Specific Trends in Pediatric Ethical Decision-Making: An 18-Year Review of Ethics Consultation Cases in a Pediatric Hospital.

This is a qualitative examination of ethics consultation requests, outcomes, and ethics committee recommendations at a tertiary/quaternary pediatric hospital in the U.S. The purpose of this review of consults over an 18-year period is to identify specific trends in the types of ethical dilemmas presented in our pediatric setting, the impact of consultation and committee development on the number and type of consults provided, and any clinical features and/or challenges that emerged and contributed to the nature of ethical situations and dilemmas. Furthermore, in reviewing clinical ethics consultation trends for nearly two decades, we can identify topic areas for further ethics education and training for ethics consultants, ethics committee members, and pediatric healthcare teams and professionals based on our experiences. Our study with nearly two decades of data prior to the COVID-19 pandemic can serve as groundwork for future comparisons of consultation requests and ethics support for pediatric hospitals prior to, during, and following a pandemic.

Understanding factors influencing primary treatment with intradetrusor onabotulinumtoxinA versus augmentation cystoplasty in patients with spina bifida.

PURPOSE: Surgical interventions in the urologic management of children with neurogenic bladder secondary to spina bifida aim to preserve upper tract function, prevent urinary tract infections, and optimize quality of life. However, since the introduction of intravesical onabotulinumtoxinA (Botox) in the management of these patients, the indications for choosing Botox over augmentation cystoplasty (AC) remain undefined. The objective of this study was to determine which factors lead patients to undergo Botox versus AC as a primary surgical treatment after failing medical management. METHODS: We retrospectively reviewed the records of pediatric patients with myelomeningocele undergoing either primary Botox or primary AC at our institution between 2013 and 2018. We recorded demographic and clinical information. We identified 10 important clinical decision-making factors: bladder trabeculation, vesicoureteral reflux, or hydronephrosis on imaging; end-filling pressure (EFP) ≥40 cm H2O, detrusor overactivity, detrusor-sphincter dyssynergia, or reduced capacity on urodynamic studies; physician-perceived bladder hostility; and patient/family desire for continence and independence. The presence of these factors was compared between patients undergoing either primary Botox or primary AC. RESULTS: We identified 14 and 50 myelomeningocele patients who underwent primary AC and primary Botox, respectively. We found no significant differences in age, sex, race, or history of reconstructive surgery (antegrade continence enema or catheterizable channel). For the 10 decision-making factors, desire for independence/continence (p = <0.001) and reduced capacity (p = 0.002) were significantly associated with AC, while trabeculation (p = 0.006), EFP ≥40 cm H2O (p = 0.029), rising slope (p = 0.019), and physician-perceived hostility (p = 0.012) were significantly more common with Botox. CONCLUSIONS: At our institution, quality of life measures prompted AC over objective urodynamic or imaging findings before attempting Botox. These findings support a shared decision-making approach when considering surgical intervention for neurogenic bladder secondary to myelomeningocele.

Risk factors for falls among adults with intellectual disabilities: A narrative review.

BACKGROUND: The prevalence of falls involving people with intellectual disabilities (ID) is high in comparison with the general population. There has been little evidence to date on the contributing risk factors. The objective of this review was to identify risk factors for people with intellectual disabilities. METHOD: Literature searches were conducted using electronic databases to explore evidence on the subject, and narrative synthesis was employed to analyse the results. RESULTS: Seven risk factors were identified: decreasing physical ability, epilepsy, paretic conditions, impulsiveness, previous falls, incontinence and non-use of assistive equipment. Thematic analysis identified factors across the four concepts: the person, the situation, ongoing and protective factors. CONCLUSION: Factors for falls involving people with intellectual disabilities are dynamic and multifactorial. Some are specific to the population; however, further research is required to develop the understanding of the possible reasons. The findings have implications across policy, education, practice and research.

Pelvic floor biofeedback therapy in children: Assessment of symptom scores in responders and non-responders.

INTRODUCTION: Pelvic Floor Biofeedback Therapy (PFBT) can be an effective treatment for pediatric lower urinary tract symptoms (LUTS). Due to differing perceptions of efficacy and practice patterns, we sought to further evaluate PFBT in our practice. We hypothesized that PFBT results in quiescence of EMG activity during voiding and improves questionnaire scores in patients with LUTS. METHODS: We retrospectively reviewed all patients undergoing PFBT and refined the analysis to females ≥6 years old with ≥2 sessions with completed voiding questionnaires pre- and post-treatment, active EMG during voiding, with non-neurogenic urinary tract complaints refractory to standard urotherapy. Validated Bladder Bowel Dysfunction (BBD) questionnaires were collected at each visit. Quiescence of EMG activity and changes in BBD score were the primary outcomes. RESULTS: 229 patients underwent ≥1 PFBT session, of which 64 females ≥6 years of age with ≥2 PFBT sessions and completed pre and post PFBT voiding questionnaires were identified. In this group, mean age at PFBT start was 10.1 (6.2-17.0). Patients completed 3.1 sessions (2-6). No difference was seen in post-void residual (PVR) between first and last session (23.8 vs 22.6 mL, P = 0.55). Median questionnaire score decreased from 18 (4-42) before to 13 (2-28) following PFBT (P < 0.0001). Responders, characterized by silencing of the EMG after PFBT, occurred in 31% (20/64). Non-responders were younger (P = 0.007) with higher pre-PFBT questionnaire scores. CONCLUSION: The use of PFBT appears to result in a significant reduction in symptom scores, though quiescence of EMG was observed following therapy in less than 1/3 of patients.

Interrater Reliability in Interpretation of Neuropathic Pediatric Urodynamic Tracings: An Expanded Multicenter Study.

PURPOSE: Urodynamic findings often guide treatment for neuropathic bladder and are reported as objective data points in multi-institutional trials. However, urodynamic interpretation can be variable. In a pilot study pediatric urologists interpreting videourodynamics exhibited only moderate agreement despite similar training and practice patterns. We hypothesized the pilot study variability would be replicated in a multi-institutional study. MATERIALS AND METHODS: We developed an anonymous electronic survey that contained 20 scenarios, each with a brief patient history, 1 urodynamic tracing and fluoroscopic imagery. All videourodynamics were completed during routine care of patients with neuropathic bladder at a single institution. Pediatric urologists from Centers for Disease Control and Prevention Urologic Protocol sites were invited to complete an interpretation instrument for each scenario. Fleiss kappa and 95% confidence limits were reported, with Fleiss kappa 1.00 corresponding to perfect agreement. RESULTS: The survey was completed by 14 pediatric urologists at 7 institutions. Substantial agreement was seen for assessment of fluoroscopic bladder shape (Fleiss kappa 0.73), while moderate agreement was observed for assessment of bladder safety, end filling detrusor pressure and bladder capacity (Fleiss kappa 0.50, 0.56 and 0.54, respectively). Fair agreement was seen for electromyographic synergy and presence of detrusor overactivity (Fleiss kappa 0.21 and 0.35, respectively). CONCLUSIONS: Experienced pediatric urologists demonstrate variability during interpretation of videourodynamic tracings. Subjectivity of assessment of electromyographic activity and detrusor overactivity was confirmed in this expanded study. Future work to improve the reliability of videourodynamic interpretation would improve the quality of clinical care and the quality of multi-institutional studies that use urodynamic data points as outcomes.

Update on Continent Catheterizable Channels and the Timing of their Complications.

PURPOSE: We previously reported catheterizable channel associated outcomes and concluded that the incidence of postoperative complications was greatest in the first 2 years after surgery. At that time our followup was short. In this series we sought to determine whether complications continued to accumulate with longer followup in an updated cohort of patients. MATERIALS AND METHODS: We comprehensively reviewed the outcomes in 81 consecutive patients who underwent construction of a MACE (Malone antegrade continence enema) and/or a Mitrofanoff channel in association with complex genitourinary reconstruction. Mean followup was 80.1 months. Outcomes of these 119 stomas were classified by Clavien-Dindo grade and time to complication. RESULTS: The 48 unique, channel related events (40.3%) necessitated a total of 70 interventions with a mean 24.2 months to the first event. Difficult catheterization was the most common event, occurring in 20.1% of channels an average of 29.9 months after surgery. Stomal stenosis was also common, developing in 12.6% of channels at an average of 19.9 months after surgery. Unique complications clustered in the first 2 years, after which there was a statistically significant decline (p = 0.0013). High grade complications similarly clustered (p <0.0001). Channel composition was significantly associated with rates of difficult catheterization events. CONCLUSIONS: Compared to our previous cohort of patients with similar volume but shorter followup, our assumption that channel associated complications cluster postoperatively and then decrease significantly was correct. Our current and more detailed series demonstrates that the rate of postoperative complications decreases with time. However, with longer followup patients continue to experience lower grade events requiring fewer interventions.

Interrater Reliability in Pediatric Urodynamic Tracings: A Pilot Study.

PURPOSE: Urodynamic studies are crucial to neuropathic bladder management and they often determine surgical intervention. However, current evidence indicates that interpretations show poor agreement across physicians. We sought to determine the interrater reliability of urodynamic interpretation in our practice. We hypothesized that there would be strong correlation among pediatric urologists of similar training in a single academic practice. MATERIALS AND METHODS: We retrospectively identified patients with neuropathic bladder who underwent urodynamics at our institution between 2014 and 2015. An anonymous electronic survey (phase I) was developed with 20 clinical scenarios, each containing a brief history, a single urodynamic tracing and an accompanying fluoroscopic image. Faculty members assessed each tracing by an online instrument developed using urodynamic reports and published literature. The primary outcome was statistical correlation across raters as measured by the Spearman correlation coefficient. In a followup study (phase II) we investigated the sources of variability in urodynamic interpretations. RESULTS: Six faculty members completed the study with a response rate of 100%. In comparing urodynamic interpretation across raters, the faculty demonstrated a weak to strong correlation (rs 0.39-0.61, p <0.001). A strong correlation was found for fluoroscopic and clinical decision making variables, while electromyography synergy and detrusor overactivity demonstrated weaker correlation across physicians. CONCLUSIONS: Faculty interpretations of urodynamic tracings showed only moderate agreement despite a close working relationship and similar training at a single institution. Variability in interpretation can strongly impact patient treatment. Therefore, further work is needed to standardize the reporting and interpretation of urodynamic studies to optimize patient care.

Modulation of the rat micturition reflex with transcutaneous ultrasound.

INTRODUCTION: Low intensity focused ultrasound has recently been identified as a novel method of stimulating targeted neurons. We hypothesized that ultrasound stimulation of the posterior tibial nerve would inhibit bladder contractions in an established rat model of rhythmic bladder contractions. METHODS: Cyclical detrusor contractions were initiated by placing a transurethral catheter in female rats and infusing saline into the bladder. Transcutaneous ultrasound pulses were then delivered to the lower extremity of a rat (overlying the posterior tibial nerve) using a single element spherically focused 250 kHz transducer. Sixty-three cycles were repeated at 2 kHz for 300 ms at peak negative pressure of 900 kPa pulsed at 0.5 Hz. RESULTS: We report successful suppression of bladder contractions using ultrasound stimulation in 10 animals. The average latency between the initiation of ultrasound and suppression of bladder contractions was 3 min 23 s (±51 s), the average time of contraction suppression was 13 min and 50 s (±2 min 25 s) and the average time from the end of ultrasound to return of contractions was 9 min 37 s (±2 min and 30 s). CONCLUSION: In this work, we demonstrate the ability of targeted transcutaneous ultrasound to inhibit rhythmic bladder contractions in anesthetized rats. Due to its non-invasive nature and ease of application, we believe ultrasound mediated suppression of the micturition reflex is potentially an ideal outpatient treatment of overactive bladder and dysfunctional elimination.

Prospective Evaluation of Sacral Neuromodulation in Children: Outcomes and Urodynamic Predictors of Success.

PURPOSE: Sacral neuromodulation has been demonstrated to improve refractory bowel bladder dysfunction in children. The purpose of the current study was to determine whether results are durable in children after longer followup, whether children with a lower body mass index are at risk for device failure and whether pretreatment urodynamic evaluation can predict posttreatment outcome. MATERIALS AND METHODS: Pediatric patients with refractory bowel bladder dysfunction were enrolled following informed consent and followed prospectively. All patients underwent preoperative videourodynamic evaluation and a 2-stage implantation procedure. Validated questionnaires were used to assess symptom severity and quality of life. Complications were analyzed with regard to treatment required and patient body mass index. RESULTS: During 45 months 30 patients were enrolled. Median age was 8.3 years at enrollment. Median followup was 14.8 months. Patients had significant improvement in quality of life and symptom scores, which persisted at the most recent followup. Patients who had uninhibited detrusor contractions on preoperative urodynamic assessment had significantly greater improvement in symptoms. Of the patients 23% had a complication requiring reoperation, most commonly neurostimulator lead breakage in those with a significantly lower body mass index. CONCLUSIONS: Sacral neuromodulation significantly improves quality of life and symptom severity in children with refractory bowel bladder dysfunction. Children gain greater benefit if they show uninhibited bladder contractions on preoperative urodynamic evaluation. Children have a high rate of lead breakage requiring operative revision, which was seen after minor trauma in those with a lower body mass index.

Bullying and lower urinary tract symptoms: why the pediatric urologist should care about school bullying.

PURPOSE: Bullying has become a social plague associated with various deleterious outcomes. We hypothesized that pediatric lower urinary tract symptoms could be associated with exposure to bullying. MATERIALS AND METHODS: We assessed exposure to school bullying via the Setting the Record Straight bullying questionnaire in children 8 to 11 years old being evaluated for lower urinary tract symptoms at our pediatric urology clinic. Lower urinary tract symptoms were quantified with the Vancouver Symptom Score. Children 8 to 11 years old presenting for pediatric well visits also completed the questionnaires. Linear regression assessed the relationship between Vancouver Symptom Score and bullying score. Categorical variables were compared by chi-square test, while continuous variables were compared using the Student t-test. RESULTS: A total of 113 children at the urology clinic and 63 children in the primary care setting consented to participate. There were significant differences between the 2 populations, including gender and race, with significantly more perpetrators of bullying in the primary care group (7.9% vs 0.9%, p = 0.02). When looking specifically at the urology group, there was a significant association between Vancouver Symptom Score and self-perceived (p <0.001) and peer perceived (p <0.001) victimization scores. In the primary care group there was also a significant association between Vancouver Symptom Score and self-perceived (p = 0.01) and peer perceived (p = 0.001) bullying perpetrator scores. Of children seen at the primary care office 33% had a significant Vancouver Symptom Score. CONCLUSIONS: Although bullying exposure is multifactorial, we found that Vancouver Symptom Score can be associated with bullying victimization and perpetrator scores.

To tell or not: parental thoughts on disclosure of urologic surgery to their child.

PURPOSE: Literature pertaining to surgical disclosure to the pediatric patient is lacking. We hypothesized parents would find it difficult to disclose urologic surgery to a child. MATERIALS AND METHODS: Parents of patients <5 years old undergoing urologic surgery were contacted for telephone survey. Parents were asked about future plans of surgical disclosure, comfort with disclosure, and any support received. RESULTS: 98 parents consented to study participation. 87% of surgeries were on the genitalia with 62% being minor genitalia surgery (i.e. circumcision). 70% of parents would tell their child about minor genital surgery while 84% would tell about major genital surgery (p=0.07). 4 of 20 parents of children undergoing hypospadias repair (major genital surgery) did not plan to tell their child about surgery. All parents of children undergoing non-genital surgery would tell. Of all parents planning to tell their children about surgery, only 14% were nervous. 34% of parents would find guidance in talking to their child helpful despite the majority (90%) stating no guidance had ever been provided. CONCLUSIONS: Parents seem comfortable discussing urologic surgeries with a child but about 1/3 would appreciate further counseling. 20% of parents of children undergoing hypospadias repair hope to avoid telling their child.

Outcomes of incontinent ileovesicostomy in the pediatric patient.

PURPOSE: Ileovesicostomy is a reconstructive option in complex urological cases but pediatric specific outcomes are lacking. We report our results with pediatric ileovesicostomy. MATERIALS AND METHODS: We retrospectively evaluated patients younger than 18 years undergoing incontinent ileovesicostomy at Vanderbilt University. History, urinary tract management and operative course were reviewed in the electronic medical record. Particular attention was given to immediate and long-term postoperative complications. RESULTS: Nine patients underwent incontinent ileovesicostomy between 2000 and 2013 at a mean age of 10.3 years (range 1.4 to 15.5). Surgical indication was sequelae of neurogenic or nonneurogenic neurogenic bladder (such as infection or worsening hydronephrosis) in 5 patients, reversal of vesicostomy in 3 and closure of cloacal exstrophy in 1. All 9 patients were thought incapable of reliable clean intermittent catheterization due to family unwillingness, poor social support or patient refusal. Median followup was 11.5 months (mean 48.2, range 1.3 to 144.8). Immediate postoperative complications included ileus requiring total parenteral nutrition and a wound infection in 1 patient. Long-term complications included urinary tract infection in 2 patients (febrile in 1 and positive culture for foul smelling urine in 1), stomal issues in 2 and temporary urethral leakage in 1. Constipation affected 3 children in long-term followup (all with neurogenic bowel preoperatively). Postoperative creatinine was stable or improved in all patients. CONCLUSIONS: Ileovesicostomy is a viable approach in children left with few other options, particularly those who are noncompliant or physically/socially unable to handle catheterization. This operation can help keep such patients out of diapers.

F2-isoprostanes as a biomarker of oxidative stress in the mouse bladder.

PURPOSE: We theorized that progressive bladder dysfunction due to clinical diagnoses such as outlet obstruction occurs as a result of cyclical oxidative stress events. We hypothesized that measurement of F2-isoprostane, a marker of lipid peroxidation, could serve as a biomarker of oxidative stress in the murine bladder. MATERIALS AND METHODS: At age 5 to 6 weeks oophorectomized female mice were subjected to 1 of 2 bladder injury models, that is partial bladder outlet obstruction or acute bladder distension. The time points studied after injury included 4, 8 and 16 weeks after obstruction, and 0 to 48 hours after acute bladder distension. In a separate group short-term repetitive acute bladder distension was performed every other day for 14 days. Bladder samples were analyzed for F2-isoprostane using gas chromatography and mass spectroscopy. Mean tissue F2-isoprostane levels were compared. RESULTS: F2-isoprostane increased significantly after 4 weeks of partial bladder outlet obstruction from 1.46 ng/gm in controls to 2.31 ng/gm at 4 weeks (p = 0.01). Eight and 16 weeks after partial bladder outlet obstruction F2-isoprostane remained significantly elevated (2.39 and 2.48 ng/gm, respectively). Acute bladder distension resulted in a significant increase in F2-isoprostane immediately after distension compared to controls (1.6 vs 0.75 ng/gm, p = 0.04). In mice that underwent repetitive acute bladder distension F2-isoprostane did not change. CONCLUSIONS: Measurement of tissue F2-isoprostane in the bladder reflects the progression of oxidative stress, primarily in chronic injury models such as partial bladder outlet obstruction. The usefulness of F2-isoprostane measurements in shorter term injury models requires further study.

Pediatric Consent on FHIR.

BACKGROUND: Standardizing and formalizing consent processes and forms can prevent ambiguities, convey a more precise meaning, and support machine interpretation of consent terms. OBJECTIVES: Our goal was to introduce a systematic approach to standardizing and digitizing pediatric consent forms, which are complex due to legal requirements for child and legal guardian involvement. METHODS: First, we reviewed the consent requirements from the Arizona regulation, and we used 21 pediatric treatment consents from five Arizona health care organizations to propose and evaluate an implementation-agnostic Consent for Treatment Framework. Second, we assessed the adequacy of the Fast Healthcare Interoperability Resources (FHIR) to support the proposed framework. RESULTS: The resulting Consent for Treatment Framework supports compliance with the state consent requirements and has been validated with pediatric consent forms. We also demonstrated that the FHIR standard has the required expressiveness to compute the framework's specifications and express the 21 consent forms. CONCLUSION: Health care organizations can apply the shared open-source code and FHIR implementation guidelines to standardize the design of machine-interpretable pediatric treatment consent forms. The resulting FHIR-based executable models may support compliance with the law and support interoperability and data sharing.

Prospective evaluation of sacral nerve modulation in children with validated questionnaires.

PURPOSE: Sacral neuromodulation for refractory urinary dysfunction in pediatrics shows promising results. We prospectively evaluated patients undergoing sacral neuromodulation using validated quality of life and bladder dysfunction questionnaires. MATERIALS AND METHODS: All patients were prospectively enrolled in the study. Two validated questionnaires were completed preoperatively, after lead placement and at all followups. The PedsQL™ 4.0 Generic Core Scale, which assesses quality of life and bladder dysfunction, was quantified using the Vancouver Nonneurogenic Lower Urinary Tract Dysfunction/Dysfunctional Elimination Syndrome (NLUTD/DES) questionnaire. The Wilcoxon matched pairs test was used for statistical analysis with p <0.05 considered significant. RESULTS: A total of 14 patients with a median age of 10 years were enrolled in the study. Median followup was 6 months. All patients underwent generator placement. No significant difference was seen in physical quality of life. Before and after lead placement mean ± SD psychosocial quality of life scores were 70.6 ± 17.4 and 81.43 ± 14.8 (p = 0.02), mean total quality of life scores were 75 ± 15.3 and 84.04 ± 13.2 (p = 0.006) and median NLUTD/DES scores were 23 ± 7.8 and 10.5 ± 7.0 (p <0.001), respectively. One month postoperatively a significant difference was seen in total quality of life and NLUTD/DES scores. Two patients required replacement of the temporary lead or generator. There were no infections. CONCLUSIONS: Patients undergoing sacral neuromodulation had significant improvement in NLUTD/DES scores, and psychosocial and overall total quality of life. Results were durable at 1 month. Continuing to follow these patients in a prospective manner with validated questionnaires will strengthen the current evidence supporting sacral neuromodulation in the pediatric population.

Incidence of abnormal imaging and recurrent pyelonephritis after first febrile urinary tract infection in children 2 to 24 months old.

PURPOSE: The AAP (American Academy of Pediatrics) no longer recommends voiding cystourethrogram in children 2 to 24 months old who present with a first urinary tract infection if renal-bladder ultrasound is normal. We identified factors associated with abnormal imaging and recurrent pyelonephritis in this population. MATERIALS AND METHODS: We retrospectively evaluated children diagnosed with a first episode of pyelonephritis at age 2 to 24 months using de-identified electronic medical record data from an institutional database. Data included age at first urinary tract infection, gender, race/ethnicity, need for hospitalization, intravenous antibiotic use, history of abnormal prenatal ultrasound, renal-bladder ultrasound and voiding cystourethrogram results, urinary tract infection recurrence and surgical intervention. Risk factors for abnormal imaging and urinary tract infection recurrence were analyzed by univariate logistic regression, the chi-square test and survival analysis. RESULTS: We identified 174 patients. Of the 154 renal-bladder ultrasounds performed 59 (38%) were abnormal. Abnormal prenatal ultrasound (p = 0.01) and the need for hospitalization (p = 0.02) predicted abnormal renal-bladder ultrasound. Of the 95 patients with normal renal-bladder ultrasound 84 underwent voiding cystourethrogram. Vesicoureteral reflux was more likely in patients who were white (p = 0.003), female (p = 0.02) and older (p = 0.04). Despite normal renal-bladder ultrasound, 23 of 84 patients (24%) had dilating vesicoureteral reflux. Of the 95 patients with normal renal-bladder ultrasound 14 (15%) had recurrent pyelonephritis and 7 (7%) went on to surgical intervention. CONCLUSIONS: Despite normal renal-bladder ultrasound after a first pyelonephritis episode, a child may still have vesicoureteral reflux, recurrent pyelonephritis and the need for surgical intervention. If voiding cystourethrogram is deferred, parents should be counseled on these risks.

Chronic cyclic bladder over distention up-regulates hypoxia dependent pathways.

PURPOSE: Bladder over distention secondary to anatomical or functional obstruction can eventually lead to pathological changes, including decreased elasticity and contractile dysfunction. We hypothesized that chronic bladder distention in a murine model would activate hypoxia dependent signaling pathways despite intermittent relief of distention. MATERIALS AND METHODS: Female C57Bl/6 mice were oophorectomized at age 5 to 6 weeks and underwent urethral catheterization and 90-minute bladder distention. Acute and chronic time points were evaluated. Bladder tissue was harvested for hematoxylin and eosin, and immunohistochemical staining with the hypoxia markers Glut-1 (EMD Millipore, Merck, Darmstadt, Germany) and Hypoxyprobe™-1. Bladder tissue was also harvested for real-time polymerase chain reaction and oxidative stress measurement. Hypoxia polymerase chain reaction arrays were done to determine changes in gene expression. Oxidative stress was measured using F2-IsoP. Functional bladder changes were evaluated using voided urine blots. RESULTS: After acute distention and 5 consecutive distentions, bladders showed marked inflammatory changes on hematoxylin and eosin staining, and evidence of tissue hypoxia on immunohistochemistry. Quantitative real-time polymerase chain reaction revealed up-regulation of hypoxia and oxidative stress related genes, including Hif1a, Arnt2, Ctgf, Gpx1 and Hmox1. Measurements of oxidative stress with F2-IsoP did not change. Voided urine blots before and after bladder distention showed marked changes with an overactive voiding pattern. CONCLUSIONS: Chronic bladder distention is possible in the female mouse. It generates hypoxic injury, as characterized functionally by increased voiding patterns. This bladder injury model might more closely replicate bladder dysfunction in patients with poor bladder emptying due to neurological disease, including those noncompliant with intermittent catheterization.

An evaluation of onobotulinumtoxinA as a therapeutic option for pediatric neurogenic detrusor overactivity.

INTRODUCTION: Neurogenic detrusor overactivity (NDO) results in involuntary detrusor contractions during bladder filling or storage risking transmission of pressure to the upper urinary tracts and/or significant incontinence. The goals of bladder management in children with NDO prioritize the preservation of renal function, prevention of UTIs, and optimizing quality of life. First-line measures include intermittent catheterization and anticholinergic medication. However, when conservative measures fail, surgical intervention may be indicated. Historically, the next step was major reconstructive surgery to create a low-pressure urinary reservoir. The introduction of intravesical botulinum neurotoxin A (BoNT/A) for use in children in 2002 offered a less invasive option for management. However, its exact role is still evolving. AREAS COVERED: This article summarizes the mechanism of action of BoNT/A for management of NDO and evaluates the current literature defining common practice and clinical efficacy in children with NDO. The findings of the recently completed phase III trial for intravesical onabotulinumtoxinA in children are discussed in detail. EXPERT OPINION: As the first BoNT/A approved for use in children with NDO, onabotulinumtoxinA appears to be a safe and less invasive alternative to major reconstructive surgery. However, data defining appropriate patient selection and its role as a long-term treatment option continue to develop.