Extracorporeal shock wave lithotripsy versus ureteroscopy for management of pediatric nephrolithiasis in upper urinary tract stones: multi-institutional outcomes of efficacy and morbidity.

INTRODUCTION: As the incidence of pediatric nephrolithiasis rises, understanding the efficacy and morbidity of surgical treatment options is critical. Currently, there are limited comparative data assessing shock wave lithotripsy (SWL) and ureteroscopy (URS) outcomes in children. OBJECTIVE: The objective of this study was to compare stone clearance, 30-day emergency department visits, and the number of general anesthetics required per stone treatment for both modalities. STUDY DESIGN: A multi-institutional retrospective review of children presenting for either URS or SWL between 2000 and 2017 was performed. Stone clearance, need for retreatment, the number of anesthetics, as well as the number and reason for emergency room visit were captured and compared between groups. Multivariate statistical analysis accounting for age, stone location, stone diameter, pre-intervention stent, and provider volume was performed for adjusted analysis. RESULTS: A total of 84 SWL and 175 URS procedures were included. Complete stone clearance and rates of residual stone fragments <4 mm after final procedure for SWL were 77.0% and 90.8% and for URS were 78.5% and 91.7%, respectively. Retreatment rates for both procedures were not significantly different (17.9% SWL vs. 18.9% URS, P = 0.85). Children who underwent SWL had lower rates of emergency room visits for infections (0% vs. 5.1%, P = 0.03) and flank pain (3.6% vs. 10.9%, P = 0.05) and required fewer general anesthetics per treatment (1.2 vs. 2.0, P < 0.01) than those who underwent URS (Figure). DISCUSSION: Stone clearance after both the initial and final treatments and need for repeat interventions were similar between surgical modalities. However, SWL carries less morbidity than URS. Specifically, patients who underwent SWL experienced lower rates of ED visits for urinary tract infection and for flank pain, parallel to conclusions in current comparative literature. In addition, SWL requires less general anesthetics (2.0 vs. 1.2), secondary to lower rates of ureteral stent placement and removal. Data on the potential risk of general anesthetics to neurodevelopment support thoughtful utilization of these medications. Limitations of this study include its retrospective nature and the prolonged 20-year time period over which data were collected. CONCLUSIONS: When adjusting for confounders, SWL and URS achieve similar stone clearance. In the setting of equivalent efficacy, considerations regarding necessity of repeat interventions, morbidity of anesthesia, and complications should be integrated into clinical practice.

A clinical pathway to minimize computed tomography for suspected nephrolithiasis in children.

INTRODUCTION: Ultrasound (US) imaging is preferred in the initial evaluation for children with suspected nephrolithiasis; however, computed tomography (CT) continues to be used in this setting with resultant unnecessary ionizing radiation exposure. The study institution implemented a standardized clinical pathway to reduce rates of CT utilization for children with nephrolithiasis. OBJECTIVE: The aim of this study was to evaluate the impact of this pathway on initial imaging strategies for children with suspected nephrolithiasis. STUDY DESIGN: A standardized pathway was designed and implemented using a systematic quality improvement process. A suspected cohort was created using 'reason for study' search terms consistent with a nephrolithiasis diagnosis. A confirmed cohort of children with a final diagnosis of nephrolithiasis was derived from this suspected cohort. The primary outcome was CT use as the initial imaging study in children with suspected or confirmed nephrolithiasis presenting to the emergency department (ED) between October 2013 and February 2018. Comparisons were made before and after pathway implementation (October 2015). Secondary outcomes included rates of CT scan within 30 days, while balancing measures included rates of admission, ED length of stay, and return visits. RESULTS: A total of 534 children with suspected (220 prepathway; 314 postpathway) and 90 children with confirmed (37 prepathway; 53 postpathway) nephrolithiasis were included. For the suspected cohort, CT scans performed as the initial imaging evaluation (9.2% vs 2.5%, P = 0.001) and at any time during the index visit (15.7% vs 5.7%, P = 0.001) decreased after pathway implementation. Within the confirmed cohort, a non-significant decrease in initial CT rates was observed after implementation. No differences were observed in admission rates or ED length of stay after implementation. A trend toward lower return visits to the ED was seen after pathway implementation (5.5% vs 2.2%, P = 0.058). DISCUSSION: Within a tertiary care pediatric ED associated with a strong institutional experience with clinical pathways, initial CT rates were decreased after pathway implementation for children with suspected nephrolithiasis. While retrospective assessment of suspected disease is limited, this is one of the first studies to address imaging patterns for nephrolithiasis beyond the final discharge diagnosis, thus capturing a broader cohort of children. Children with suspected nephrolithiasis can be safely managed with an US-first approach, and postvisit CT scans are rarely necessary for management. CONCLUSIONS: A standardized clinical pathway for suspected nephrolithiasis can reduce rates of initial and overall CT utilization without adversely impacting downstream care.

A Societies for Pediatric Urology survey of opioid prescribing practices after ambulatory pediatric urology procedures.

INTRODUCTION: Opioid dependence and abuse has been declared a national public health emergency, and overprescribing of opioids after surgery has been identified as a driving factor. To date, opioid prescribing after pediatric urology ambulatory surgery has not been well-described. OBJECTIVE: The study's objective was to assess pediatric urologists' practices in prescribing opioids for routine ambulatory procedures. STUDY DESIGN: A 23-question survey was created, including eight case vignettes describing routine procedures (orchiopexy, hydrocele repair, circumcision) across three age groups (8 months, 3 years, 13 years). Multiple choice questions asked about typical opioid type and duration for each case. Respondent attitudes and practice types were also evaluated. The survey was administered through the Societies for Pediatric Urology. RESULTS: Of the 102 respondents, 48% reported prescribing postoperative opioids for all cases described (Figure 1). Fourteen percent reported prescribing no opioids for all cases. Longer prescription duration was associated with older age (p = 0.003). Acetaminophen-hydrocodone was prescribed most commonly, while a few respondents reported prescribing acetaminophen-codeine. North Central and Southeastern respondents were more likely to prescribe opioids for all cases described (p = 0.003). The majority of respondents work in academic settings and had >10 years in practice. Only 16% believe that their patients take the majority of opioids prescribed, while only 35% provide education to their patients on proper disposal. DISCUSSION: There is significant variability in reported opioid prescribing practices after ambulatory procedures amongst pediatric urologists. Only 16% of respondents believe that patients take the majority of opioids prescribed, and only 14% reported never prescribing opioids for these procedures. There is an opportunity for guidelines and standardization of care for postoperative analgesia in this patient population. Given that overprescribing can lead to abuse and misuse, further work needs to be done to establish postoperative analgesia needs and to educate providers and families on proper prescribing and disposal. CONCLUSION: Pediatric urologists report prescribing opioids frequently after routine ambulatory procedures in infants, children, and adolescents despite believing that patients do not take the majority of the prescribed medication.

A critical appraisal of continence in bladder exstrophy: Long-term outcomes of the complete primary repair.

INTRODUCTION: Long-term continence outcomes for patients with bladder exstrophy are lacking in the literature. The complete primary repair of exstrophy (CPRE) is a widely adopted approach that seeks to normalize anatomy at the initial repair, thereby allowing early bladder filling and cycling. Previous reports of continence following CPRE, however, are limited by variable follow-up duration and continence definitions. OBJECTIVE: To assess continence and factors associated with a positive outcome in a cohort of patients following CPRE with long-term follow-up. STUDY DESIGN: A retrospective chart review was conducted of all patients with primary bladder closure using CPRE at the present institution for classic bladder exstrophy from 1990 to 2010. Patients <6 years of age or with an incomplete continence assessment at last follow-up were excluded. Continence was defined as voiding volitionally with dry intervals of ≥3 h, which was consistent with other high-volume series in the literature. RESULTS: Twenty-nine of the 52 patients (56%) were eligible for inclusion. Twelve patients were continent at last follow-up, including seven boys and five girls. Mean follow-up for the entire cohort was 148 months. The Summary table displays comparisons between continent and incontinent patients. Of patients achieving continence, 42% did not require further continence operations, while 17% required only one additional continence operation. DISCUSSION: Long-term CPRE continence rates were lower than previously reported, but comparable to other series in the literature. Of those achieving continence, 59% will do so with zero or one additional operation. Sex and osteotomy status were not associated with continence outcomes, although age at follow-up was a predictor of continence, favoring older patients in the present series. The study was limited by lack of standardized, patient-reported continence outcomes and by the retrospective nature of the review. However, the data add to the literature of long-term continence outcomes and are important for counseling families both at initial repair and follow-up. CONCLUSIONS: Complete primary repair of exstrophy can achieve continence without additional operations in a subset of patients. Some patients, however, may not achieve continence until adolescence, underscoring the need for long-term urologic follow-up in patients with bladder exstrophy.

Controlled drug misuse by Certified Registered Nurse Anesthetists.

The primary purpose of this study was to determine the prevalence of controlled drug misuse among actively practicing Certified Registered Nurse Anesthetists (CRNAs). A second purpose was to determine variance in controlled drug misuse by the variables of age, sex, population and geographic area of residence, type of anesthesia position currently held, and number of years in anesthesia practice. The research data were obtained through self-administered surveys mailed to 2,500 actively practicing CRNAs throughout the United States. With a response rate of 68.4% (1,709 of 2,500), the survey instrument allowed for stratification according to admitted misuse of controlled drugs commonly used in the clinical practice of anesthesia. The established prevalence of controlled drug misuse in the target population was found to be 9.8% of the sample (167 of 1,709 respondents), with the majority indicating a distinct proclivity for polydrug misuse. The survey results were comparable with those of studies involving anesthesiologists and registered nurses with the notable exception of the preferred drugs for misuse. A strong relationship existed between sex, number of years in clinical anesthesia practice, and the likelihood for controlled drug misuse, thus indicating a potential predictor of which CRNAs may misuse controlled drugs. In addition, a significant relationship existed between recency of controlled drug misuse and drug(s) of choice (P = .05). Recommendations include specific tactics for strengthening drug misuse education and prevention. Also, modifications in research design and additional studies in the research area are suggested.

The Sox10(Dom) mouse: modeling the genetic variation of Waardenburg-Shah (WS4) syndrome.

Hirschsprung disease (HSCR) is a multigenic neurocristopathy clinically recognized by aganglionosis of the distal gastrointestinal tract. Patients presenting with aganglionosis in association with hypopigmentation are classified as Waardenburg syndrome type 4 (Waardenburg-Shah, WS4). Variability in the disease phenotype of WS4 patients with equivalent mutations suggests the influence of genetic modifier loci in this disorder. Sox10(Dom)/+ mice exhibit variability of aganglionosis and hypopigmentation influenced by genetic background similar to that observed in WS4 patients. We have constructed Sox10(Dom)/+ congenic lines to segregate loci that modify the neural crest defects in these mice. Consistent with previous studies, increased lethality of Sox10(Dom)/+ animals resulted from a C57BL/6J locus(i). However, we also observed an increase in hypopigmentation in conjunction with a C3HeB/FeJLe-a/a locus(i). Linkage analysis localized a hypopigmentation modifier of the Dom phenotype to mouse chromosome 10 in close proximity to a previously reported modifier of hypopigmentation for the endothelin receptor B mouse model of WS4. To evaluate further the role of SOX10 in development and disease, we have performed comparative genomic analyses. An essential role for this gene in neural crest development is supported by zoo blot hybridizations that reveal extensive conservation throughout vertebrate evolution and by similar Northern blot expression profiles between mouse and man. Comparative sequence analysis of the mouse and human SOX10 gene have defined the exon-intron boundaries of SOX10 and facilitated mutation analysis leading to the identification of two new SOX10 mutations in individuals with WS4. Structural analysis of the HMG DNA-binding domain was performed to evaluate the effect of human mutations in this region.

Fluorescence-based mutation detection. Single-strand conformation polymorphism analysis (F-SSCP).

Conventional SSCP analysis of DNA amplified by polymerase chain reaction (PCR-SSCP) is one of the simplest and most reliable tools for identifying point mutations, and small insertions or deletions. The sensitivity of the technique is increased by using the Applied Biosystems (ABI) semiautomated DNA sequencer equipped with GENESCAN 672 software for F-SSCP. The four-dye ABI system permits a red dye-labeled internal lane standard to be run in the same lanes as the DNA being examined, leaving three dye colors for labeling DNA of interest. The internal lane standard is used to normalize gels or correct for minor differences in apparent electrophoretic mobility between lanes. Correction for these lane-dependent differences in migration and the capability to stack data from two different lanes on the computer screen makes it possible to detect sequence variants that produce very small mobility shifts. Coelectrophoresis of control and unknown DNA in the same lane, using different dye labels for each, is also helpful for detecting sequence variants that produce small mobility changes. Multiplexing multiple F-SSCP targets in the same lane increases sample throughput.

Structural changes in Clostridium botulinum type E after treatment with boticin S5 1 .

Treatment with boticin S5(1), a bacteriocin produced by a nontoxigenic organism closely related to Clostridium botulinum type E, caused extensive changes in the structure of a sensitive C. botulinum type E strain. Nucleoid deoxyribonucleic acid, normally seen as fine filaments scattered throughout the cell, was aggregated into dense deoxyribonucleic acid masses. Mesosomes appeared to undergo structural rearrangement from lamellar to vesicular configuration. Eventual dissolution of cell contents left bacterial ghosts composed of seemingly intact cell walls with remnants of the cytoplasmic membrane and internal structures. The morphological changes observed in boticin-treated strain 070 cells were very similar to those produced by a bacteriocin-like substance from phage type 71 Staphylococcus aureus on sensitive beta-hemolytic streptococci. A similarity in the mode of action of the two bactericidal agents is suggested.

Purification and some properties of two boticins.

Two bacteriocins (boticins) were elaborated without induction by strain S5, a nontoxigenic variant of Clostridium botulinum type E. After separation of the two active entities by gel filtration on Sephadex G-50, a large particle with boticin activity was isolated by density gradient ultracentrifugation, and a small soluble boticin was purified by continuous curtain electrophoresis and chromatography on sulfoethyl-Sephadex. Large and small boticins were purified 200- and 3,000-fold, respectively, with yields of 50% or more. The small boticin, a basic substance with molecular weight under 30,000, was the predominant species; the large boticin, a negatively charged particle with particle weight greater than 40 x 10(6), represented less than 20% of the total activity. Both purified boticins were resistant to heat and were attacked by proteolytic enzymes, but the large boticin was less thermostable and less sensitive to proteolytic enzymes than was the smaller variety. The activity of the large boticin was not reduced by treatment with urea or deoxyribonuclease. Both boticins exhibited sporostatic and bactericidal activities for C. botulinum type E, strain 070. A suspension of type E strain 070 vegetative cells was rendered nonviable within 9 min by the small boticin. The lethal action of this bacteriocin was not reversed by trypsin.