Treatment modalities for paediatric functional daytime lower urinary tract disorders: an updated review.

Paediatric functional bladder disorders especially those causing daytime symptoms are a common cause of significant psychosocial and/or physical morbidity and impaired quality of life. Despite the availability of many therapeutic modalities, a significant number of children appear to be refractory to treatment and continue to have symptoms. In this review, we aim to evaluate the current evidence in the use of existing and novel therapeutic options for the management of daytime lower urinary tract disorders in children. We also aim to highlight the controversies around the terminology and diagnosis of paediatric lower urinary tract dysfunction (LUTD) and specific conditions. The article will then provide a reasonable critique of the existing and emerging treatment modalities in functional daytime LUTD in children including their mode of action, efficacy, indications, and recent advances. These include standard urotherapy, specific urotherapy comprised of biofeedback, alarm therapy and electrical neural stimulation and pharmacotherapy involving selective and non-selective anticholinergics, ß3 adrenergic agonists, alpha blockers and botulinum toxin. A better understanding of this common clinical problem may help clinicians achieve better profiling of these children's diagnoses to further enable specific, targeted treatment.

A review article about new treatment options for otherwise healthy children with long-term urinary symptoms occurring during the daytime Management of paediatric functional daytime LUT disorders is complex and may benefit from a combination of treatment modalities. Urotherapy and anticholinergics appear to be effective in the majority however, non-responders warrant careful re-evaluation to characterize the specific type of LUTD to target appropriate treatment. Various novel therapies and adjuncts have been shown effective and range from smartphone apps, bladder alarms, neuromodulation systems and more effective drug delivery systems. Despite being effective, non-selective antimuscarinics are less favoured for long-term use in children due to the side-effect profile. Therefore, more selective anticholinergics, ß3 agonists and combination treatment options are being evaluated to improve compliance while maintaining/enhancing treatment efficacy. Use of alpha blockers and intravesical injection of botulinum toxin have shown promising results especially in refractory cases.

An Economic Evaluation of a Web-Based Management Support System for Children With Urinary Incontinence: The eADVICE Trial.

PURPOSE: Children who require specialist outpatient care typically wait substantial periods during which their condition may progress, making treatment more difficult and costly. Timely and effective therapy during this period may reduce the need for lengthy specialist care. This study evaluated the cost-effectiveness of an individualized, evidence-informed, web-based program for children with urinary incontinence awaiting a specialist appointment (Electronic Advice and Diagnosis Via the Internet following Computerized Evaluation [eADVICE]) compared to usual care. eADVICE was supervised by a primary physician and delivered by an embodied conversational agent. MATERIALS AND METHODS: A trial-based cost-effectiveness analysis was performed from the perspective of the health care funder as a substudy of eADVICE, a multicenter, waitlist-controlled, randomized trial. Outcomes measures were incremental cost per incremental change in continence status and quality of life on an intention-to-treat basis. Uncertainty was examined using cost-effectiveness planes, scenarios, and 1-way sensitivity analyses. Costs were valued in 2021 Australian dollars. RESULTS: The use of eADVICE was found to be cost saving and beneficial (dominant) over usual care, with a higher proportion of children dry over 14 days at 6 months (risk difference 0.13; 95%CI 0.02-0.23, P = .03) and mean health care costs reduced by $188 (95%CI $61-$315) per participant. CONCLUSIONS: An individualized, evidence-informed, web-based program delivered by an embodied conversational agent is likely cost saving for children with urinary incontinence awaiting a specialist appointment. The potential economic impact of such a program is favorable and substantial, and may be transferable to outpatient clinic settings for other chronic health conditions.

The rationale for bladder washouts in children with neurogenic bladder.

Children with a neurogenic bladder are at risk of developing recurrent urinary tract infections and long-term kidney failure. Due to an altered lower urinary tract, children may be overtreated for simple bacteriuria or undertreated for a potentially severe urinary tract infection. This group of patients represent high users of healthcare, and are at risk of colonization and development of antibiotic resistance. Bladder washouts with non-antibiotic electrochemically activated solutions are a potential new prophylactic option for patients with bladder dysfunction when clean intermittent catheterization has resulted in chronic bacteriuria.

Lack of consensus in atypical congenital obstructive urethral lesions in children: Snapshot of the web-based ObsCUre (obstruction to the child urethra) study.

Background: Atypical Congenital Obstructive Urethral Lesions (ACOUL) are uncommon causes of urethral obstruction in children. They include Cobb's collar or Moorman's ring, Type III posterior urethral valve (PUV), congenital urethral narrowing and anterior urethral valves. This study is aimed to evaluate the knowledge and current practice amongst clinicians attending to ACOUL. An international online case based questionnaire was performed. Materials and methods: A survey was administered to members of international urological societies. It included 22 clinical questions on cases with ACOUL (14 questions suitable for statistical analysis) using cases of Type I PUV as controls. Two sets of paired questions evaluated change in opinion(s) after additional information was provided. Results: One hundred twenty-one participants responded with 71% reporting exposure of less than 5 cases per annum. In questions regarding diagnosis between 11.6% (14/121) and 21.5% (26/121) of participants identified the ACOUL as PUV. Among them, 66% of respondents agreed on ACOUL's causative role in urethral obstruction. Gini coefficient was consistently lower for ACOUL compared to PUV: diagnosis (mean 0.33 vs. 0.44) and prognosis (0.23 vs. 0.43). High intra-rater concordance (kappa 0.420.57) was observed for paired questions-a mean of 5.79% (7.44% and 4.13% for questions 10 and 12, 16 and 17, respectively) of participants changed their answers from an alternate diagnosis to the correct diagnosis of ACOUL after viewing endoscopic images. High variation in management of ACOUL was noted (Gini 0.51). Conclusions: This global snapshot survey identified substantial inconsistency among clinicians dealing with ACOUL. Although rarely encountered in clinical practice, better overall education of ACOUL is warranted.

Reduction of Urinary Tract Infection in Pediatric Surgical Patients Using NSQIP-P and Quality Improvement Methodology.

BACKGROUND: Hospital acquired urinary tract infections (UTIs) have a detrimental effect on patients, families and hospital resources. The Sydney Children's Hospital Network (SCHN) participates in the National Surgical Quality Improvement Program - Pediatric (NSQIP-P) to monitor post operative complications. NSQIP-P data revealed that the median UTI rate at SCHN was 1.75% in 2019, 3.5 times higher than the NSQIP-P target rate of 0.5%. Over three quarters of the NSQIP-P identified UTI cases also had a urinary catheterization performed intra-operatively. A quality improvement project was conducted between mid-2018 to 2021 to minimise catheter associated UTIs (CAUTIs) at SCHN. STUDY DESIGN: NSQIP-P samples pediatric (<18 years) surgical cases from an 8-day cycle operative log. NSQIP-P data is statistically analysed by the American College of Surgeons and provides biannual internationally benchmarked reports. The project utilized Clinical Redesign Methodology with a six-phase process for quality improvement projects. The project utilized Clinical Redesign Methodology with a six-phase process for quality improvement projects. RESULTS: The objectives of the project were to reduce urinary catheter duration of use, educate parents/carers and improve catheter care and insertion technique by health staff. The duration of a urinary catheter in situ reduced from a median of 4.5 days to 3 days from 2017 to 2021. The median NSQIP-P UTI rate at SCHN was reduced by 47.4% from 1.75% in 2019 to 0.9% in 2022. CONCLUSION: A multifactorial approach in quality improvement has been shown to be an effective strategy to reduce UTI rates at SCHN and patient outcomes were improved within a three-year time frame. Whilst this project has reduced UTI rates at SCHN, there remain opportunities for further improvement.

A Randomized Controlled Trial of a Web-Based Management Support System for Children With Urinary Incontinence: The eADVICE Trial.

PURPOSE: Children referred to specialist outpatient clinics by primary care providers often have long waiting times before being seen. We assessed whether an individualized, web-based, evidence-informed management support for children with urinary incontinence while waiting reduced requests for specialist appointments. MATERIALS AND METHODS: A multicenter, waitlisted randomized controlled trial was conducted for children (5-18 years) with urinary incontinence referred to tertiary pediatric continence clinics. Participants were randomized to the web-based eHealth program electronic Advice and Diagnosis Via the Internet following Computerized Evaluation (eADVICE), which used an embodied conversational agent to engage with the child at the time of referral (intervention) or 6 months later (control). The primary outcome was the proportion of participants requesting a clinic appointment at 6 months. Secondary outcomes included persistent incontinence, and the Paediatric incontinence Questionnaire (PinQ) score. RESULTS: From 2018 to 2020, 239 children enrolled, with 120 randomized to eADVICE and 119 to the control arm. At baseline, participants' mean age was 8.8 years (SD 2.2), 62% were males, mean PinQ score was 5.3 (SD 2.2), 36% had daytime incontinence, and 97% had nocturnal enuresis. At 6 months, 78% of eADVICE participants vs 84% of controls requested a clinic visit (relative risk 0.92, 95% CI 0.79, 1.06, P = .3), and 23% eADVICE participants vs 10% controls were completely dry (relative risk 2.23, 95% CI 1.10, 4.50, P = .03). The adjusted mean PinQ score was 3.5 for eADVICE and 3.9 for controls (MD -0.37, 95% CI -0.71, -0.03, P = .03). CONCLUSIONS: The eADVICE eHealth program for children awaiting specialist appointments doubled the proportion who were dry at 6 months and improved quality of life but did not reduce clinic appointment requests.

Pharmacological interventions for the management of cystinuria: a systematic review.

BACKGROUND: Cystinuria is a rare genetic kidney stone disease, with no cure. Current treatments involve lowering urinary cystine levels and increasing cystine solubility. This systematic review evaluates the available literature regarding non-surgical interventions for cystinuria. METHODS: Key electronic databases were searched for studies that described the clinical management of cystinuria with high diuresis, alkalinizing agents and thiol-based drugs that were published between 2000 and 2022. Observational studies were included if they contained clinical investigation with at least one previous or current episode of cystine stones, urine cystine levels > 250 mg/L and patients being managed with urinary dilution, alkalinizing agents or other pharmacological agents. All included studies were assessed for study design, patient characteristics and outcomes. A qualitative and critical analysis was performed whereby study quality was assessed using Methodological Index for Non-Randomized Studies (MINORS). Two authors performed the quality assessment and excluded the studies with a low MINORS score. RESULTS: Fourteen studies met the review inclusion and quality criteria. Of the fourteen studies, two reported treatment using alkalinizing agents, six reported treatment using thiol-based drugs, and six reported combination treatment using alkalinizing agents and thiol-based drugs. These studies indicated that first-line therapies, including high fluid intake and urinary alkalinization, increased urine volume to > 3 L/day and urinary pH > 7.0, and were associated with reduced urinary cystine levels and cystine stone formation. Second-line therapy with cystine-binding thiol drugs, such as tiopronin and D-penicillamine, reduced urinary cystine levels, cystine crystal volume and increased cystine solubility, resulting in decreased cystine stone formation and stone recurrence rate. Further, combined intervention with alkalinizing agents and thiol-based drugs synergistically reduced stone recurrence. CONCLUSION: Cystinuria treatment may require a combined approach of high diuresis, alkalinization and pharmacological interventions with regular monitoring of urinary pH, cystine levels, cystine crystal volume and solubility. However, poor adherence to treatment is relatively frequent, hence the pressing urgency for improved therapies and treatments.

Laparoscopic versus open pyeloplasty in paediatric pelvi-ureteric junction obstruction.

AIM: Compared to open pyeloplasty (OP), we hypothesised that laparoscopic pyeloplasty (LP) is associated with early recovery, a shorter length of stay (LOS) and less analgesia requirement. METHODS: Between 2011 and 2016, 146 dismembered pyeloplasty cases were reviewed, of which 113 were in the OP group and 33 were in the LP group. We evaluated both groups regarding operative time, LOS, success rate, complications rate and analgesia requirement. Subgroup analysis was done for patients above the age of 5 years, and within the OP group (dorsal lumbotomy (DL) vs. loin incision (LI)). RESULTS: The success rate was 96% in the open group and 97% in the laparoscopic group. The median operative time was significantly shorter in the open group for the entire cohort (127 vs. 200 min; P < 0.05), and in children older than 5 years (n = 41, 134 vs. 225 min; P < 0.05). Other parameters were similar in both groups. The median LOS was significantly shorter (2 vs. 4 days; P < 0.05), and the median analgesia requirement was less (0.44 vs. 0.64 mg/kg morphine; P < 0.05) in the DL (n = 60) compared to LI (n = 53). CONCLUSION: Both OP and LP dismembered approaches are equally effective in treating pelvi-ureteric junction obstruction. Overall, the LOS, complications rate and analgesia requirement were not significantly different; however, the operative time was significantly longer in LP.

Optimising the management of children with concomitant bladder dysfunction and behavioural disorders.

Bladder dysfunction and behavioural disorders in children are commonly concomitant; hence, it is difficult to treat each in isolation. Pharmacotherapy is common treatment for behavioural disorders, and these medications may have intended or unintended positive or negative bladder sequelae. This review identifies the literature regarding the effects of behavioural pharmacotherapy on bladder functioning and possible bladder management strategies in children with concomitant behaviour and bladder disorders to enable clinicians to better manage both conditions. A PROSPERO registered PRISMA-guided review of three major databases was performed. After an initial scoping study revealed significant heterogeneity, a narrative approach was undertaken to discuss the results of all relevant cases relating to children being treated with pharmacotherapy for behaviour disorders and outcomes related to bladder function. Studies were screened to identify those that described effects of commonly prescribed medications in children with behavioural disorders such as stimulants, alpha 2 agonists, tricyclic antidepressants (TCA), serotonin and noradrenergic reuptake inhibitors (SNRI), selective serotonin reuptake inhibitors (SSRI) and antipsychotics, and the findings and implications were summarised. The review identified 46 studies relevant to behavioural pharmacotherapy and bladder function (stimulants (n = 9), alpha 2 agonists (n = 2), TCAs (n = 7), SNRIs (n = 8), SSRIs (n = 8) and antipsychotics (n = 6). Six studies focused specifically on bladder management in children with behavioural disorders with concurrent behavioural pharmacotherapy. This review identifies useful factors that may assist clinicians with predicting unintended bladder effects following initiation of behavioural pharmacotherapy to facilitate the best approach to the treatment of bladder dysfunction in children with behavioural disorders. With this evidence, we have provided a useful decision-making algorithm to aide clinicians in the management of these dual pathologies.

Quality of life and psychological aspects in children with overactive bladder treated with parasacral transcutaneous electrical nerve stimulation - A prospective multicenter study.

OBJECTIVE: To assess the impact of parasacral transcutaneous electrical nerve stimulation (parasacral TENS) on quality of life (QoL) and psychological aspects in children treated for overactive bladder (OAB). METHODS: This international, multicenter, prospective cohort study involved individuals of 6-16 years of age under TENS treatment for OAB. The study was conducted between June 2016 and December 2019 in four participating centers: two in Australia, one in Germany and one in Brazil. Patients with anatomical and/or neurological abnormalities of the urinary tract were excluded. Questionnaires were applied before and after parasacral TENS treatment: the Dysfunctional Voiding Symptom Score (DVSS), used in Brazil, or the International Consultation on Incontinence Questionnaire - Pediatric Lower Urinary Tract Symptoms (ICIQ-CLUTS), used in Germany and Australia, to analyze urinary symptoms; the Strengths and Difficulties Questionnaire (SDQ) to assess emotional and behavioral aspects; and the Pediatric Incontinence Questionnaire (PinQ) for bladder-specific Qol. RESULTS: Fifty-three patients (28 girls and 25 boys) with a mean age of 8.64 ± 2.63 years were included. Median DVSS was 11 (range 6-13.5) and 3 (range 0-7), (p < 0.001), and median ICIQ-CLUTS was 12 (range 9-14) and 9 (range 5.7-12), (p < 0.001), before and after treatment, respectively. Median PinQ score decreased from 47.8 (range 38.9-59.7) to 39 (range 29-53.15) following treatment (p = 0.04). Median total SDQ score before and after treatment was 17 (range 13.5-21) and 15 (range 12-21), respectively (p = 0.939). CONCLUSION: Parasacral TENS was associated with a significant improvement in urinary symptoms and QoL; however, there was no change in psychological symptoms, as measured using the SDQ.

Peritesticular scarring: An unusual presentation of hemophilia B.

Hemophilia is an inherited clotting disorder that typically presents as spontaneous hemorrhage or prolonged, excessive bleeding following minor trauma. Abnormalities of the genitourinary tract are a rare manifestation of the disease. Here, we report a case of undiagnosed hemophilia B in a teenage boy presenting with worsening testicular pain and a dumbbell-shaped testis. Scrotal ultrasound identified the presence of a hypoechogenic band constricting the left testicle. Surgical exploration of the left testis was performed with release and sampling of the fibrous tunica vaginalis tissue responsible for the testicular deformity. Histopathological analysis revealed evidence of chronic interstitial inflammation with hypocellular keloid-like fiber formation suggestive of old hemorrhage. The procedure was complicated by a delayed scrotal hematoma. Coagulation studies confirmed a prolonged activated partial thromboplastin time and factor IX assay of 5%. Scrotal evacuation with the administration of intraoperative tranexamic acid achieved effective hemostasis. The patient is doing well with ongoing hematology review and prophylactic recombinant factor IX administration.

Parental decision regret among Australian parents after consenting to or refusing hypospadias repair for their son: Results of a survey with controls.

INTRODUCTION: Parental decision regret in hypospadias surgery is a recognised source of long-lasting psycho-social morbidity. High parental decision regret after their child's hypospadias repair is reported. The aim of this study is to report on decision regret in Australian parents, who accepted and declined surgery for their son and explore underlying factors for decision-making, satisfaction, and regret. MATERIALS AND METHODS: An online anonymous survey was administered to three groups of parents: 1) parents who consented for hypospadias repair, 2) parents who declined repair and 3) a control group who requested circumcision for their child. Operations occurred between 2010 and 2020 in two paediatric hospitals in New South Wales, Australia. The survey included a validated decision regret assessment tool and additional questions to explore the possible basis of the opinions. RESULTS: One hundred and eighteen parents (invited - 381, completed - 116, response rate - 31%) participated in the survey. Decision regret was present in group 1 (n = 89) - 55% (moderate-to-severe 15%), in group 2 (n = 14) - 71% (moderate-to-severe 57%), and in the control group (n = 15) - 15% (moderate-to-severe 8%) of parents. There was a significant difference in the median decision regret score between all three groups. Parents who chose hypospadias repair were mostly concerned about function. CONCLUSIONS: The prevalence of decision regret among Australian parents who consented for their son's hypospadias repair was lower compared with the mean decision regret reported in the literature to date (55% vs 65%). Decision regret and its severity were highest among parents who declined hypospadias repair. New strategies are needed to reduce decision regret in parents whether they elect for surgery or not.

Effectiveness of standard urotherapy (basic bladder advice) and combination therapies in managing bladder dysfunction in children with treated behavioral disorders: Results of a prospective cohort (DABBED) study.

AIMS: We evaluated the efficacy of standard urotherapy and combination therapies in treatment of bladder dysfunction in children with treated behavioral disorders. METHODS: Prospective study of children (6-16 years) with bladder dysfunction and behavioral disorders was conducted between March 2018-2020. Eligible children were initially offered standard urotherapy and those with no response at 3 months were offered combination therapies. Symptomatic response, changes in Akbal score and PinQ score were reported at 6 months and outcomes were correlated to behavioral diagnoses and medications. RESULTS: Thirty-nine consecutive children (male = 27, mean age [SD] 10.3 [±2.0] years) were recruited, of whom 29 completed the study (five lost to follow-up, three non-compliant to treatment, two excluded). Thirty-four (87%) children had attention deficit/hyperactivity disorder. Monosymptomatic nocturnal enuresis (n = 11) and non-monosymptomatic enuresis (n = 17) were the commonest diagnoses. Following 3-month review, 14 (38%) children continued to receive standard urotherapy, while 15 (41%) children were transitioned to combination therapy. At 6-month review, complete/partial response was seen in 62% (23/37) and no response in 16% (6/37); with 32% (12/37) responding to standard urotherapy alone. Akbal symptom scores (15.9-11.5; P < 0.01) and PinQ scores (26.0-19.5; P = 0.008) improved significantly at 6-month follow-up. Type of underlying behavioral disorder(s) or medications for behavioral disorder did not influence the outcomes. CONCLUSION: This study confirms that children with underlying behavioral disorders are able to have a good response to the appropriate therapy for their bladder dysfunction with a third of children responding to standard urotherapy alone.

The microbiome and host mucosal interactions in urinary tract diseases.

The urinary tract consists of the bladder, ureters, and kidneys, and is an essential organ system for filtration and excretion of waste products and maintaining systemic homeostasis. In this capacity, the urinary tract is impacted by its interactions with other mucosal sites, including the genitourinary and gastrointestinal systems. Each of these sites harbors diverse ecosystems of microbes termed the microbiota, that regulates complex interactions with the local and systemic immune system. It remains unclear whether changes in the microbiota and associated metabolites may be a consequence or a driver of urinary tract diseases. Here, we review the current literature, investigating the impact of the microbiota on the urinary tract in homeostasis and disease including urinary stones, acute kidney injury, chronic kidney disease, and urinary tract infection. We propose new avenues for exploration of the urinary microbiome using emerging technology and discuss the potential of microbiome-based medicine for urinary tract conditions.

Parental decision regret in childhood hypospadias surgery: A systematic review.

We conducted a systematic review of the literature to establish the prevalence of and predictive factors for parental decision regret in hypospadias surgery. A search strategy without language restrictions was developed with expert help, and two reviewers undertook independent study selection. Five studies were included in this review (four for quantitative analysis) with a total of 783 participants. The mean overall prevalence of parental decision regret was 65.2% (moderate to severe - 20.3%). Although significant predictors of regret were identified (post-operative complications, small size glans, meatal location, decision conflict between parents, parental educational level and others), they had unexplained discordance between studies. Parental decision regret after proximal hypospadias surgery and refusing surgery was inadequately reported. In conclusion, even though the prevalence of parental decision regret after consenting for the hypospadias repair appears to be high, risk factors associated with it were discordant suggesting imprecision in estimates due to unknown confounders.

Impact of Training on Awareness and Knowledge of Service Providers About Maternal Near-Miss Events in Maharashtra, India.

OBJECTIVE: To improve the awareness and knowledge regarding Maternal Near Miss (MNM) among health service providers in the selected districts and women's hospitals in Maharashtra, India. METHODS: A one-day training programme on MNM was conducted at four Family Welfare Training Centres in the state of Maharashtra, India, for the health service providers, viz. gynaecologists, pathologists, anaesthesiologists, medical officers, staff nurses, other paramedical workers of the selected 29 districts/women's hospitals in Maharashtra. A total of 147 participants participated in the training programme. The participants filled a questionnaire before (pretest) and after the training (post-test) with the same set of questions pertaining to knowledge on the basic and operational aspects of MNM. RESULTS: There was a significant improvement in the level of knowledge (post-test responses vs pretest responses) about the correct definition and classification of MNM, as per the instructions in the MNM-R guidelines by the Government of India. The service providers informed regarding the challenges in the implementation of the MNM-R guidelines at their hospitals such as shortage of manpower in terms of specialists and need of quality assurance. CONCLUSION: The training programme improved the knowledge of the service providers about MNM, which would help them to implement the MNM-R guidelines effectively at their hospitals. This training effectively upgraded the knowledge level, and therefore, such trainings should be organized for all obstetricians, high-dependency unit (HDU) personnel and critical care teams.

Hemiscrotal agenesis with complete testicular descent in Van der Woude syndrome: a new phenotypic feature.

Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) spectrum are due to genetic variants in the IRF6 which phenotypically has been known to manifest with midline defects such as cleft lip and palate in VWS and additional nail, limb and genital anomalies in PPS. We report a case of VWS with the previously unrecognised phenotypic feature of hemiscrotal agenesis. While bifid scrotum has been reported in the more severe PPS, neither VWS nor PPS have previously noted hemiscrotal agenesis as part of the phenotypic picture. Hemiscrotal agenesis without evidence of any genetic anomaly has only been reported four times in the literature to date with two of these being accompanied by complete testicular descent. Treatment options include topical androgen application and/or scrotoplasty to allow for adequate testicular thermoregulation and development to occur.