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  • 1
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S753-S753
    Abstract: Streptococcus pneumoniae is the most common pyogenic bacteria associated with CAP in children, but the proportion of cases might be underestimated because of the low sensitivity of current standard diagnostic methods. Nasopharyngeal (NP) carriage of pneumococcus commonly precedes the development of pneumococcal pneumonia, and facilitates pneumococcus interactions with other respiratory pathogens and the host immune response. This study investigated the relationship between pneumococcal carriage and the severity of CAP in children. Methods We conducted a prospective, multicenter, observational study for CAP among previously healthy children aged 2 months through 18 years in six children’s hospitals in Ohio. Blood, pleural fluid, and NP swabs were collected for pathogen detection by culture and/or polymerase chain reaction (PCR). S. pneumoniae was quantified in NP swabs by real-time PCR. Patient management followed the standard of care in each study site. Results Among 441 children with radiologically confirmed CAP, 156 (35.4%) had no bacterial or viral pathogens identified as etiologic agents. NP pneumococcal carriage rate in this group was 34.6%. Children with CAP and pneumococcal carriage (53/156) were younger (5.9 vs. 9.6 years, P 〈 0.001) than those with no carriage (103/156). Median neutrophil counts and median procalcitonin concentrations were significantly higher in the pneumococcal carriage group (12,030 vs. 8,370 cells/mm3 and 1.0 vs. 0.5 mg/dl, respectively; P 〈 0.05 for both) than in the non-carriage group. Children with documented pneumococcal carriage received respiratory support more frequently (50.0% vs. 28.2%, p = 0.012) and had a longer duration of hospitalization (3.5 ± 3.8 vs. 2.1 ± 2.0 days, P = 0.026) than those without pneumococcal carriage. Age was not associated with any of the variables used to assess clinical disease severity. Conclusion Pneumococcal carriage was associated with higher inflammatory markers and greater clinical disease severity in children with CAP in whom no pathogens were identified by standard diagnostics. This suggests that NP carriage of pneumococcus in children with CAP may modulate the host immune response and possibly influence clinical disease severity. Disclosures Octavio Ramilo, MD, Bill & Melinda Gates Foundation: Research Grant; Janssen: Research Grant; Merck: Advisory Board; NIH: Research Grant; Ohio Children’s Hospital Association (OCHA): Research Grant; Pfizer: Advisory Board, Consultant, Lectures; Sanofi/Medimmune: Advisory Board.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2757767-3
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  • 2
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S911-S912
    Abstract: Worldwide, pneumonia is the leading cause of death in children 〈 5 years of age and the second most common reason for hospitalization in children in the United States and Europe. This study was designed to describe the clinical characteristics and etiology of community-acquired pneumonia (CAP) in children. Methods We conducted a prospective, multicenter, observational study of CAP among previously healthy children aged 2 months through 18 years in six children’s hospitals in Ohio. Blood, pleural fluid, and nasopharyngeal swabs were collected for pathogen detection by culture and/or molecular diagnostics. Patient clinical management including antibiotic therapy and respiratory support, followed the standard of care at each study site. Follow-up information regarding clinical outcomes was collected via a survey 6–8 weeks after enrollment. Results We enrolled 441 children (n = 380, 86% hospitalized) with CAP from 2015 to 2018. Median age was 5 years (IQR: 2.1–8.9y). Intensive care and respiratory support were required for 15% and 49% of children, respectively. Consolidation and pleural effusion were identified in 26% and 21%, respectively. Among hospitalized children, 99% received antibiotics during hospitalization, and 91% continued antibiotic treatment at discharge. There were no children with any kind of sequelae or deaths from CAP, but 4.4% were readmitted within 30 days after discharge. Pathogens were identified in 64% patients; including pyogenic bacteria in 4%, atypical bacteria in 9%, and viruses in 56%. A total of 18 (4%) children had both bacterial (9 pyogenic and 9 mycoplasma) and viral pathogens. Among children with a virus detected (n = 245), 17% had more than one virus. The most commonly detected bacteria were M. pneumoniae (n = 39) and S. pneumoniae (n = 10). Rhinovirus was the most common virus detected (RV; n = 81, 28%), followed by respiratory syncytial virus (RSV; n = 75, 26%). Conclusion In this multicenter cohort, the most commonly detected viruses in children with CAP were RV and RSV, and M. pneumoniae and S. pneumoniae among bacteria. Clinical outcomes in children with CAP were overall good, but there was a high burden of hospitalization and antibiotic use. Disclosures Octavio Ramilo, MD, Bill & Melinda Gates Foundation: Research Grant; Janssen: Research Grant; Merck: Advisory Board; NIH: Research Grant; Ohio Children’s Hospital Association (OCHA): Research Grant; Pfizer: Advisory Board, Consultant, Lectures; Sanofi/Medimmune: Advisory Board.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2757767-3
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  • 3
    In: The Journal of Pediatrics, Elsevier BV, Vol. 170 ( 2016-03), p. 227-233.e6
    Type of Medium: Online Resource
    ISSN: 0022-3476
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 2005245-5
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  • 4
    In: AEM Education and Training, Wiley, Vol. 5, No. 3 ( 2021-07)
    Abstract: There is a need for pediatric emergency medicine (PEM) researchers, but the current state of PEM fellow research training is not well described. We sought to (1) describe resources and gaps in PEM fellowship research training and (2) assess agreement between fellow and program director (PD) perceptions of these in fellow research experience. Methods Surveys were distributed electronically to U.S. PEM fellows and PDs from March to April 2020. Fellows and PDs were queried on program research infrastructure and current gaps in fellow research experience. For programs that had at least one fellow and PD response, each fellow response was compared to their PD’s corresponding response (reference standard). For each binary survey item, we determined the percent of responses with agreement between the fellow and PD. Results Of 79 fellowship programs, 70 (89%) were represented with at least one response, including responses from 59 PDs (75%) and 218 fellows (39% of all fellows, representing 80% of programs). Fellows and PDs identified mentorship and faculty engagement as the most important needs for successful fellowship research; for every one fellow there was a median of 0.8 potential faculty mentors in the division. Twenty percent of fellows were not satisfied with mentorship opportunities. There was no association between fellow career research intent (high, defined as ≥20% dedicated time, or low) with current year of training (p = 0.88), program size (p = 0.67), and area of research focus (p = 0.40). Fellows were often unaware of research being performed by division faculty. Conclusion PEM fellows were not consistently aware of resources available to support research training. To better support PEM fellows’ research training, many programs may need to expand mentorship and increase fellows’ awareness of local and external resources and opportunities.
    Type of Medium: Online Resource
    ISSN: 2472-5390 , 2472-5390
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2881270-0
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  • 5
    In: Open Forum Infectious Diseases, Oxford University Press (OUP)
    Abstract: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among SARS-CoV-2 infected children and determined if SARS-CoV-2 test result status modified the associations. Methods We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary outcome was to determine if the SARS-CoV-2 test result modified the associations. Results We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2 positive children, procalcitonin ≥0.5 ng/mL [9.14 (2.90, 28.80)], ferritin & gt;500 ng/mL [aOR (95%CI): 7.95 (1.89, 33.44)], D-dimer ≥1500 ng/mL [4.57 (1.12, 18.68)] , serum glucose ≥120 mg/dL [2.01 (1.06, 3.81)], and lymphocyte count & lt;1.0×109/L [3.21 (1.34, 7.69)], and platelet count & lt;150×109/L [2.82 (1.31, 6.07)] were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-Reactive Protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. Conclusions Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children and elevated serum procalcitonin, CRP, and D-dimer, and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared to those testing negative.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2757767-3
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  • 6
    In: Journal of the Pediatric Infectious Diseases Society, Oxford University Press (OUP), Vol. 13, No. 4 ( 2024-04-24), p. 257-259
    Abstract: 14% of children with SARS-CoV-2 infections had radiographic pneumonia. Hypoxemia, cough, higher temperature, and older age were associated with pneumonias. In children tested, SARS-CoV-2 test results were not associated with radiographic pneumonia.
    Type of Medium: Online Resource
    ISSN: 2048-7207
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2668791-4
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  • 7
    In: JAMA Network Open, American Medical Association (AMA), Vol. 5, No. 1 ( 2022-01-11), p. e2142322-
    Type of Medium: Online Resource
    ISSN: 2574-3805
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
    detail.hit.zdb_id: 2931249-8
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  • 8
    In: JAMA Network Open, American Medical Association (AMA), Vol. 5, No. 7 ( 2022-07-22), p. e2223253-
    Abstract: Little is known about the risk factors for, and the risk of, developing post–COVID-19 conditions (PCCs) among children. Objectives To estimate the proportion of SARS-CoV-2–positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2–negative children, and to assess factors associated with PCCs. Design, Setting, and Participants This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2–positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2–negative controls. Exposure SARS-CoV-2 detected via nucleic acid testing. Main Outcomes and Measures Post–COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey. Results Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2–positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference, 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2–positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR] , 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31] ; ≥7 symptoms: aOR, 4.59 [95% CI, 2.50-8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99] ). SARS-CoV-2–positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321 [2.7%; 95% CI, 1.9%-3.7%] ; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391 [10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%] ). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00] ). Conclusions and Relevance In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.
    Type of Medium: Online Resource
    ISSN: 2574-3805
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
    detail.hit.zdb_id: 2931249-8
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  • 9
    In: Journal of the Pediatric Infectious Diseases Society, Oxford University Press (OUP), Vol. 12, No. 2 ( 2023-02-27), p. 83-88
    Abstract: The absence of consensus for outcomes in pediatric antibiotic trials is a major barrier to research harmonization and clinical translation. We sought to develop expert consensus on study outcomes for clinical trials of children with mild community-acquired pneumonia (CAP). Methods Applying the Delphi method, a multispecialty expert panel ranked the importance of various components of clinical response and treatment failure outcomes in children with mild CAP for use in research. During Round 1, panelists suggested additional outcomes in open-ended responses that were added to subsequent rounds of consensus building. For Rounds 2 and 3, panelists were provided their own prior responses and summary statistics for each item in the previous round. The consensus was defined by & gt;70% agreement. Results The expert panel determined that response to and failure of treatment should be addressed at a median of 3 days after initiation. Complete or substantial improvement in fever, work of breathing, dyspnea, tachypnea when afebrile, oral intake, and activity should be included as components of adequate clinical response outcomes. Clinical signs and symptoms including persistent or worsening fever, work of breathing, and reduced oral intake should be included in treatment failure outcomes. Interventions including receipt of parenteral fluids, supplemental oxygen, need for high-flow nasal cannula oxygen therapy, and change in prescription of antibiotics should also be considered in treatment failure outcomes. Conclusions Clinical response and treatment failure outcomes determined by the consensus of this multidisciplinary expert panel can be used for pediatric CAP studies to provide objective data translatable to clinical practice.
    Type of Medium: Online Resource
    ISSN: 2048-7207
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2668791-4
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  • 10
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 145, No. 6 ( 2020-06-01)
    Abstract: Host biomarkers predict disease severity in adults with community-acquired pneumonia (CAP). We evaluated the association of the white blood cell (WBC) count, absolute neutrophil count (ANC), C-reactive protein (CRP), and procalcitonin with the development of severe outcomes in children with CAP. METHODS: We performed a prospective cohort study of children 3 months to 18 years of age with CAP in the emergency department. The primary outcome was disease severity: mild (discharged from the hospital), mild-moderate (hospitalized but not moderate-severe or severe), moderate-severe (eg, hospitalized with receipt of intravenous fluids, supplemental oxygen, complicated pneumonia), and severe (eg, intensive care, vasoactive infusions, chest drainage, severe sepsis). Outcomes were examined within the cohort with suspected CAP and in a subset with radiographic CAP. RESULTS: Of 477 children, there were no statistical differences in the median WBC count, ANC, CRP, or procalcitonin across severity categories. No biomarker had adequate discriminatory ability between severe and nonsevere disease (area under the curve [AUC]: 0.53–0.6 for suspected CAP and 0.59–0.64 for radiographic CAP). In analyses adjusted for age, antibiotic use, fever duration, and viral pathogen detection, CRP was associated with moderate-severe disease (odds ratio 1.12; 95% confidence interval, 1.0–1.25). CRP and procalcitonin revealed good discrimination of children with empyema requiring chest drainage (AUC: 0.83) and sepsis with vasoactive infusions (CRP AUC: 0.74; procalcitonin AUC: 0.78), although prevalence of these outcomes was low. CONCLUSIONS: WBC count, ANC, CRP, and procalcitonin are generally not useful to discriminate nonsevere from severe disease in children with CAP, although CRP and procalcitonin may have some utility in predicting the most severe outcomes.
    Type of Medium: Online Resource
    ISSN: 0031-4005 , 1098-4275
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 2020
    detail.hit.zdb_id: 1477004-0
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