Longitudinal Quality of Life and Glycemic Outcomes of Total Pancreatectomy With Islet Autotransplantation in Children With Chronic Pancreatitis Followed in a Pediatric Multidisciplinary Pancreas Clinic.

BACKGROUND: Total pancreatectomy with islet autotransplantation (TPIAT) is a potentially curative treatment for patients with chronic pancreatitis (CP) refractory to medical and endoscopic therapies. Patients often receive the initial follow-up medical care at the surgery-performing center, but then may follow up closer to where they live. We sought to describe the characteristics and outcomes of pediatric patients who underwent TPIAT at a national surgical referral center and were subsequently followed at our regional subspecialty center, the Children's Hospital Colorado. METHODS: We performed a retrospective analysis of baseline and outcomes data for the 10 pediatric patients who underwent TPIAT from 2007 to 2020 and received follow-up care at our institution. RESULTS: All patients had a diagnosis of CP, and nine of 10 patients had an identified underlying genetic risk factor. Insulin usage was common immediately following TPIAT, but at 1 year of follow-up, five of nine patients (55.6%) were insulin-independent and nine of nine had an HbA1c below 6.5%. For the four patients on insulin 1 year after TPIAT, total daily insulin dose ranged from 0.06 to 0.71 units/kg/day. All patients who underwent mixed meal tolerance testing had a robust peak C-peptide response at 1 year. There were significant improvements in nausea, school/work absences, narcotic dependence, and pancreas-related hospital admissions 1 year after TPIAT. CONCLUSIONS: Patients followed at our center had long-term improvements with low-insulin usage, detectable C-peptide, and improved pancreatitis-related outcomes after TPIAT. Pediatric patients who undergo TPIAT can be successfully co-managed in conjunction with the original surgery-performing center.

Risk Factors for the Development of Febrile Recurrences in Children with a History of Urinary Tract Infection.

OBJECTIVE: To identify risk factors for febrile recurrence of urinary tract infections (UTIs) in children with a history of UTI. STUDY DESIGN: We included 500 children aged 2-72 months with a history of UTI who were followed prospectively for approximately 2 years in the context of 2 previously conducted studies (Randomized Intervention for Children with Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation). We identified significant risk factors for febrile recurrences among children not receiving antimicrobial prophylaxis using univariate and multivariate logistic regression. RESULT: On univariate analysis, non-Black race, febrile index UTI, bowel-bladder dysfunction, grade IV vesicoureteral reflux, renal scarring at baseline, and renal-bladder ultrasound abnormalities were associated with febrile recurrence. On multivariate analysis, the following variables independently increased the odds of febrile recurrences (OR; 95% CI): non-Black race (7.1; 1.5-127.9), bowel-bladder dysfunction (2.6; 1.1-5.3), febrile index UTI (2.5; 1.1-6.9), abnormalities on renal-bladder ultrasound scan (2.6; 1.2-5.6), grade IV vesicoureteral reflux (3.9; 1.4-10.5), and renal scarring at baseline (4.7; 1.2-19.1). CONCLUSIONS: Non-Black race and grade IV vesicoureteral reflux increased the odds of febrile recurrence of UTI. Although our findings should stimulate other studies to further explore the relationship between race and UTIs, given that the link between race and UTI recurrence is unclear, race should not be used to make decisions regarding management of children with a UTI.

Risk Factors for Delayed Antimicrobial Treatment in Febrile Children with Urinary Tract Infections.

OBJECTIVES: To identify factors associated with delayed antimicrobial treatment in febrile children with urinary tract infection (UTI). STUDY DESIGN: We reviewed data from 802 children with UTI enrolled in 2 previously conducted prospective studies (Randomized Intervention for Children with Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation) and extracted data on possible predictors of delayed treatment including age, sex, history of UTI, ethnicity, race, primary caregiver's education level, insurance, and income. We used univariate and multivariable analyses to investigate the relationship between these predictors and treatment delay. RESULTS: We included 660 febrile patients with a mean age of 17.0 months old. Older age and commercial insurance were associated with delayed treatment on univariate analysis. Compared with younger children, treatment was delayed by an average of 26.2 hours in children ≥12 months of age. This relationship remained significant on multivariable analysis. Treatment also was delayed by an average of 12.6 hours in patients with commercial insurance. Race, ethnicity, primary caregiver's education level, and income were not associated with delayed treatment. CONCLUSIONS: Older age was a consistent predictor of delayed antimicrobial treatment. Delays in the initiation of antimicrobial therapy for UTI has previously been associated with renal scarring. Educating parents with older children regarding the management of fever as well as providers regarding prompt evaluation and management may help to reduce renal scarring.

Adverse Events of Antibiotics Used to Treat Acute Otitis Media in Children: A Systematic Meta-Analysis.

OBJECTIVE: To characterize the incidence of adverse events (AEs) associated with antibiotics used to treat acute otitis media in children. STUDY DESIGN: We searched MEDLINE for studies conducted between January 1, 1966, and August 25, 2018. Two authors independently assessed potential studies and extracted the data. We included published randomized controlled trials, cross-sectional studies, and cohort studies that evaluated the incidence of diarrhea, generalized rash, diaper rash, and candidal diaper dermatitis associated with the use of amoxicillin, amoxicillin/clavulanate, azithromycin, cefdinir, and placebo in children with acute otitis media. RESULTS: We included 82 studies in the meta-analysis. The incidence of diarrhea, listed from lowest to highest, was azithromycin (2.2%), placebo (6.9%), low-dose amoxicillin (8.7%), cefdinir (13.0%), high-dose amoxicillin (13.8%), and high-dose amoxicillin/clavulanate (18.9%). The incidence of generalized rash, listed from lowest to highest, was azithromycin (1.4%), placebo (2.3%), low-dose amoxicillin (2.9%), high-dose amoxicillin/clavulanate (4.9%), and high-dose amoxicillin (6.5%). In studies of low-dose amoxicillin, we found a higher incidence of diarrhea in studies that used daily diaries to collect information about diarrhea and a lower incidence of generalized rash in studies that reported only rashes judged to be secondary to antibiotic use. CONCLUSIONS: The incidence of AEs varies widely depending on which antibiotic is used and how the information on AEs was collected or reported. The AEs rates reported here may be helpful to clinicians when choosing an antibiotic to treat acute otitis media.

Dimercaptosuccinic acid scan or ultrasound in screening for vesicoureteral reflux among children with urinary tract infections.

BACKGROUND: There is considerable interest in detecting vesicoureteral reflux (VUR) because its presence, especially when severe, has been linked to an increased risk of urinary tract infections and renal scarring. Voiding cystourethrography (VCUG), also known as micturating cystourethrography, is the gold standard for the diagnosis of VUR, and the grading of its severity. Because VCUG requires bladder catheterisation and exposes children to radiation, there has been a growing interest in other screening strategies that could identify at-risk children without the risks and discomfort associated with VCUG. OBJECTIVES: The objective of this review is to evaluate the accuracy of two alternative imaging tests - the dimercaptosuccinic acid renal scan (DMSA) and renal-bladder ultrasound (RBUS) - in diagnosing VUR and high-grade VUR (Grade III-V VUR). SEARCH METHODS: We searched MEDLINE, EMBASE, BIOSIS, and the Cochrane Register of Diagnostic Test Accuracy Studies from 1985 to 31 March 2016. The reference lists of relevant review articles were searched to identify additional studies not found through the electronic search. SELECTION CRITERIA: We considered published cross-sectional or cohort studies that compared the results of the index tests (DMSA scan or RBUS) with the results of radiographic VCUG in children less than 19 years of age with a culture-confirmed urinary tract infection. DATA COLLECTION AND ANALYSIS: Two authors independently applied the selection criteria to all citations and independently abstracted data. We used the bivariate model to calculate summary sensitivity and specificity values. MAIN RESULTS: A total of 42 studies met our inclusion criteria. Twenty studies reported data on the test performance of RBUS in detecting VUR; the summary sensitivity and specificity estimates were 0.44 (95% CI 0.34 to 0.54) and 0.78 (95% CI 0.68 to 0.86), respectively. A total of 11 studies reported data on the test performance of RBUS in detecting high-grade VUR; the summary sensitivity and specificity estimates were 0.59 (95% CI 0.45 to 0.72) and 0.79 (95% CI 0.65 to 0.87), respectively. A total of 19 studies reported data on the test performance of DMSA in detecting VUR; the summary sensitivity and specificity estimates were 0.75 (95% CI 0.67 to 0.81) and 0.48 (95% CI 0.38 to 0.57), respectively. A total of 10 studies reported data on the accuracy of DMSA in detecting high-grade VUR. The summary sensitivity and specificity estimates were 0.93 (95% CI 0.77 to 0.98) and 0.44 (95% CI 0.33 to 0.56), respectively. AUTHORS' CONCLUSIONS: Neither the renal ultrasound nor the DMSA scan is accurate enough to detect VUR (of all grades). Although a child with a negative DMSA test has an < 1% probability of having high-grade VUR, performing a screening DMSA will result in a large number of children falsely labelled as being at risk for high-grade VUR. Accordingly, the usefulness of the DMSA as a screening test for high-grade VUR should be questioned.

Inadequate harms reporting in randomized control trials of antibiotics for pediatric acute otitis media: a systematic review.

INTRODUCTION: Reporting of harms in randomized control trials is often inconsistent and inadequate. OBJECTIVE: To assess the quality of harms reporting in randomized control trials evaluating the efficacy of antibiotics used to treat pediatric acute otitis media and to investigate whether connections to pharmaceutical companies or the publication of the CONSORT-Harms extension influenced the quality of harms reporting. STUDY DESIGN AND SETTING: We considered randomized control trials that evaluated the efficacy and safety of antibiotic treatment for uncomplicated acute otitis media in children aged 0-19. We evaluated the quality of harms reporting using a 19-item checklist addressing the recommendations endorsed in the CONSORT-Harms extension. RESULTS: 160 studies met our inclusion criteria. Overall quality of reporting relating to harms was low; on average studies adhered to 55.2% of the checklist items on the quality of harms reporting. The reporting of methods relating the measurement of harms was particularly lacking; studies adhered to an average of only 33.2% of the checklist items. The overall quality of reporting did not change after the publication of the CONSORT-Harms extension. The overall quality of reporting did not differ significantly in reports with or without declared connections to pharmaceutical companies (mean quality score of 56.8% vs 52.0%, respectively). CONCLUSIONS: Harms reporting in pediatric randomized trials, especially the reporting of methods used to collect harms data, remains inadequate.

Development and Validation of a Calculator for Estimating the Probability of Urinary Tract Infection in Young Febrile Children.

Importance: Accurately estimating the probability of urinary tract infection (UTI) in febrile preverbal children is necessary to appropriately target testing and treatment. Objective: To develop and test a calculator (UTICalc) that can first estimate the probability of UTI based on clinical variables and then update that probability based on laboratory results. Design, Setting, and Participants: Review of electronic medical records of febrile children aged 2 to 23 months who were brought to the emergency department of Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania. An independent training database comprising 1686 patients brought to the emergency department between January 1, 2007, and April 30, 2013, and a validation database of 384 patients were created. Five multivariable logistic regression models for predicting risk of UTI were trained and tested. The clinical model included only clinical variables; the remaining models incorporated laboratory results. Data analysis was performed between June 18, 2013, and January 12, 2018. Exposures: Documented temperature of 38°C or higher in children aged 2 months to less than 2 years. Main Outcomes and Measures: With the use of culture-confirmed UTI as the main outcome, cutoffs for high and low UTI risk were identified for each model. The resultant models were incorporated into a calculation tool, UTICalc, which was used to evaluate medical records. Results: A total of 2070 children were included in the study. The training database comprised 1686 children, of whom 1216 (72.1%) were female and 1167 (69.2%) white. The validation database comprised 384 children, of whom 291 (75.8%) were female and 200 (52.1%) white. Compared with the American Academy of Pediatrics algorithm, the clinical model in UTICalc reduced testing by 8.1% (95% CI, 4.2%-12.0%) and decreased the number of UTIs that were missed from 3 cases to none. Compared with empirically treating all children with a leukocyte esterase test result of 1+ or higher, the dipstick model in UTICalc would have reduced the number of treatment delays by 10.6% (95% CI, 0.9%-20.4%). Conclusions and Relevance: UTICalc estimates the probability of UTI by evaluating the risk factors present in the individual child. As a result, testing and treatment can be tailored, thereby improving outcomes for children with UTI.

Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning.

The renal stroma is an embryonic cell population located in the cortex that provides a structural framework as well as a source of endothelial progenitors for the developing kidney. The exact role of the renal stroma in normal kidney development hasn't been clearly defined. However, previous studies have shown that the genetic deletion of Foxd1, a renal stroma specific gene, leads to severe kidney malformations confirming the importance of stroma in normal kidney development. This study further investigates the role of renal stroma by ablating Foxd1-derived stroma cells themselves and observing the response of the remaining cell populations. A Foxd1cre (renal stroma specific) mouse was crossed with a diphtheria toxin mouse (DTA) to specifically induce apoptosis in stromal cells. Histological examination of kidneys at embryonic day 13.5-18.5 showed a lack of stromal tissue, mispatterning of renal structures, and dysplastic and/or fused horseshoe kidneys. Immunofluorescence staining of nephron progenitors, vasculature, ureteric epithelium, differentiated nephron progenitors, and vascular supportive cells revealed that mutants had thickened nephron progenitor caps, cortical regions devoid of nephron progenitors, aberrant vessel patterning and thickening, ureteric branching defects and migration of differentiated nephron structures into the medulla. The similarities between the renal deformities caused by Foxd1 genetic knockout and Foxd1DTA mouse models reveal the importance of Foxd1 in mediating and maintaining the functional integrity of the renal stroma.