Oral versus intravenous empirical antibiotics in children and adolescents with uncomplicated bone and joint infections: a nationwide, randomised, controlled, non-inferiority trial in Denmark.

BACKGROUND: Bone and joint infections (BJIs) are treated with intravenous antibiotics, which are burdensome and costly. No randomised controlled studies have compared if initial oral antibiotics are as effective as intravenous therapy. We aimed to investigate the efficacy and safety of initial oral antibiotics compared with initial intravenous antibiotics followed by oral antibiotics in children and adolescents with uncomplicated BJIs. METHODS: From Sept 15, 2020, to June 30, 2023, this nationwide, randomised, non-inferiority trial included patients aged 3 months to 17 years with BJIs who presented to one of the 18 paediatric hospital departments in Denmark. Exclusion criteria were severe infection (ie, septic shock, the need for acute surgery, or substantial soft tissue involvement), prosthetic material, comorbidity, previous BJIs, or antibiotic therapy for longer than 24 h before inclusion. Patients were randomly assigned (1:1), stratified by C-reactive protein concentration (<35 mg/L vs ≥35 mg/L), to initially receive either high-dose oral antibiotics or intravenous ceftriaxone (100 mg/kg per day in one dose). High-dose oral antibiotics were coformulated amoxicillin (100 mg/kg per day) and clavulanic acid (12·5 mg/kg per day) in three doses for patients younger than 5 years or dicloxacillin (200 mg/kg per day) in four doses for patients aged 5 years or older. After a minimum of 3 days, and upon clinical improvement and decrease in C-reactive protein, patients in both groups received oral antibiotics in standard doses. The primary outcome was sequelae after 6 months in patients with BJIs, defined as any atypical mobility or function of the affected bone or joint, assessed blindly, in all randomised patients who were not terminated early due to an alternative diagnosis (ie, not BJI) and who attended the primary outcome assessment. A risk difference in sequelae after 6 months of less than 5% implied non-inferiority of the oral treatment. Safety outcomes were serious complications, the need for surgery after initiation of antibiotics, and treatment-related adverse events in the as-randomised population. This trial was registered with ClinicalTrials.gov, NCT04563325. FINDINGS: 248 children and adolescents with suspected BJIs were randomly assigned to initial oral antibiotics (n=123) or initial intravenous antibiotics (n=125). After exclusion of patients without BJIs (n=54) or consent withdrawal (n=2), 101 patients randomised to oral treatment and 91 patients randomised to intravenous treatment were included. Ten patients did not attend the primary outcome evaluation. Sequelae after 6 months occurred in none of 98 patients with BJIs in the oral group and none of 84 patients with BJIs in the intravenous group (risk difference 0, one-sided 97·5% CI 0·0 to 3·8, pnon-inferiority=0·012). Surgery after randomisation was done in 12 (9·8%) of 123 patients in the oral group compared with seven (5·6%) of 125 patients in the intravenous group (risk difference 4·2%, 95% CI -2·7 to 11·5). We observed no serious complications. Rates of adverse events were similar across both treatment groups. INTERPRETATION: In children and adolescents with uncomplicated BJIs, initial oral antibiotic treatment was non-inferior to initial intravenous antibiotics followed by oral therapy. The results are promising for oral treatment of uncomplicated BJIs, precluding the need for intravenous catheters and aligning with the principles of antimicrobial stewardship. FUNDING: Innovation Fund Denmark and Rigshospitalets Forskningsfond.

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)."

Prevalence, Safety, and Metabolic Control Among Danish Children and Adolescents with Type 1 Diabetes Using Open-Source Automated Insulin Delivery Systems.

Background: Treatment of type 1 diabetes mellitus (T1DM) has become increasingly technical with rapid developments in integration of pumps and sensors to regulate insulin dosage, and patient-initiated solutions as open-source automated insulin delivery (OS-AID) systems, have gained popularity in people with diabetes. Studies have shown increased glycemic control and mental wellbeing in users of OS-AID systems. The aim of this study was to estimate the prevalence, the effect on metabolic control, the risk, and the effect on everyday life for users and their parents of OS-AID systems in Danish children and adolescents with T1DM. Methods: This retrospective cohort study recruited participants through pediatric diabetes outpatient clinics and social media. Surveys were distributed and current and retrospective data on glycemic control (HbA1c, time in range [TIR] etc.) were collected. Results: Fifty-six users of OS-AID systems out of 2950 Danish children and adolescents with T1DM were identified from all outpatient clinics in Denmark. Thirty-one responded on contact and were included (55% of the identified), median age 12 [interquartile range: 11-14] years, 51% females, and mean duration of use of OS-AID systems 2.37 ± 0.86 years. Glycemic control increased significantly with TIR increasing from mean 62.29% ± 13.68% to 70.12% ± 10.08%, *P < 0.01, and HbA1c decreasing from mean 50.13 ± 5.76 mmol/mol (6.7% ± 2.7%) to 47.86 ± 6.24 mmol/mol (6.5% ± 2.7%), **P < 0.05. No changes were found in safety parameters. Parents reported better quality of sleep evaluated by Pittsburgh Sleep Quality Index. Conclusion: This study is the first to provide knowledge on pediatric users of OS-AID systems in Denmark and found a prevalence of 1.89% for OS-AID systems, improved TIR, and no increased risk associated with use of OS-AID systems.

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.

Oral-only antibiotics for bone and joint infections in children: study protocol for a nationwide randomised open-label non-inferiority trial.

INTRODUCTION: Children with bone and joint infections are traditionally treated with intravenous antibiotics for 3-10 days, followed by oral antibiotics. Oral-only treatment has not been tested in randomised trials. METHODS AND ANALYSIS: Children (3 months to 18 years) will be randomised 1:1 with the experimental group receiving high-dose oral antibiotics and the control group receiving intravenous antibiotics with a shift in both groups to standard oral antibiotics after clinical and paraclinical improvement. Children in need of acute surgery or systemic features requiring intravenous therapy, including septic shock, are excluded. The primary outcome is defined as a normal blinded standardised clinical assessment 6 months after end of treatment. Secondary outcomes are non-acute treatment failure and recurrent infection. Outcomes will be compared by a non-inferiority assumption with an inferiority margin of 5%. ETHICS AND DISSEMINATION: The trial has the potential to reduce unnecessary hospitalisation and use of intravenous antibiotics in children with bone or joint infections. Due to the close follow-up, exclusion of severely ill children and predefined criteria for discontinuation of the allocated therapy, we expect the risk of treatment failure to be minimal. TRIAL REGISTRATION NUMBER: NCT04563325.

GFR measurements and ultrasound findings in 154 children with a congenital solitary functioning kidney.

BACKGROUND: Multicystic dysplastic kidney (MCDK) and unilateral renal agenesis (URA) are the most common reasons for a congenital solitary functioning kidney (SFK). We aimed to assess the presence of abnormalities in the congenital SFK and evaluate kidney function using chrome EDTA (CrEDTA) measurements. METHODS: We retrospectively reviewed the medical records of 154 children with MCDK and URA in the period from 2005 to 2022 to analyze results from ultrasound scans and CrEDTA glomerular filtration rate (GFR) examinations. RESULTS: Of 154 children with a solitary kidney due to MCDK (62%) or URA (38%), abnormalities on the congenital SFK were found in 13 children (8%). The abnormalities spontaneously resolved in 6 children (46%). The most common abnormality was hydronephrosis. Compensatory hypertrophy was found in 17% of the children within the first 6 months of life. 116 children (90%) had a standard GFR (sdGFR) above 75% of expected for the age. Out of those with a sdGFR below 75% of expected, 3 (23%) had abnormalities in the congenital SFK. There was no difference in sdGFR between children with MCDK and URA. CONCLUSIONS: Our study is the first using CrEDTA for GFR measurements and suggests that most children with a congenital SFK due to MCDK or URA have a kidney function within expected for the age. Compensatory hypertrophy of the SFK is found in a minority of children within the first six months of life, suggesting that this process is developing over time. The prevalence of abnormalities in the SFK seems low, however those with abnormalities (e.g. hydronephrosis) are at higher risk of reduced sdGFR.

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.

Epidemiology and diagnostic trends of congenital adrenal hyperplasia in Denmark: a retrospective, population-based study.

Background: The prevalence of newborns with congenital adrenal hyperplasia (CAH) detected by neonatal screening is well-described, but data including patients diagnosed later in life are extremely limited. This study aimed to describe diagnostic trends for all patients with CAH in Denmark. Methods: A nationwide population-based registry study including medical record review. Findings: We identified 462 patients (290 females) with any form of CAH. The prevalence of CAH combined was 15.1 (95% confidence interval [CI]: 12.3-16.1) and 9.0 (CI: 7.6-10.4) per 100,000 newborn females and males. There was a prevalence of salt-wasting (SW), simple-virilizing (SV), and non-classic (NC) CAH due to 21-hydroxylase deficiency of: SW-CAH: 6.4 (CI: 5.3-7.6) and 5.6 (CI: 4.6-6.8); SV-CAH: 2.0 (CI: 1.4-2.8) and 1.6 (CI: 1.0-2.7); and NC-CAH: 5.5 (CI: 4.4-6.9) and 2.5 (CI: 1.7-3.7) per 100,000 newborn females and males, respectively. Diagnosis of NC-CAH increased significantly during the course of the study. There was a female preponderance for SV-CAH (ratio: 1.8) and NC-CAH (ratio: 3.2). Median age at diagnosis, females and males respectively: SW-CAH: 4 (interquartile range [IQR]: 0-11) and 14 (IQR: 8-24) days, SV-CAH: 3.1 (IQR: 1.2-6.6) and 4.8 (IQR: 3.2-6.9) years, and NC-CAH: 15.5 (IQR: 7.9-22.5) and 9.4 (IQR: 7.2-23.2) years. Interpretation: The combined prevalence of CAH was 15.1 and 9.0 per 100,000 newborn females and males, respectively. The female preponderance was primarily due to diagnosis of more females than males with NC-CAH. Funding: International Fund of Congenital Adrenal Hyperplasia, Health Research Fund of Central Denmark Region, Aase and Einar Danielsen Fund, and "Fonden til Lægevidenskabens Fremme".

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.

Long COVID symptoms and duration in SARS-CoV-2 positive children - a nationwide cohort study.

Most children have a mild course of acute COVID-19. Only few mainly non-controlled studies with small sample size have evaluated long-term recovery from SARS-CoV-2 infection in children. The aim of this study was to evaluate symptoms and duration of 'long COVID' in children. A nationwide cohort study of 37,522 children aged 0-17 years with RT-PCR verified SARS-CoV-2 infection (response rate 44.9%) and a control group of 78,037 children (response rate 21.3%). An electronic questionnaire was sent to all children from March 24th until May 9th, 2021. Symptoms lasting > 4 weeks were common among both SARS-CoV-2 children and controls. However, SARS-CoV-2 children aged 6-17 years reported symptoms more frequently than the control group (percent difference 0.8%). The most reported symptoms among pre-school children were fatigue Risk Difference (RD) 0.05 (CI 0.04-0.06), loss of smell RD 0.01 (CI 0.01-0.01), loss of taste RD 0.01 (CI 0.01-0.02) and muscle weakness RD 0.01 (CI 0.00-0.01). Among school children the most significant symptoms were loss of smell RD 0.12 (CI 0.12-0.13), loss of taste RD 0.10 (CI 0.09-0.10), fatigue RD 0.05 (CI 0.05-0.06), respiratory problems RD 0.03 (CI 0.03-0.04), dizziness RD 0.02 (CI 0.02-0.03), muscle weakness RD 0.02 (CI 0.01-0.02) and chest pain RD 0.01 (CI 0.01-0.01). Children in the control group experienced significantly more concentration difficulties, headache, muscle and joint pain, cough, nausea, diarrhea and fever than SARS-CoV-2 infected. In most children 'long COVID' symptoms resolved within 1-5 months. CONCLUSIONS: Long COVID in children is rare and mainly of short duration. WHAT IS KNOWN: • There are increasing reports on 'long COVID' in adults. • Only few studies have evaluated the long-term recovery from COVID-19 in children, and common for all studies is a small sample size (median number of children included 330), and most lack a control group. WHAT IS NEW: • 0.8% of SARS-CoV-2 positive children reported symptoms lasting >4 weeks ('long COVID'), when compared to a control group. • The most common 'long COVID' symptoms were fatigue, loss of smell and loss of taste, dizziness, muscle weakness, chest pain and respiratory problems. • These 'long COVID' symptoms cannot be assigned to psychological sequelae of social restrictions. • Symptoms such as concentration difficulties, headache, muscle- and joint pain as well as nausea are not 'long COVID' symptoms. • In most cases 'long COVID' symptoms resolve within 1-5 months.

Center differences in diabetes treatment outcomes among children with type 1 diabetes: A nationwide study of 3866 Danish children.

OBJECTIVE: Mean differences in HbA1c across centers are well established, but less well understood. The aim was to assess whether differences in patient case-mix can explain the variation in mean HbA1c between pediatric diabetes centers in Denmark. The association between HbA1c , frequency of blood glucose monitoring (BGM), treatment modality, and center visits was investigated. RESEARCH DESIGN AND METHODS: This longitudinal nationwide study included 3866 Danish children with type 1 diabetes from 2013 to 2017 (n = 12,708 child-year observations) from 16 different pediatric diabetes centers. Mean HbA1c , proportion of children reaching HbA1c treatment target (HbA1c  ≤ 58 mmol/mol [7.5%]) were compared across centers using linear regression models. This was done with and without adjustment for socioeconomic characteristics (patient case-mix). RESULTS: The mean difference in HbA1c during follow-up was 11.6 mmol/mol (95% CI 7.9, 15.3) (1.1% [95% CI 0.7, 1.4]) when comparing the centers with the lowest versus highest mean HbA1c . The difference was attenuated and remained significant after adjustment for the patient case-mix (difference: 10.5 mmol/mol [95% CI 6.8, 14.2] (1.0% [95% CI 0.6, 1.3])). Overall, 6.8% of the differences in mean HbA1c across centers were explained by differences in the patient case-mix. Across centers, more frequent BGM was associated with lower HbA1c . The proportion of insulin pump users and number of visits was not associated with HbA1c . CONCLUSION: In a setting of universal health care, large differences in HbA1c across centers were found, and could not be explained by patient background, number of visits or use of technology. Only BGM was associated with center HbA1c .

Comparison and characteristics of children successfully treated for daytime urinary incontinence.

INTRODUCTION: Daytime urinary incontinence (DUI) is defined as an involuntary leakage of urine during daytime in children 5 years or older. It is a common disorder in the pediatric population most often caused by an overactive bladder (OAB). A stepwise approach is recommended in the treatment of DUI, with standard urotherapy (SU) being first line treatment followed by pharmacological treatment when SU is unsuccessful. To our knowledge few studies have compared patients achieving continence solely on urotherapy with patients achieving continence on a combination of urotherapy and pharmacological treatment in the pediatric population. OBJECTIVE: The aim of the study was to characterize and compare children suffering from OAB and DUI who became continent solely on urotherapy with patients achieving continence on a combination of urotherapy and pharmacological treatment. METHODS: All children successfully treated for DUI from 2015 to 2020 were retrospectively analyzed and compared using data from patient's records, 48-h flow-volume charts, and uroflowmetry analysis. RESULTS: 180 children were successfully treated for DUI. Of these 23 (13%) had bowel dysfunction, 94 (52%) were successfully treated with standard urotherapy (SU) and 64 (35%) needed pharmacological treatment. Children who achieved continence on a combination of SU and pharmacological treatment had a significantly higher baseline voiding frequency (7.6 and 6.5 respectively, p=0.007) and more baseline incontinence episodes during daytime when compared to children who became dry solely on urotherapy (2.2 and 1.1 respectively, p < 0.001). Both groups had a similar baseline age (p=0.96) and received a similar duration of standard urotherapy prior to the eventual pharmacological treatment (p = 0.73). DISCUSSION: Most children achieved daytime continence solely on standard urotherapy. We found that children requiring additional pharmacological treatment to achieve continence suffer from a more severe overactive bladder. As such it could be speculated that children with high voiding frequencies and multiple daily incontinence episodes may benefit from adding anticholinergics to SU earlier during the course of treatment, than what is recommended by the International Children's Continence Society (ICCS) today. However prospective interventional studies are needed for safe conclusions. CONCLUSION: Our comparison showed that children requiring a combination of SU and pharmacological treatment to achieve continence, had a significantly higher baseline voiding frequency and more baseline incontinence episodes when compared to children requiring only SU to achieve continence.

COVID-19 reopening causes high risk of irritant contact dermatitis in children.

INTRODUCTION: Childhood irritant contact dermatitis (ICD) is the most common cause for developing chronic hand eczema as an adult. The COVID-19 reopening in Denmark included regulations introducing frequent hand washing. The aim of the present study was to evaluate if frequent hand washing increases the incidence of ICD in children. METHODS: We conducted an observational study in Denmark during the reopening of schools and daycare facilities for children aged 0-12 years (April 22nd to May 1st 2020). A questionnaire was sent out to parents in four municipalities consisting of 20 questions about frequency of hand washing, use of hand sanitiser, symptoms of ICD, atopic dermatitis, allergy and predispositions. RESULTS: The study included 6,273 children. In children without any prior symptoms of dermatitis, 42.4% experienced ICD (dry, red and itchy skin) due to increased hand hygiene. Schoolchildren had a 1.5 times greater relative risk of developing ICD than preschool children. Frequency of hand washing was a strong risk factor, whereas this was not the case for alcohol-based hand sanitiser. Hand washing 7-10 times/day and >10 times/day increased the relative risk by 1.83 and 2.23 times, respectively. CONCLUSIONS: A higher frequency of hand washing during the COVID-19 reopening increased the incidence of ICD in children. Hand hygiene is essential in our fight against novel coronavirus, but prophylactic initiatives are important to reduce the possible long-term consequences of ICD in children. FUNDING: none TRIAL REGISTRATION: Clinicaltrials.gov (NCT04375410).

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.

Bladder and bowel dysfunction and the resolution of urinary incontinence with successful management of bowel symptoms in children.

AIM: To investigate the effect of treating defecation problems on urinary incontinence in children suffering from combined urinary bladder and bowel dysfunction (BBD). METHODS: We established a clinical database from medical records of all children referred to the urinary incontinence and gastroenterology outpatient clinics with BBD. The following variables were extracted: symptoms of constipation, faecal incontinence, urinary incontinence, age at onset of symptoms, treatment, including duration and response. All children went through the same treatment protocol. Faecal disorders were treated primarily and once relieved, the daytime incontinence was managed and followed by intervention for nocturnal enuresis. RESULTS: In total, 73 children were included in the study. The treatment regimen resulted in resolution of the defecation disorder in 96% of the patients. Of the children with daytime urinary incontinence, 68% had at least a 50% reduction in number of daytime incontinence episodes by successful relief of bowel dysfunction and 27% became completely continent during daytime. Only 17% of the children suffering from enuresis had a significant reduction in number of wet nights after relief of their faecal problem. CONCLUSION: The empirical treatment approach of managing bowel symptoms before intervening for bladder dysfunction in children with BBD is found to be appropriate.

Normal Levels of Plasma Free Carnitine and Acylcarnitines in Follow-Up Samples from a Presymptomatic Case of Carnitine Palmitoyl Transferase 1 (CPT1) Deficiency Detected Through Newborn Screening in Denmark.

Carnitine palmitoyl transferase (CPT) 1 A deficiency is a rare disorder of hepatic long-chain fatty acid oxidation. CPT1 deficiency is included in newborn screening programs in a number of countries to allow presymptomatic detection and early treatment of affected patients.We present a case of presymptomatic CPT1A deficiency detected through newborn screening in Denmark with diagnostic levels of carnitine and acylcarnitines in the initial dried blood spot. Levels of plasma-free carnitine and acylcarnitines in follow-up samples were normal, but reverted to diagnostic levels when the patient developed clinical symptoms at the age of 8 months. At that time, a diagnosis of CPT1A deficiency was confirmed by sequence analysis of the CPT1A gene revealing homozygosity for a novel c.167C>T variation in exon 3. Enzyme activity measurements showed a relatively mild enzyme defect with a decreased residual enzyme activity of 17-25%. We conclude that CPT1A gene testing and/or enzyme assay is mandatory to confirm an abnormal newborn screen suggesting CPT1A deficiency to avoid delayed diagnoses.