Background and aims: Body fat distribution, i.e., visceral (VAT), subcutaneous adipose tissue (SAT) and intramuscular fat, is important for disease prevention, but sex and ethnic differences are not well understood. Our aim was to identify anthropometric, demographic, and lifestyle predictors for these outcomes. Methods and results: The cross-sectional ShapeUp!Kids study was conducted among five ethnic groups aged 5-18 years. All participants completed questionnaires, anthropometric measurements, and abdominal MRI scans. VAT and SAT areas at four lumbar levels and muscle density were assessed manually. General linear models were applied to estimate coefficients of determination (R2) and to compare the fit of VAT and SAT prediction models. After exclusions, the study population had 133 male and 170 female participants. Girls had higher BMI-z scores, waist circumference (WC), and SAT than boys but lower VAT/SAT and muscle density. SAT, VAT, and VAT/SAT but not muscle density differed significantly by ethnicity. R2 values were higher for SAT than VAT across groups and improved slightly after adding WC. For SAT, R2 increased from 0.85 to 0.88 (girls) and 0.62 to 0.71 (boys) when WC was added while VAT models improved from 0.62 to 0.65 (girls) and 0.57 to 0.62 (boys). VAT values were significantly lower among Blacks than Whites with little difference for the other groups. Conclusion: This analysis in a multiethnic population identified BMI-z scores and WC as the major predictors of MRI-derived SAT and VAT and highlights the important ethnic differences that need to be considered in diverse populations. (c) 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

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.

Identify visceral adipose tissue (VAT) thresholds associated with increased cardiometabolic disease risk. Beyond overall obesity, VAT storage is associated with adverse metabolic parameters that increase the risk of heart disease, stroke, and type II diabetes. Computed tomography (CT) and magnetic resonance imaging (MRI) technologies have been used to define thresholds of VAT associated with MetS, however these techniques are of limited availability for clinical risk assessment. Dual energy X-ray absorptiometry (DXA) is accurate compared to VAT measures from CT and MRI, however differences in scanning region and algorithms results in device-specific VAT estimates. We recently generated cross-calibration equations for DXA systems, allowing DXA measures to be compared to CT and MRI and providing more access to VAT assessments for the determination of VAT thresholds as well as the ability to assess presence of “risky” VAT levels in clinical practice. The purpose of this review was to identify published studies defining VAT thresholds to determine characteristics that define the “risky” threshold. We identified previously published studies establishing VAT thresholds associated with increased cardiometabolic risk, obtained using CT, MRI, and DXA imaging technologies. We compared characteristics of these studies to determine the factors necessary to identify “risky” VAT thresholds. We identified 46 studies that derived VAT-specific thresholds associated with MetS in adults, published across populations with diverse sample size, age, and ethnicity. Lower average VAT as well as risk thresholds were found in females. When stratified by age or menopausal status, lower VAT thresholds were primarily observed in lower age or premenopausal categories. Values varied across ethnicities, with level thresholds often lower in Asian populations (70- 136 cm2) compared to Caucasian (85.6-165.9 cm2) and other populations. A universal VAT threshold is not yet feasible, supporting the need for more population-specific thresholds to identify increased MetS risk. Excess VAT accumulation above a certain threshold is strongly linked to MetS risk, however the need for age-, sex- and ethnic-specific thresholds in necessary. The development of thresholds based on sex is necessary to reduce the risk of underestimation of “risky” VAT in females. Additionally, these findings suggest that different adipose tissue regions may have differential effects on metabolic disease risk among race/ethnic groups.

Background Individuals in isolated conditions and extreme environments can experience debilitating side effects from their environment, which may include a significant decrease in fat-free mass (FFM) from disuse and inadequate nutrition. At its most severe, the decrease in FFM may lead to sarcopenia and frailty. Although there are dietary and physical activity countermeasures, there lacks accessible methods to quantify regional and total FFM during long-isolated missions. The objective of this study was to determine the strengths and weaknesses of three-dimensional optical (3DO) imaging for monitoring body shape and composition in either simulated or actual remote and isolated environments.Methods Thirty healthy adults (ASTRO, male = 15) and twenty-two Antarctic Expeditioners (ABCS, male = 18) were assessed for body composition using a whole-body 3DO scanner. The 3D mesh was used as the 3DO scanner’s output. ASTRO participants completed duplicate whole-body 3DO scans while standing and inverted by gravity boots plus a single dual-energy X-ray absorptiometry (DXA) scan. The inverted scans were used as an analog for fluid redistribution from gravity changes. 3DO body composition estimates were compared to DXA with linear regression and reported with the coefficient of determination (R2) and root mean square error (RMSE). Duplicate 3DO scans were used for test-retest precision, which was reported with the percent coefficient of variation (%CV) and RMSE. ABCS participants received only duplicate whole-body 3DO scans on a monthly basis. An existing body composition model was used to estimate fat mass (FM) and FFM composition and longitudinal change from 3DO meshes.Results Standing ASTRO 3DO meshes achieved an R2 of 0.76, 0.97, and 0.78 with an RMSE of 2.62 kg, 2.04 kg, and 0.06 kg for FM, FFM, and visceral adipose tissue (VAT), respectively, in comparison to DXA. Inverted 3DO meshes achieved an R2 of 0.52, 0.93, and 0.39 with an RMSE of 2.84 kg, 3.23 kg, and 0.11 kg for FM, FFM, and visceral adipose tissue (VAT), respectively, in comparison to DXA. Test-retest precision of inverted 3DO meshes had good precision in total fat-free as well as arm, leg, and trunk fat-free mass (%CV = 2.3%, 2.95%, 1.34%, and 1.55%; RMSE = 1.32, 0.12, 0.14, and 0.47 kg, respectively). For the ABCS arm, mean weight, FM, and FFM changes were − 0.47 kg, 0.06 kg, and − 0.54 kg, respectively.Conclusion Simulated weightlessness and fluid redistribution decreased the accuracy of estimated body composition values from 3DO scans. However, FFM was the most robust. Overall, 3DO imaging showed good absolute accuracy and precision for body composition assessment in isolated conditions and remote environments.

Background. Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of childhood diabetes. However, the influence of demographic factors on presentation are not well-defined. Methods. We included children from 12 centers who were <18 years with DKA (glucose > 300 mg/dL, serum pH < 7.25, or serum bicarbonate <15 mEq/L) enrolled in the Pediatric Emergency Care Applied Research Network (PECARN) Fluid Therapies Under Investigation in DKA (FLUID) Trial. Data were also collected for children who presented to the centers during the enrollment period but were not enrolled due to disease or treatment-related reasons. We compared demographic, clinical, and biochemical findings among children with newly and previously diagnosed diabetes and children in different age groups. Results. Of the 1,679 DKA episodes in 1,553 children, 799 (47.5%) episodes occurred in children with newly diagnosed diabetes and 396 (23.6%) were severe (pH < 7.1). Newly diagnosed children <6 years of age were not more likely to have severe DKA in terms of pH, but had more severe hypocarbia and higher blood urea nitrogen levels, factors previously associated with the risk of cerebral injury. Lower socioeconomic status (SES) (based on family income and maternal education level) were associated with more severe DKA in new onset children, and recurrent DKA in the previously diagnosed children. Conclusions. Greater efforts are needed to identify the children with diabetes early and to prevent recurrent DKA, particularly among children in low-SES groups. Young children with DKA may need more intensive monitoring due to higher risk of cerebral injury.

Children with sickle cell disease (SCD) commonly experience vaso-occlusive pain episodes (VOE) due to sickling of erythrocytes, which often requires care in the emergency department. Our objective was to assess the use and impact of intranasal fentanyl for the treatment of children with SCD-VOE on discharge from the emergency department in a multicenter study. We conducted a cross-sectional study at 20 academic pediatric emergency departments in the United States and Canada. We used logistic regression to test bivariable and multivariable associations between the outcome of discharge from the emergency department and candidate variables theoretically associated with discharge. The study included 400 patients; 215 (54%) were female. The median age was 14.6 (interquartile range 9.8, 17.6) years. Nineteen percent (n = 75) received intranasal fentanyl in the emergency department. Children who received intranasal fentanyl had nearly nine-fold greater adjusted odds of discharge from the emergency department compared to those who did not (adjusted odds ratio 8.99, 95% CI 2.81-30.56, p < .001). The rapid onset of action and ease of delivery without intravenous access offered by intranasal fentanyl make it a feasible initial parenteral analgesic in the treatment of children with SCD presenting with VOE in the acute-care setting. Further study is needed to determine potential causality of the association between intranasal fentanyl and discharge from the emergency department observed in this multicenter study.

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.

To the Editor: Patients with sickle cell disease (SCD) commonly experience vaso-occlusive pain episodes (VOE), which accounts for 78% of all emergency department (ED) visits among patients with SCD.1 SCD-VOE pain is often under-, and inconsistently, treated in the ED.2 In 2014, the National Heart, Lung, and Blood Institute (NHLBI) put forth guidelines to direct the care of patients presenting with VOE.3 Key guideline recommendations include: (1) triage as high priority with rapid evaluation of patients presenting with VOE, (2) use of parenteral opioids for moderate-to-severe pain with administration ≤30 min after ED triage or ≤ 60 min after registration, (3) pain reassessment and subsequent parenteral opioid dosing every 15–30 min until pain is controlled, (4) the administration of non-steroidal anti-inflammatory drugs (NSAIDS) as an analgesic adjuvant (if no contraindications exist), and (5) in euvolemic patients with SCD-VOE who are unable to drink fluids, intravenous hydration at no more than maintenance rate to avoid over-hydration. Our objective was to assess adherence to all NHLBI recommendations and the impact of timely opioid administration on hospital admission in a study of 20 academic pediatric EDs in the United States and Canada. A cross-sectional study was performed at 20 academic, pediatric EDs across the United States and Canada (19 in the United States and one in Canada) (Supplemental Methods). International Classification of Disease Ninth and Tenth Revision code ED diagnoses of VOE were used to identify consecutive patients. To include the traditionally more severe genotypes of SCD, children with sickle cell anemia (hemoglobin-SS disease or hemoglobin Sβo-Thalassemia) aged 3–21 years who presented with VOE pain of any severity were included. Children who were diagnosed in the ED with acute chest syndrome or pregnancy were excluded. To determine adherence to the 2014 NHLBI recommendations, the date and time of: ED arrival, triage, patient rooming, initial pain assessment, intravenous (IV) catheter placement, first parenteral opioid administration (including intranasal fentanyl at some sites), pain reassessment, and second parenteral opioid administration were collected. Assigned Emergency Severity Index (ESI) triage score, type of parenteral opioid administered, IV fluid administration, and disposition from the ED were collected. ED arrival (i.e., the earliest time of ED arrival, registration, triage time, or time to room, whichever came first) was used for time to outcome measures. Descriptive statistics were calculated for adherence to each of the 2014 NHLBI recommendations for the management of acute VOE. Univariable logistic regression was used to assess factors associated with receipt of first parenteral opioid within ≤60 min and the relationship between time of opioid administration and hospital admission. Kruskal-Wallis and Wilcoxon rank-sum tests were used to test for associations between continuous variables and Chi-Square tests were used to test for associations between categorical variables. All statistics were conducted using SAS version 9.4. Over half of the 400 patients were female (n = 215, 54%) (median age 14.6 years [IQR 9.8, 17.6]). Most patients had hemoglobin-SS (92%, n = 367) and 8% (n = 33) had hemoglobin Sβo Thalassemia. MedED arrival times to evaluation and treatment were as follows: time to first pain assessment 8 min (IQR 3, 20), time to IV catheter placement 52 min (IQR 33, 81), time to first parenteral opioid administration 62 min (IQR 37, 98), and time from first to second parenteral opioid 67 min (IQR 46, 101). The proportion of children who received NHLBI recommended evaluation and treatments is in Table 1. Most patients were assigned the recommended ESI triage score of ≤2. Pain was assessed and documented in 99% (n = 395) of all charts. Most patients had pain reassessed (n = 363, 91%). Pain reassessment after the administration of the first parenteral opioid occurred at a median of 20 min (IQR 5, 46). The median number of pain reassessments per ED visit was 4 (IQR 3, 6). Site variation was observed for NHLBI guideline adherence for first parenteral opioid administration ≤60 min from ED arrival (range 0–90% adherent; range median 24–144 min), and time between first and second opioid doses (range median 29–122 min). Fewer than half of patients received parenteral opioids within the recommended ≤60 min of ED arrival (Table 1). Twenty-five percent (n = 101) received parenteral opioids ≤30 min of triage and 28% (n = 110) received parenteral opioids between 31 and 60 min after triage. Forty-three percent (n = 173) received the first parenteral opioid >60 min after triage. There was no significant difference in median time to first- or second-parenteral opioid administration based on patient age or sex (eTables 1 and 2). Children who presented during afternoon shifts were less likely to receive parenteral opioids in ≤60 min from arrival compared to overnight (eTable 3). Of 75 patients who received intranasal fentanyl as their first parenteral opioid, 65 (87%) received it ≤60 min compared with 125/314 (40%) by 60 min for those who received IV delivery of the first-parenteral opioid dose (P < 0.001). Children who received intranasal fentanyl had greater odds of receiving parenteral opioids in ≤60 min from arrival (OR 9.83, 95% CI 4.87–19.85). The median number of parenteral opioid doses administered in the ED was 2 (IQR 1, 3). There were 270 (68%) children who received ≥2 parenteral opioid doses and 6% of these received a second dose within 30 min of the first-parenteral opioid. Overall, 4.5% (n = 18) patients received both the first-parenteral opioid within 60 min from ED arrival and the second dose within 30 min of the first dose. An oral opioid was given to 98 patients (25%). IV fluids (bolus and/or maintenance fluid) were administered to 84% (n = 335) of patients.4 Intravenous ketorolac was given to 66% (n = 265) of patients (Table 1). The median ED length of stay from arrival to disposition order placed was 5 h (IQR 4, 6), and 67% (n = 268) required admission to the hospital. There was no association between time to delivery of first-parenteral opioid and admission (p = .45). Children who received their second-parenteral opioid ≤30 or ≤ 60 min from the first-parenteral opioid did not have significantly different odds of hospital admission when compared to children who received their second parenteral opioid >30 min or > 60 min, respectively. In our multicenter study of NHLBI pediatric ED SCD-VOE guideline adherence, pain was frequently and rapidly assessed. However, fewer than half of patients received parenteral opioids within the recommended 60 min, and few received both the first and second doses of parenteral opioids in NHLBI-recommended timeframes. Some institutions have adopted automated systems to universally assign high-acuity ESI scores (i.e., ≤2) to patients with SCD,5 which may help standardize this step. Given delays identified in the placement of an IV, nurse-initiated SCD-pain protocols may be a feasible strategy to improve adherence to rapid delivery of first dose of parenteral opioids. Historically, only 20% of hospitals have used SCD care protocols,6 although this practice is increasing. Quality improvement initiatives utilizing pain protocols suggest reduced time from arrival to parenteral opioid administration for VOE.7 Prior studies have not assessed the time to IV catheter placement, which could be an important bottleneck that may be targeted in future initiatives. Difficult IV access, high patient volume, and high acuity in the ED often challenge optimal timing of IV placement. Parenteral opioids remain the mainstay of treatment for SCD-VOE. Our observation of poor guideline adherence to administer timely initial parenteral opioids aligns with those in prior studies.2 Furthermore, the majority of patients failed to receive timely administration of a second dose of parenteral opioids within 30 min of the first. The creation of personalized pain management plans, use of intranasal medications including fentanyl, diamorphine, or hydromorphone, and allowing nurse-initiated administration of parenteral opioids in these plans may shorten the time to parenteral opioid administration. The American Society of Hematology recently put forth guidelines for the management of acute and chronic pain from SCD These guidelines were disseminated by the American College of Emergency Physicians. Our results serve as a baseline for future comparisons and the impact of this dissemination in the future studies is warranted. Our data do not support prior findings suggesting time between the administration of the first- and second-parenteral opioid is associated with lower odds of hospitalization. Quality improvement efforts have focused on reducing the time to administration of the first-parenteral opioid, which remains an important goal from the perspective of reducing patient suffering, though it may not reduce hospital admissions. This study has several limitations. We did not account for the role of provider implicit bias and racism which may contribute to delays in opioid administration as SCD predominately affects Black patients. We did not account for patients who may have taken oral NSAIDS or opioids prior to arrival. We also did not control for patient/parental preference for timing of opioid administration. Lastly, our findings may not be reflective of non-academic and non-pediatric facilities. Our findings highlight significant delays in the adherence to important recommendations from the NHLBI. Namely, the time to delivery of initial and subsequent parenteral opioids was suboptimal and may relate to delays in IV catheter placement. Our findings allow for targeted initiatives to increase adherence to NHLBI guidelines for the treatment of patients with SCD-VOE in the ED. Drs. Morris and Rachel Richards had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors contributed to the data collection. Dr. Casper and Ms. Richards were responsible for all statistical analyses. Drs. Rees and Morris were responsible for the manuscript preparation. All authors assisted with data interpretation and revised and critically reviewed the manuscript. This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS, or the U.S. Government. This study was supported by the NIH/NHLBI under award number R34HL122557 (to CRM), and in part by NIH/NCCIH K24AT009893 (to CRM) and the Pediatric Emergency Care Applied Research Network (PECARN), supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS), in the Maternal and Child Health Bureau (MCHB), under the Emergency Medical Services for Children (EMSC) program through the following cooperative agreements: DCC-University of Utah, GLEMSCRN-Nationwide Children's Hospital, HOMERUN-Cincinnati Children's Hospital Medical Center, PEMNEWS-Columbia University Medical Center, PRIME-University of California at Davis Medical Center, CHaMP node- State University of New York at Buffalo, WPEMR- Seattle Children's Hospital, and SPARC- Rhode Island Hospital/Hasbro Children's Hospital. NB received funding from the NIH/NHLBI under award number 1K23HL140142 and 1K23HL140142-03S1, from the Doris Duke Charitable Foundation COVID19 Fund to Retain Clinical Scientists- PeRSEVERE Program at Emory University School of Medicine, and the Georgia Clinical and Translational Science Alliance under award UL1-TR002378. The funders had no role in the design and conduct of the study, the collection, management, analysis, and interpretation of the data, or the preparation, review, approval of the manuscript, or decision to submit the manuscript for publication. No authors have potential conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject of their manuscript. A waiver of consent was granted because all data were retrospectively extracted. The data may be made available upon reasonable request. Appendix S1 Supplementary Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

BACKGROUND/OBJECTIVES:Body size and shape have increased over the past several decades with one in five adolescents now having obesity according to objective anthropometric measures such as weight, height, and body mass index (BMI). The gradual physical changes and their consequences may not be fully appreciated upon visual inspection by those managing the long-term health of adolescents. This study aimed to develop humanoid avatars representing the gradual changes in adolescent body size and shape over the past five decades and to align avatars with key BMI percentile cut points for underweight, normal weight, overweight, and obesity. PARTICIPANTS/METHODS:Participants included 223 children and adolescents between the ages of 5 and 18 years approximately representative of the race/ethnicity and BMI of the noninstitutionalized US population. Each participant completed a three-dimensional whole-body scan, and the collected data was used to develop manifold regression models for generating humanoid male and female avatars from specified ages, weights, and heights. Secular changes in the mean weights and heights of adolescents were acquired from six U.S. National Health and Nutrition Surveys beginning in 1971-1974 and ending in 2015-2018. Male and female avatars at two representative ages, 10 and 15 years, were developed for each survey and at the key BMI percentile cut points based on data from the 2015-2018 survey. RESULTS:The subtle changes in adolescent Americans' body size and shape over the past five decades are represented by 24 male and female 10- and 15-year-old avatars and 8 corresponding BMI percentile cut points. CONCLUSIONS:The current study, the first of its kind, aligns objective physical examination weights and heights with the visual appearance of adolescents. Aligning the biometric and visual information may help improve awareness and appropriate clinical management of adolescents with excess adiposity passing through health care systems. TRIAL REGISTRATION:ClinicalTrials.Gov NCT03706612.

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.

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.

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.

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.

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. [Ann Emerg Med. 2023;82:167-178.]

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%, I 2 = 71%], specificity 40% (95% CI: 30%–50%, I 2 = 75%), and a negative predictive value of 100% (95% CI: 95%–100%, I 2 = 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.

IMPORTANCE: 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. OBJECTIVE: To evaluate whether different fluid protocols affect the rate of normalization of biochemical derangements during DKA treatment. DESIGN, SETTING, PaRTICIPANTS: The current analysis involved moderate or severe DKA episodes (n=714) in children <18 years enrolled in the Fluid Therapies Under Investigation in DKA (FLUID) Trial. INTERVENTION: Children were assigned to one of four treatment groups using a 2-by-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 vs slow fluid infusion arms during the initial 4 hours of treatment. The anion gap also decreased more rapidly in the fast vs slow infusion arms during the initial 4 and 8 hours. 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 hours. Potassium levels decreased, while chloride levels increased more rapidly with 0.90% vs 0.45% saline. Hyperchloremic acidosis occurred more frequently in patients in the fast arms (46.1%) vs slow arms (35.2%). CONCLUSIONS AND RELEVANCE: 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.

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.