Publications by authors named "Aris Garro"

50 Publications

Predictors of Invasive Herpes Simplex Virus Infection in Young Infants.

Pediatrics 2021 Sep;148(3)

Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Objectives: To identify independent predictors of and derive a risk score for invasive herpes simplex virus (HSV) infection.

Methods: 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.

Results: 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] <14 and 6.4 [95% CI: 2.3 to 17.8] 14-28 days, respectively, compared with >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).

Conclusions: A novel HSV risk score identified infants at extremely low risk for invasive HSV who may not require routine testing or empirical treatment.
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http://dx.doi.org/10.1542/peds.2021-050052DOI Listing
September 2021

Serologic response to antigens varies with clinical phenotype in children and young adults with Lyme disease.

J Clin Microbiol 2021 Aug 11:JCM0134421. Epub 2021 Aug 11.

Division of Emergency Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Lyme disease is commonly diagnosed by serologic response to and related species, but the relationship between serologic targets and clinical features is unknown. We developed a multi-antigen Luminex-based panel and evaluated IgG responses in 527 children 1 to 21 years of age assessed for Lyme disease across 4 Pedi Lyme Net emergency departments, including 127 Lyme cases defined by either an erythema migrans (EM) lesion or positive C6 enzyme immunoassay followed by immunoblot and 400 patients considered clinical mimics. Of 42 antigens tested, 26 elicited specific reactivity in Lyme patients, without marked age-dependent variation. Children with single EM lesions typically lacked -specific IgG. By principal component analysis, children with early disseminated and late Lyme disease clustered separately from clinical mimics and also from each other. Neurological disease and arthritis exhibited distinct serologic responses, with OspC variants overrepresented in neurological disease and p100, BmpA, p58 and p45 overrepresented in arthritis. Machine learning identified a 3-antigen panel (VlsE_Bb, p41_Bb, OspC_Bafz) that distinguished Lyme disease from clinical mimics with a sensitivity of 86.6% (95% confidence interval [CI] 80.3-92.1) and a specificity of 95.5% (95% CI 93.4-97.4). Sensitivity was much lower in early Lyme disease (38.5%, 95% CI 15.4-69.2). Interestingly, 17 children classified as Lyme mimics had a positive 3-antigen panel, suggesting that more comprehensive serologic analysis could help refine Lyme diagnosis. In conclusion, multiplex antigen panels provide a novel approach to understanding the immune response in Lyme disease, potentially helping to facilitate accurate diagnosis and to understand differences between clinical stages.
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http://dx.doi.org/10.1128/JCM.01344-21DOI Listing
August 2021

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

Pediatrics 2021 Sep 9;148(3). Epub 2021 Aug 9.

Department of Psychology, University of California, Davis, Davis, California.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1542/peds.2021-050243DOI Listing
September 2021

Electrocardiogram as a Lyme Disease Screening Test.

J Pediatr 2021 Jul 12. Epub 2021 Jul 12.

Division of Emergency Medicine, Boston Children's Hospital, Boston, MA.

Objective: To examine the association between electrocardiographic (ECG) evidence of carditis at the time of Lyme disease evaluation and a diagnosis of Lyme disease.

Study Design: We performed an 8-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 as the presence of an erythema migrans lesion or a positive 2-tier Lyme disease serology. We used logistic regression to measure the association between Lyme disease and atrioventricular (AV) block or any ECG evidence of carditis.

Results: Of the 546 children who had an ECG obtained, 214 (39%) had Lyme disease. Overall, 42 children had ECG evidence of carditis, of whom 24 had 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 (OR 4.7, 95% CI 1.8-12.1) and any ECG evidence of carditis (OR 2.3, 95% CI 1.2-4.3) were both associated with diagnosis of Lyme disease.

Conclusions: 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.
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http://dx.doi.org/10.1016/j.jpeds.2021.07.010DOI Listing
July 2021

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

Diabetes Care 2021 Sep 29;44(9):2061-2068. Epub 2021 Jun 29.

Department of Pediatrics, University of California Davis Health, University of California, Davis, School of Medicine, Sacramento.

Objective: 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.

Research Design And Methods: The current analysis involved moderate or severe DKA episodes ( = 714) in children age <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).

Results: 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%).

Conclusions: 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.
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http://dx.doi.org/10.2337/dc20-3113DOI Listing
September 2021

Validation of Septic Knee Monoarthritis Prediction Rule in a Lyme Disease Endemic Area.

Pediatr Emerg Care 2021 May 13. Epub 2021 May 13.

From the *Brown University, Providence, RI †Division of Pediatric Emergency Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA ‡Division of Pediatric Emergency Medicine, Children's Hospital of Wisconsin, Milwaukee, WI §Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA ∥Departments of Pediatrics and Emergency Medicine, Hasbro Children's Hospital, Providence, RI ¶Division of Emergency Medicine, Nemours/A.I. duPont Hospital for Children, Wilmington, DE #Department of Emergency Medicine, Children's Minnesota, Minneapolis, MN **Division of Emergency Medicine, Boston Children's Hospital, Boston, MA.

Objective: In Lyme disease endemic areas, Lyme and septic arthritis often present similarly. A published septic knee arthritis clinical prediction rule includes 2 high-risk predictors: absolute neutrophil count of 10,000 cells/mm or greater and erythrocyte sedimentation rate of 40 mm/h or greater. The objective of the study was to externally validate this prediction rule in a multicenter prospective cohort.

Methods: We enrolled a prospective cohort of children with knee monoarthritis undergoing evaluation for Lyme disease at 1 of 8 Pedi Lyme Net emergency departments located in endemic areas. We defined a case of septic arthritis with a positive synovial fluid culture or a synovial fluid white blood cell count of 50,000 or greater per high powered field with a positive blood culture and Lyme arthritis with a positive or equivocal C6 EIA, followed by a positive supplemental immunoblot. Other children were classified as having inflammatory arthritis. We report the performance of the septic arthritis clinical prediction rule in our study population.

Results: Of the 543 eligible children, 13 had septic arthritis (2.4%), 234 Lyme arthritis (43.1%), and 296 inflammatory arthritis (54.5%). Of the 457 children (84.2%) with available laboratory predictors, all children with septic arthritis were classified as high risk (sensitivity, 100%; 95% confidence interval [CI], 62.8%-100%; specificity, 68.1%; 95% CI, 63.6-73.3; negative predictive value, 278/278 [100%]; 95% CI, 98.6%-100%). Of the 303 low-risk children, 52 (17.2%) underwent diagnostic arthrocentesis.

Conclusions: The septic knee arthritis clinical prediction rule accurately distinguished between septic and Lyme arthritis in an endemic area. Clinical application may reduce unnecessary invasive diagnostic procedures.
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http://dx.doi.org/10.1097/PEC.0000000000002455DOI Listing
May 2021

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

Pediatr Infect Dis J 2021 04;40(4):306-309

Pediatric Emergency Medicine, Division of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts.

Background: 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.

Methods: 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.

Results: 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%).

Conclusions: 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.
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http://dx.doi.org/10.1097/INF.0000000000003003DOI Listing
April 2021

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

JAMA Netw Open 2020 12 1;3(12):e2025481. Epub 2020 Dec 1.

Department of Pediatrics, University of California, Davis School of Medicine, Sacramento.

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

Objective: To investigate risk factors for AKI and its association with neurocognitive outcomes in pediatric DKA.

Design, Setting, And Participants: 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.

Exposures: DKA requiring intravenous insulin therapy.

Main Outcomes And Measures: 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.

Results: 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 < .001), higher heart rate (AOR for 1-SD increase in z-score, 1.20; 95% CI, 1.09-1.32; P < .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 < .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.

Conclusions And Relevance: 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.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.25481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718599PMC
December 2020

Pediatric Lyme Disease Biobank, United States, 2015-2020.

Emerg Infect Dis 2020 12;26(12):3099-3101

In 2015, we founded Pedi Lyme Net, a pediatric Lyme disease research network comprising 8 emergency departments in the United States. Of 2,497 children evaluated at 1 of these sites for Lyme disease, 515 (20.6%) were infected. This network is a unique resource for evaluating new approaches for diagnosing Lyme disease in children.
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http://dx.doi.org/10.3201/eid2612.200920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706969PMC
December 2020

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

Diabetes Care 2020 11 22;43(11):2768-2775. Epub 2020 Sep 22.

Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT.

Objective: 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.

Research Design And Methods: 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.

Results: Among all patients, moderate/severe DKA was associated with lower intelligence quotient (IQ) (β = -0.12, < 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, < 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.

Conclusions: 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.
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http://dx.doi.org/10.2337/dc20-0187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576431PMC
November 2020

Hypertension during Diabetic Ketoacidosis in Children.

J Pediatr 2020 08 6;223:156-163.e5. Epub 2020 May 6.

Department of Pediatrics, University of California Davis Health, University of California Davis, School of Medicine, Sacramento, CA. Electronic address:

Objectives: 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.

Study Design: This was a planned secondary analysis of data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in DKA 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.

Results: 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. More severe acidosis and lower Glasgow Coma Scale scores were associated with hypertension occurring at any time during DKA treatment.

Conclusions: 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 Glasgow Coma Scale scores during DKA treatment, suggesting that hypertension might be centrally mediated.
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http://dx.doi.org/10.1016/j.jpeds.2020.04.066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414786PMC
August 2020

Development of a pediatric Lyme meningitis symptom measurement instrument using a Delphi technique.

Ticks Tick Borne Dis 2020 07 23;11(4):101418. Epub 2020 Mar 23.

Division of Emergency Medicine, Harvard Medical School; Boston, MA and Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, USA.

Published Lyme meningitis treatment studies are limited by outcome measures that cannot capture day-to-day differences in clinical improvement. Our goal was to use expert consensus to develop a daily measurement instrument for assessing clinical improvement in children with Lyme meningitis. We assembled a panel of 24 nationally recognized Lyme disease experts to develop a pediatric daily symptom measurement instrument. Experts responded to four rounds of surveys, receiving feedback about the previous round prior to each subsequent round with anonymity for participants and responses. Using modified Delphi methods, we established a novel Lyme meningitis outcome instrument. The final Pediatric Lyme Meningitis Symptom Measurement instrument includes five items: headache (Likert scale), neck pain/stiffness (Likert scale), fever (yes/no), light sensitivity (yes/no) and vision problems (yes/no). We defined three consecutive days with a symptom score of zero as the minimum to define clinical improvement. Using expert consensus, we developed a novel Pediatric Lyme Meningitis Symptom Measurement instrument to measure treatment response daily for children with Lyme meningitis enrolled in clinical studies.
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http://dx.doi.org/10.1016/j.ttbdis.2020.101418DOI Listing
July 2020

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

Pediatrics 2020 04 23;145(4). Epub 2020 Mar 23.

Division of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts.

Background: 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.

Methods: 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 >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 >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).

Results: 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.

Conclusions: The modified Boston and Philadelphia criteria misclassified a substantial number of infants 29 to 60 days old with IBI, including those with bacterial meningitis.
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http://dx.doi.org/10.1542/peds.2019-3538DOI Listing
April 2020

Diagnostic Performance of C6 Enzyme Immunoassay for Lyme Arthritis.

Pediatrics 2020 01 13;145(1). Epub 2019 Dec 13.

Department of Pediatrics and Emergency Medicine, Hasbro Children's Hospital and Alpert Medical School, Brown University, Providence, Rhode Island.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: In Lyme disease endemic areas, a C6 EIA result could be used to guide initial clinical decision-making, without misclassifying children with septic arthritis.
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http://dx.doi.org/10.1542/peds.2019-0593DOI Listing
January 2020

The Lyme Disease Polymerase Chain Reaction Test Has Low Sensitivity.

Vector Borne Zoonotic Dis 2020 04 10;20(4):310-313. Epub 2019 Dec 10.

Departments of Pediatrics and Emergency Medicine, Rhode Island Hospital, Providence, Rhode Island.

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.
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http://dx.doi.org/10.1089/vbz.2019.2547DOI Listing
April 2020

Neighborhood Risk and Hospital Use for Pediatric Asthma, Rhode Island, 2005-2014.

Prev Chronic Dis 2019 05 30;16:E68. Epub 2019 May 30.

Hassenfeld Child Health Innovation Institute, Providence, Rhode Island.

Introduction: Studies consistently show that children living in poor neighborhoods have worse asthma outcomes. The objective of our study was to assess the association between negative neighborhood factors (ie, neighborhood risk) and pediatric asthma hospital use.

Methods: This retrospective study used data from children aged 2 to 17 years in a statewide (Rhode Island) hospital network administrative database linked to US Census Bureau data. We defined an asthma visit as an International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code of 493 in any diagnosis field. We used 8 highly correlated measures for each census-block group to construct an index of neighborhood risk. We used maps and linear regression to assess the association of neighborhood risk with average annual census-block-group rates of asthma emergency department visits and hospitalizations. We used multivariable analyses to identify child characteristics and neighborhood risk associated with an asthma revisit, accounting for the child's sociodemographic information, season, and multiple measurements per child.

Results: From 2005 through 2014, we counted 359,195 visits for 146,889 children. Of these, 12,699 children (8.6%) had one or more asthma visits. Linear regression results showed 1.18 (95% confidence interval, 1.06-1.30) more average annual emergency departments visits per 100 children and 0.41 (95% confidence interval, 0.34-0.47) more average annual hospitalizations per 100 children in neighborhoods in the highest-risk index quintile than in neighborhoods in the lowest-risk index quintile.

Conclusion: Interventions to improve asthma outcomes among children should move beyond primary care or clinic settings and involve a careful evaluation of social context and environmental triggers.
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http://dx.doi.org/10.5888/pcd16.180490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549429PMC
May 2019

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

J Hosp Med 2019 08 12;14(8):492-495. Epub 2019 May 12.

Division of Emergency Medicine, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

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.
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http://dx.doi.org/10.12788/jhm.3202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686736PMC
August 2019

A minority of children diagnosed with Lyme disease recall a preceding tick bite.

Ticks Tick Borne Dis 2019 04 26;10(3):694-696. Epub 2019 Feb 26.

Division of Emergency Medicine, Rhode Island Hospital, Providence, RI, United States.

Of 1770 children undergoing emergency department evaluation for Lyme disease, 362 (20.5%) children had Lyme disease. Of those with an available tick bite history, only a minority of those with Lyme disease had a recognized tick bite (60/325; 18.5%, 95% confidence interval 14.6-23.0%). Lack of a tick bite history does not reliably exclude Lyme disease.
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http://dx.doi.org/10.1016/j.ttbdis.2019.02.015DOI Listing
April 2019

Two-Tier Lyme Disease Serology Test Results Can Vary According to the Specific First-Tier Test Used.

J Pediatric Infect Dis Soc 2020 Apr;9(2):128-133

Division of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts.

Background: Variability in 2-tier Lyme disease test results according to the specific first-tier enzyme immunoassay (EIA) in children has not been examined rigorously. In this study, we compared paired results of clinical 2-tier Lyme disease tests to those of the C6 peptide EIA followed by supplemental immunoblotting (C6 2-tier test).

Methods: We performed a prospective cohort study of children aged ≥1 to ≤21 years who were undergoing evaluation for Lyme disease in the emergency department at 1 of 6 centers located in regions in which Lyme disease is endemic. The clinical first-tier test and a C6 EIA were performed on the same serum sample with supplemental immunoblotting if the first-tier test result was either positive or equivocal. We compared the results of the paired clinical and C6 2-tier Lyme disease test results using the McNemar test.

Results: Of the 1714 children enrolled, we collected a research serum sample from 1584 (92.4%). The clinical 2-tier EIA result was positive in 316 (19.9%) children, and the C6 2-tier test result was positive or equivocal in 295 (18.6%) children. The clinical and C6 2-tier test results disagreed more often than they would have by chance alone (P = .002). Of the 39 children with either a positive clinical or C6 2-tier test result alone, 2 children had an erythema migrans (EM) lesion, and 29 had symptoms compatible with early disseminated Lyme disease.

Conclusions: Two-tier Lyme disease test results differed for a substantial number of children on the basis of the specific first-tier test used. In children for whom there is a high clinical suspicion for Lyme disease and who have an initially negative test result, clinicians should consider retesting for Lyme disease.
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http://dx.doi.org/10.1093/jpids/piy133DOI Listing
April 2020

Higher C6 enzyme immunoassay index values correlate with a diagnosis of noncutaneous Lyme disease.

Diagn Microbiol Infect Dis 2019 Jun 8;94(2):160-164. Epub 2018 Dec 8.

Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

The correlation between the Food and Drug Administration-cleared C6 enzyme immunoassay (EIA) C6 index values and a diagnosis of Lyme disease has not been examined. We used pooled patient-level data from 5 studies of adults and children with Lyme disease and control subjects who were tested with the C6 EIA. We constructed a receiver operating characteristic curve using regression clustered by study and measured the area under the curve (AUC) to examine the accuracy of the C6 index values in differentiating between patients with noncutaneous Lyme disease and control subjects. In the 4821 included patients, the C6 index value had excellent ability to distinguish between patients with noncutaneous Lyme disease and control subjects [AUC 0.99; 95% confidence interval (CI) 0.99-1.00]. An index value cut point of ≥3.0 had a sensitivity of 90.9% (95% CI, 87.8-93.3) and specificity of 99.0% (95% CI, 98.6-99.2%) for Lyme disease.
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http://dx.doi.org/10.1016/j.diagmicrobio.2018.12.001DOI Listing
June 2019

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

Pediatr Emerg Care 2021 May;37(5):e227-e229

Division of Emergency Medicine, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.

Abstract: 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.
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http://dx.doi.org/10.1097/PEC.0000000000001639DOI Listing
May 2021

Positive 2-Tiered Lyme Disease Serology is Uncommon in Asymptomatic Children Living in Endemic Areas of the United States.

Pediatr Infect Dis J 2019 05;38(5):e105-e107

Department of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts.

Knowing the frequency of positive Lyme disease serology in children without signs of infection facilitates test interpretation. Of 315 asymptomatic children from Lyme disease endemic regions, 32 had positive or equivocal C6 enzyme-linked immunoassays, but only 5 had positive IgG or IgM supplemental immunoblots (1.6%; 95% confidence interval: 0.7%-3.7%).
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http://dx.doi.org/10.1097/INF.0000000000002157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355375PMC
May 2019

Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis.

N Engl J Med 2018 Jun;378(24):2275-2287

From the Departments of Emergency Medicine (N.K., L.T.), Pediatrics (N.K., N.S.G.), and Psychology (S.G., C.S.P.), University of California Davis Health, University of California, Davis, School of Medicine, Sacramento; the Department of Pediatrics, University of Utah School of Medicine, Salt Lake City (J.E.S., C.S.O., T.C.C., J.M.D.); the Division of Emergency Medicine, Department of Pediatrics, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus (M.J.S.); the Division of Emergency Medicine, Department of Pediatrics, Colorado Children's Hospital, University of Colorado-Denver School of Medicine, Aurora (A.R.); the Division of Emergency Medicine, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston (J.K.M.); the Division of Emergency Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania (S.R.M.), and the Division of Emergency Medicine, Nemours/A.I. duPont Hospital for Children, Sidney Kimmel Medical College at Thomas Jefferson University (J.E.B., A.D.D.) - both in Philadelphia; the Division of Emergency Medicine, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston (L.E.N.); the Departments of Emergency Medicine and Pediatrics, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence (A.G.); the Division of Emergency Medicine, Department of Pediatrics, Children's National Medical Center, George Washington School of Medicine and Health Sciences, Washington, DC (K.M.B.); the Division of Emergency Medicine, Department of Pediatrics, St. Louis Children's Hospital, Washington University School of Medicine in St. Louis, St. Louis (K.S.Q.); the Division of Emergency Medicine, Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago (J.L.T.); and the Division of Emergency Medicine, Department of Pediatrics, New York Presbyterian Morgan Stanley Children's Hospital, Columbia University College of Physicians and Surgeons, New York (M.Y.K.); and the Department of Psychology, Tufts University, Medford, MA (C.S.P.).

Background: Diabetic ketoacidosis in children may cause brain injuries ranging from mild to severe. Whether intravenous fluids contribute to these injuries has been debated for decades.

Methods: We conducted a 13-center, randomized, controlled trial that examined the effects of the rate of administration and the sodium chloride content of intravenous fluids on neurologic outcomes in children with diabetic ketoacidosis. Children were randomly assigned to one of four treatment groups in a 2-by-2 factorial design (0.9% or 0.45% sodium chloride content and rapid or slow rate of administration). The primary outcome was a decline in mental status (two consecutive Glasgow Coma Scale scores of <14, on a scale ranging from 3 to 15, with lower scores indicating worse mental status) during treatment for diabetic ketoacidosis. Secondary outcomes included clinically apparent brain injury during treatment for diabetic ketoacidosis, short-term memory during treatment for diabetic ketoacidosis, and memory and IQ 2 to 6 months after recovery from diabetic ketoacidosis.

Results: A total of 1389 episodes of diabetic ketoacidosis were reported in 1255 children. The Glasgow Coma Scale score declined to less than 14 in 48 episodes (3.5%), and clinically apparent brain injury occurred in 12 episodes (0.9%). No significant differences among the treatment groups were observed with respect to the percentage of episodes in which the Glasgow Coma Scale score declined to below 14, the magnitude of decline in the Glasgow Coma Scale score, or the duration of time in which the Glasgow Coma Scale score was less than 14; with respect to the results of the tests of short-term memory; or with respect to the incidence of clinically apparent brain injury during treatment for diabetic ketoacidosis. Memory and IQ scores obtained after the children's recovery from diabetic ketoacidosis also did not differ significantly among the groups. Serious adverse events other than altered mental status were rare and occurred with similar frequency in all treatment groups.

Conclusions: Neither the rate of administration nor the sodium chloride content of intravenous fluids significantly influenced neurologic outcomes in children with diabetic ketoacidosis. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration; PECARN DKA FLUID ClinicalTrials.gov number, NCT00629707 .).
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http://dx.doi.org/10.1056/NEJMoa1716816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051773PMC
June 2018

Hip Synovial Fluid Cell Counts in Children From a Lyme Disease Endemic Area.

Pediatrics 2018 05 18;141(5). Epub 2018 Apr 18.

Divisions of Emergency Medicine and

Background: Patients with septic hip arthritis require surgical drainage, but they can be difficult to distinguish from patients with Lyme arthritis. The ability of synovial fluid white blood cell (WBC) counts to help discriminate between septic and Lyme arthritis of the hip has not been investigated.

Methods: We assembled a retrospective cohort of patients ≤21 years of age with hip monoarticular arthritis and a synovial fluid culture obtained who presented to 1 of 3 emergency departments located in Lyme disease endemic areas. Septic arthritis was defined as a positive synovial fluid culture result or synovial fluid pleocytosis (WBC count ≥50 000 cells per µL) with a positive blood culture result. Lyme arthritis was defined as positive 2-tiered Lyme disease serology results and negative synovial fluid bacterial culture results. All other patients were classified as having other arthritis. We compared median synovial fluid WBC counts by arthritis type.

Results: Of the 238 eligible patients, 26 (11%) had septic arthritis, 32 (13%) had Lyme arthritis, and 180 (76%) had other arthritis. Patients with septic arthritis had a higher median synovial fluid WBC count (126 130 cells per µL; interquartile range 83 303-209 332 cells per µL) than patients with Lyme arthritis (53 955 cells per µL; interquartile range 33 789-73 375 cells per µL). Eighteen patients (56%) with Lyme arthritis had synovial fluid WBC counts ≥50 000 cells per µL. Of the 94 patients who underwent surgical drainage, 13 were later diagnosed with Lyme arthritis.

Conclusions: In Lyme disease endemic areas, synovial fluid WBC counts cannot always help differentiate septic from Lyme arthritis. Rapid Lyme diagnostics could help avoid unnecessary operative procedures in patients with Lyme arthritis.
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http://dx.doi.org/10.1542/peds.2017-3810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914490PMC
May 2018

Relationship between breastfeeding and asthma prevalence in young children exposed to adverse childhood experiences.

J Asthma 2019 02 13;56(2):142-151. Epub 2018 Mar 13.

a Department of Epidemiology , Brown University, School of Public Health , Rhode Island , USA.

Objective: To investigate if duration of supplemental breastfeeding is associated with a lower asthma risk and whether adverse childhood experiences (ACEs) early in life influence this relationship in children ages 3 to 5 years.

Methods: Data were from the 2011-2012 National Survey of Children's Health, a nationally representative cross-sectional survey. Modified Poisson regression models were used to estimate incident risk ratios (IRR) for lifetime and current asthma in young children aged 3 to 5 years (n = 15,642). We tested for effect measure modification using stratified analyses.

Results: Exclusive breastfeeding for at least 6 months or supplemental breastfeeding for children ≥12 months significantly reduced the risk of lifetime asthma prevalence compared to never breastfed children (IRR 0.64; 95% CI: 0.46-0.88, p = 0.007; and IRR 0.68; 95% CI: 0.47-0.99, p = 0.044, respectively), adjusted for covariates. In stratified analyses, breastfeeding reduced the risk of lifetime asthma for children who experienced 1 ACE but not for children who experienced 2 or more ACEs.

Conclusion: Exclusive breastfeeding for at least 6 months, with and without supplementation, appears to prevent asthma or delay its onset. The protective effect of breastfeeding was attenuated among children who experienced more than 2 ACEs. The known harmful effects that ACEs have on children's health may outweigh the benefits of breastfeeding in reducing the risk of a child developing asthma. Understanding how specific time periods in a child's life may be most affected by exposure to early life adversities, along with the protective effect of breastfeeding against asthma, are important areas of further study.
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http://dx.doi.org/10.1080/02770903.2018.1441869DOI Listing
February 2019

Cerebrospinal Fluid Reference Values for Young Infants Undergoing Lumbar Puncture.

Pediatrics 2018 03 2;141(3). Epub 2018 Feb 2.

Divisions of Hospital Medicine.

Objectives: 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.

Methods: 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 >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.

Results: 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; < .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; < .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; < .001).

Conclusions: 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.
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http://dx.doi.org/10.1542/peds.2017-3405DOI Listing
March 2018

Herpes Simplex Virus Infection in Infants Undergoing Meningitis Evaluation.

Pediatrics 2018 02 3;141(2). Epub 2018 Jan 3.

Division of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts.

Background: Although neonatal herpes simplex virus (HSV) is a potentially devastating infection requiring prompt evaluation and treatment, large-scale assessments of the frequency in potentially infected infants have not been performed.

Methods: We performed a retrospective cross-sectional study of infants ≤60 days old who had cerebrospinal fluid culture testing performed in 1 of 23 participating North American emergency departments. HSV infection was defined by a positive HSV polymerase chain reaction or viral culture. The primary outcome was the proportion of encounters in which HSV infection was identified. Secondary outcomes included frequency of central nervous system (CNS) and disseminated HSV, and HSV testing and treatment patterns.

Results: Of 26 533 eligible encounters, 112 infants had HSV identified (0.42%, 95% confidence interval [CI]: 0.35%-0.51%). Of these, 90 (80.4%) occurred in weeks 1 to 4, 10 (8.9%) in weeks 5 to 6, and 12 (10.7%) in weeks 7 to 9. The median age of HSV-infected infants was 14 days (interquartile range: 9-24 days). HSV infection was more common in 0 to 28-day-old infants compared with 29- to 60-day-old infants (odds ratio 3.9; 95% CI: 2.4-6.2). Sixty-eight (0.26%, 95% CI: 0.21%-0.33%) had CNS or disseminated HSV. The proportion of infants tested for HSV (35%; range 14%-72%) and to whom acyclovir was administered (23%; range 4%-53%) varied widely across sites.

Conclusions: An HSV infection was uncommon in young infants evaluated for CNS infection, particularly in the second month of life. Evidence-based approaches to the evaluation for HSV in young infants are needed.
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http://dx.doi.org/10.1542/peds.2017-1688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810597PMC
February 2018

Accuracy of Clinician Suspicion of Lyme Disease in the Emergency Department.

Pediatrics 2017 Dec;140(6)

Departments of Pediatrics and Emergency Medicine, Brown University and Rhode Island Hospital, Providence, Rhode Island.

Background: To make initial management decisions, clinicians must estimate the probability of Lyme disease before diagnostic test results are available. Our objective was to examine the accuracy of clinician suspicion for Lyme disease in children undergoing evaluation for Lyme disease.

Methods: We assembled a prospective cohort of children aged 1 to 21 years who were evaluated for Lyme disease at 1 of the 5 participating emergency departments. Treating physicians were asked to estimate the probability of Lyme disease (on a 10-point scale). We defined a Lyme disease case as a patient with an erythema migrans lesion or positive 2-tiered serology results in a patient with compatible symptoms. We calculated the area under the curve for the receiver operating curve as a measure of the ability of clinician suspicion to diagnose Lyme disease.

Results: We enrolled 1021 children with a median age of 9 years (interquartile range, 5-13 years). Of these, 238 (23%) had Lyme disease. Clinician suspicion had a minimal ability to discriminate between children with and without Lyme disease: area under the curve, 0.75 (95% confidence interval, 0.71-0.79). Of the 554 children who the treating clinicians thought were unlikely to have Lyme disease (score 1-3), 65 (12%) had Lyme disease, and of the 127 children who the treating clinicians thought were very likely to have Lyme disease (score 8-10), 39 (31%) did not have Lyme disease.

Conclusions: Because clinician suspicion had only minimal accuracy for the diagnosis of Lyme disease, laboratory confirmation is required to avoid both under- and overdiagnosis.
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http://dx.doi.org/10.1542/peds.2017-1975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703778PMC
December 2017

Unraveling Diagnostic Uncertainty Surrounding Lyme Disease in Children with Neuropsychiatric Illness.

Child Adolesc Psychiatr Clin N Am 2018 Jan 21;27(1):27-36. Epub 2017 Oct 21.

Division of Pediatric Emergency Medicine, Alpert Medical School of Brown University, Rhode Island Hospital - Hasbro Children's Hospital, 125 Whipple Street, UEMF Suite-3rd Floor, Providence, RI 02908, USA.

Lyme disease is endemic in parts of the United States, including New England, the Atlantic seaboard, and Great Lakes region. The presentation has various manifestations, many of which can mimic psychiatric diseases in children. Distinguishing manifestations of Lyme disease from those of psychiatric illnesses is complicated by inexact diagnostic tests and misuse of these tests when they are not clinically indicated. This article aims to describe manifestations of Lyme disease in children with an emphasis on Lyme neuroborreliosis. Clinical scenarios will be presented and discussed. Finally, recommendations for clinical psychiatrists who encounter children with possible Lyme disease are presented.
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http://dx.doi.org/10.1016/j.chc.2017.08.010DOI Listing
January 2018

Managing Peripheral Facial Palsy.

Ann Emerg Med 2018 May 27;71(5):618-624. Epub 2017 Oct 27.

Division of Emergency Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA.

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http://dx.doi.org/10.1016/j.annemergmed.2017.08.039DOI Listing
May 2018
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