First name
Aris
Last name
Garro

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

Serum Sodium Concentration and Mental Status in Children With Diabetic Ketoacidosis.

Year of Publication

2021

Date Published

2021 Aug 09

ISSN Number

1098-4275

Abstract

<p><strong>OBJECTIVES: </strong>Diabetic ketoacidosis (DKA) is typically characterized by low or low-normal serum sodium concentrations, which rise as hyperglycemia resolves. In retrospective studies, researchers found associations between declines in sodium concentrations during DKA and cerebral injury. We prospectively investigated determinants of sodium concentration changes and associations with mental status alterations during DKA.</p>

<p><strong>METHODS: </strong>Using data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in Diabetic Ketoacidosis Trial, we compared children who had declines in glucose-corrected sodium concentrations with those who had rising or stable concentrations. Children were randomly assigned to 1 of 4 intravenous fluid protocols that differed in infusion rate and sodium content. Data from the first 4, 8, and 12 hours of treatment were analyzed for 1251, 1086, and 877 episodes, respectively.</p>

<p><strong>RESULTS: </strong>In multivariable analyses, declines in glucose-corrected sodium concentrations were associated with higher sodium and chloride concentrations at presentation and with previously diagnosed diabetes. Treatment with 0.45% (vs 0.9%) sodium chloride fluids was also associated with declines in sodium concentration; however, higher rates of fluid infusion were associated with declines in sodium concentration only at 12 hours. Frequencies of abnormal Glasgow Coma Scale scores and clinical diagnoses of cerebral injury were similar in patients with and without declines in glucose-corrected sodium concentrations.</p>

<p><strong>CONCLUSIONS: </strong>Changes in glucose-corrected sodium concentrations during DKA treatment are influenced by the balance of free-water loss versus sodium loss at presentation and the sodium content of intravenous fluids. Declines in glucose-corrected sodium concentrations are not associated with mental status changes during treatment.</p>

DOI

10.1542/peds.2021-050243

Alternate Title

Pediatrics

PMID

34373322

Title

Electrocardiogram as a Lyme Disease Screening Test.

Year of Publication

2021

Date Published

2021 Jul 12

ISSN Number

1097-6833

Abstract

<p><strong>OBJECTIVE: </strong>To examine the association between electrocardiographic (ECG) evidence of carditis at the time of Lyme disease evaluation and a diagnosis of Lyme disease.</p>

<p><strong>STUDY DESIGN: </strong>We performed an eight-center prospective cohort study of children undergoing emergency department evaluation for Lyme disease limited to those who had an ECG obtained by their treating clinicians. The study cardiologist reviewed all ECGs flagged as abnormal by the study sites to assess for ECG evidence of carditis. We defined Lyme disease with the presence of an erythema migrans lesion or a positive two-tier Lyme disease serology. We used logistic regression to measure the association between Lyme disease and AV block or any ECG evidence of carditis.</p>

<p><strong>RESULTS: </strong>Of the 546 children who had an ECG obtained, 214 (39%) had Lyme disease. Overall, 42 children had ECG evidence of carditis of which 24 had atrioventricular (AV) block (20 first degree). Of the patients with ECG evidence of carditis, only 21 (50%) had any cardiac symptoms. The presence of AV block (odds ratio 4.7, 95% confidence interval 1.8-12.1) and any ECG evidence of carditis (odds ratio 2.3, 95% confidence interval 1.2-4.3) were both associated with diagnosis of Lyme disease.</p>

<p><strong>CONCLUSIONS: </strong>ECG evidence of carditis, especially AV block, was associated with a diagnosis of Lyme disease. ECG evidence of carditis can be used as a diagnostic biomarker for Lyme disease to guide initial management while awaiting Lyme disease test results.</p>

DOI

10.1016/j.jpeds.2021.07.010

Alternate Title

J Pediatr

PMID

34265339

Title

Effects of Fluid Rehydration Strategy on Correction of Acidosis and Electrolyte Abnormalities in Children With Diabetic Ketoacidosis.

Year of Publication

2021

Date Published

2021 Jun 29

ISSN Number

1935-5548

Abstract

<p><strong>OBJECTIVE: </strong>Fluid replacement to correct dehydration, acidosis, and electrolyte abnormalities is the cornerstone of treatment for diabetic ketoacidosis (DKA), but little is known about optimal fluid infusion rates and electrolyte content. The objective of this study was to evaluate whether different fluid protocols affect the rate of normalization of biochemical derangements during DKA treatment.</p>

<p><strong>RESEARCH DESIGN AND METHODS: </strong>The current analysis involved moderate or severe DKA episodes ( = 714) in children age &lt;18 years enrolled in the Fluid Therapies Under Investigation in DKA (FLUID) Trial. Children were assigned to one of four treatment groups using a 2 × 2 factorial design (0.90% or 0.45% saline and fast or slow rate of administration).</p>

<p><strong>RESULTS: </strong>The rate of change of pH did not differ by treatment arm, but Pco increased more rapidly in the fast versus slow fluid infusion arms during the initial 4 h of treatment. The anion gap also decreased more rapidly in the fast versus slow infusion arms during the initial 4 and 8 h. Glucose-corrected sodium levels remained stable in patients assigned to 0.90% saline but decreased in those assigned to 0.45% saline at 4 and 8 h. Potassium levels decreased, while chloride levels increased more rapidly with 0.90% versus 0.45% saline. Hyperchloremic acidosis occurred more frequently in patients in the fast arms (46.1%) versus the slow arms (35.2%).</p>

<p><strong>CONCLUSIONS: </strong>In children treated for DKA, faster fluid administration rates led to a more rapid normalization of anion gap and Pco than slower fluid infusion rates but were associated with an increased frequency of hyperchloremic acidosis.</p>

DOI

10.2337/dc20-3113

Alternate Title

Diabetes Care

PMID

34187840

Title

Validation of the Rule of 7's for Identifying Children at Low-risk for Lyme Meningitis.

Year of Publication

2021

Number of Pages

306-309

Date Published

2021 Apr 01

ISSN Number

1532-0987

Abstract

<p><b>BACKGROUND: </b>The Rule of 7's classifies children as low-risk for Lyme meningitis with the absence of the following: ≥7 days of headache, any cranial neuritis or ≥70% cerebrospinal fluid mononuclear cells. We sought to broadly validate this clinical prediction rule in children with meningitis undergoing evaluation for Lyme disease.</p><p><b>METHODS: </b>We performed a patient-level data meta-analysis of 2 prospective and 2 retrospective cohorts of children ≤21 years of age with cerebrospinal fluid pleocytosis who underwent evaluation for Lyme disease. We defined a case of Lyme meningitis with a positive 2-tier serology result (positive or equivocal first-tier enzyme immunoassay followed by a positive supplemental immunoblot). We applied the Rule of 7's and report the accuracy for the identification of Lyme meningitis.</p><p><b>RESULTS: </b>Of 721 included children with meningitis, 178 had Lyme meningitis (24.7%) and 543 had aseptic meningitis (75.3%). The pooled data from the 4 studies showed the Rule of 7's has a sensitivity of 98% [95% confidence interval (CI): 89%-100%, I2 = 71%], specificity 40% (95% CI: 30%-50%, I2 = 75%), and a negative predictive value of 100% (95% CI: 95%-100%, I2 = 55%).</p><p><b>CONCLUSIONS: </b>The Rule of 7's accurately identified children with meningitis at low-risk for Lyme meningitis for whom clinicians should consider outpatient management while awaiting Lyme disease test results.</p>

DOI

10.1097/INF.0000000000003003

Alternate Title

Pediatr Infect Dis J

PMID

33710975

Title

Frequency and Risk Factors of Acute Kidney Injury During Diabetic Ketoacidosis in Children and Association With Neurocognitive Outcomes.

Year of Publication

2020

Number of Pages

e2025481

Date Published

2020 Dec 01

ISSN Number

2574-3805

Abstract

<p><strong>Importance: </strong>Acute kidney injury (AKI) occurs commonly during diabetic ketoacidosis (DKA) in children, but the underlying mechanisms and associations are unclear.</p>

<p><strong>Objective: </strong>To investigate risk factors for AKI and its association with neurocognitive outcomes in pediatric DKA.</p>

<p><strong>Design, Setting, and Participants: </strong>This cohort study was a secondary analysis of data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in DKA Study, a prospective, multicenter, randomized clinical trial comparing fluid protocols for pediatric DKA in 13 US hospitals. Included DKA episodes occurred among children age younger than 18 years with blood glucose 300 mg/dL or greater and venous pH less than 7.25 or serum bicarbonate level less than 15 mEq/L.</p>

<p><strong>Exposures: </strong>DKA requiring intravenous insulin therapy.</p>

<p><strong>Main Outcomes and Measures: </strong>AKI occurrence and stage were assessed using serum creatinine measurements using Kidney Disease: Improving Global Outcomes criteria. DKA episodes with and without AKI were compared using univariable and multivariable methods, exploring associated factors.</p>

<p><strong>Results: </strong>Among 1359 DKA episodes (mean [SD] patient age, 11.6 [4.1] years; 727 [53.5%] girls; 651 patients [47.9%] with new-onset diabetes), AKI occurred in 584 episodes (43%; 95% CI, 40%-46%). A total of 252 AKI events (43%; 95% CI, 39%-47%) were stage 2 or 3. Multivariable analyses identified older age (adjusted odds ratio [AOR] per 1 year, 1.05; 95% CI, 1.00-1.09; P = .03), higher initial serum urea nitrogen (AOR per 1 mg/dL increase, 1.14; 95% CI, 1.11-1.18; P &lt; .001), higher heart rate (AOR for 1-SD increase in z-score, 1.20; 95% CI, 1.09-1.32; P &lt; .001), higher glucose-corrected sodium (AOR per 1 mEq/L increase, 1.03; 95% CI, 1.00-1.06; P = .001) and glucose concentrations (AOR per 100 mg/dL increase, 1.19; 95% CI, 1.07-1.32; P = .001), and lower pH (AOR per 0.1 increase, 0.63; 95% CI, 0.51-0.78; P &lt; .001) as variables associated with AKI. Children with AKI, compared with those without, had lower scores on tests of short-term memory during DKA (mean [SD] digit span recall: 6.8 [2.4] vs 7.6 [2.2]; P = .02) and lower mean (SD) IQ scores 3 to 6 months after recovery from DKA (100.0 [12.2] vs 103.5 [13.2]; P = .005). Differences persisted after adjusting for DKA severity and demographic factors, including socioeconomic status.</p>

<p><strong>Conclusions and Relevance: </strong>These findings suggest that AKI may occur more frequently in children with greater acidosis and circulatory volume depletion during DKA and may be part of a pattern of multiple organ injury involving the kidneys and brain.</p>

DOI

10.1001/jamanetworkopen.2020.25481

Alternate Title

JAMA Netw Open

PMID

33275152

Title

Cognitive Function Following Diabetic Ketoacidosis in Children With New-Onset or Previously Diagnosed Type 1 Diabetes.

Year of Publication

2020

Date Published

2020 Sep 22

ISSN Number

1935-5548

Abstract

<p><strong>OBJECTIVE: </strong>This study assessed whether a single diabetic ketoacidosis (DKA) episode is associated with cognitive declines in children with newly diagnosed type 1 diabetes and whether the same is true in children who had previously been diagnosed after accounting for variations in glycemic control and other relevant factors.</p>

<p><strong>RESEARCH DESIGN AND METHODS: </strong>We prospectively enrolled 758 children, 6-18 years old, who presented with DKA in a randomized multisite clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. A total of 392 children with DKA had new onset of type 1 diabetes, and the rest were previously diagnosed. Neurocognitive assessment occurred 2-6 months after the DKA episode. A comparison group of 376 children with type 1 diabetes, but no DKA exposure, was also enrolled.</p>

<p><strong>RESULTS: </strong>Among all patients, moderate/severe DKA was associated with lower intelligence quotient (IQ) (β = -0.12, &lt; 0.001), item-color recall (β = -0.08, = 0.010), and forward digit span (β = -0.06, = 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (β = -0.08, = 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA were independently associated with lower IQ (β = -0.10 and β = -0.09, respectively, &lt; 0.01) and higher HbA was associated with lower item-color recall (β = -0.10, = 0.007) after hypoglycemia, diabetes duration, and socioeconomic status were accounted for.</p>

<p><strong>CONCLUSIONS: </strong>A single DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. Sizable IQ declines are detectable in children with known diabetes, suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia.</p>

DOI

10.2337/dc20-0187

Alternate Title

Diabetes Care

PMID

32962981

Title

Hypertension During Diabetic Ketoacidosis in Children.

Year of Publication

2020

Date Published

2020 May 06

ISSN Number

1097-6833

Abstract

<p><strong>OBJECTIVES: </strong>To characterize hemodynamic alterations occurring during diabetic ketoacidosis (DKA) in a large cohort of children and to identify clinical and biochemical factors associated with hypertension.</p>

<p><strong>STUDY DESIGN: </strong>This was a planned secondary analysis of data from the Pediatric Emergency Care Applied Research Network (PECARN) Fluid Therapies Under Investigation in DKA (FLUID) Study, a randomized clinical trial of fluid resuscitation protocols for children in DKA. Hemodynamic data (heart rate, blood pressure) from children with DKA were assessed in comparison with normal values for age and sex. Multivariable statistical modeling was used to explore clinical and laboratory predictors of hypertension.</p>

<p><strong>RESULTS: </strong>Among 1258 DKA episodes, hypertension was documented at presentation in 154 (12.2%) and developed during DKA treatment in an additional 196 (15.6%), resulting in a total of 350 DKA episodes (27.8%) in which hypertension occurred at some time. Factors associated with hypertension at presentation included more severe acidosis, (lower pH and lower PCO), and stage 2 or 3 Acute Kidney Injury (AKI). More severe acidosis and lower Glasgow Coma Scale (GCS) scores were associated with hypertension occurring at any time during DKA treatment.</p>

<p><strong>CONCLUSIONS: </strong>Despite dehydration, hypertension occurs in a substantial number of children with DKA. Factors associated with hypertension include greater severity of acidosis, lower PCO and lower GCS scores during DKA treatment, suggesting that hypertension might be centrally mediated.</p>

DOI

10.1016/j.jpeds.2020.04.066

Alternate Title

J. Pediatr.

PMID

32387716

Title

The Lyme Disease Polymerase Chain Reaction Test Has Low Sensitivity.

Year of Publication

2019

Date Published

2019 Dec 10

ISSN Number

1557-7759

Abstract

<p>The Lyme PCR is a direct detection test, but has not been rigorously evaluated in children undergoing evaluation for acute Lyme disease. We performed a six-center prospective cohort study of children aged 1 to 21 years undergoing acute evaluation for Lyme disease. For this planned secondary analysis, we limited our cohort to children undergoing evaluation for Lyme disease who had any Lyme PCR test obtained by a treating clinician (blood, synovial fluid, or cerebrospinal fluid). We defined a case of Lyme disease with a positive two-tier Lyme disease serology: a positive or equivocal enzyme immunoassay followed by a positive supplemental immunoblot interpreted using standard criteria. We report the test characteristics of Lyme PCR for the diagnosis of Lyme disease. We identified 124 children of whom 54 (43.5%) had Lyme disease. Overall, 23 had a positive PCR test (sensitivity 41.8%; 95% confidence interval [CI] 29.7-55.0; specificity 100%, 95% CI: 94.2-100). All children with a positive Lyme PCR also had a positive two-tiered Lyme disease serology. The Lyme disease PCR test did not improve the diagnosis of children undergoing evaluation for acute Lyme disease. Given the additional costs of this low utility test, clinicians should not order Lyme PCR testing in the acute care setting.</p>

DOI

10.1089/vbz.2019.2547

Alternate Title

Vector Borne Zoonotic Dis.

PMID

31821110

Title

Diagnostic Performance of C6 Enzyme Immunoassay for Lyme Arthritis.

Year of Publication

2019

Date Published

2019 Dec 13

ISSN Number

1098-4275

Abstract

<p><strong>OBJECTIVES: </strong>In Lyme disease endemic areas, initial management of children with arthritis can be challenging because diagnostic tests take several days to return results, leading to potentially unnecessary invasive procedures. Our objective was to examine the role of the C6 peptide enzyme immunoassay (EIA) test to guide initial management.</p>

<p><strong>METHODS: </strong>We enrolled children with acute arthritis undergoing evaluation for Lyme disease presenting to a participating Pedi Lyme Net emergency department (2015-2019) and performed a C6 EIA test. We defined Lyme arthritis with a positive or equivocal C6 EIA test result followed by a positive supplemental immunoblot result and defined septic arthritis as a positive synovial fluid culture result or a positive blood culture result with synovial fluid pleocytosis. Otherwise, children were considered to have inflammatory arthritis. We report the sensitivity and specificity of the C6 EIA for the diagnosis of Lyme arthritis.</p>

<p><strong>RESULTS: </strong>Of the 911 study patients, 211 children (23.2%) had Lyme arthritis, 11 (1.2%) had septic arthritis, and 689 (75.6%) had other inflammatory arthritis. A positive or equivocal C6 EIA result had a sensitivity of 100% (211 out of 211; 95% confidence interval [CI]: 98.2%-100%) and specificity of 94.2% (661 out of 700; 95% CI: 92.5%-95.9%) for Lyme arthritis. None of the 250 children with a positive or equivocal C6 EIA result had septic arthritis (0%; 95% CI: 0%-1.5%), although 75 children underwent diagnostic arthrocentesis and 27 underwent operative joint washout.</p>

<p><strong>CONCLUSIONS: </strong>In Lyme disease endemic areas, a C6 EIA result could be used to guide initial clinical decision-making, without misclassifying children with septic arthritis.</p>

DOI

10.1542/peds.2019-0593

Alternate Title

Pediatrics

PMID

31836615

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