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.

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.

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.

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.

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.

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.

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.

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.

Insights From the Geographic Spread of the Lyme Disease Epidemic.

Background: Lyme disease is the most common reportable zoonotic infection in the United States. Recent data suggest spread of the Ixodes tick vector and increasing incidence of Lyme disease in several states, including Pennsylvania. We sought to determine the clinical presentation and healthcare use patterns for pediatric Lyme disease in western Pennsylvania. Methods: The electronic medical records of all patients with an International Classification of Disease, Ninth Revision, diagnosis of Lyme disease between 2003 and 2013 at Children's Hospital of Pittsburgh were individually reviewed to identify confirmed cases of Lyme disease. The records of 773 patients meeting these criteria were retrospectively analyzed for patient demographics, disease manifestations, and healthcare use. Results: An Lyme disease increased exponentially in the pediatric population of western Pennsylvania. There was a southwestward migration of Lyme disease cases, with a shift from rural to nonrural zip codes. Healthcare provider involvement evolved from subspecialists to primary care pediatricians and emergency departments (EDs). Patients from nonrural zip codes more commonly presented to the ED, while patients from rural zip codes used primary care pediatricians and EDs equally. Conclusions: The current study details the conversion of western Pennsylvania from a Lyme-naive to a Lyme-epidemic area, highlighting changes in clinical presentation and healthcare use over time. Presenting symptoms and provider type differed between those from rural and nonrural zip codes. By elucidating the temporospatial epidemiology and healthcare use for pediatric Lyme disease, the current study may inform public health measures regionally while serving as an archetype for other areas at-risk for Lyme disease epidemics.

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.

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.

Development and validation of a continuously age-adjusted measure of patient condition for hospitalized children using the electronic medical record.

Awareness of a patient's clinical status during hospitalization is a primary responsibility for hospital providers. One tool to assess status is the Rothman Index (RI), a validated measure of patient condition for adults, based on empirically derived relationships between 1-year post-discharge mortality and each of 26 clinical measurements available in the electronic medical record. However, such an approach cannot be used for pediatrics, where the relationships between risk and clinical variables are distinct functions of patient age, and sufficient 1-year mortality data for each age group simply do not exist. We report the development and validation of a new methodology to use adult mortality data to generate continuously age-adjusted acuity scores for pediatrics. Clinical data were extracted from EMRs at three pediatric hospitals covering 105,470 inpatient visits over a 3-year period. The RI input variable set was used as a starting point for the development of the pediatric Rothman Index (pRI). Age-dependence of continuous variables was determined by plotting mean values versus age. For variables determined to be age-dependent, polynomial functions of mean value and mean standard deviation versus age were constructed. Mean values and standard deviations for adult RI excess risk curves were separately estimated. Based on the "find the center of the channel" hypothesis, univariate pediatric risk was then computed by applying a z-score transform to adult mean and standard deviation values based on polynomial pediatric mean and standard deviation functions. Multivariate pediatric risk is estimated as the sum of univariate risk. Other age adjustments for categorical variables were also employed. Age-specific pediatric excess risk functions were compared to age-specific expert-derived functions and to in-hospital mortality. AUC for 24-h mortality and pRI scores prior to unplanned ICU transfers were computed. Age-adjusted risk functions correlated well with similar functions in Bedside PEWS and PAWS. Pediatric nursing data correlated well with risk as measured by mortality odds ratios. AUC for pRI for 24-h mortality was 0.93 (0.92, 0.94), 0.93 (0.93, 0.93) and 0.95 (0.95, 0.95) at the three pediatric hospitals. Unplanned ICU transfers correlated with lower pRI scores. Moreover, pRI scores declined prior to such events. A new methodology to continuously age-adjust patient acuity provides a tool to facilitate timely identification of physiologic deterioration in hospitalized children.

Evaluation of Electronic Medical Record Vital Sign Data Versus a Commercially Available Acuity Score in Predicting Need for Critical Intervention at a Tertiary Children's Hospital.

OBJECTIVES: Evaluate the ability of vital sign data versus a commercially available acuity score adapted for children (pediatric Rothman Index) to predict need for critical intervention in hospitalized pediatric patients to form the foundation for an automated early warning system. DESIGN: Retrospective review of electronic medical record data. SETTING: Academic children's hospital. PATIENTS: A total of 220 hospitalized children 6.7 ± 6.7 years old experiencing a cardiopulmonary arrest (condition A) and/or requiring urgent intervention with transfer (condition C) to the ICU between January 2006 and July 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Physiologic data 24 hours preceding the event were extracted from the electronic medical record. Vital sign predictors were constructed using combinations of age-adjusted abnormalities in heart rate, systolic and diastolic blood pressures, respiratory rate, and peripheral oxygen saturation to predict impending deterioration. Sensitivity and specificity were determined for vital sign-based predictors by using 1:1 age-matched and sex-matched non-ICU control patients. Sensitivity and specificity for a model consisting of any two vital sign measurements simultaneously outside of age-adjusted normal ranges for condition A, condition C, and condition A or C were 64% and 54%, 57% and 53%, and 59% and 54%, respectively. The pediatric Rothman Index (added to the electronic medical record in April 2009) was evaluated in a subset of these patients (n = 131) and 16,138 hospitalized unmatched non-ICU control patients for the ability to predict condition A or C, and receiver operating characteristic curves were generated. Sensitivity and specificity for a pediatric Rothman Index cutoff of 40 for condition A, condition C, and condition A or C were 56% and 99%, 13% and 99%, and 28% and 99%, respectively. CONCLUSIONS: A model consisting of simultaneous vital sign abnormalities and the pediatric Rothman Index predict condition A or C in the 24-hour period prior to the event. Vital sign only prediction models have higher sensitivity than the pediatric Rothman Index but are associated with a high false-positive rate. The high specificity of the pediatric Rothman Index merits prospective evaluation as an electronic adjunct to human-triggered early warning systems.

Follistatin-like protein 1 is a critical mediator of experimental Lyme arthritis and the humoral response to Borrelia burgdorferi infection.

Follistatin-like protein 1 (FSTL-1) has recently been described as a critical mediator of CIA and a marker of disease activity. Lyme arthritis, caused by Borrelia burgdorferi, shares similarities with autoimmune arthritis and the experimental murine model collagen-induced arthritis (CIA). Because FSTL-1 is important in CIA and autoimmune arthritides, and Lyme arthritis shares similarities with CIA, we hypothesized that FSTL-1 may be an important mediator of Lyme arthritis. We demonstrate for the first time that FSTL-1 is induced by B. burgdorferi infection and is required for the development of Lyme arthritis in a murine model, utilizing a gene insertion to generate FSTL-1 hypomorphic mice. Using qPCR and qRT-PCR, we found that despite similar early infectious burden, FSTL-1 hypomorphic mice have improved spirochetal clearance in the face of attenuated arthritis and inflammatory cytokine production. Further, FSTL-1 mediates pathogen-specific antibody production and antigen recognition when assessed by ELISA and one- and two-dimensional immunoblotting. This study is the first to describe a role for FSTL-1 in the development of Lyme arthritis and anti-Borrelia response, and the first to demonstrate a role for FSTL-1 in response to infection, highlighting the potential for FSTL-1 as a target in the treatment of B. burgdorferi infection.

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.

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.