The orchestration of gene expression and the editing role of microRNA.

In this short educational communication the ESPU Research Committee presents the role of non-coding RNA and how these can affect gene expression. In particular we discuss the role of microRNA on post transcriptional changes and how these may cause pathological conditions within Pediatric Urology and how microRNA could be useful in future clinical practice.

Study protocol for a parallel-group randomized controlled multi-center trial evaluating the additional effect of continuous ultrasound bladder monitoring in urotherapy for children with functional daytime urinary incontinence (SENS-U trial).

BACKGROUND: Lower urinary tract dysfunction or functional urinary incontinence is a common condition with a prevalence up to 21% between 6 and 8 year-old children. It is associated with an impaired quality of life, lower self-esteem, and social stigmatization. Urotherapy is the first treatment of choice for functional daytime urinary incontinence (DUI) in children. Alarm therapy can be a part of urotherapy as it provides the child adequate feedback on wetting accidents. Current alarm systems notify either at a set interval or give a notification when wetting has already occurred to prompt the child to go to the toilet. These alarms do not teach the child the interpretation of the bladder sensation preceding wetting accidents. A new wearable bladder sensor, the SENS-U, recently became available. This is a relative small, wireless ultrasonic sensor, which continuously monitors bladder filling. The SENS-U is able to provide an alarm at the exact moment voiding is warranted. It facilitates the child to learn the sensation of bladder filling preceding voiding in an easier way, increasing the learning curve throughout treatment. Its additional effect in urotherapy on continence and cost-effectiveness is to be determined. METHODS/DESIGN: This is a multi-center clinical superiority parallel-group randomized controlled trial including a total of 480 children. Participants between 6 and 16 years of age with functional DUI in which urotherapy is offered as the next treatment of choice are eligible. Four centers, two academic hospitals, and two general care (peripheral) centers are participating. Participants will be randomized at a 1:1:1 ratio into three groups: urotherapy (care as usual), urotherapy with the SENS-U added for 3 consecutive weeks throughout the training, or urotherapy with a SHAM device for 3 weeks. The primary outcome is number of wetting accidents per week after 3 months of training, compared between the SENS-U and the SHAM device. The magnitude of the placebo effect will be assessed by comparing the results of the SHAM group versus the control (care as usual) group. DISCUSSION: To our knowledge, this is the first trial studying not only the effect but also the cost-effectiveness of alarm interventions as commonly added in urotherapy. TRIAL REGISTRATION: ISRCTN44345202 . Registered on March 2022.

COVID-19 and research in pediatric urology.

COVID-19 began in December 2019 then spread worldwide. Providers, including pediatric urologists, had to adapt their clinical processes, and many non-covid research activities were suspended. COVID-19 impacts how research is financed, performed, and published, and is itself the subject of intense research. We present current research and publications specifically related to the urinary tract and the pediatric population.

Definitions, indications and practice of urotherapy in children and adolescents: - A standardization document of the International Children's Continence Society (ICCS).

BACKGROUND: Urotherapy is an umbrella term for all non-surgical, non-pharmacological interventions for lower urinary tract disorders (LUTD) in children and adolescents. Urotherapy is a specialized practice, which has become mainstay therapy not only for daytime urinary incontinence, but also for nocturnal enuresis, functional constipation and fecal incontinence. The aim of urotherapy is to achieve the normalization of the micturition and bowel pattern and to prevent further functional disturbances by repeated training. It is well known that in the treatment of adult and childhood incontinence a team approach is best, where there are shared areas of expertise and also discipline-specific expertise available. AIM: We present a consensus view from a cross-professional team of experts affiliated with the International Children's Continence Society on definitions, indications and practice of urotherapy. This is a selective, non-systematic review with practical recommendations for the implementation and research on urotherapy. METHODS: The document uses the globally accepted ICCS terminology. Evidence-based literature serves as the basis, but in areas lacking in primary evidence, expert consensus is used. Before submission, a full draft was made available to all ICCS members for additional comments. RESULTS: Urotherapy uses non-pharmacological, non-surgical methods and focuses on behavioral interventions, largely based on cognitive-behavioral psychotherapy (CBT). Standard urotherapy comprises components such as provision of information, instructions, life-style advice, counselling and registration of symptoms. Specific urotherapy is tailored towards specific disorders and includes alarm treatment, biofeedback training, pelvic floor training, neurostimulation and other interventions. Fig. 1. Urotherapy is a treatment that addresses all aspects of incontinence, leading to the best clinical outcome. This includes somatic, psychosocial, and behavioral problems and quality of life. Therefore urotherapy is recommended by the ICCS as the first-line treatment for most types of LUTD. The document is intended to be clinically useful in primary, secondary and tertiary care.

SENS-U: clinical evaluation of a full-bladder notification - a pilot study.

INTRODUCTION: Urinary incontinence is one of the most commonly treated disorders in children at school age. Recently, a new, wearable bladder sensor became available, the SENS-U Bladder Sensor. The SENS-U is a small, wireless ultrasonic sensor, which continuously monitors the bladder filling and provides a personalized notification when it is time to go to the toilet. In this study, the aim was to examine the performance of the SENS-U as a full-bladder-based notification system in children during daily life activities. PATIENTS AND METHODS: In this pilot study, children (6-16 years) who were admitted for an inpatient bladder training were included. Parallel to one training day, the child would wear the SENS-U to estimate the bladder filling and it informed the child when the bladder was almost full. When the child received a full-bladder notification, the child was taught to inform the urotherapist/researcher, in order to determine the level of response. RESULTS: Fifteen patients (boys/girls: 7/8; mean age: 11.5 ± 1.7 years) were included. Based on a personalized volume-based threshold, the SENS-U notified these children of a full bladder with a median notification rate of 92.9%. In the remaining cases, children voided before the threshold was reached (e.g. defecation). Children responded positively to the notification of the SENS-U, resulting in a median level of response equal to 100%. CONCLUSION: The SENS-U was able to monitor the natural bladder filling accurately during activities of daily living and provided a personalized notification to the children when it was almost time to go to the toilet. Future research will focus on investigating the efficacy of the SENS-U compared to daily clinical practices.

Does a serious game increase intrinsic motivation in children receiving urotherapy?

INTRODUCTION: Urotherapy is considered the treatment of choice for children suffering daytime urinary incontinence (DUI). Urotherapy intends to improve bladder dysfunction for children with DUI. For children with refractory DUI, an intensive inpatient bladder training program exists, which focuses on relearning, concentration on, and awareness of the bladder. Children's motivation and adherence are key determinants of a successful training outcome. It is hypothesized that motivation endurance throughout the treatment process may be enhanced by a serious game training tool, which could make the training more appealing and rewarding. OBJECTIVE: The study explores intrinsic motivation in children receiving bladder training for DUI and whether using a serious game improves their intrinsic motivation. STUDY DESIGN: In this pragmatic study, 50 children were allowed to choose among receiving bladder training with (intervention group) or without the application of a serious game (control group). At 4, 8, and 12 weeks of training, children and parents were asked to complete the Intrinsic Motivation Inventory (IMI). Children also completed the Pediatric Urinary Incontinence Quality of Life Tool (PinQ) before the start of the training and 6 months thereafter. At 6-month follow-up, patients were ask to participate in two focus groups, wherein the children discussed how they used the serious game and which improvements they would prefer. RESULTS: Children who received standard bladder training with the addition of a serious game did not differ in terms of intrinsic motivation from children who underwent standard bladder training only. Training results were equal in both the groups, with 80% good or improved. Incontinence-related quality of life (QoL) improved accordingly. DISCUSSION: In contrast to the study expectations, this game did not increase intrinsic motivation. Findings on training and QoL results are consistent with those of previous studies in both interventions. Although a randomized design could have yielded more valid results than this preference-based approach, the latter is more congruent with clinical practice. In contrast to existing bladder diary apps, this game offers a combination of child-friendly instructions, explanation of bladder (dys)function, and keeping a bladder diary. Mobile devices are playing an increasingly important role in health care; therefore, an urotherapy app can be a complementary therapeutic tool. CONCLUSION: Most children find it attractive to combine bladder training with a serious game. However, no added value was found regarding intrinsic motivation and training results. All children with persistent DUI in this cohort were highly motivated to complete an intensive bladder training program.

Central inhibition of refractory overactive bladder complaints, results of an inpatient training program.

SHORT INTRODUCTION: Overactive bladder (OAB) in children has an overall reported incidence of 16.6-17.8%, with its prevalence of 0.2-9% varying largely between age and gender. OAB is the most important burden in pediatric urology because of the limited effect of treatment. OAB with imperative urge and/or urge incontinence can often be successfully treated with urotherapy and pharmacological treatment. Nevertheless, approximately 20% of patients are considered to be therapy resistant for common treatment options. For the latter group, an inpatient cognitive and biofeedback training program for children has been developed. OBJECTIVE: Our objective is to evaluate the effect of an inpatient cognitive and biofeedback training program for children with urge complaints and urge incontinence based on overactive bladder (OAB) after failed earlier treatment by anticholinergic medication and by outpatient urotherapy. A search for predictors for success of treatment outcome is included in the study. STUDY DESIGN: Seventy children with therapy refractory incontinence based on OAB went through a 10-day in-hospital training program between 2007 and 2010. The children were aged between 7 and 13 years (mean 9.29 years) and 48 (68.6%) were male. An essential part of this program is teaching the children central inhibition of their bladder to suppress bladder overactivity. Before attending this training program patients had on average 41.1 months of fruitless treatment by urotherapy and medication, and if needed preceding surgery for meatus correction or deobstruction. The training result was evaluated 6 months after completion of the inpatient training program. A questionnaire was subsequently conducted 2 years after the training to evaluate the long-term efficacy of this program. RESULTS: Six months after training, evaluation showed that 30 of the 70 patients (42.9%) were free of complaints, 22 (31.4%) had a significant reduction in complaints and 18 (25.7%) had no improvement. Logistic regression analysis was used to look at several variables predicting training outcome. A higher age during clinical training was found to be a predictor for a good training outcome. After 2 years, 44 (62.9%) patients were reached for long-term follow-up. Of these patients, 28 (63.6%) reported a good effect of the training and 11 (25%) experienced no improvement in symptoms compared with before clinical training. Objectively, 26 (59.1%) were dry and 18 (40.9%) were incontinent to some extent. A total of 30 (68.2%) patients had not relapsed into urge complaints (McNemar's test P-value <0.05). DISCUSSION: Age was found to be a predictor of a good training result, which is in line with the findings of other publications where children above the age of 8 demonstrate better and faster training results. The absolute number of participants to perform statistical analysis on was low, even though it was the number maximally achievable in this cohort, possibly explaining how other variables could not be found to predict training outcome. No differences in outpatient therapy results were observed between patients having received earlier outpatient urotherapy in our hospital when compared with being trained elsewhere. This is coherent with previous research indicating that for outpatient training, the attention offered to the child is of paramount importance. Regarding long-term follow-up, keeping in mind long-term follow-up patient numbers were incomplete, a good effect of the training was seen with a clear reduction in incontinence complaints. Far fewer children are suffering from urge complaints, although some patients had relapsed into urge complaints. CONCLUSION: The inpatient cognitive and biofeedback training program for refractory OAB complaints has been demonstrated to cure or improve 74.3% of patients, and conveyed favorable long-term results in approximately 75.0% of patients. A higher age during clinical training was found to be a predictor for good training outcome.

The relationship between children with voiding problems and their parents.

PURPOSE: We determined whether parents of children with overactive bladder and dysfunctional voiding had had similar symptoms in childhood. MATERIALS AND METHODS: A case-control study was done in parents with and without children with overactive bladder or dysfunctional voiding. All were recruited from an outpatient clinic. Diagnoses in children were made according to the International Children's Continence Society standardization report. Childhood symptoms in parents were assessed by a 19-item questionnaire and current urogenital symptoms were assessed by the Urogenital Distress Inventory. Comparisons between groups were made with categorical and interval statistics. RESULTS: A total of 173 cases and 98 controls were entered in the study. Statistically significantly more mothers of children with overactive bladder or dysfunctional voiding reported having had similar symptoms in childhood than mothers of children without lower urinary tract symptoms. Overactive bladder symptoms of childhood persisted into adulthood. No association between childhood dysfunctional voiding symptoms and adult emptying disorders was noted. Fathers of children with overactive bladder reported to have stopped bed-wetting at a significantly later age than control fathers. CONCLUSIONS: Results reveal an association between overactive bladder symptoms in children and their parents. To a lesser extent this finding also holds true for dysfunctional voiding symptoms.