First name
Stephen
Middle name
B
Last name
Freedman

Title

Post-COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection.

Year of Publication

2022

Number of Pages

e2223253

Date Published

07/2022

ISSN Number

2574-3805

Abstract

Importance: 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.

DOI

10.1001/jamanetworkopen.2022.23253

Alternate Title

JAMA Netw Open

PMID

35867061

Title

Association of Herpes Simplex Virus Testing with Hospital Length of Stay for Infants ≤60 Days of Age Undergoing Evaluation for Meningitis.

Year of Publication

2019

Number of Pages

E1-E4

Date Published

2019 May 12

ISSN Number

1553-5606

Abstract

Although neonatal herpes simplex virus (HSV) causes significant morbidity, utilization of the cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) test remains variable. Our objective was to examine the association of CSF HSV PCR testing with length of stay (LOS) in a 20-center retrospective cohort of hospitalized infants aged ≤60 days undergoing evaluation for meningitis after adjustment for patient-level factors and clustering by center. Of 20,496 eligible infants, 7,399 (36.1%) had a CSF HSV PCR test performed, and 46 (0.6% of those tested) had a positive test. Infants who had a CSF HSV PCR test performed had a 23% longer hospital LOS (incident rate ratio 1.23; 95% CI: 1.14-1.33). Targeted CSF HSV PCR testing may mitigate the impact on LOS for low-risk infants.

DOI

10.12788/jhm.3202

Alternate Title

J Hosp Med

PMID

31112493

Title

Outcomes of SARS-CoV-2-Positive Youths Tested in Emergency Departments: The Global PERN-COVID-19 Study.

Year of Publication

2022

Number of Pages

e2142322

Date Published

2022 01 04

ISSN Number

2574-3805

Abstract

<p><strong>Importance: </strong>Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized.</p>

<p><strong>Objective: </strong>To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED).</p>

<p><strong>Design, Setting, and Participants: </strong>This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021.</p>

<p><strong>Exposures: </strong>Acute SARS-CoV-2 infection was determined by nucleic acid (eg, polymerase chain reaction) testing.</p>

<p><strong>Main Outcomes and Measures: </strong>Severe outcomes, a composite measure defined as intensive interventions during hospitalization (eg, inotropic support, positive pressure ventilation), diagnoses indicating severe organ impairment, or death.</p>

<p><strong>Results: </strong>Among 3222 enrolled youths who tested positive for SARS-CoV-2 infection, 3221 (&gt;99.9%) had index visit outcome data available, 2007 (62.3%) were from the United States, 1694 (52.6%) were male, and 484 (15.0%) had a self-reported chronic illness; the median (IQR) age was 3 (0-10) years. After 14 days of follow-up, 735 children (22.8% [95% CI, 21.4%-24.3%]) were hospitalized, 107 (3.3% [95% CI, 2.7%-4.0%]) had severe outcomes, and 4 children (0.12% [95% CI, 0.03%-0.32%]) died. Characteristics associated with severe outcomes included being aged 5 to 18 years (age 5 to &lt;10 years vs &lt;1 year: odds ratio [OR], 1.60 [95% CI, 1.09-2.34]; age 10 to &lt;18 years vs &lt;1 year: OR, 2.39 [95% CI 1.38-4.14]), having a self-reported chronic illness (OR, 2.34 [95% CI, 1.59-3.44]), prior episode of pneumonia (OR, 3.15 [95% CI, 1.83-5.42]), symptoms starting 4 to 7 days prior to seeking ED care (vs starting 0-3 days before seeking care: OR, 2.22 [95% CI, 1.29-3.82]), and country (eg, Canada vs US: OR, 0.11 [95% CI, 0.05-0.23]; Costa Rica vs US: OR, 1.76 [95% CI, 1.05-2.96]; Spain vs US: OR, 0.51 [95% CI, 0.27-0.98]). Among a subgroup of 2510 participants discharged home from the ED after initial testing and who had complete follow-up, 50 (2.0%; 95% CI, 1.5%-2.6%) were eventually hospitalized and 12 (0.5%; 95% CI, 0.3%-0.8%) had severe outcomes. Compared with hospitalized SARS-CoV-2-negative youths, the risk of severe outcomes was higher among hospitalized SARS-CoV-2-positive youths (risk difference, 3.9%; 95% CI, 1.1%-6.9%).</p>

<p><strong>Conclusions and Relevance: </strong>In this study, approximately 3% of SARS-CoV-2-positive youths tested in EDs experienced severe outcomes within 2 weeks of their ED visit. Among children discharged home from the ED, the risk was much lower. Risk factors such as age, underlying chronic illness, and symptom duration may be useful to consider when making clinical care decisions.</p>

DOI

10.1001/jamanetworkopen.2021.42322

Alternate Title

JAMA Netw Open

PMID

35015063

Title

Predictors of Invasive Herpes Simplex Virus Infection in Young Infants.

Year of Publication

2021

Date Published

2021 Aug 26

ISSN Number

1098-4275

Abstract

<p><strong>OBJECTIVES: </strong>To identify independent predictors of and derive a risk score for invasive herpes simplex virus (HSV) infection.</p>

<p><strong>METHODS: </strong>In this 23-center nested case-control study, we matched 149 infants with HSV to 1340 controls; all were ≤60 days old and had cerebrospinal fluid obtained within 24 hours of presentation or had HSV detected. The primary and secondary outcomes were invasive (disseminated or central nervous system) or any HSV infection, respectively.</p>

<p><strong>RESULTS: </strong>Of all infants included , 90 (60.4%) had invasive and 59 (39.6%) had skin, eyes, and mouth disease. Predictors independently associated with invasive HSV included younger age (adjusted odds ratio [aOR]: 9.1 [95% confidence interval (CI): 3.4-24.5] &lt;14 and 6.4 [95% CI: 2.3 to 17.8] 14-28 days, respectively, compared with &gt;28 days), prematurity (aOR: 2.3, 95% CI: 1.1 to 5.1), seizure at home (aOR: 6.1, 95% CI: 2.3 to 16.4), ill appearance (aOR: 4.2, 95% CI: 2.0 to 8.4), abnormal triage temperature (aOR: 2.9, 95% CI: 1.6 to 5.3), vesicular rash (aOR: 54.8, (95% CI: 16.6 to 180.9), thrombocytopenia (aOR: 4.4, 95% CI: 1.6 to 12.4), and cerebrospinal fluid pleocytosis (aOR: 3.5, 95% CI: 1.2 to 10.0). These variables were transformed to derive the HSV risk score (point range 0-17). Infants with invasive HSV had a higher median score (6, interquartile range: 4-8) than those without invasive HSV (3, interquartile range: 1.5-4), with an area under the curve for invasive HSV disease of 0.85 (95% CI: 0.80-0.91). When using a cut-point of ≥3, the HSV risk score had a sensitivity of 95.6% (95% CI: 84.9% to 99.5%), specificity of 40.1% (95% CI: 36.8% to 43.6%), and positive likelihood ratio 1.60 (95% CI: 1.5 to 1.7) and negative likelihood ratio 0.11 (95% CI: 0.03 to 0.43).</p>

<p><strong>CONCLUSIONS: </strong>A novel HSV risk score identified infants at extremely low risk for invasive HSV who may not require routine testing or empirical treatment.</p>

DOI

10.1542/peds.2021-050052

Alternate Title

Pediatrics

PMID

34446535

Title

The Champagne Tap: Time to Pop the Cork?

Year of Publication

2020

Number of Pages

1194-1198

Date Published

2020 11

ISSN Number

1553-2712

Abstract

<p><strong>BACKGROUND: </strong>A "champagne tap" is a lumbar puncture with no cerebrospinal fluid (CSF) red blood cells (RBCs). Clinicians disagree whether the absence of CSF white blood cells (WBCs) is also required.</p>

<p><strong>AIMS: </strong>As supervising providers frequently reward trainees after a champagne tap, we investigated how varying the definition impacted the frequency of trainee accolades.</p>

<p><strong>MATERIALS &amp; METHODS: </strong>We performed a secondary analysis of a retrospective cross-sectional study of infants ≤60&nbsp;days of age who had a CSF culture performed in the emergency department (ED) at one of 20 centers participating in a Pediatric Emergency Medicine Collaborative Research Committee (PEM CRC) endorsed study. Our primary outcomes were a champagne tap defined by either a CSF RBC count of 0&nbsp;cells/mm regardless of CSF WBC count or both CSF RBC and WBC counts of 0&nbsp;cells/mm .</p>

<p><strong>RESULTS: </strong>Of the 23,618 eligible encounters, 20,358 (86.2%) had both a CSF RBC and WBC count obtained. Overall, 3,147 (13.3%) had a CSF RBC count of 0&nbsp;cells/mm and 377 (1.6%) had both CSF WBC and RBC counts of 0&nbsp;cells/mm (relative rate 8.35, 95% confidence interval 7.51 to 9.27).</p>

<p><strong>CONCLUSIONS: </strong>In infants, a lumbar puncture with a CSF RBC count of 0&nbsp;cells/mm regardless of the CSF WBC count occurred eight-times more frequently than one with both CSF WBC and RBC counts of 0&nbsp;cells/mm . A broader champagne tap definition would allow more frequent recognition of procedural success, with the potential to foster a supportive community during medical training, potentially protecting against burnout.</p>

DOI

10.1111/acem.13966

Alternate Title

Acad Emerg Med

PMID

32187765

Title

Predicting Adverse Outcomes for Shiga Toxin-Producing E. coli Infections in Emergency Departments.

Year of Publication

2021

Date Published

2021 Jan 05

ISSN Number

1097-6833

Abstract

<p><strong>OBJECTIVE: </strong>To assess the performance of a hemolytic uremic syndrome (HUS) severity score among children with Shiga toxin-producing Escherichia coli (STEC) infections and HUS by stratifying them according to their risk of adverse events. The score has not been previously evaluated in a North American acute care setting.</p>

<p><strong>STUDY DESIGN: </strong>We reviewed medical records of children &lt;18 years old infected with STEC and treated in one of 38 participating EDs in North America between 2011 and 2015. The HUS severity score [hemoglobin (g/dL) plus two-times serum creatinine (mg/dL)] was calculated using first available laboratory results. Children with scores &gt;13 were designated as high-risk. We assessed score performance to predict severe adverse events (ie, dialysis, neurologic complication, respiratory failure and death) using discrimination and net benefit (i.e. threshold probability), with subgroup analyses by age and day-of-illness.</p>

<p><strong>RESULTS: </strong>A total of 167 children had HUS, of whom 92.8% (155/167) had relevant data to calculate the score; 60.6% (94/155) experienced a severe adverse event. Discrimination was acceptable overall (AUC 0.71, 95% CI 0.63, 0.79) and better among children &lt;5 years old (AUC 0.77, 95% CI 0.68, 0.87). For children &lt;5 years, greatest net benefit was achieved for a threshold probability &gt;26%.</p>

<p><strong>CONCLUSIONS: </strong>The HUS severity score was able to discriminate between high- and low-risk children &lt;5 years old with STEC-associated HUS at a statistically acceptable level; however, it did not appear to provide clinical benefit at a meaningful risk threshold.</p>

DOI

10.1016/j.jpeds.2020.12.077

Alternate Title

J Pediatr

PMID

33417918

Title

Performance of the Modified Boston and Philadelphia Criteria for Invasive Bacterial Infections.

Year of Publication

2020

Date Published

2020 Mar 23

ISSN Number

1098-4275

Abstract

<p><strong>BACKGROUND: </strong>The ability of the decades-old Boston and Philadelphia criteria to accurately identify infants at low risk for serious bacterial infections has not been recently reevaluated.</p>

<p><strong>METHODS: </strong>We assembled a multicenter cohort of infants 29 to 60 days of age who had cerebrospinal fluid (CSF) and blood cultures obtained. We report the performance of the modified Boston criteria (peripheral white blood cell count [WBC] ≥20 000 cells per mm, CSF WBC ≥10 cells per mm, and urinalysis with &gt;10 WBC per high-power field or positive urine dip result) and modified Philadelphia criteria (peripheral WBC ≥15 000 cells per mm, CSF WBC ≥8 cells per mm, positive CSF Gram-stain result, and urinalysis with &gt;10 WBC per high-power field or positive urine dip result) for the identification of invasive bacterial infections (IBIs). We defined IBI as bacterial meningitis (growth of pathogenic bacteria from CSF culture) or bacteremia (growth from blood culture).</p>

<p><strong>RESULTS: </strong>We applied the modified Boston criteria to 8344 infants and the modified Philadelphia criteria to 8131 infants. The modified Boston criteria identified 133 of the 212 infants with IBI (sensitivity 62.7% [95% confidence interval (CI) 55.9% to 69.3%] and specificity 59.2% [95% CI 58.1% to 60.2%]), and the modified Philadelphia criteria identified 157 of the 219 infants with IBI (sensitivity 71.7% [95% CI 65.2% to 77.6%] and specificity 46.1% [95% CI 45.0% to 47.2%]). The modified Boston and Philadelphia criteria misclassified 17 of 53 (32.1%) and 13 of 56 (23.3%) infants with bacterial meningitis, respectively.</p>

<p><strong>CONCLUSIONS: </strong>The modified Boston and Philadelphia criteria misclassified a substantial number of infants 29 to 60 days old with IBI, including those with bacterial meningitis.</p>

DOI

10.1542/peds.2019-3538

Alternate Title

Pediatrics

PMID

32205466

Title

Predicting Hemolytic Uremic Syndrome and Renal Failure in Shiga Toxin-Producing Escherichia coli Infected Children.

Year of Publication

2019

Date Published

2019 May 24

ISSN Number

1537-6591

Abstract

<p><strong>BACKGROUND: </strong>Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care.</p>

<p><strong>METHODS: </strong>We conducted a multicenter, historical-cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children &lt;18 years who submitted STEC-positive specimens between January 2011 and December 2015 at a participating study institution were eligible.</p>

<p><strong>RESULTS: </strong>Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors of HUS included younger age (OR: 0.77; 95%CI: 0.69, 0.85/year), leukocyte count ≥13.0x103/μL (2.54; 1.42, 4.54), higher hematocrit (1.83; 1.21, 2.77/5% increase) and serum creatinine (10.82; 1.49, 78.69/1 mg/dL increase), platelet count &lt;250 ×103/μL (1.92; 1.02, 3.60), lower serum sodium (1.12; 1.02, 1.23/1 mmol/L decrease), and intravenous fluid administration initiated ≥4 days following diarrhea onset (2.50; 1.14, 5.46). A longer interval from diarrhea onset to index visit was associated with reduced HUS risk (0.70; 0.54, 0.90). RRT predictors included female sex (2.27; 1.14, 4.50), younger age (0.83; 0.74, 0.92/year), lower serum sodium (1.15; 1.04, 1.27/mmol/L decrease), higher leukocyte count ≥13.0x103/μL (2.35; 1.17, 4.72) and creatinine (7.75; 1.20, 50.16/1 mg/dL increase) concentrations, and initial intravenous fluid administration ≥4 days following diarrhea onset (2.71; 1.18, 6.21).</p>

<p><strong>CONCLUSIONS: </strong>The complex nature of STEC infection renders predicting its course a challenge. Risk factors we identified highlight the importance of avoiding dehydration and performing close clinical and laboratory monitoring.</p>

DOI

10.1093/cid/ciz432

Alternate Title

Clin. Infect. Dis.

PMID

31125419

Title

Test Characteristics of Cerebrospinal Fluid Gram Stain to Identify Bacterial Meningitis in Infants Younger Than 60 Days.

Year of Publication

2018

Date Published

2018 Nov 12

ISSN Number

1535-1815

Abstract

<p>In our cohort of 20,947 infants aged 60 days or younger, cerebrospinal fluid Gram stain had a sensitivity of 34.3% (95% confidence interval, 28.1%-41.1%) and a positive predictive value of 61.4% (95% confidence interval, 52.2%-69.8%) for positive cerebrospinal fluid culture, suggesting that Gram stain alone may lead to both underdiagnosis and overdiagnosis of bacterial meningitis.</p>

DOI

10.1097/PEC.0000000000001639

Alternate Title

Pediatr Emerg Care

PMID

30422943

Title

Cerebrospinal Fluid Reference Values for Young Infants Undergoing Lumbar Puncture.

Year of Publication

2018

Date Published

2018 Feb 02

ISSN Number

1098-4275

Abstract

<p><strong>OBJECTIVES: </strong>To determine age-specific reference values and quantify age-related changes for cerebrospinal fluid (CSF) white blood cell (WBC) counts and protein and glucose concentrations in infants ≤60 days of age.</p>

<p><strong>METHODS: </strong>This multicenter, cross-sectional study included infants ≤60 days old with CSF cultures and complete CSF profiles obtained within 24 hours of presentation. Those with conditions suspected or known to cause abnormal CSF parameters (eg, meningitis) and those with a hospital length of stay of &gt;72 hours were excluded. Reference standards were determined for infants ≤28 days of age and 29 to 60 days of age by using the third quartile +1.5 interquartile range for WBC and protein and the first quartile -1.5 interquartile range for glucose. CSF parameter centile curves based on age were calculated by using the LMST method.</p>

<p><strong>RESULTS: </strong>A total of 7766 patients were included. CSF WBC counts were higher in infants ≤28 days of age (upper bound: 15 cells/mm) than in infants 29 to 60 days of age (upper bound: 9 cells/mm;&lt; .001). CSF protein concentrations were higher in infants ≤28 days of age (upper bound: 127 mg/dL) than in infants 29 to 60 days of age (upper bound: 99 mg/dL;&lt; .001). CSF glucose concentrations were lower in infants ≤28 days of age (lower bound: 25 mg/dL) than in infants 29 to 60 days of age (lower bound: 27 mg/dL;&lt; .001).</p>

<p><strong>CONCLUSIONS: </strong>The age-specific CSF WBC count, protein concentration, and glucose concentration reference values identified in this large, multicenter cohort of infants can be used to interpret the results of lumbar puncture in infants ≤60 days of age.</p>

DOI

10.1542/peds.2017-3405

Alternate Title

Pediatrics

PMID

29437883

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