Suprapubic Aspiration vs Clean-Catch Urine Sampling.

PURPOSE: Reliable urine samples are of eminent importance when diagnosing urinary tract infections (UTIs) in children. Noninvasive procedures are convenient but likely to be contaminated. This study aimed to compare the diagnostic accuracy of urine samples obtained by the midstream clean-catch method (CCU) to urine obtained by suprapubic aspiration (SPA) and to evaluate the ability of urinary dipstick to predict true infection. MATERIALS AND METHODS: Retrospectively, data on children <2 years of age seen at our center for suspicion of UTI who had a CCU and a SPA performed the same day were included. Any growth in SPA was considered significant, whereas for CCU we tested 2 cutoff values of 104 and 105 CFU/ml, along with urinary dipstick results. RESULTS: A total of 223 children were included. Using a cutoff of ≥104 CFU/ml, 16.6% of the cohort (37 cases) would be misdiagnosed if relying only on CCU. Using ≥105 CFU/ml, the rate was 24.6% (55 cases). Evaluating leukocyte esterase on urinary dipstick, a large difference between using CCU (sensitivity 94.7%, specificity 14.4%) and SPA (sensitivity 78.9%, specificity 82.2%) became obvious. CONCLUSIONS: A large number of children will be misdiagnosed if relying on CCU specimens compared to SPA. Relying on a negative leukocyte esterase dipstick test to rule out a UTI is not sufficient in a child with high suspicion of such an infection. SPA is a safe procedure, and we thus recommend its use to avoid delay of treatment and unnecessary invasive followup investigations.

Risk factors for kidney scarring and vesicoureteral reflux in 421 children after their first acute pyelonephritis, and appraisal of international guidelines.

BACKGROUND: Acute pyelonephritis (AP) is a common bacterial infection in childhood. Follow-up guidelines on these children are controversial. This study aimed to identify risk factors for kidney scarring and vesicoureteral reflux (VUR). Furthermore, international follow-up guidelines were used for simulation to evaluate sensitivity and specificity. METHODS: Urinary culture-confirmed first-time AP patients (aged 0-14 years) were enrolled (n = 421) from review of patient charts. All underwent kidney ultrasound (US) and a technetium-99m-dimercaptosuccinic acid (DMSA) scan or technetium-99m-mercaptoacetyltriglycine scinti-renography (MAG3) at 4-6 months of follow-up. The international guidelines used for simulation were from the National Institute of Health UK (NICE), the American Association of Paediatrics (AAP) and the Swedish Paediatric Society (SPS). RESULTS: 17.8% presented with an abnormal DMSA/MAG3 at follow-up, 7.1% were diagnosed with VUR grades III-V and 4.7% were admitted for surgery. Non-Escherichia coli infections, abnormal kidney US, elevated creatinine and delayed response to treatment (>48 h) were risk factors for abnormal DMSA findings and VUR grades III-V. NICE and SPS guidelines showed best sensitivity in diagnosing VUR grades III-V (75%) compared with AAP (56%). CONCLUSIONS: Risk factors are helpful in identifying the children in need of further investigations and minimizing invasive work-up for the rest. International guidelines on follow-up detect a varying number of children with kidney damage and/or significant VUR. Future work must focus on identifying more specific risk factors, better imaging, or specific biomarkers, to enhance sensitivity and specificity in detecting the children at high risk for developing recurrent infections and/or nephropathy.

Dissatisfaction with school toilets is associated with bladder and bowel dysfunction.

Poor quality of school toilets is reportedly an issue in many countries and has been correlated with toilet refusal in children. The aim of this study was to evaluate the association between perceived school toilet quality, behaviour regarding toilet visits, and symptoms of bladder and bowel dysfunction (BBD). Pupils in Danish schools were invited to complete online questionnaires regarding toilet behaviour, perception of school toilet standards/quality, and symptoms of BBD. Teachers at the same schools were asked about the quality of the toilets. We recruited 19,577 children from 252 different schools. More than half of the children (50% boys and 60% girls) were dissatisfied with the toilet facilities. One-fourth of the children (28% of girls, 23% of boys) reported avoiding the use of school toilets. We found a strong correlation between being dissatisfied with school toilets, toilet avoidance, and symptoms of BBD.Conclusion: The majority of Danish children are unhappy with their school toilet facilities. Symptoms of BBD are associated with subjective toilet dissatisfaction and toilet visit postponement. Because children spend a significant part of their day at school, access to satisfactory toilet facilities is of utmost importance for their well-being. What is Known • Bladder and bowel dysfunction is common in childhood with urinary incontinence, constipation, and faecal incontinence being cardinal symptoms. • Behaviour regarding toilet visits contributes to the aetiology, and we know that toilet avoidance can lead to abnormal bladder and bowel function. What is New • Most children are not satisfied with their school toilets, and many avoid toilet visits. • Dissatisfaction with the school toilets is related to toilet avoidance and bladder and bowel dysfunction in school children regardless of age and gender.

Children with acute pyelonephritis need medical re-evaluation when home-treated with oral antibiotics.

AIM: To investigate the efficacy and safety of home-treatment with oral piv-mecillinam or amoxicillin-clavulanate in children with acute pyelonephritis. METHODS: Children aged over 6 months diagnosed with culture confirmed pyelonephritis at Danish Paediatric Departments were home-treated with piv-mecillinam (tablets) or amoxicillin-clavulanate (liquid or tablets). Follow-up was performed by phone (second treatment day) and clinical review of the patients in the hospital (day three). RESULTS: Four hundred eighteen children were included. In total, 333/418 (80%) responded well to the initial oral antibiotic treatment. 85/418 (20%) were changed to another treatment of these 47/418 (11%) to a second-line oral antibiotic and 38/418 (9%) to intravenous antibiotics due to insufficient clinical improvement or bacterial resistance. Bacterial resistance was similar for piv-mecillinam and amoxicillin-clavulanate: 4/74 (5%) versus 33/333 (10%) (p = 0.22). Insufficient clinical improvement, despite no resistance, primarily occurred in children treated with piv-mecillinam: 16/74 (22%) versus 28/344 (8%) (p < 0.001), and predominantly occurred in piv-mecillinam treated children <5 years: 7/20 (35%) versus 9/54 (17%) (p < 0.05), potentially because of problems with piv-mecillinam tablets. In the study population no cases of death or septicemia developed after start of initial oral treatment. CONCLUSION: A home-treatment regime for pyelonephritis in children >6 months is safe; however, during treatment, clinical re-evaluation is required as in 20% of cases a change in treatment was necessary.

Novel and recurrent variants in AVPR2 in 19 families with X-linked congenital nephrogenic diabetes insipidus.

Congenital nephrogenic diabetes insipidus (CNDI) is characterized by the reduced ability of renal collecting duct cells to reabsorb water in response to the antidiuretic effect of vasopressin. Chronic polyuria and polydipsia are the hallmarks of the disease. Approximately 90% of all patients with CNDI have X-linked inherited disease caused by variants in the arginine vasopressin receptor 2 (AVPR2) gene. We present genetic findings in 34 individuals from 19 kindreds including one or more family members with CNDI. Coding regions of AVPR2 were sequenced bi-directionally. We identified eight novel disease-causing variants in AVPR2, p.Arg68Alafs*124, p.Ser171Arg, p.Gln174Pro, p.Trp200Arg, p.Gly201Cys, p.Gly220Arg, p.Val226Glu, and p.Gln291Pro in nine kindreds. In all three families with more than one affected individual, the novel variants segregated with the disease. We also identified eight recurrent disease-causing variants, p.Val88Met, p.Leu111Valfs*80, p.Arg113Trp, p.Tyr124*, p.Ser167Leu, p.Thr207Asn, p.Arg247Alafs*12, and p.Arg337* in ten kindreds. Our findings contribute to the growing list of AVPR2 variants causing X-linked CNDI. CONCLUSION: Being a rapid diagnostic tool for CNDI, direct sequencing of AVPR2 should be encouraged in newborns with familial predisposition to CNDI. What is Known: • Disease-causing variants in AVPR2 cause X-linked congenital nephrogenic diabetes insipidus (CNDI). • DNA sequencing of AVPR2 is rapid, facilitates differential diagnosis, early intervention, and genetic diagnosis thus reducing morbidity in CNDI. What is New: • We identified eight novel disease-causing variants in AVPR2: p.Arg68Alafs*124, p.Ser171Arg, p.Gln174Pro, p.Trp200Arg, p.Gly201Cys, p.Gly220Arg, p.Val226Glu, and p.Gln291Pro, thereby adding to the growing list of AVPR2 disease-causing variants and emphasizing the importance of genetic testing in CNDI.

Determination of the renal concentration capacity following intravenous administration of dDAVP in healthy humans.

The synthetic AVP analogue 1-desamino-8-d-arginine-vasopressin (dDAVP) is used for treatment of polyuric disorders. Lack of commercially available assays limits the usefulness of dDAVP as a diagnostic tool in the assessment of renal concentrating capacity. We aimed to develop a specific radioimmunoassay (RIA) for determination of plasma dDAVP (pdDAVP) in order to investigate the relationship between pdDAVP levels and urine osmolality (Uosm). Further, we aimed to determine the onset, duration, and maximum concentrating capacity following intravenous (i.v.) bolus dDAVP injection. The dDAVP assay was based on a well-established RIA for measurements of AVP. Fourteen healthy subjects (aged 15-18 years) participated. Blood and urine samples were collected prior to and after i.v. bolus of 0.03 µg/kg dDAVP. Diuresis and Uosm was measured for nine hours following dDAVP administration. PdDAVP and Uosm were analyzed.We established a specific RIA for the measurement of pdDAVP. All subjects reached maximal pdDAVP concentration (Cmax) 30 minutes following infusion, and a rise in Uosm after 60 minutes. Maximal Uosm varied between subjects, with no direct correlation to the achieved pdDAVP levels. We found no significant intra-individual variation between two dDAVP infusions and the effect was reproducible in terms of Cmax and maximal Uosm. We characterized the relationship between pdDAVP and Uosm after dDAVP bolus injection in healthy adolescents using our dDAVP assay. Maximal Uosm achieved correlated with the baseline Uosm levels and seemed unrelated to achieved pdDAVP levels. The urine concentrating response was maintained at least eight hours.

Transcutaneous Electrical Nerve Stimulation in Children with Monosymptomatic Nocturnal Enuresis: A Randomized, Double-Blind, Placebo Controlled Study.

PURPOSE: In a third of all children with monosymptomatic nocturnal enuresis their condition is refractory to first line treatments. Transcutaneous electrical nerve stimulation has been documented to be efficacious in children with daytime incontinence. We investigated the effect of transcutaneous electrical nerve stimulation in children with monosymptomatic nocturnal enuresis without nocturnal polyuria. MATERIALS AND METHODS: Children with monosymptomatic nocturnal enuresis (3 or more wet nights per week) and no nocturnal polyuria were randomized to treatment with active or sham transcutaneous electrical nerve stimulation involving 1-hour sessions twice daily for 10 weeks in a double-blind design. RESULTS: Of the 52 children with monosymptomatic nocturnal enuresis included in the study 47 completed treatment (mean age 9.5 ± 2.1 years, 38 males). None of the children experienced a full response with complete remission of enuresis. Treatment with transcutaneous electrical nerve stimulation did not lead to significant changes in number of wet nights, nocturnal urine production on wet or dry nights, maximum voided volume with and without first morning voided volume, or voiding frequency when comparing parameters before and after treatment. CONCLUSIONS: The present study demonstrates no anti-enuretic effect of transcutaneous electrical nerve stimulation in children with monosymptomatic nocturnal enuresis without nocturnal polyuria. Nocturnal urine production and bladder capacity remained unchanged during and after treatment with transcutaneous electrical nerve stimulation.

Transcutaneous Electrical Nerve Stimulation Combined with Oxybutynin is Superior to Monotherapy in Children with Urge Incontinence: A Randomized, Placebo Controlled Study.

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.

No immediate effect on urodynamic parameters during transcutaneous electrical nerve stimulation (TENS) in children with overactive bladder and daytime incontinence-A randomized, double-blind, placebo-controlled study.

AIM: To evaluate the immediate effect on natural fill urodynamic parameters and bladder function during transcutaneous electrical nerve stimulation (TENS) in children with overactive bladder (OAB) and daytime urinary incontinence (DUI). MEETHODS: In this double-blind, placebo-controlled study, 24 children with severe OAB and DUI (mean age 8.5 ± 1.2 years) underwent 48-h natural fill urodynamics. After 24 h of baseline investigation, the children were randomized to either active continuous TENS (n = 12) or placebo TENS (n = 12) over the sacral S2-S3 outflow. The urodynamic recordings were analyzed manually for three different bladder contraction patterns resulting in a void. The number of bladder contractions not leading to a void was also calculated. Maximum voided volume (MVV) and average voided volume (AVV) were identified for both the baseline and the intervention day. RESULTS: We found that TENS had no immediate objective effect on bladder capacity. The difference (before minus after treatment) in MVV/EBC in the active TENS group = 0.03 ± 0.23 versus placebo TENS group = -0.01 ± 0.10 (P = 0.61). Also, there was no significant difference in the proportion of different bladder contraction types between the two groups. TENS did not significantly influence the number of bladder contractions not leading to a void. Results are presented as mean ± SD. CONCLUSION: There is no immediate objective effect of TENS on bladder activity assessed by natural fill urodynamics in children with OAB and DUI.

Optimizing response to desmopressin in patients with monosymptomatic nocturnal enuresis.

Most patients with monosymptomatic nocturnal enuresis can be effectively treated with an enuresis alarm or antidiuretic therapy (desmopressin), depending on the pathophysiology of the condition in the individual patient. Desmopressin is first-line therapy for enuresis caused by nocturnal polyuria, an excessive urine output during the night. However, in a recent study, around one-third of patients thought to be resistant to desmopressin were subsequently treated effectively with desmopressin monotherapy in a specialist centre. The aim of this article is to review best practice in selecting patients for desmopressin treatment, as well as outline eight recommendations for maximizing the chances of treatment success in patients receiving desmopressin. The roles of formulation, dose, timing of administration, food and fluid intake, inter-individual variation in response, body weight, adherence, withdrawal strategies and combination therapies are discussed in light of the most recent research on desmopressin and enuresis. Possible reasons for suboptimal treatment response are explored and strategies to improve outcomes in patients for whom desmopressin is an appropriate therapy are presented. Through optimization of the treatment plan in primary and specialist care centres, the hope is that fewer patients with this distressing and often embarrassing condition will experience unnecessary delays in receiving appropriate care and achieving improvements.

Combination treatment of nocturnal enuresis with desmopressin and indomethacin.

BACKGROUND: We investigated the effect of combining indomethacin and desmopressin in treating children with monosymptomatic nocturnal enuresis (MNE) and desmopressin-resistant nocturnal polyuria. METHODS: Twenty-three children with MNE, nocturnal polyuria, and partial or no response to desmopressin were recruited from incontinence clinics of our tertiary referral center. We used a randomized single-arm crossover placebo-controlled study design consisting of two 3-week treatment periods with a combination of desmopressin (0.4 mg) and indomethacin (50 mg) or desmopressin and placebo at bedtime. Home recordings at baseline and for the final 2 weeks of each treatment period were performed and included nocturnal urine output measurements. The number of dry nights achieved and reduction in the nocturnal urine output were the main effect parameters. Student's t test and Pearson's correlation coefficient were used for statistical analysis. RESULTS: The addition of indomethacin to desmopressin significantly reduced nocturnal urine output (from 324 ± 14 ml to 258 ± 13 ml, p < 0.001). This did not lead to more dry nights in all children, and we found no statistically significant reduction in enuresis frequency (from 68 % ± 0.1 to 56 % ± 0.1, p = 0.24). CONCLUSIONS: Addition of indomethacin to desmopressin can further reduce nocturnal urine output in children with MNE and desmopressin-resistant nocturnal polyuria. The combination treatment does not, however, improve outcome in terms of frequency of nights with enuresis. The dissociation of antidiuretic and antienuretic effect may reflect nocturnal bladder reservoir dysfunction in children who present with normal daytime bladder function.