National Pediatrician-Scientist Collaborative Workgroup comment on new ACGME requirements' impact on pediatric physician-scientists.

BACKGROUND: The ACGME recently released its recommendation for updates to the program requirements for pediatrics. These updates proposed changes to allocation of resident clinical time and a greater emphasis on individualization. The potential impact of these changes on the training of physician-scientists is discussed. METHODS: Discussion of the proposed changes was held within the members of the National Pediatrician-Scientist Collaborative Workgroup, a group that represents scientists, trainees, program directors, chairs, and physician-scientist educators at nearly 30 residency programs from across the US with a focus on understanding and developing optimal approaches to physician-scientist training. Consideration was given to the both the personal and institutional impact of the proposal for physician-scientist development. RESULTS: Both threats and opportunities were identified. Key opportunities include the enhanced individualized training time that could be used to explore research. Threats include re-allocation of clinical training time that may strain institutions financially, expand clinical service requirements for other early career stage individuals, and alter exposure to a broad range of pediatric specialists and sub-specialists that impact career development. CONCLUSION: The NPSCW encourages consideration of the impact of changing program requirements on physician-scientist development to include ongoing discussion amongst mentors, programs, and trainees to understand and mitigate impact of new program requirements on the development of pediatrician-scientists.

Outcomes in Pediatric Central Line-associated Bloodstream Infections Treated With Antimicrobial Locks: A 14-Year Retrospective Analysis.

BACKGROUND: Central line-associated bloodstream infections (CLABSI) are the most common healthcare-associated infection in children. Antimicrobial lock therapy (ALT) is a recommended component of CLABSI treatment; however, studies characterizing pediatric ALT-based CLABSI therapy are few. METHODS: All CLABSI treated with ALT at a single tertiary-care pediatric hospital for years 2004-2018 were identified by retrospective chart review and demographic, clinical, microbiological and pharmacy data were extracted. Three clinical outcomes were defined: CLABSI clearance, central venous catheter (CVC) removal and infection recurrence. Factors associated with these outcomes were examined and patterns in pathogen occurrence were described. RESULTS: During the study period, 1188 CLABSI treated with ALT were identified. In all, 969 (85%) CLABSI initially cleared. In the CLABSI with initial clearance, CVCs were retained a median of 63 days after infection onset, and 20% recurred. Skin-colonizing microbes ( Staphylococcus aureus , coagulase-negative Staphylococci) were more likely to produce monomicrobial infections, whereas bowel-colonizing microbes ( Escherichia coli , Enterococci) were more associated with polymicrobial infections. In a multivariate model, infection history, resistant pathogens and CVC type were strongly correlated with infection recurrence, whereas bone marrow transplant status, neutrophil count and line type were correlated with CVC removal. CONCLUSIONS: Optimal therapeutic approaches to pediatric CLABSI remain uncertain, including the utility of ALT. Prior reports of ALT use in children have been smaller in size and largely described hematology-oncology or hemodialysis populations. We describe trends in pediatric CLABSI, including efficacy among solid organ transplant recipients and children with short-gut syndrome. These data provide guidance on selecting CLABSI for optimal ALT use.

Gonococcal Infection and Ventriculoperitoneal Shunts.

ABSTRACT: Neisseria gonorrhoea e and Chlamydia trachomatis are pathogens commonly isolated in pelvic inflammatory disease. Neisseria gonorrhoea e may uncommonly spread outside the urogenital tract to cause complications. We present 2 cases of adolescents with ventriculoperitoneal shunt infection due to N. gonorrhoea e, requiring shunt externalization.

The Impact of Operative Intervention in Pediatric Lyme Arthritis.

BACKGROUND: Lyme arthritis often presents as acute monoarticular arthritis challenging to distinguish from septic arthritis. Typical management for Lyme arthritis entails antibiotic therapy, while septic arthritis usually warrants operative debridement. During the period when Western Pennsylvania transitioned to a Lyme-endemic region, many children underwent operative intervention who were ultimately diagnosed with Lyme arthritis due to diagnostic ambiguity. We examined the impact of the operative intervention on pediatric Lyme arthritis outcomes. METHODS: We conducted a retrospective cohort study of patients admitted to a tertiary care children's hospital who were diagnosed with Lyme arthritis from 2008 to 2018 using chart review. Inclusion criteria were positive Lyme serology by Centers for Disease Control and Prevention (CDC) definition, clinical arthritis, and negative bacterial cultures. We recorded clinical presentation, laboratory data, details of hospitalization, costs, and outcomes after therapy to compare the impact of antibiotics alone (nonoperative group) versus antibiotics plus operative debridement (operative group). RESULTS: A total of 149 patients met the inclusion criteria. Overall, 47 (32%) patients underwent orthopaedic intervention. Operative management was associated with increased length (3.17 vs. 1.40 d) and cost ($27,850 vs. $10,716) of admission. The clinical resolution was documented in 57/58 patients (98%) in the nonoperative group and 41/42 patients (98%) in the operative group. The median duration to resolution was 21 days for both groups. CONCLUSIONS: Operative management of pediatric patients with Lyme arthritis is associated with increased resource utilization and costs while being similarly efficacious to nonoperative management. As the US Lyme epidemic expands, improved diagnosis and management of acute undifferentiated arthritis may prevent unneeded operative intervention. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Pediatric decision limits for serologic screening of Lyme disease.

BACKGROUND: Laboratory diagnosis of Lyme disease (LD) relies on a two-tier protocol. We have observed disproportionate equivocal serologies in children requiring reflex western blot (WB) using manufacturer-provided ranges based on adult studies. We aimed to determine appropriate ranges for our pediatric population. METHODS: We performed a one-year retrospective institutional review of all 2755 children with LD testing with the Vidas® Lyme IgM II/IgG II immunoassays with reflex to WB for equivocal/positive serologies. Results were assessed by frequency distributions, optimization via percent agreement analysis, and clinical adjudication. RESULTS: The proposed ranges for IgM (negative ≤0.20, equivocal ≥0.21 to <0.32, positive ≥0.32) and IgG (negative ≤0.50, positive >0.50) allowed for a decrease in the IgM equivocal rate (7% to 2%) and IgG positive rate (15% to 13%). There was a decrease in the positive percent agreement between tiers (95% to 83% and 98% to 95%) with increase in the negative (32% to 63% and 70% to 81%) and overall (65% to 73% and 85% to 88%) percent agreements for IgM and IgG, respectively. Of 15 IgM serologies reclassified as negative with a positive WB and not positive for IgG, 8 were clinically negative, 5 were clinically positive, and two had insufficient history. Of the 10 IgG serologies reclassified as negative with a positive WB 3 were clinically positive, 6 were clinically negative and one had insufficient history. CONCLUSIONS: Our modified ranges are more suitable for our pediatric population while reducing overdiagnosis, unnecessary treatment, diagnostic uncertainty, and turnaround time.

Pediatric Faculty and Trainee Attitudes Toward the COVID-19 Pandemic.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented event in modern medicine. In this study, we evaluate pediatric faculty and trainee attitudes and perspectives related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their roles in the COVID-19 pandemic. METHODS: We surveyed a pediatric hospital's faculty and trainees (n = 701) in April 2020 about their concerns related to SARS-CoV-2, trust in current recommendations, and attitudes toward trainee roles. We used descriptive statistics to analyze results and compared across sex and roles using logistic regression. RESULTS: Among 320 respondents (46% response rate), 73% were concerned with personal risk of SARS-CoV-2 infection and 88% were concerned with loved ones' risk. Twenty-four percent were concerned because of personal risk factors. Nearly half expressed concerns as their family's major provider and about salary changes (48% and 46%). Seventy-nine percent were concerned about lack of personal protective equipment and 43% about redeployment. Respondents endorsed varying levels of trust in recommendations related to COVID-19. Nearly three-fourths (72%) felt trainees are essential personnel. The majority were receptive to returning to usual patient care and training as the pandemic progresses. Significant differences exist across sex and roles related to levels of concern, trust, and trainee roles. CONCLUSIONS: In this study, we assess the concerns and perspectives of pediatric faculty and trainees related to the COVID-19 pandemic. Most view trainees as essential personnel and recognize the importance of direct patient care in their training. These results can be used to inform policy changes and trainee roles as the COVID-19 pandemic progresses.

Perspectives from the Society for Pediatric Research: advice on sustaining science and mentoring during COVID-19.

The COVID-19 pandemic will leave an indelible mark on the careers of current medical trainees. Given the disruptions to medical education, economic impact on institutions, and the uncertainties around future job prospects, trainees are facing unprecedented challenges. This situation is especially concerning for futures of pediatric physician-scientist trainees, where concerns regarding maintaining the pipeline were well documented prior to the emergence of COVID-19. In this Perspectives article, we leverage the unique expertise of our workgroup to address concerns of physician-scientist trainees and to provide suggestions on how to navigate career trajectories in the post-COVID-19 era. We identified and addressed four major areas of concern: lack of in-person conferences and the associated decrease access to mentors and networking activities, decreased academic productivity, diminished job prospects, and mental health challenges. We also suggest actions for trainees, mentors and educational leaders, and institutions to help support trainees during the pandemic, with a goal of maintaining the pediatric physician-scientist pipeline.

Predicting outcomes in central venous catheter salvage in pediatric central line-associated bloodstream infection.

OBJECTIVE: Central line-associated bloodstream infections (CLABSIs) are a common, costly, and hazardous healthcare-associated infection in children. In children in whom continued access is critical, salvage of infected central venous catheters (CVCs) with antimicrobial lock therapy is an alternative to removal and replacement of the CVC. However, the success of CVC salvage is uncertain, and when it fails the catheter has to be removed and replaced. We describe a machine learning approach to predict individual outcomes in CVC salvage that can aid the clinician in the decision to attempt salvage. MATERIALS AND METHODS: Over a 14-year period, 969 pediatric CLABSIs were identified in electronic health records. We used 164 potential predictors to derive 4 types of machine learning models to predict 2 failed salvage outcomes, infection recurrence and CVC removal, at 10 time points between 7 days and 1 year from infection onset. RESULTS: The area under the receiver-operating characteristic curve varied from 0.56 to 0.83, and key predictors varied over time. The infection recurrence model performed better than the CVC removal model did. CONCLUSIONS: Machine learning-based outcome prediction can inform clinical decision making for children. We developed and evaluated several models to predict clinically relevant outcomes in the context of CVC salvage in pediatric CLABSI and illustrate the variability of predictors over time.

Association of Bacteremia with Vaccination Status in Children Aged 2 to 36 Months.

OBJECTIVE: To determine the association between bacteremia and vaccination status in children aged 2-36 months presenting to a pediatric emergency department. STUDY DESIGN: Retrospective cohort study of children aged 2-36 months with blood cultures obtained in the pediatric emergency department between January 2013 and December 2017. The exposure of interest was immunization status, defined as number of Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae vaccinations, and the main outcome positive blood culture. Subjects with high-risk medical conditions were excluded. RESULTS: Of 5534 encounters, 4742 met inclusion criteria. The incidence of bacteremia was 1.5%. The incidence of contaminated blood culture was 5.0%. The relative risk of bacteremia was 0.79 (95% CI 0.39-1.59) for unvaccinated and 1.20 (95% CI 0.52-2.75) for undervaccinated children relative to those who had received age-appropriate vaccines. Five children were found to have S pneumoniae bacteremia and 1 child had Hib bacteremia; all of these subjects had at least 3 sets of vaccinations. No vaccine preventable pathogens were isolated from blood cultures of unvaccinated children. We found no S pneumoniae or Hib in children 2-6 months of age who were not fully vaccinated due to age (95% CI 0-0.13%) and the contamination rate in this group was high compared with children 7-36 months (6.6% vs 3.7%). CONCLUSIONS: Bacteremia in young children is an uncommon event. Contaminated blood cultures were more common than pathogens. Bacteremia from S pneumoniae or Hib is uncommon and, in this cohort, was independent of vaccine status.

Corticosteroids to prevent kidney scarring in children with a febrile urinary tract infection: a randomized trial.

BACKGROUND: To evaluate the efficacy of adjuvant systemic corticosteroids in reducing kidney scarring. A previous study suggested that use of adjuvant systemic corticosteroids reduces kidney scarring in children radiologically confirmed to have extensive pyelonephritis. Efficacy of corticosteroids for children with febrile urinary tract infection (UTI) has not been studied. METHODS: Children aged 2 months to 6 years with their first febrile UTI were randomized to corticosteroids or placebo for 3 days (both arms received antimicrobial therapy); kidney scarring was assessed using 99mTc-dimercaptosuccinic acid kidney scan 5-24 months after the initial UTI. RESULTS: We randomized 546 children of which 385 had a UTI and 254 had outcome kidney scans (instead of the 320 planned). Rates of kidney scarring were 9.8% (12/123) and 16.8% (22/131) in the corticosteroid and placebo groups, respectively (p = 0.16), corresponding to an absolute risk reduction of 5.9% (95% confidence interval: - 2.2, 14.1). CONCLUSION: While children randomized to adjuvant corticosteroids tended to develop fewer kidney scars than children who were randomized to receive placebo, a statistically significant difference was not achieved. However, the study was limited by not reaching its intended sample size. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov , NCT01391793, Registered 7/12/2011 Graphical abstract.

Use of C-Reactive Protein and Ferritin Biomarkers in Daily Pediatric Practice.

Recent pediatric clinical research has begun to focus on risk stratification tools using multibiomarker models. C-reactive protein (CRP) and ferriti biomarkers are widely available and used to varying degrees in daily practice, but there is no single source examining the evidence behind their use.We set out to summarize the evidence behind the use of CRP and ferritin biomarkers in pediatric practice and to begin development of a consensus for their future use for pediatricians.All the literature involving CRP and ferritin in pediatrics available on PubMed was surveyed. Research applicable to daily pediatric practice was summarized in the body of the article. Pediatric clinicians of various subspecialties contributed to the summary of the use of CRP and ferritin biomarkers in clinical practice in various disease processes. A clinical decision pathway is described, and evidence is summarized.CRP and ferritin biomarkers have diverse uses with various cutoff values in the literature, making their use in daily practice difficult. Elevation of these markers coincides with their significant elevation in uncontrolled inflammation.CRP and ferritin biomarkers are widely used in pediatrics. This review provides a resource summarizing evidence into a single source. There is sufficient evidence to indicate that these biomarkers of inflammation can be useful in guiding clinical decision making in specific clinical scenarios; however, further work is needed to improve their use in clinical practice.

A Decision Tree Using Patient Characteristics to Predict Resistance to Commonly Used Broad-Spectrum Antibiotics in Children With Gram-Negative Bloodstream Infections.

BACKGROUND: As rates of multidrug-resistant gram-negative infections rise, it is critical to recognize children at high risk of bloodstream infections with organisms resistant to commonly used empiric broad-spectrum antibiotics. The objective of the current study was to develop a user-friendly clinical decision aid to predict the risk of resistance to commonly prescribed broad-spectrum empiric antibiotics for children with gram-negative bloodstream infections. METHODS: This was a longitudinal retrospective cohort study of children with gram-negative bacteria cared for at a tertiary care pediatric hospital from June 2009 to June 2015. The primary outcome was a bloodstream infection due to bacteria resistant to broad-spectrum antibiotics (ie, cefepime, piperacillin-tazobactam, meropenem, or imipenem-cilastatin). Recursive partitioning was used to develop the decision tree. RESULTS: Of 689 episodes of gram-negative bloodstream infections included, 31% were resistant to broad-spectrum antibiotics. The decision tree stratified patients into high- or low-risk groups based on prior carbapenem treatment, a previous culture with a broad-spectrum antibiotic resistant gram-negative organism in the preceding 6 months, intestinal transplantation, age ≥3 years, and ≥7 prior episodes of gram-negative bloodstream infections. The sensitivity for classifying high-risk patients was 46%, and the specificity was 91%. CONCLUSION: A decision tree offers a novel approach to individualize patients' risk of gram-negative bloodstream infections resistant to broad-spectrum antibiotics, distinguishing children who may warrant even broader antibiotic therapy (eg, combination therapy, newer ß-lactam agents) from those for whom standard empiric antibiotic therapy is appropriate. The constructed tree needs to be validated more widely before incorporation into clinical practice.

Increasing Burden of Lyme Carditis in United States Children's Hospitals.

We sought to characterize the shifting epidemiology and resource utilization of Lyme disease and associated carditis in US children's hospitals. We hypothesized that the Lyme carditis burden has increased and that hospitalizations for Lyme carditis are costlier than those for Lyme disease without carditis. The PHIS database was queried for Lyme disease encounters between January 1, 2007 and December 31, 2013. Additional diagnostic codes consistent with carditis identified Lyme carditis cases. Demographic, clinical, and resource utilization data were analyzed. All costs were adjusted to 2014 US dollars. Lyme disease was identified in 3620 encounters with 189 (5%) associated with carditis. Lyme disease (360 cases in 2007 vs. 672 in 2013, p = 0.01) and Lyme carditis (17 cases in 2007 vs. 40 in 2013, p = 0.03) both significantly increased in frequency. This is primarily accounted for by their increase within the Midwest region. Carditis frequency among cases of Lyme disease was stable (p = 0.15). Encounters for Lyme carditis are dramatically costlier than those for Lyme disease without carditis [median $9104 (3741-19,003) vs. 922 (238-4987), p < 0.001] The increase in Lyme carditis cases in US children's hospitals is associated with an increased Lyme disease incidence, suggesting that there has not been a change in its virulence or cardiac tropism. The increasing number of serious cardiac events and costs associated with Lyme disease emphasize the need for prevention and early detection of disease and control of its spread.

Serious Bacterial Infections in Neonates Presenting Afebrile With History of Fever.

BACKGROUND: Infants ≤28 days of age with fever are frequently hospitalized while undergoing infectious evaluation. We assessed differences in rates of serious bacterial infection (SBI; bacteremia, bacterial meningitis, urinary tract infection) and invasive bacterial infection (IBI; bacteremia, bacterial meningitis) among the following neonates: (1) febrile at presentation (FP), (2) afebrile with history of fever without subsequent fever during hospitalization, and (3) afebrile with history of fever with subsequent fever during hospitalization. METHODS: We performed a single-center retrospective study of neonates evaluated for SBI during emergency department evaluation between January 1, 2006, and December 31, 2017. Patients were categorized into FP, afebrile with no subsequent fever (ANF), and afebrile with subsequent fever (ASF) groups. We compared rates of SBI and IBI between groups using logistic regression and assessed time to fever development using time-to-event analysis. RESULTS: Of 931 neonates, 278 (29.9%) were in the ANF group, 93 (10.0%) were in the ASF group, and 560 (60.2%) were in the FP group. Odds of SBI in neonates ANF were 0.42 (95% confidence interval [CI] 0.23-0.79) compared with infants FP, although differences in IBI were not statistically significant (0.52, 95% CI 0.19-1.51). In infants ASF, median time to fever was 5.6 hours (interquartile range, 3.1-11.4). Infants ASF had higher odds of SBI compared to infants FP (odds ratio 1.93, 95% CI 1.07-3.50). CONCLUSIONS: Neonates with history of fever who remain afebrile during hospitalization may have lower odds for SBI and be candidates for early discharge after an observation period.

Immature neutrophils in young febrile infants.

BACKGROUND: To describe the diagnostic value of the absolute band count (ABC) and ratio of immature to total neutrophils (I:T) for invasive bacterial infections (IBIs; bacterial meningitis and bacteraemia) among young febrile infants. METHODS: We performed a cross-sectional study in a paediatric emergency department of febrile infants ≤60 days over 12 years to evaluate the accuracy of the ABC and I:T for IBI. RESULTS: Of 2930 included patients, 75 (2.6%) had IBIs. The area under the curve (AUC; 95% CI) for ABC was 0.69 (0.62 to 0.76) with sensitivity 0.27 (0.17 to 0.38) and specificity 0.94 (0.93 to 0.95) at cutoff ≥1500 cells/µL. The AUC for I:T was 0.65 (0.59 to 0.72) with sensitivity 0.29 (0.19 to 0.41) and specificity 0.88 (0.87 to 0.89) at cutoff ≥0.2. Only the ABC in infants 29-60 days was minimally accurate. CONCLUSION: The ABC and I:T were generally inaccurate for detecting IBI in febrile infants. Guidelines without these parameters may be better for risk assessment.

Factors associated with serious bacterial infections in infants ≤60 days with hypothermia in the emergency department.

BACKGROUND: We sought to investigate risk factors for serious bacterial infection (SBI: bacterial meningitis, bacteremia, and urinary tract infection [UTI]) among infants ≤60 days of age presenting to the emergency department (ED) with hypothermia (temperature < 36 °C). METHODS: We performed a single center study over a 12-year period including all patients ≤60 days old with hypothermia, excluding patients who did not receive a blood culture and patients who received antibiotics prior to culture acquisition. The primary outcome was SBI. Secondary outcomes were mortality and herpes simplex infection. We performed multivariable logistic regression to identify risk factors for primary outcomes reporting adjusted odds ratios with 95% confidence intervals (aOR, 95% CI). RESULTS: 360 infants were identified. 10/360 (2.8%) had an SBI. All episodes of SBI occurred in infants ≤28 days of age. Two patients had meningitis, two had meningitis with bacteremia, one had isolated bacteremia, and five had UTI. Associated diagnoses included prematurity (46.9%), hyperbilirubinemia (28.3%) and dehydration (14.7%). In multivariable analysis, presentation at 15-28 days (7.60, 1.81-31.86; p = 0.005) compared to 0-14 days, higher absolute neutrophil count (1.25, 1.04-1.50; p = 0.015) and lower platelet count (0.99, 0.99-1.00; p = 0.046) were associated with SBI. Three patients without SBI died during or soon after their hospitalization. One patient had positive testing for herpes simplex. CONCLUSION: In this cohort of hypothermic infants, 2.8% had a SBI. Age of presentation, ANC, and lower platelet count were associated with serious infections. Hypothermic infants presenting to the ED carry significant morbidity and require prospective study to better risk-stratify this population.

Host and Bacterial Markers that Differ in Children with Cystitis and Pyelonephritis.

OBJECTIVE: To determine whether treatment for urinary tract infections in children could be individualized using biomarkers for acute pyelonephritis. STUDY DESIGN: We enrolled 61 children with febrile urinary tract infections, collected blood and urine samples, and performed a renal scan within 2 weeks of diagnosis to identify those with pyelonephritis. Renal scans were interpreted centrally by 2 experts. We measured inflammatory proteins in blood and urine using LUMINEX or an enzyme-linked immunosorbent assay. We evaluated serum RNA expression using RNA sequencing in a subset of children. Finally, for children with Escherichia coli isolated from urine cultures, we performed a polymerase chain reaction for 4 previously identified virulence genes. RESULTS: Urinary markers that best differentiated pyelonephritis from cystitis included chemokine (C-X-C motif) ligand (CXCL)1, CXCL9, CXCL12, C-C motif chemokine ligand 2, INF γ, and IL-15. Serum procalcitonin was the best serum marker for pyelonephritis. Genes in the interferon-γ pathway were upregulated in serum of children with pyelonephritis. The presence of E coli virulence genes did not correlate with pyelonephritis. CONCLUSIONS: Immune response to pyelonephritis and cystitis differs quantitatively and qualitatively; this may be useful in differentiating these 2 conditions.

Should Children With Constipation Undergo Blood Lead Level Screening?

This study aimed to compare the prevalence of elevated blood lead level in children with constipation to the population prevalence. We reviewed the charts of 441 children who were screened with a blood lead level on presenting to the gastroenterology clinic at UPMC Children's Hospital of Pittsburgh for evaluation of constipation. The prevalence of blood lead level greater than 5 µg/dL was 1.36% (6/441; 95% confidence interval = 1.23% to 1.49%), which is significantly lower than the 4.01% prevalence in the population reported by the Center for Disease Control and Prevention. No patients had a blood lead level greater than 10 µg/dL. Age under 5 years old showed an increased odds of lead level greater than 5 µg/dL (odds ratio = 7.5; 95% confidence interval = 1.2 to 47.3, P < .05). We concluded that children seen in the gastroenterology clinic for constipation are unlikely to have an elevated blood lead level on routine screening.