Results of a study examining the use of onabotulinumtoxinA in pediatric patients with overactive bladder.

BACKGROUND: There is a lack of approved treatments for pediatric patients with overactive bladder (OAB) with inadequate response to anticholinergic therapy. OnabotulinumtoxinA 100U is approved to treat OAB in adults based on data from randomized, pivotal trials. OBJECTIVE: To investigate the efficacy and safety of onabotulinumtoxinA treatment of OAB in children aged 12-17 years who were not adequately managed with anticholinergics. STUDY DESIGN: In this multinational, multicenter, randomized, double-blind, parallel-group, multiple-dose study (NCT02097121), pediatric patients with OAB were randomized 1:1:1 to receive onabotulinumtoxinA 25U, 50U, or 100U (≤6 U/kg). Patients could request retreatment starting at week 12. The primary endpoint was change from baseline to week 12 after treatment 1 in daily frequency of daytime urinary incontinence (UI) episodes. Safety assessments evaluated treatment-emergent adverse events (TEAEs). RESULTS: Of 68 screened patients, 55 received ≥1 treatment. Mean age was 14 years; 85.5% of patients were female. At week 12 after treatment 1, least squares mean change from baseline in daily frequency of daytime UI episodes showed a numerically greater reduction in the 100U arm (-2.4) versus the 25U arm (-1.4; P = 0.38), with a significant within-group change from baseline in the 100U arm (P = 0.0027). Achievement of treatment response was significantly greater with onabotulinumtoxinA 100U vs 25U (Figure). Median time to request retreatment was ≥16 weeks in all groups. The most frequently reported TEAEs were nasopharyngitis (10.9%) and urinary tract infection (UTI; 10.9%). Urinary retention was observed in 1 patient during treatment cycle 2; there were no serious TEAEs of UTI or urinary retention. Throughout 2 additional treatment cycles continued efficacy for the 100U dose arm was observed along with a consistent safety profile. DISCUSSION: Change in daily frequency of UI episodes at week 12 in treatment cycle 1 was not significantly different between arms. However, ≥50% response rate was significantly higher with onabotulinumtoxinA 100U versus 25U. Enrollment challenges that lowered the sample size could have reduced statistical power. Also, the lack of a placebo arm and the observed benefit with the 25U comparator limited interpretation. CONCLUSIONS: OnabotulinumtoxinA injections were well tolerated in children with OAB at all doses studied. Although the primary endpoint was not met, the significantly greater treatment response rate observed with onabotulinumtoxinA 100U versus 25U suggests additional benefit of the higher dose, without additional safety concerns.

Implementation of a health system intervention to reduce time from presentation to surgical intervention for pediatric testicular torsion.

PURPOSE: Testicular salvage rates for torsion are time-dependent1. Door to detorsion time has been identified as an independent testicular survival factor2. We describe an initiative to reduce door to incision (DTI) time for pediatric testicular torsion. MATERIALS AND METHODS: An institutional multidisciplinary quality improvement initiative with a primary outcome of reducing DTI time for pediatric testicular torsion was developed with multidisciplinary stakeholders. Several process and balancing measures were used as secondary outcomes to help interpret and verify the observed change in DTI time. Interventions were implemented in cycles. Initial interventions standardized assessment of suspected torsion by Emergency Medicine utilizing a validated scoring system. A threshold Testicular Workup for Ischemia and Suspected Torsion (TWIST) score led to parallel notification of essential services for rapid assessment and case prioritization3. Subsequently, bedside ultrasound in the Emergency Department was implemented. Progress was tracked in a live dashboard and analyzed with X-mR process control charts and Nelson rules. These tools are used in quality improvement and process control to demonstrate the significance of changes as they are being implemented, prior to when traditional hypothesis testing would be able to do so. We aimed to increase the proportion of cases with DTI times under 4 h from 64% to >90% within one year. RESULTS: We observed 22 torsion cases prior to and 62 following initial implementation. The percentage of cases with DTI times under 4 h improved from 64% to 95%. At week 29, a shift identified a significant change on the X chart, with reduction in mean DTI time from 221 to 147 min. At the same time, a shift on the mR chart identified reduction in patient-to-patient variation. Mean time from arrival to Urology evaluation decreased from 140 to 56 min, mean time from arrival to scrotal ultrasound decreased from 70 to 36 min, and mean time from scrotal ultrasound to surgical incision decreased from 128 to 80 min. These improvements highlight the two key successes of our project: application of the TWIST score and bedside ultrasound for rapid assessment of suspected testicular torsions, and parallel processing of the evaluation and management. CONCLUSIONS: Implementation of a protocol for pediatric testicular torsion increased the proportion of cases with DTI time <4 h to 95%, decreased mean DTI time, and decreased variation. Our protocol provides a model to improve timeliness of care in treating pediatric testicular torsion.

Feasibility of establishing a multi-center research database using the electronic health record: The PURSUIT network.

BACKGROUND: Although multi-center research is needed in pediatric urology, collaboration is impeded by differences in physician documentation and research resources. Electronic health record (EHR) tools offer a promising avenue to overcome these barriers. OBJECTIVE: To assess the accuracy, completeness, and utilization of structured data elements across multiple practices. STUDY DESIGN: A standardized template was developed and implemented at five academic pediatric urology practices to document clinic visits for patients with congenital hydronephrosis and/or vesicoureteral reflux. Data from standardized elements in the template and from pre-existing EHR fields were extracted into a secure database. A 20% random sample of infants with data from structured elements from 1/1/2020 and 4/30/2021 were identified and compared to manual chart review at sites with >100 charts; all other sites reviewed at least 20 charts. Manual chart review was standardized across sites and included: clinic and operative notes, orders linked to the clinic encounter, radiology results, and active medications. Accuracy of data extraction was evaluated by computing the kappa statistic and percentage agreement. For sites that had adopted the templates prior to 6/1/2019 (early adopters), a list of eligible patients with an initial clinic visit from 1/1/2020-7/27/2020 was generated using standardized reporting techniques and confirmed by manual chart review. Physician utilization of the template was then calculated by comparing patients with data obtained from the note template to the generated list of eligible patients. RESULTS: 230 patient records met study criteria. Agreement between manual chart review and data extracted from the EHR was high (>85%). Race, ethnicity and insurance data were misclassified in about 10-15% of cases; this was due to site-specific differences in how these fields were coded. Renal ultrasound was misclassified 12% of the time; this was primarily due to outside images documented in radiology results but not included in the clinical note. All other data elements had >90% agreement (Figure). Template utilization for early adopters was >75% (75.5-87.5%). DISCUSSION: This is the first study in urology to demonstrate that use of structured data elements can support multi-center research. Limitations include: inclusion of only academic sites with the Epic EHR and lack of data on utilization and sustainability at sites without a prior history of structured template use. CONCLUSIONS: Multi-center research collaboration using EHR-based data collection tools is feasible with generally high accuracy compared to manual chart review. Additionally, sites with a long history of template adoption have high levels of provider utilization.

Urology Residency Training in Medically Underserved Areas Through the Integration of a Federally Qualified Health Center Rotation.

OBJECTIVE: To identify workforce related barriers to urologic care in Medically Underserved Areas (MUA) and Health Professional Shortage Areas (HPSA). Federally Qualified Health Centers (FQHC) are community-based organizations that aim to close gaps, but little is known about exposure to underserved areas during residency training. METHODS: The objective of this study was to characterize the experiences of urology residents who participated in a rotation within a FQHC. The study consisted of: (1) 12-item post-rotation self-assessment (2) review of career paths of former graduates who completed the rotation, and (3) retrospective review of patients treated at FQHC from 2016 to 2018. RESULTS: There were a total of 1735 patient visits, 97 were for cystoscopy, 76.36% of patients had Medicaid or no insurance. There were 1092 unique patients seen and 281 (25.73%) were referred for surgery. A majority of residents (100%) stated they had a better appreciation of treating patients in underserved areas. A majority of residents (71.6%) of residents said they were more likely to practice in an underserved area after residency. Among former graduates who rotated through the clinic, 100% (n = 4) were practicing in a MUA or HPSA. CONCLUSION: The integration of an FQHC during urology residency training was associated with highly favorable satisfaction by trainees. Given persistent workforce related shortages in urology, these findings support exposure to medically underserved areas during training.

Antireflux Surgery at National Surgical Quality Improvement Program-Pediatric Hospitals.

PURPOSE: This study aims to examine contemporary practice patterns and compare short-term outcomes for vesicoureteral reflux procedures (ureteral reimplant/endoscopic injection) using National Surgical Quality Improvement Program-Pediatric data. MATERIALS AND METHODS: Procedure-specific variables for antireflux surgery were developed to capture data not typically collected in National Surgical Quality Improvement Program-Pediatric (eg vesicoureteral reflux grade, urine cultures, 31-60-day followup). Descriptive statistics were performed, and logistic regression assessed associations between patient/procedural factors and outcomes (urinary tract infection, readmissions, unplanned procedures). RESULTS: In total, 2,842 patients (median age 4 years; 76% female; 68% open reimplant, 6% minimally invasive reimplant, 25% endoscopic injection) had procedure-specific variables collected from July 2016 through June 2018. Among 88 hospitals, a median of 24.5 procedures/study period were performed (range 1-148); 95% performed ≥1 open reimplant, 30% ≥1 minimally invasive reimplant, and 70% ≥1 endoscopic injection, with variability by hospital. Two-thirds of patients had urine cultures sent preoperatively, and 76% were discharged on antibiotics. Outcomes at 30 days included emergency department visits (10%), readmissions (4%), urinary tract infections (3%), and unplanned procedures (2%). Over half of patients (55%) had optional 31-60-day followup, with additional outcomes (particularly urinary tract infections) noted. Patients undergoing reimplant were younger, had higher reflux grades, and more postoperative occurrences than patients undergoing endoscopic injections. CONCLUSIONS: Contemporary data indicate that open reimplant is still the most common antireflux procedure, but procedure distribution varies by hospital. Emergency department visits are common, but unplanned procedures are rare, particularly for endoscopic injection. These data provide basis for comparing short-term complications and developing standardized perioperative pathways for antireflux surgery.

Interpretation of uroflow curves: A global survey measuring inter and intra rater reliability.

INTRODUCTION: There is a large amount of intra and inter observer variability in defining curve shapes. This study aims to evaluate inter and intra rater reliability (RR) on evaluating uroflow curves in a broad spectrum of international practitioners. METHODS: Eight hundred sixty-four questionnaires were sent by email to health professionals that care for children with voiding dysfunction. It included demographic questions and 11 different uroflow curves and two duplicates. RESULTS: Four hundred forty-one emails were opened and 29.5% of those responded. Seventy percent of responders were physicians, including 46% pediatric urologists. Europe, South America, North America, Oceania, and Asia represented respondents. For the repeated bell smooth curve the intra rater agreement was 82.1% utilizing the International Children's Continence Society (ICCS) classification and 92.3% for the shape of the curve (bell, plateau, and tower [BPT]) (P = .04). For the repeated interrupted plateau curve it was 69.5% and 97.5% for ICCS and for the continuity of the curve (smooth or fractionated [SF]) classifications, respectively (P < .001). The curves were then divided into two groups for evaluation of inter RR. For the set of seven smooth curves, the inter RR was low in all classifications with α = .282, .497, and .242 for ICCS, SF, and BPT, respectively. The group of six fractionated curves showed a slightly better agreement with α = .533, .404, and .662 for ICCS, SF, and BPT, respectively. CONCLUSIONS: This is the largest study looking at inter and intra RR of uroflows in a disparate population of readers. It was evident from our findings that inter RR was poor and additionally intra RR was equally poor, indicating the unreliability of uroflow shapes to be used for research purposes.

Identification of an occult recto-prostatic fistula with cystoscopy-assisted air colostogram.

INTRODUCTION: Anorectal malformations (ARM) in newborns classically present with the absence of a normal anus or an abnormally located anus. In a male infant with a high ARM, an initial diverting colostomy is later followed by a definitive posterior sagittal anorectoplasty (PSARP). Prior to definitive surgery an augmented-pressure colostogram is performed to identify the location of the fistula between the rectum and urogenital tract. However, on occasion, the augmented-pressure colostogram fails to identify the location of the fistula tract. We present a case of ARM where augmented-pressure colostogram failed to identify a fistula tract, thus requiring an alternative diagnostic approach. PRESENTATION OF CASE: A newborn male presented with a high anorectal malformation and suspected rectourinary fistula on initial augmented-pressure colostogram. The patient ultimately underwent a laparoscopic assisted PSARP after cystoscopy with air colostogram identified the exact location of the fistulous connection in the prostatic urethra. DISCUSSION: Augmented-pressure colostogram remains the gold standard in diagnosing rectourinary fistulae in cases of ARM. However, a number of alternative and adjunctive techniques have been proposed in recent years. We provide a brief review of the literature in addition to a case presentation highlighting the potential benefits of pre-operative cystoscopy-assisted air colostogram in male patients with ARM. CONCLUSION: Cystoscopy-assisted air colostogram via a distal mucous fistula can be utilized as an alternative diagnostic modality, especially when the augmented-pressure distal colostogram fails to identify rectourinary fistulae in high anorectal malformations.

Strategies for Attracting Women and Underrepresented Minorities in Urology.

PURPOSE OF REVIEW: This article summarizes the current state of underrepresented minorities (URM) and women within urology. Specific strategies to promote the recruitment and retention of URM and women within urology are discussed. RECENT FINDINGS: Minorities and women remain underrepresented within urology, a disparity that has roots as early as medical school and persists throughout residency and practice. This is likely due to implicit and explicit bias, lack of role models, and persistent disparities in compensation and promotion. Strategies to improve recruitment and retention of these individuals should focus on increasing early exposure to urology, opportunities for mentorship, and support in professional development. Creation of a supportive institutional culture, consideration of alternative career advancement paths, and intentional diversity-focused recruitment efforts are also critical. Successful recruitment and retention of URM and women in urology requires specific, directed efforts to increase opportunities for exposure, mentorship, and career promotion at a programmatic, institutional, and national level.

Knowledge and Practices of Physicians and Nurses Related to Urine Cultures in Catheterized Patients: An Assessment of Adherence to IDSA Guidelines.

BACKGROUND: A positive urine culture often drives initiation of antimicrobials even in the absence of symptoms. Our objectives were to evaluate the knowledge and practice patterns related to ordering urine cultures in patients with indwelling urinary catheters. METHODS: We performed chart reviews of catheter-associated urinary tract infections (CAUTIs) at our academic health care system between October 1, 2015, and September 30, 2017, to assess practice patterns related to the assessment of potential CAUTIs. Following this, we surveyed physicians and nurses about indications for ordering urine cultures in catheterized patients between January 11, 2018, and April 17, 2018. The accuracy of these indications was assessed based on Infectious Diseases Society of America CAUTI and asymptomatic bacteriuria guidelines. RESULTS: On chart review, we identified 184 CAUTIs in 2 years. In 159 episodes (86%), urine cultures were ordered inappropriately. In 114 episodes (62%), CAUTI criteria were met by "pan-culturing" rather than symptom-directed testing. Twenty cases (11%) experienced partial or delayed management of other infections, drug adverse events, and Clostridioides difficile infections (CDIs). On our survey, we received 405 responses, for a response rate of 45.3%. Mean scores varied by occupation and level of training. Nurses were more likely than physicians to consider change in appearance (61% vs 23%; P < .05) and odor (74% vs 42%; P < .05) of urine as indications to order urine cultures. CONCLUSIONS: Our data reveal specific knowledge gaps among physicians and nurses related to ordering urine cultures in catheterized patients. The practice of pan-culturing and inappropriate urine culture orders may contribute to overdiagnosis of surveillance CAUTIs, delay in diagnosis of alternative infections, and excess CDIs.

Robot-Assisted Excision of Congenital Mega-Seminal Vesicle Associated with Zinner's Syndrome.

Background: Abnormalities of mesonephric ducts are rare congenital conditions, which can present with vague symptoms in otherwise healthy men. Zinner's syndrome is the association of an enlarged seminal vesicle cyst with ipsilateral renal agenesis, which can be symptomatic and require operative interventions. Case: We present the case of an otherwise healthy 24-year-old man who presented with a symptomatic 15 cm seminal vesicle cyst, which was completely excised using a robot-assisted approach. Conclusion: Use of robotic surgery for excision of large seminal vesicle cysts is a safe and effective operative procedure.

House staff communication training and patient experience scores.

OBJECTIVE: To assess whether communication training for housestaff via role-playing exercises (1) is well-received and (2) improves patient experience scores in housestaff clinics. METHODS: We conducted a pre-post study in which the housestaff for 3 adult hospital departments participated in communication trainingled by trained faculty in small groups . Sessions centered on a published 5-step strategy for opening patient-centered interviews using department-specific role-playing exercises. Housestaff completed post-training questionnaires. For one month prior to and one month following the training, patients in the housestaff clinics completed surveys with CG-CAHPS questions regarding physician communication, immediately following clinic visits. Pre-and post -intervention results for top-box scores were compared. RESULTS: Forty -four of a possible 45 housestaff (97.8%) participated, with 31 (70.5%) indicating that the role-playing exercise increased their perception of the 5-step strategy. No differences on patient responses to CG-CAHPS questions were seen when comparing 63 pre-intervention patients surveys to 77 post-intervention surveys. CONCLUSION: Demonstrating an improvement in standard patient experience surveys in resident clinics may require ongoing communication coaching and investigation of the "hidden curriculum" of training.

Distinguishing pediatric and adolescent renal cell carcinoma from other renal malignancies.

PURPOSE: Renal cell carcinoma (RCC) represents a small proportion of renal malignancies early in life. Distinguishing RCC from other malignancies is important as treatment strategies may differ. We analyze the Surveillance Epidemiology, and End Results (SEER) database to identify predictive factors of RCC in the pediatric population with renal tumors. METHODS: We queried SEER to identify patients from ages 0 to 19 diagnosed with a renal malignancy between 1973 and 2013. Cases were sorted using histology and site codes. Age-adjusted standardized incidence rates (SIR) were calculated. We compared differences in characteristics between cancer types. A logistic regression model and a nomogram were created to identify predictors of RCC. RESULTS: A total of 3,670 patients were identified, of which 281 (7.7%) were diagnosed with RCC. The SIR of RCC increased with age. After age 12, RCC was found in >50% of all newly diagnosed cases. On multivariate analysis, RCC was associated with smaller tumor size (P < 0.001), increasing age (P < 0.001), black race (P < 0.001), and localized stage (P < 0.001). The nomogram predicted RCC pathology with a concordance index of 0.965. CONCLUSIONS: RCC in childhood and adolescence is relatively uncommon; however, it accounts for >50% of renal malignancies after age 12. For every year of increasing age, the odds of having an RCC diagnosis are increased by 50%. The odds of a renal tumor being RCC are increased in black children, those with localized disease, and those with smaller tumors. In these specific populations, RCC should be favored in the differential diagnosis of the renal mass.

Acute Bladder Necrosis after Pelvic Arterial Embolization for Pelvic Trauma: Lessons Learned from Two Cases of Immediate Postembolization Bladder Necrosis.

We report two cases of acute bladder injury with bladder neck necrosis identified during the initial operative evaluation and within the early postprocedural period in patients with significant pelvic trauma requiring pelvic vascular embolization. To our knowledge, this is the first report of bladder neck necrosis found during the initial intraoperative surgical evaluation or early postoperative setting.

Pediatric incidental appendectomy: a systematic review.

Incidental appendectomy is the removal of the vermiform appendix accompanying another operation, without evidence of acute appendicitis. It is generally performed to eliminate the risk of future appendicitis. The risks and benefits of incidental appendectomy during various operations in children have been debated for over a century, but need to be revisited in light of innovations in medical practice, including minimally invasive surgery, improved imaging techniques, and use of the appendix as a tubular conduit for reconstruction. A detailed review was undertaken of the techniques, pathology, risks of appendectomy, utility of the appendix, and incidental appendectomy in the treatment of specific pediatric medical conditions. A comprehensive literature search was performed, and retrieved results were reviewed for relevance to the topic. The decision to perform a pediatric incidental appendectomy relies on informed consideration of the individual patient's co-morbid conditions, the indication for the initial operation, the future utility of the appendix, and the risk of future appendiceal pathology. The discussion includes a variety of situations and comorbid conditions that may influence a surgeon's decision to perform incidental appendectomy.

An unusual destination for magnetic foreign bodies.

Rare earth metal magnets (Buckyballs and similar products) remain an important public health risk for children. We report the presentation, course, and treatment of a boy who inserted a string of 30 magnets through his urethra into his bladder and review the diagnostic as well as the therapeutic options for foreign bodies inserted into the pediatric urogenital tract.

Surface-modified nanoparticles enhance transurothelial penetration and delivery of survivin siRNA in treating bladder cancer.

Penetration of the bladder permeability barrier (BPB) is a major challenge when treating bladder diseases via intravesical delivery. To increase transurothelial migration and tissue and tumor cell uptake, poly(lactic-co-glycolic acid; PLGA) nanoparticles (NP) were modified by addition of a low molecular weight (2.5 or 20 kDa) positively charged mucoadhesive polysaccharide, chitosan, to the NP surface. In designing these NPs, we balanced the adhesive properties of chitosan with the release and bioactivity of the siRNA. Chitosan-functionalized NPs demonstrated increased binding to and uptake in intravesically instilled mouse bladders and human ureter at 10 times the level of unmodified NPs. Furthermore, we extended the bioactivity of survivin siRNA in vitro for up to 9 days and demonstrated a decrease in proliferation when using chitosan-modified NPs relative to unmodified NPs. In addition, treatment of xenograft tumors with chitosan-modified NPs that encapsulate survivin siRNA (NP-siSUR-CH2.5) resulted in a 65% reduction in tumor volume and a 75% decrease in survivin expression relative to tumors treated with blank chitosan NPs (NP-Bk-CH2.5). Our low molecular weight chitosan delivery system has the capacity to transport large amounts of siRNA across the urothelium and/or to the tumor site, thus increasing therapeutic response.

Clitoral epidermoid cyst presenting as pseudoclitoromegaly of pregnancy.

Objective Acquired clitoromegaly is rare and may result from hormonal and nonhormonal causes, and evaluation of the pregnant patient with clitoromegaly invokes a specific set of differential diagnoses. Methods Case report. Results We describe the case of a young woman with pregnancy-associated clitoral enlargement whose hormonal evaluation proved negative. Further investigation concluded that an epidermoid cyst was the culprit of her pseudoclitoromegaly. The patient underwent successful surgical resection and has had no recurrence at her subsequent pregnancy. Conclusion We review the differential diagnosis of clitoromegaly, including hormonal and nonhormonal causes, with focus on the evaluation of pregnancy-associated clitoromegaly.

Caucasian male infants and boys with hypospadias exhibit reduced anogenital distance.

BACKGROUND: Animal models of endocrine dysfunction have associated male genital defects with reduced anogenital distance (AGD). Human studies have correlated shorter AGD with exposure to putative endocrine disruptors in the environment but have not examined AGD in hypospadiac boys. We measured AGD in boys with hypospadias and those with normal genitals. METHODS: Data were collected prospectively on boys undergoing urologic procedures at the University of California San Francisco and the Children's Hospital of Oakland, CA, USA. Data included age, race, height, weight, BMI, urologic diagnoses and AGD. To minimize any potential effects of race on observed AGD, we examined only Caucasian boys. Differences between boys with hypospadias and those with normal genitals were examined through two-tailed Student's t-tests. RESULTS: One hundred and nineteen Caucasian boys ranging in age from 4 to 86 months underwent AGD measurement, of which 42 and 77 were boys with normal genitals and hypospadias, respectively. The mean (±SD) AGD of boys with hypospadias was 67 ± 1.2 versus 73 ± 1 mm for boys with normal genitals (P = 0.002). In these age-unmatched patient groups, there were also differences in age, height and weight (P = 0.0001, 0.0002 and 0.0004, respectively). After age matching (all <2 years of age), boys with hypospadias (n= 26) still featured a shorter AGD than boys with normal genitals (n= 26; 62 ± 2 versus 68 ± 2 mm respectively, P = 0.033) but the differences in age, height and weight were no longer significant. CONCLUSIONS: In humans, hypospadias may indeed be associated with reduced AGD. Additional studies are needed to corroborate these preliminary findings and to determine their etiology.