Clinical and Laboratory Predictors of Dehydration Severity in Children With Diabetic Ketoacidosis.

STUDY OBJECTIVE: Our primary objective was to characterize the degree of dehydration in children with diabetic ketoacidosis (DKA) and identify physical examination and biochemical factors associated with dehydration severity. Secondary objectives included describing relationships between dehydration severity and other clinical outcomes. METHODS: In this cohort study, we analyzed data from 753 children with 811 episodes of DKA in the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation Study, a randomized clinical trial of fluid resuscitation protocols for children with DKA. We used multivariable regression analyses to identify physical examination and biochemical factors associated with dehydration severity, and we described associations between dehydration severity and DKA outcomes. RESULTS: Mean dehydration was 5.7% (SD 3.6%). Mild (0 to <5%), moderate (5 to <10%), and severe (≥10%) dehydration were observed in 47% (N=379), 42% (N=343), and 11% (N=89) of episodes, respectively. In multivariable analyses, more severe dehydration was associated with new onset of diabetes, higher blood urea nitrogen, lower pH, higher anion gap, and diastolic hypertension. However, there was substantial overlap in these variables between dehydration groups. The mean length of hospital stay was longer for patients with moderate and severe dehydration, both in new onset and established diabetes. CONCLUSION: Most children with DKA have mild-to-moderate dehydration. Although biochemical measures were more closely associated with the severity of dehydration than clinical assessments, neither were sufficiently predictive to inform rehydration practice.

Clinical Characteristics of Children with Cerebral Injury preceding Treatment of Diabetic Ketoacidosis.

Previous studies have identified more severe acidosis and higher blood urea nitrogen (BUN) as risk factors for cerebral injury during treatment of diabetic ketoacidosis (DKA) in children; however, cerebral injury also can occur before DKA treatment. We found that lower pH and higher BUN levels also were associated with cerebral injury at presentation.

A Clinical Prediction Rule for Bacterial Musculoskeletal Infections in Children with Monoarthritis in Lyme Endemic Regions.

STUDY OBJECTIVE: Children with a bacterial musculoskeletal infection (MSKI) require prompt identification and treatment. In Lyme disease endemic areas, children with an MSKI can present similarly to those with Lyme arthritis. Our goal was to derive a clinical prediction rule to accurately identify children at a low risk for an MSKI. METHODS: We enrolled children with monoarthritis presenting to 1 of 6 Pedi Lyme Net centers and performed a procalcitonin (PCT) and a first-tier Lyme C6 enzyme immunoassay (EIA) test. Our primary outcome was an MSKI (septic arthritis, osteomyelitis, or pyomyositis). Using recursive partitioning with k-fold cross validation, we derived a clinical prediction rule to identify children at a low risk of an MSKI. We calculated the accuracy of our novel rule in a derivation cohort. RESULTS: Of the 735 children in the derivation cohort with an available research biosample, 39 (5%) had an MSKI (18 had septic arthritis, 20 had osteomyelitis, and 1 had pyomyositis), 260 (37%) had Lyme arthritis, and 436 (53%) had other inflammatory arthritis. Children with a PCT level of more than or equal to 0.50 ng/mL and those with a C-reactive protein (CRP) level of more than or equal to 0.6 mg/dL with a negative Lyme C6 EIA were classified as not low risk for an MSKI. Of the 451 (61%) children categorized as low risk, none had an MSKI (sensitivity 100%, 95% confidence interval 91.0% to 100%; specificity 74.2%, 95% confidence interval 70.5% to 77.6%). CONCLUSION: A novel clinical decision rule that includes PCT, CRP, and a first-tier Lyme EIA was highly sensitive for MSKIs. Although broader external validation is required, the application of this rule may safely reduce invasive testing, procedures, and treatment for low risk children.

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.

Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis.

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 .).

Serologic Response to Borrelia Antigens Varies with Clinical Phenotype in Children and Young Adults with Lyme Disease.

Lyme disease is commonly diagnosed by serologic response to Borrelia burgdorferi and related species, but the relationship between serologic targets and clinical features is unknown. We developed a multiantigen 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 immunoblotting 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 Borrelia-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, and OspC_Bafz) that distinguished Lyme disease from clinical mimics with a sensitivity of 86.6% (95% confidence interval [CI], 80.3 to 92.1) and a specificity of 95.5% (95% CI, 93.4 to 97.4). Sensitivity was much lower in early Lyme disease (38.5%; 95% CI, 15.4 to 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.

Electrocardiogram as a Lyme Disease Screening Test.

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.

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.

Association of RNA Biosignatures With Bacterial Infections in Febrile Infants Aged 60 Days or Younger.

IMPORTANCE: Young febrile infants are at substantial risk of serious bacterial infections; however, the current culture-based diagnosis has limitations. Analysis of host expression patterns ("RNA biosignatures") in response to infections may provide an alternative diagnostic approach. OBJECTIVE: To assess whether RNA biosignatures can distinguish febrile infants aged 60 days or younger with and without serious bacterial infections. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational study involving a convenience sample of febrile infants 60 days or younger evaluated for fever (temperature >38° C) in 22 emergency departments from December 2008 to December 2010 who underwent laboratory evaluations including blood cultures. A random sample of infants with and without bacterial infections was selected for RNA biosignature analysis. Afebrile healthy infants served as controls. Blood samples were collected for cultures and RNA biosignatures. Bioinformatics tools were applied to define RNA biosignatures to classify febrile infants by infection type. EXPOSURE: RNA biosignatures compared with cultures for discriminating febrile infants with and without bacterial infections and infants with bacteremia from those without bacterial infections. MAIN OUTCOMES AND MEASURES: Bacterial infection confirmed by culture. Performance of RNA biosignatures was compared with routine laboratory screening tests and Yale Observation Scale (YOS) scores. RESULTS: Of 1883 febrile infants (median age, 37 days; 55.7% boys), RNA biosignatures were measured in 279 randomly selected infants (89 with bacterial infections-including 32 with bacteremia and 15 with urinary tract infections-and 190 without bacterial infections), and 19 afebrile healthy infants. Sixty-six classifier genes were identified that distinguished infants with and without bacterial infections in the test set with 87% (95% CI, 73%-95%) sensitivity and 89% (95% CI, 81%-93%) specificity. Ten classifier genes distinguished infants with bacteremia from those without bacterial infections in the test set with 94% (95% CI, 70%-100%) sensitivity and 95% (95% CI, 88%-98%) specificity. The incremental C statistic for the RNA biosignatures over the YOS score was 0.37 (95% CI, 0.30-0.43). CONCLUSIONS AND RELEVANCE: In this preliminary study, RNA biosignatures were defined to distinguish febrile infants aged 60 days or younger with vs without bacterial infections. Further research with larger populations is needed to refine and validate the estimates of test accuracy and to assess the clinical utility of RNA biosignatures in practice.

Relationships among biochemical measures in children with diabetic ketoacidosis.

OBJECTIVES: Investigating empirical relationships among laboratory measures in children with diabetic ketoacidosis (DKA) can provide insights into physiological alterations occurring during DKA. We determined whether alterations in laboratory measures during DKA conform to theoretical predictions. METHODS: We used Pearson correlation statistics and linear regression to investigate correlations between blood glucose, electrolytes, pH and PCO2 at emergency department presentation in 1,681 pediatric DKA episodes. Among children with repeat DKA episodes, we also assessed correlations between laboratory measures at the first vs. second episode. RESULTS: pH and bicarbonate levels were strongly correlated (r=0.64), however, pH and PCO2 were only loosely correlated (r=0.17). Glucose levels were correlated with indicators of dehydration and kidney function (blood urea nitrogen (BUN), r=0.44; creatinine, r=0.42; glucose-corrected sodium, r=0.32). Among children with repeat DKA episodes, PCO2 levels tended to be similar at the first vs. second episode (r=0.34), although pH levels were only loosely correlated (r=0.19). CONCLUSIONS: Elevated glucose levels at DKA presentation largely reflect alterations in glomerular filtration rate. pH and PCO2 are weakly correlated suggesting that respiratory responses to acidosis vary among individuals and may be influenced by pulmonary and central nervous system effects of DKA.

Accuracy of plain radiographs to exclude the diagnosis of intussusception.

OBJECTIVES: To prospectively determine the test characteristics of the 3-view abdominal radiograph to decrease the likelihood of ileocolic intussusception. METHODS: We conducted a prospective cross-sectional study of children aged 3 months to 3 years suspected of having intussusception at a children's hospital emergency department. Clinicians obtained supine, prone, and left lateral decubitus radiographs. We determined the presence or absence of intussusception by air enema, ultrasound, operative report, or clinical follow-up. A masked pediatric radiologist reviewed all radiographs. The criteria evaluated were whether air was visualized in the ascending colon on each view and in the transverse colon on the supine view. RESULTS: Nineteen (14.8%) of 128 patients had intussusception. Using air in the ascending colon on all 3 views as the diagnostic criteria, the test characteristics of the 3-view radiograph were sensitivity, 100% (95% confidence interval [CI], 79.1-100); specificity, 17.4% (95% CI, 11.1-26.1); negative predictive value, 100% (95% CI, 79.1-100); and likelihood ratio of a negative test, 0. When 2 or more of 3 views had air in the ascending colon, sensitivity decreased to 89.5% (95% CI, 75.7-100) and specificity improved to 45.0% (95% CI, 35.6-54.3). Air in the transverse colon had moderate sensitivity, 84.2% (95% CI, 67.8-100), but further improved specificity, 63.3% (95% CI, 54.2-72.4). CONCLUSIONS: The presence of air in the ascending colon on the 3-view abdominal radiograph can decrease the likelihood of or exclude intussusception. When clinical suspicion is low, the presence of specific criterion on a 3-view abdominal radiograph series may obviate the need for further studies.

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.

Serious Bacterial Infections in Young Febrile Infants With Positive Urinalysis Results.

It is unknown whether febrile infants 29 to 60 days old with positive urinalysis results require routine lumbar punctures for evaluation of bacterial meningitis. OBJECTIVE: To determine the prevalence of bacteremia and/or bacterial meningitis in febrile infants ≤60 days of age with positive urinalysis (UA) results. METHODS: Secondary analysis of a prospective observational study of noncritical febrile infants ≤60 days between 2011 and 2019 conducted in the Pediatric Emergency Care Applied Research Network emergency departments. Participants had temperatures ≥38°C and were evaluated with blood cultures and had UAs available for analysis. We report the prevalence of bacteremia and bacterial meningitis in those with and without positive UA results. RESULTS: Among 7180 infants, 1090 (15.2%) had positive UA results. The risk of bacteremia was higher in those with positive versus negative UA results (63/1090 [5.8%] vs 69/6090 [1.1%], difference 4.7% [3.3% to 6.1%]). There was no difference in the prevalence of bacterial meningitis in infants ≤28 days of age with positive versus negative UA results (∼1% in both groups). However, among 697 infants aged 29 to 60 days with positive UA results, there were no cases of bacterial meningitis in comparison to 9 of 4153 with negative UA results (0.2%, difference -0.2% [-0.4% to -0.1%]). In addition, there were no cases of bacteremia and/or bacterial meningitis in the 148 infants ≤60 days of age with positive UA results who had the Pediatric Emergency Care Applied Research Network low-risk blood thresholds of absolute neutrophil count <4 × 103 cells/mm3 and procalcitonin <0.5 ng/mL. CONCLUSIONS: Among noncritical febrile infants ≤60 days of age with positive UA results, there were no cases of bacterial meningitis in those aged 29 to 60 days and no cases of bacteremia and/or bacterial meningitis in any low-risk infants based on low-risk blood thresholds in both months of life. These findings can guide lumbar puncture use and other clinical decision making.

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

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.

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

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 (n = 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 Pco2 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 Pco2 than slower fluid infusion rates but were associated with an increased frequency of hyperchloremic acidosis.

The Lyme Disease Polymerase Chain Reaction Test Has Low Sensitivity.

Background: The Lyme PCR is a direct detection test, but has not been rigorously evaluated in children undergoing evaluation for acute Lyme disease. Methods: 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. Results: 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. Conclusions: 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.

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.

Diagnostic Performance of C6 Enzyme Immunoassay for Lyme Arthritis.

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.

Diagnostic Accuracy of Non-Invasive Thermal Evaluation of Ventriculoperitoneal Shunt Flow in Shunt Malfunction: A Prospective, Multi-Site, Operator-Blinded Study.

BACKGROUND: Thermal flow evaluation (TFE) is a non-invasive method to assess ventriculoperitoneal shunt function. Flow detected by TFE is a negative predictor of the need for revision surgery. Further optimization of testing protocols, evaluation in multiple centers, and integration with clinical and imaging impressions prompted the current study. OBJECTIVE: To compare the diagnostic accuracy of 2 TFE protocols, with micropumper (TFE+MP) or without (TFE-only), to neuro-imaging in patients emergently presenting with symptoms concerning for shunt malfunction. METHODS: We performed a prospective multicenter operator-blinded trial of a consecutive series of patients who underwent evaluation for shunt malfunction. TFE was performed, and preimaging clinician impressions and imaging results were recorded. The primary outcome was shunt obstruction requiring neurosurgical revision within 7 d. Non-inferiority of the sensitivity of TFE vs neuro-imaging for detecting shunt obstruction was tested using a prospectively determined a priori margin of -2.5%. RESULTS: We enrolled 406 patients at 10 centers. Of these, 68/348 (20%) evaluated with TFE+MP and 30/215 (14%) with TFE-only had shunt obstruction. The sensitivity for detecting obstruction was 100% (95% CI: 88%-100%) for TFE-only, 90% (95% CI: 80%-96%) for TFE+MP, 76% (95% CI: 65%-86%) for imaging in TFE+MP cohort, and 77% (95% CI: 58%-90%) for imaging in the TFE-only cohort. Difference in sensitivities between TFE methods and imaging did not exceed the non-inferiority margin. CONCLUSION: TFE is non-inferior to imaging in ruling out shunt malfunction and may help avoid imaging and other steps. For this purpose, TFE only is favored over TFE+MP.

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.