Empiric antibiotics for children with suspected Lyme disease.

In our prospective cohort of children undergoing evaluation for non-cutaneous Lyme disease, 02 (13.9% of those with Lyme disease) were not initially treated with an appropriate antibiotics and 356 (13.3% without Lyme disease) received potentially unnecessary antibiotics. Rapid and accurate diagnostics are needed to further improve initial antibiotic treatment decisions.

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

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/mm3 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], 77.2%-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.

Seasonality of Acute Lyme Disease in Children.

Due to the life cycle of its vector, Lyme disease has known seasonal variation. However, investigations focused on children have been limited. Our objective was to evaluate the seasonality of pediatric Lyme disease in three endemic regions in the United States. We enrolled children presenting to one of eight Pedi Lyme Net participating emergency departments. Cases were classified based on presenting symptoms: early (single erythema migrans (EM) lesion), early-disseminated (multiple EM lesions, headache, cranial neuropathy, or carditis), or late (arthritis). We defined a case of Lyme disease by the presence of an EM lesion or a positive two-tier Lyme disease serology. To measure seasonal variability, we estimated Fourier regression models to capture cyclical patterns in Lyme disease incidence. While most children with early or early-disseminated Lyme disease presented during the summer months, children with Lyme arthritis presented throughout the year. Clinicians should consider Lyme disease when evaluating children with acute arthritis throughout the year.

Two-Tier Lyme Disease Serology in Children with Previous Lyme Disease.

Background: A history of Lyme disease can complicate the interpretation of Lyme disease serology in acutely symptomatic patients. Materials and Methods: We prospectively enrolled children undergoing evaluation for Lyme disease in the emergency department of one of eight participating Pedi Lyme Net centers. We selected symptomatic children with a Lyme disease history (definite, probable, or none) as well as an available research biosample. We defined a Lyme disease case with either an erythema migrans (EM) lesion or positive two-tier serology with compatible symptoms. Using a generalized estimating equation, we examined the relationship between time from previous Lyme disease diagnosis and current Lyme disease after adjustment for patient demographics and symptoms as well as clustering by center. Results: Of 2501 prospectively enrolled study patients, 126 (5.0%) reported a history of definite or probable Lyme disease. Of these children with previous Lyme disease, 47 met diagnostic criteria for Lyme disease at the time of enrollment (37.3%; 95% confidence interval [CI] 29.1-45.7%); 2 had an EM lesion, and 45 had positive two-tier Lyme disease serology. Over time from the previous Lyme disease diagnosis, the less likely the patient met diagnostic criteria for Lyme disease (adjusted odds ratio 0.62 per time period; 95% CI 0.46-0.84). Conclusions: For children with a history of Lyme disease before enrollment, one-third met the diagnostic criteria for acute Lyme disease with a declining rate over time from previous Lyme disease diagnosis. Novel Lyme disease diagnostics are needed to help distinguish acute from previous Lyme disease.

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

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.

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

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 mm3, CSF WBC ≥10 cells per mm3, and urinalysis with >10 WBC per high-power field or positive urine dip result) and modified Philadelphia criteria (peripheral WBC ≥15 000 cells per mm3, CSF WBC ≥8 cells per mm3, 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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

Cerebrospinal Fluid Reference Values for Young Infants Undergoing Lumbar Puncture.

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/mm3) than in infants 29 to 60 days of age (upper bound: 9 cells/mm3; P < .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; P < .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; P < .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.

Herpes Simplex Virus Infection in Infants Undergoing Meningitis Evaluation.

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.

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

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.

Concomitant Bacterial Meningitis in Infants With Urinary Tract Infection.

To determine age-stratified prevalence of concomitant bacterial meningitis in infants ≤60 days with a urinary tract infection, we performed a 23-center, retrospective study of 1737 infants with urinary tract infection. Concomitant bacterial meningitis was rare, but more common in infants 0-28 days of age [0.9%; 95% confidence interval (CI): 0.4%-1.9%) compared with infants 29-60 days of age (0.2%; 95% CI: 0%-0.8%).

Interview-based Qualitative Research in Emergency Care Part II: Data Collection, Analysis and Results Reporting.

Qualitative methods are increasingly being used in emergency care research. Rigorous qualitative methods can play a critical role in advancing the emergency care research agenda by allowing investigators to generate hypotheses, gain an in-depth understanding of health problems or specific populations, create expert consensus, and develop new intervention and dissemination strategies. In Part I of this two-article series, we provided an introduction to general principles of applied qualitative health research and examples of its common use in emergency care research, describing study designs and data collection methods most relevant to our field (observation, individual interviews, and focus groups). Here in Part II of this series, we outline the specific steps necessary to conduct a valid and reliable qualitative research project, with a focus on interview-based studies. These elements include building the research team, preparing data collection guides, defining and obtaining an adequate sample, collecting and organizing qualitative data, and coding and analyzing the data. We also discuss potential ethical considerations unique to qualitative research as it relates to emergency care research.

Qualitative Research in Emergency Care Part I: Research Principles and Common Applications.

Qualitative methods are increasingly being used in emergency care research. Rigorous qualitative methods can play a critical role in advancing the emergency care research agenda by allowing investigators to generate hypotheses, gain an in-depth understanding of health problems or specific populations, create expert consensus, and develop new intervention and dissemination strategies. This article, Part I of a two-article series, provides an introduction to general principles of applied qualitative health research and examples of its common use in emergency care research, describing study designs and data collection methods most relevant to our field, including observation, individual interviews, and focus groups. In Part II of this series, we will outline the specific steps necessary to conduct a valid and reliable qualitative research project, with a focus on interview-based studies. These elements include building the research team, preparing data collection guides, defining and obtaining an adequate sample, collecting and organizing qualitative data, and coding and analyzing the data. We also discuss potential ethical considerations unique to qualitative research as it relates to emergency care research.

Imaging of pediatric head injury in the emergency department.

OBJECTIVES: Computed tomography (CT) is the standard for immediate imaging of head-injured children, but it uses radiation that predisposes to malignancy. The study goals were to describe imaging practices in this population and to identify barriers to rapid magnetic resonance imaging (MRI) use. METHODS: A cross-sectional survey of physicians who care for pediatric patients in emergency departments was conducted. Survey questions included hospital characteristics, access to imaging technology, use of imaging studies, and use of radiation reduction practices. RESULTS: A total of 459 eligible respondents completed the questionnaire, which represented a response rate of 24.1%. Almost all the respondents (97.7%) reported that radiation concerns influence clinical management of children and adolescents with head trauma. Head CT use was more frequently reported than MRI (55.3% vs 1.5% reported use in more than 10% of patients, respectively). Frequent CT use was associated with practice in community hospitals (P = 0.005), whereas pediatric residency training and pediatric volumes greater than 30,000 visits per year were associated with less frequent use (P = 0.015 and P = 0.028, respectively). In 94.5% of the respondents, reported CT was always available compared with 24.3% reporting MRI as always available (P < 0.001). Reported obstacles to MRI as a screening tool for head-injured children included limited scanner availability (93.5%), patient intolerance of MRI (87.2%), and longer acquisition times (83.3%). CONCLUSIONS: Concerns about radiation exposure motivate change of practice in the management of head-injured children and adolescents. Head CT use is greater at hospitals with lower pediatric volumes, community hospitals, and by providers without pediatric residency training. Obstacles to increased use of MRI or head-injured children include availability, patient intolerance, and long scan acquisition times.

Caregiver expectations of clinicians during the asthma diagnostic process in young children: thematic analysis of focus groups.

OBJECTIVE: Asthma is difficult to diagnose in young children, and the subjective experience of caregivers varies. Clinicians' ability to meet caregiver expectations during the diagnostic process improves the caregiver-clinician relationship, and effectiveness of disease management strategies. METHODS: We performed thematic analysis of seven focus groups (FGs) with 38 caregivers of children 1-6 years old diagnosed with asthma in the preceding 12 months. Caregivers were classified as satisfied or dissatisfied with clinicians during the asthma diagnostic process. Differential themes in these two groups identified caregiver expectations that determined satisfaction with the diagnostic process. RESULTS: Caregiver expectations during the asthma diagnostic process included (1) provision of a diagnostic strategy, (2) acknowledgment of caregiver advocacy, (3) addressing caregiver's beliefs about treatment with asthma medications before a diagnosis was confirmed, and (4) discussing asthma specialist involvement in the diagnosis. Higher perceived severity of a child's illness made caregiver expectations more difficult to meet. CONCLUSIONS: We conclude that clinicians considering an asthma diagnosis in young children must include a diagnostic strategy that is congruent with the caregiver's beliefs about the underlying illness, use of medication, and asthma specialist involvement. Perceived illness severity must also be accounted for when designing a diagnostic strategy.