A randomised, double-blind, placebo-controlled clinical trial assessing the efficacy of bedtime buddy® for the treatment of nocturnal enuresis in children.

BACKGROUND: Nocturnal enuresis (NE), or 'bedwetting', is a form of night-time urinary incontinence occurring in younger children. A diagnosis of NE can be socially disruptive and psychologically stressful for a child. The most common strategies used by parents to manage NE are waking the child during the night to use the bathroom and limiting the child's water intake before going to bed. Behavioural or educational therapies for NE such as urotherapy or bladder retraining are widely accepted and considered as a mainstream treatment option for non-neurogenic lower urinary tract dysfunction in children. Pharmacotherapy also plays an ancillary role. However, there is no gold standard therapy or intervention to effectively manage NE. METHODS: This study aims to determine the efficacy of a herbal combination in the treatment of NE in children. The target population for this study is 80 children aged between 6 and 14 years old (males and females) who have primary nocturnal enuresis ≥3 per week (wet nights). The active group will receive one or two capsules per day containing 420 mg of a proprietary blend of Urox® (Seipel Group, Brisbane, Australia) containing Cratevox™ (Crataeva nurvala L; Capparidaceae; Varuna) stem bark extract standardised for 1.5% lupeol: non-standardised Equisetum arvense L. (Equisetaceae; Horsetail) stem extract; and, non-standardised Lindera aggregata Sims. The primary outcome for this study is the frequency of nocturia. Secondary outcomes include safety, quality of life, and daytime incontinence. Each participation will be involved in the trial for 32 weeks including contact with the research team every 2 weeks for the first 8 weeks and then every 8 weeks until trial completion. DISCUSSION: This study examines a novel treatment for an under-researched health condition affecting many children. Despite the availability of several therapies for NE, there is insufficient evidence to support the use of any one intervention and as such this randomised placebo-controlled phase II trial will be an important contribution to understanding potential new treatments for this condition. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registration Number: 12618000288224. PROTOCOL: 23 February 2018, version 1.1.

Imipramine for refractory daytime incontinence in the pediatric population.

INTRODUCTION AND OBJECTIVE: Lower urinary tract (LUT) and voiding dysfunction constitute a large percentage of pediatric urology referrals. Children with urinary incontinence unresponsive to behavioral modifications and traditional pharmacotherapy including anticholinergics and alpha blockers remain a challenge. We evaluated the impact of imipramine on treatment outcomes in children with refractory incontinence. STUDY DESIGN: Children ≤18 years of age with refractory non-neurogenic daytime incontinence prescribed imipramine were identified. Patient demographics and baseline testing were assessed, as well as medication dosing and side effects of all patients. The Vancouver Symptom Score (VSS) was completed at the initial consultation and each subsequent clinic visit. The questionnaire was self-administered and completed by patients and/or parents. Treatment success was defined as per the International Children's Continence Society (ICCS). RESULTS: One hundred and three patients (55 males and 48 females) met the inclusion criteria. The intention-to-treat response rate was 65% (complete 44, partial response 23). Sixteen (15.6%) patients were non-responders and 20 (19.4%) were lost to follow-up. There was no statistical difference between all groups with regards to age, baseline VSS, and dose. Of those children with complete follow-up (n = 83), 44 (53%) experienced complete treatment response. Pre- and post-VSS were statistically different in both complete and partial response groups (complete 19.5-9.5; p < 0.0001; partial 19.7-13; p = 0.0002) (Table). Side effects were reported by 11 out of 83 (13.3%) patients; partial responders experienced a higher likelihood of side effects (26.1%; p = 0.03). DISCUSSION: The mainstay of LUT dysfunction management in children is implementation of a bowel program and timed voiding regimen, with additional treatment modalities and pharmacotherapy added depending upon prevailing symptomatology. Daytime incontinence refractory urotherapy, anticholinergics, and/or non-selective alpha blockers can be difficult to treat, and can be unresponsive to parasacral transcutaneous electrical nerve stimulation (TENS) and percutaneous tibial nerve stimulation (PTNS). We observed that over half of children with refractory daytime incontinence reported complete resolution of daytime accidents with imipramine. Limitations of the study include the retrospective nature, relatively small sample size and lack of control group. CONCLUSIONS: Two-thirds of children with refractory daytime incontinence experienced treatment response to imipramine, adding a valuable tool to the pediatric urologist's armamentarium in managing select, challenging patients.

Novel uses for antidiuresis.

Overactive bladder (OAB) is a bothersome condition that affects millions of people worldwide. It consists of urgency, incontinence, frequency and nocturia. Treatment, in the form of lifestyle interventions, bladder training and pelvic floor muscle exercises, aim to alleviate symptoms. These treatment modalities have drawbacks, including being time consuming and require stamina on the part of the patient and treating physician. Drugs may be used if conservative measures fail or in combination with them. Antimuscarinics are the mainstay of OAB medication but may cause dry mouth, blurred vision or constipation. It is, therefore, crucial that new treatment modalities are sought to help with this potentially debilitating condition. Antidiuresis, using desmopressin, forms a potential candidate for a novel treatment. As the bladder fills with urine, symptoms of OAB are experienced by patients. It would be reasonable to hypothesise that if the rate of bladder filling is reduced then so would the symptoms of OAB. Desmopressin reduces the production of urine by the kidneys, therefore reducing the amount of urine in the bladder and, therefore, the symptoms of OAB. Desmopressin has been used previously in small single centre trials in neurogenic OAB patients with some success but recently two multi-centre, multinational randomised placebo controlled trials using this concept have been completed in idiopathic OAB sufferers and reported in the literature. The results were quite promising although there were minor side effects. These trials suggest that this potential novel treatment modality for OAB sufferers might avoid the necessity for invasive treatments, such as botulinum toxin, neuromodulation or surgery, in some instances. These trials also open the way to combination therapy with current treatment modalities of OAB.

[Efficacy of the pharmacotherapy of secondary enuresis in children].

43 children, 8-16 years old, suffering from secondary nocturnal enuresis were treated using different schemes. The most effective treatment of patients with only nocturnal enuresis was using a complex of nootropic psychostimulant medications (Fesam, B vitamins, apilak, Ca Glycerophosphat) with xanthinol nicotinat and combined treatment with the help of day-light therapy (motivating and regimen measures).

Evaluation and treatment of nonmonosymptomatic nocturnal enuresis: a standardization document from the International Children's Continence Society.

PURPOSE: This document represents the consensus guidelines recommended by the ICCS on how to evaluate and treat children with nonmonosymptomatic nocturnal enuresis (NMNE). The document is intended to be clinically useful in primary, secondary and tertiary care. MATERIALS AND METHODS: Discussions were held by the board of the ICCS and a committee was appointed to draft this document. The document was then made available to the members of the society on the web site. The comments were vetted and amendments were made as necessary to the document. RESULTS: The main scope of the document is the treatment of NMNE with drugs other than desmopressin-based therapy. Guidelines on the assessment, and nonpharmacologic and pharmacologic management of children with NMNE are presented. CONCLUSIONS: The text should be regarded as an expert statement, not a formal systematic review of evidence-based medicine. It so happens that the evidence behind much of what we do in the care of enuretic children is quite weak. We do, however, intend to present what evidence there is, and to give preference to this rather than to experience-based medicine, whenever possible.

Ephedrine hydrochloride: novel use in the management of resistant non-neurogenic daytime urinary incontinence in children.

OBJECTIVE: To determine whether the adrenoceptor agonist, ephedrine hydrochloride, is an effective treatment for resistant non-neurogenic daytime urinary incontinence in children. METHODS: From 2000 to 2010, eighteen children with resistant non-neurogenic daytime urinary incontinence were treated with oral ephedrine hydrochloride at our institution. Sixteen were female and two were male. Median age at treatment was 12 years (range 5-15 years). Two children had spina bifida occulta. There were no other co-morbidities. Multiple anticholinergics were prescribed and dose maximized to support a bladder and bowel training programme, without achieving continence in this resistant group of children. Pre-treatment urodynamics were normal in 10, but revealed an open bladder neck in 8 patients. None showed detrusor over-activity. Oral ephedrine hydrochloride was started at 7.5 mg or 15 mg twice daily and titrated up to a maximum of 30 mg four times daily according to response. RESULTS: Median follow-up was 7 years (range 6-8 years). Seventeen children (94%) reported improvement in symptoms and six (33%) achieved complete urinary continence. All patients maintained compliant bladders on post-treatment urodynamics. Seven of the 8 previously open bladder necks were closed. No patients reported any significant side effects. Patients with open bladder necks on pre-treatment urodynamics were more likely to show a full response to ephedrine (odds ratio 15; 95% CI 1.2-185.2). CONCLUSIONS: Oral ephedrine hydrochloride is an effective treatment for carefully selected children with resistant non-neurogenic daytime urinary incontinence.

Initial trial of timed voiding is warranted for all children with daytime incontinence.

OBJECTIVES: To analyze the relationship between potential prognostic factors and early success after treatment of childhood daytime urinary incontinence without anticholinergic medication. METHODS: A total of 63 patients with daytime urinary incontinence met the inclusion criteria for a retrospective review of the effect of a timed voiding regimen. The severity, duration, and frequency of wetting, along with age, sex, and uroflow parameters, were recorded. Statistical analysis was used to determine the factors predictive of improvement in wetting without anticholinergic treatment. RESULTS: Of 315 children evaluated with daytime incontinence, only 24% were treated with nonanticholinergic methods. At the first follow-up visit, 6.3% of patients treated without anticholinergics became dry, 38.1% showed significant improvement, 36.5% were slightly improved, and 19.0% were unchanged. Age, sex, duration or severity of wetting, constipation, bladder capacity, and uroflow pattern and parameters were not predictive of early improvement with timed voiding. Patients with good compliance with timed voiding were significantly more likely to improve than those with poor compliance (P = 0.014). CONCLUSIONS: The results of our study have indicated that anticholinergic therapy appears to be overused as a first-line treatment for children with daytime urinary incontinence in our clinic population. The lack of reliable predictive factors regarding the response to nonanticholinergic treatment suggests a trial of timed voiding should be used as an initial treatment for all children with daytime urinary incontinence. Almost 45% of our patients had significant improvement in the frequency of wetting within 4 months without anticholinergics.