Publications by authors named "Jonathan E Bennett"

32 Publications

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

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

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

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

Download full-text PDF

Source
http://dx.doi.org/10.1128/JCM.01344-21DOI Listing
August 2021

Electrocardiogram as a Lyme Disease Screening Test.

J Pediatr 2021 Jul 12. Epub 2021 Jul 12.

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

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

Study Design: We performed an 8-center prospective cohort study of children undergoing emergency department evaluation for Lyme disease limited to those who had an ECG obtained by their treating clinicians. The study cardiologist reviewed all ECGs flagged as abnormal by the study sites to assess for ECG evidence of carditis. We defined Lyme disease as the presence of an erythema migrans lesion or a positive 2-tier Lyme disease serology. We used logistic regression to measure the association between Lyme disease and atrioventricular (AV) block or any ECG evidence of carditis.

Results: Of the 546 children who had an ECG obtained, 214 (39%) had Lyme disease. Overall, 42 children had ECG evidence of carditis, of whom 24 had AV block (20 first-degree). Of the patients with ECG evidence of carditis, only 21 (50%) had any cardiac symptoms. The presence of AV block (OR 4.7, 95% CI 1.8-12.1) and any ECG evidence of carditis (OR 2.3, 95% CI 1.2-4.3) were both associated with diagnosis of Lyme disease.

Conclusions: ECG evidence of carditis, especially AV block, was associated with a diagnosis of Lyme disease. ECG evidence of carditis can be used as a diagnostic biomarker for Lyme disease to guide initial management while awaiting Lyme disease test results.
View Article and Find Full Text PDF

Download full-text PDF

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

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

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

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

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

Research Design And Methods: The current analysis involved moderate or severe DKA episodes ( = 714) in children age <18 years enrolled in the Fluid Therapies Under Investigation in DKA (FLUID) Trial. Children were assigned to one of four treatment groups using a 2 × 2 factorial design (0.90% or 0.45% saline and fast or slow rate of administration).

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

Conclusions: In children treated for DKA, faster fluid administration rates led to a more rapid normalization of anion gap and Pco than slower fluid infusion rates but were associated with an increased frequency of hyperchloremic acidosis.
View Article and Find Full Text PDF

Download full-text PDF

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

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

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

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

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

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

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

Conclusions: The septic knee arthritis clinical prediction rule accurately distinguished between septic and Lyme arthritis in an endemic area. Clinical application may reduce unnecessary invasive diagnostic procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PEC.0000000000002455DOI Listing
May 2021

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

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

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

Background: The Rule of 7's classifies children as low-risk for Lyme meningitis with the absence of the following: ≥7 days of headache, any cranial neuritis or ≥70% cerebrospinal fluid mononuclear cells. We sought to broadly validate this clinical prediction rule in children with meningitis undergoing evaluation for Lyme disease.

Methods: We performed a patient-level data meta-analysis of 2 prospective and 2 retrospective cohorts of children ≤21 years of age with cerebrospinal fluid pleocytosis who underwent evaluation for Lyme disease. We defined a case of Lyme meningitis with a positive 2-tier serology result (positive or equivocal first-tier enzyme immunoassay followed by a positive supplemental immunoblot). We applied the Rule of 7's and report the accuracy for the identification of Lyme meningitis.

Results: Of 721 included children with meningitis, 178 had Lyme meningitis (24.7%) and 543 had aseptic meningitis (75.3%). The pooled data from the 4 studies showed the Rule of 7's has a sensitivity of 98% [95% confidence interval (CI): 89%-100%, I2 = 71%], specificity 40% (95% CI: 30%-50%, I2 = 75%), and a negative predictive value of 100% (95% CI: 95%-100%, I2 = 55%).

Conclusions: The Rule of 7's accurately identified children with meningitis at low-risk for Lyme meningitis for whom clinicians should consider outpatient management while awaiting Lyme disease test results.
View Article and Find Full Text PDF

Download full-text PDF

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

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

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

In 2015, we founded Pedi Lyme Net, a pediatric Lyme disease research network comprising 8 emergency departments in the United States. Of 2,497 children evaluated at 1 of these sites for Lyme disease, 515 (20.6%) were infected. This network is a unique resource for evaluating new approaches for diagnosing Lyme disease in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2612.200920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706969PMC
December 2020

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

Neurosurgery 2020 10;87(5):939-948

Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuros/nyaa128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566379PMC
October 2020

Diagnostic Performance of C6 Enzyme Immunoassay for Lyme Arthritis.

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

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

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

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

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

Conclusions: In Lyme disease endemic areas, a C6 EIA result could be used to guide initial clinical decision-making, without misclassifying children with septic arthritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2019-0593DOI Listing
January 2020

The Lyme Disease Polymerase Chain Reaction Test Has Low Sensitivity.

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

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

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

Download full-text PDF

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

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

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

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

Of 1770 children undergoing emergency department evaluation for Lyme disease, 362 (20.5%) children had Lyme disease. Of those with an available tick bite history, only a minority of those with Lyme disease had a recognized tick bite (60/325; 18.5%, 95% confidence interval 14.6-23.0%). Lack of a tick bite history does not reliably exclude Lyme disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ttbdis.2019.02.015DOI Listing
April 2019

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

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

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

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

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

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

Conclusions: Two-tier Lyme disease test results differed for a substantial number of children on the basis of the specific first-tier test used. In children for whom there is a high clinical suspicion for Lyme disease and who have an initially negative test result, clinicians should consider retesting for Lyme disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jpids/piy133DOI Listing
April 2020

A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections.

JAMA Pediatr 2019 04;173(4):342-351

Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland.

Importance: In young febrile infants, serious bacterial infections (SBIs), including urinary tract infections, bacteremia, and meningitis, may lead to dangerous complications. However, lumbar punctures and hospitalizations involve risks and costs. Clinical prediction rules using biomarkers beyond the white blood cell count (WBC) may accurately identify febrile infants at low risk for SBIs.

Objective: To derive and validate a prediction rule to identify febrile infants 60 days and younger at low risk for SBIs.

Design, Setting, And Participants: Prospective, observational study between March 2011 and May 2013 at 26 emergency departments. Convenience sample of previously healthy febrile infants 60 days and younger who were evaluated for SBIs. Data were analyzed between April 2014 and April 2018.

Exposures: Clinical and laboratory data (blood and urine) including patient demographics, fever height and duration, clinical appearance, WBC, absolute neutrophil count (ANC), serum procalcitonin, and urinalysis. We derived and validated a prediction rule based on these variables using binary recursive partitioning analysis.

Main Outcomes And Measures: Serious bacterial infection, defined as urinary tract infection, bacteremia, or bacterial meningitis.

Results: We derived the prediction rule on a random sample of 908 infants and validated it on 913 infants (mean age was 36 days, 765 were girls [42%], 781 were white and non-Hispanic [43%], 366 were black [20%], and 535 were Hispanic [29%]). Serious bacterial infections were present in 170 of 1821 infants (9.3%), including 26 (1.4%) with bacteremia, 151 (8.3%) with urinary tract infections, and 10 (0.5%) with bacterial meningitis; 16 (0.9%) had concurrent SBIs. The prediction rule identified infants at low risk of SBI using a negative urinalysis result, an ANC of 4090/µL or less (to convert to ×109 per liter, multiply by 0.001), and serum procalcitonin of 1.71 ng/mL or less. In the validation cohort, the rule sensitivity was 97.7% (95% CI, 91.3-99.6), specificity was 60.0% (95% CI, 56.6-63.3), negative predictive value was 99.6% (95% CI, 98.4-99.9), and negative likelihood ratio was 0.04 (95% CI, 0.01-0.15). One infant with bacteremia and 2 infants with urinary tract infections were misclassified. No patients with bacterial meningitis were missed by the rule. The rule performance was nearly identical when the outcome was restricted to bacteremia and/or bacterial meningitis, missing the same infant with bacteremia.

Conclusions And Relevance: We derived and validated an accurate prediction rule to identify febrile infants 60 days and younger at low risk for SBIs using the urinalysis, ANC, and procalcitonin levels. Once further validated on an independent cohort, clinical application of the rule has the potential to decrease unnecessary lumbar punctures, antibiotic administration, and hospitalizations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapediatrics.2018.5501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450281PMC
April 2019

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

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

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

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

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diagmicrobio.2018.12.001DOI Listing
June 2019

Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis.

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

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

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

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

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

Conclusions: Neither the rate of administration nor the sodium chloride content of intravenous fluids significantly influenced neurologic outcomes in children with diabetic ketoacidosis. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration; PECARN DKA FLUID ClinicalTrials.gov number, NCT00629707 .).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa1716816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051773PMC
June 2018

Economic Analysis of Diagnostic Imaging in Pediatric Patients With Suspected Appendicitis.

Acad Emerg Med 2018 07 24;25(7):785-794. Epub 2018 Mar 24.

Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, NY.

Objective: The use of computed tomography (CT) and ultrasound (US) in patients with acute abdominal pain has substantial variation across pediatric emergency departments (EDs). This study compares the cost of diagnosing and treating suspected appendicitis across a multicenter network of children's hospitals.

Methods: This study is a secondary analysis using deidentified data of a prospective, observational study of patients with suspected appendicitis at nine pediatric EDs. The study included patients 3 to 18 years old who presented to the ED with acute abdominal pain of <96 hours' duration.

Results: Our data set contained 2,300 cases across nine sites. There was an appendicitis rate of 31.8% and perforation rate of 25.7%. Sites correctly diagnosed appendicitis in over 95% of cases. The negative appendicitis rate ranged from 2.5% to 4.7% while the missed appendicitis rate ranged from 0.3% to 1.1% with no significant differences in these rates across site. Across sites, we found a strong positive correlation (0.95) between CT rate and total cost per case and a strong negative correlation (-0.71) between US rate and cost. The cost per case at US sites was 5.2% ($367) less than at CT sites (p < 0.001). Similarly, costs per case at mixed sites were 3.4% ($244) less than at CT sites (p < 0.001). Comparing costs among CT sites or among US sites, the cost per case generally increased as the images per case increased among both CT sites and US sites, but the costs were universally higher at CT sites.

Conclusions: Our results provide support for US as the primary imaging modality for appendicitis. Sites that preferentially utilized US had lower costs per case than sites that primarily used CT. Imaging rates across sites varied due to practice patterns and resulted in a significant cost consequence without higher rates for negative appendectomies or missed appendicitis cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acem.13387DOI Listing
July 2018

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

Pediatrics 2017 Dec;140(6)

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

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

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

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

Conclusions: Because clinician suspicion had only minimal accuracy for the diagnosis of Lyme disease, laboratory confirmation is required to avoid both under- and overdiagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2017-1975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703778PMC
December 2017

Accuracy of Complete Blood Cell Counts to Identify Febrile Infants 60 Days or Younger With Invasive Bacterial Infections.

JAMA Pediatr 2017 11 6;171(11):e172927. Epub 2017 Nov 6.

Departments of Emergency Medicine and Pediatrics, University of California, Davis Health, Sacramento.

Importance: Clinicians often risk stratify young febrile infants for invasive bacterial infections (IBIs), defined as bacteremia and/or bacterial meningitis, using complete blood cell count parameters.

Objective: To estimate the accuracy of individual complete blood cell count parameters to identify febrile infants with IBIs.

Design, Setting, And Participants: Planned secondary analysis of a prospective observational cohort study comprising 26 emergency departments in the Pediatric Emergency Care Applied Research Network from 2008 to 2013. We included febrile (≥38°C), previously healthy, full-term infants younger than 60 days for whom blood cultures were obtained. All infants had either cerebrospinal fluid cultures or 7-day follow-up.

Main Outcomes And Measures: We tested the accuracy of the white blood cell count, absolute neutrophil count, and platelet count at commonly used thresholds for IBIs. We determined optimal thresholds using receiver operating characteristic curves.

Results: Of 4313 enrolled infants, 1340 (31%; 95% CI, 30% to 32%) were aged 0 to 28 days, 2412 were boys (56%), and 2471 were white (57%). Ninety-seven (2.2%; 95% CI, 1.8% to 2.7%) had IBIs. Sensitivities were low for common complete blood cell count parameter thresholds: white blood cell count less than 5000/µL, 10% (95% CI, 4% to 16%) (to convert to 109 per liter, multiply by 0.001); white blood cell count ≥15 000/µL, 27% (95% CI, 18% to 36%); absolute neutrophil count ≥10 000/µL, 18% (95% CI, 10% to 25%) (to convert to  × 109 per liter, multiply by 0.001); and platelets <100  × 103/µL, 7% (95% CI, 2% to 12%) (to convert to × 109 per liter, multiply by 1). Optimal thresholds for white blood cell count (11 600/µL), absolute neutrophil count (4100/µL), and platelet count (362 × 103/µL) were identified in models that had areas under the receiver operating characteristic curves of 0.57 (95% CI, 0.50-0.63), 0.70 (95% CI, 0.64-0.76), and 0.61 (95% CI, 0.55-0.67), respectively.

Conclusions And Relevance: No complete blood cell count parameter at commonly used or optimal thresholds identified febrile infants 60 days or younger with IBIs with high accuracy. Better diagnostic tools are needed to risk stratify young febrile infants for IBIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapediatrics.2017.2927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583058PMC
November 2017

The Yale Observation Scale Score and the Risk of Serious Bacterial Infections in Febrile Infants.

Pediatrics 2017 Jul 6;140(1). Epub 2017 Jun 6.

Departments of Emergency Medicine, and.

Objectives: To assess the performance of the Yale Observation Scale (YOS) score and unstructured clinician suspicion to identify febrile infants ≤60 days of age with and without serious bacterial infections (SBIs).

Methods: We performed a planned secondary analysis of a prospective cohort of non-critically ill, febrile, full-term infants ≤60 days of age presenting to 1 of 26 participating emergency departments in the Pediatric Emergency Care Applied Research Network. We defined SBIs as urinary tract infections, bacteremia, or bacterial meningitis, with the latter 2 considered invasive bacterial infections. Emergency department clinicians applied the YOS (range: 6-30; normal score: ≤10) and estimated the risk of SBI using unstructured clinician suspicion (<1%, 1%-5%, 6%-10%, 11%-50%, or >50%).

Results: Of the 4591 eligible infants, 444 (9.7%) had SBIs and 97 (2.1%) had invasive bacterial infections. Of the 4058 infants with YOS scores of ≤10, 388 (9.6%) had SBIs (sensitivity: 51/439 [11.6%]; 95% confidence interval [CI]: 8.8%-15.0%; negative predictive value: 3670/4058 [90.4%]; 95% CI: 89.5%-91.3%) and 72 (1.8%) had invasive bacterial infections (sensitivity 23/95 [24.2%], 95% CI: 16.0%-34.1%; negative predictive value: 3983/4055 [98.2%], 95% CI: 97.8%-98.6%). Of the infants with clinician suspicion of <1%, 106 had SBIs (6.4%) and 16 (1.0%) had invasive bacterial infections.

Conclusions: In this large prospective cohort of febrile infants ≤60 days of age, neither the YOS score nor unstructured clinician suspicion reliably identified those with invasive bacterial infections. More accurate clinical and laboratory predictors are needed to risk stratify febrile infants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2017-0695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495524PMC
July 2017

A Clinical Score to Predict Appendicitis in Older Male Children.

Acad Pediatr 2017 04 24;17(3):261-266. Epub 2016 Nov 24.

Department of Pediatrics, Columbia University, New York, NY.

Objective: To develop a clinical score to predict appendicitis among older, male children who present to the emergency department with suspected appendicitis.

Methods: Patients with suspected appendicitis were prospectively enrolled at 9 pediatric emergency departments. A total of 2625 patients enrolled; a subset of 961 male patients, age 8-18 were analyzed in this secondary analysis. Outcomes were determined using pathology, operative reports, and follow-up calls. Clinical and laboratory predictors with <10% missing data and kappa > 0.4 were entered into a multivariable model. Resultant β-coefficients were used to develop a clinical score. Test performance was assessed by calculating the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios.

Results: The mean age was 12.2 years; 49.9% (480) had appendicitis, 22.3% (107) had perforation, and the negative appendectomy rate was 3%. In patients with and without appendicitis, overall imaging rates were 68.6% (329) and 84.4% (406), respectively. Variables retained in the model included maximum tenderness in the right lower quadrant, pain with walking/coughing or hopping, and the absolute neutrophil count. A score ≥8.1 had a sensitivity of 25% (95% confidence interval [CI], 20%-29%), specificity of 98% (95% CI, 96%-99%), and positive predictive value of 93% (95% CI, 86%-97%) for ruling in appendicitis.

Conclusions: We developed an accurate scoring system for predicting appendicitis in older boys. If validated, the score might allow clinicians to manage a proportion of male patients without diagnostic imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.acap.2016.11.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562406PMC
April 2017

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

JAMA 2016 Aug 23-30;316(8):846-57

Division of Emergency Medicine, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2016.9207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122927PMC
September 2016

Accuracy of plain radiographs to exclude the diagnosis of intussusception.

Pediatr Emerg Care 2012 Sep;28(9):855-8

Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, NY, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PEC.0b013e318267ea38DOI Listing
September 2012

Validation and refinement of a prediction rule to identify children at low risk for acute appendicitis.

Arch Pediatr Adolesc Med 2012 Aug;166(8):738-44

Department of Pediatrics Columbia University College of Physicians and Surgeons, New York, New York, USA.

Objective: To validate and refine a clinical prediction rule to identify which children with acute abdominal pain are at low risk for appendicitis (Low-Risk Appendicitis Rule).

Design: Prospective, multicenter, cross-sectional study.

Setting: Ten pediatric emergency departments.

Participants: Children and adolescents aged 3 to 18 years who presented with suspected appendicitis from March 1, 2009, through April 30, 2010.

Main Outcome Measures: The test performance of the Low-Risk Appendicitis Rule.

Results: Among 2625 patients enrolled, 1018 (38.8% [95% CI, 36.9%-40.7%]) had appendicitis. Validation of the rule resulted in a sensitivity of 95.5% (95% CI, 93.9%-96.7%), specificity of 36.3% (33.9%-38.9%), and negative predictive value of 92.7% (90.1%-94.6%). Theoretical application would have identified 573 (24.0%) as being at low risk, misclassifying 42 patients (4.5% [95% CI, 3.4%-6.1%]) with appendicitis. We refined the prediction rule, resulting in a model that identified patients at low risk with (1) an absolute neutrophil count of 6.75 × 103/μL or less and no maximal tenderness in the right lower quadrant or (2) an absolute neutrophil count of 6.75 × 103/μL or less with maximal tenderness in the right lower quadrant but no abdominal pain with walking/jumping or coughing. This refined rule had a sensitivity of 98.1% (95% CI, 97.0%-98.9%), specificity of 23.7% (21.7%-25.9%), and negative predictive value of 95.3% (92.3%-97.0%).

Conclusions: We have validated and refined a simple clinical prediction rule for pediatric appendicitis. For patients identified as being at low risk, clinicians should consider alternative strategies, such as observation or ultrasonographic examination, rather than proceeding to immediate computed tomographic imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/archpediatrics.2012.490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790639PMC
August 2012

Diagnostic value of immature neutrophils (bands) in the cerebrospinal fluid of children with cerebrospinal fluid pleocytosis.

Pediatrics 2009 Jun 18;123(6):e967-71. Epub 2009 May 18.

Division of Emergency Medicine, Rady Children's Hospital San Diego, 3020 Children's Way, MC 5075, San Diego, CA 92123, USA.

Objective: We evaluated the diagnostic utility of the presence and number of cerebrospinal fluid (CSF) bands in distinguishing bacterial from aseptic meningitis among children with CSF pleocytosis.

Methods: We identified retrospectively a cohort of children 29 days to 19 years of age with CSF pleocytosis (> or =10 x 10(6) leukocytes per L) who were treated in the emergency departments of 8 pediatric centers between January 2001 and June 2004 and whose CSF was evaluated for the presence of bands. We performed bivariate and multivariate analyses to determine the ability of CSF bands to distinguish bacterial from aseptic meningitis.

Results: Among 1116 children whose CSF was evaluated for the presence of bands, 48 children (4% of study patients) had bacterial meningitis. Bacterial meningitis, compared with aseptic meningitis, was associated with a greater CSF band proportion (0.03 vs 0.01; difference: 0.02; 95% confidence interval: 0.00-0.04) and CSF absolute band count (392 x 10(6) cells per L vs 3 x 10(6) cells per L; difference: 389 x 10(6) cells per L; 95% confidence interval: -77 x 10(6) cells per L to 855 x 10(6) cells per L). In addition, 29% of patients with bacterial meningitis, compared with 18% of patients with aseptic meningitis, had any bands detected in the CSF. After adjustment for other factors associated with bacterial meningitis, however, CSF band presence, CSF absolute band count, and CSF band proportion were not independently associated with bacterial meningitis.

Conclusion: In this multicenter study, neither the presence nor quantity of CSF bands independently predicted bacterial meningitis among children with CSF pleocytosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2008-1742DOI Listing
June 2009

Effect of antibiotic pretreatment on cerebrospinal fluid profiles of children with bacterial meningitis.

Pediatrics 2008 Oct;122(4):726-30

Children's Hospital Boston and Harvard Medical School,, Boston, MA 02115, USA.

Objective: The goal of this study was to evaluate the effect of antibiotic administration before lumbar puncture on cerebrospinal fluid profiles in children with bacterial meningitis.

Methods: We reviewed the medical records of all children (1 month to 18 years of age) with bacterial meningitis who presented to 20 pediatric emergency departments between 2001 and 2004. Bacterial meningitis was defined by positive cerebrospinal fluid culture results for a bacterial pathogen or cerebrospinal fluid pleocytosis with positive blood culture and/or cerebrospinal fluid latex agglutination results. Probable bacterial meningitis was defined as positive cerebrospinal fluid Gram stain results with negative results of bacterial cultures of blood and cerebrospinal fluid. Antibiotic pretreatment was defined as any antibiotic administered within 72 hours before the lumbar puncture.

Results: We identified 231 patients with bacterial meningitis and another 14 with probable bacterial meningitis. Of those 245 patients, 85 (35%) had received antibiotic pretreatment. After adjustment for patient age, duration and severity of illness at presentation, and bacterial pathogen, longer duration of antibiotic pretreatment was not significantly associated with cerebrospinal fluid white blood cell count, cerebrospinal fluid absolute neutrophil count. However, antibiotic pretreatment was significantly associated with higher cerebrospinal fluid glucose and lower cerebrospinal fluid protein levels. Although these effects became apparent earlier, patients with >or=12 hours of pretreatment, compared with patients who either were not pretreated or were pretreated for <12 hours, had significantly higher median cerebrospinal fluid glucose levels (48 mg/dL vs 29 mg/dL) and lower median cerebrospinal fluid protein levels (121 vs 178 mg/dL).

Conclusions: In patients with bacterial meningitis, antibiotic pretreatment is associated with higher cerebrospinal fluid glucose levels and lower cerebrospinal fluid protein levels, although pretreatment does not modify cerebrospinal fluid white blood cell count or absolute neutrophil count results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2007-3275DOI Listing
October 2008

Predicting pertussis in infants.

Pediatr Emerg Care 2008 Jan;24(1):16-20

Division of Emergency Medicine, Thomas Jefferson University Medical College, A.I. duPont Hospital for Children, Nemours Children's Clinic, Wilmington, DE 19899, USA.

Background: The incidence of reported cases of pertussis is increasing, despite high rates of vaccination among infants and children. The burden of disease, and rates of complication and death are highest among infants. The limited availability of a timely reliable confirmatory test for pertussis hinders early identification of infected infants.

Objective: Our objective is to identify clinical and laboratory predictors for pertussis among infants.

Methods: Demographic, clinical, and laboratory data were collected from the medical records of all infants aged 12 months or younger who underwent confirmatory testing (culture, direct fluorescent assay, or polymerase chain reaction) for Bordetella pertussis from January 1, 2001, to July 31, 2005. The association of 15 variables with a positive pertussis test was analyzed using univariate and multivariate analysis, and when appropriate, using receiver operating characteristics.

Results: We reviewed the medical records of 141 infants who were tested for pertussis. The mean age was 88 days, and the most common chief complaints were cough and breathing difficulty. Eighteen patients (13%) had a positive pertussis test, and 123 (87%) had a negative test. Bronchiolitis and upper respiratory tract infection were the most common discharge diagnoses among infants with a negative test. The 2 groups were similar with respect to sex, history of cough, vomiting, fever, symptoms of apparent life-threatening event, presence of fever, or hypoxia, and heart rate. Infants who were younger (55 days vs 93 days, P = 0.02), evaluated between July and October (23% vs 9%, P = 0.02), less tachypneic (39 breaths/min vs 47 breaths/min, P = 0.02), had higher white blood cell counts (20,000/microL vs 15,000/microL, P = 0.02), higher percentage of lymphocytes (72 vs 55, P = 0.00), and higher absolute lymphocyte counts ([ALC] 14,536/microL vs 8357/microL, P = 0.00) were more likely to have a positive test. Receiver operating characteristics for ALC demonstrated an area under the curve of 0.81, with a 95% confidence interval of 0.72 to 0.90. An ALC cutoff point of 9400 was determined to maximize sensitivity (89%) and specificity (75%). The negative predictive value of this cutoff point was 97%, and the positive likelihood ratio was 3.6, with a 95% confidence interval of 2.3 to 5.4.

Conclusions: Among infants who underwent confirmatory testing for pertussis, those who are younger, evaluated between July and October, less tachypneic, have higher white blood cell counts, higher percentage of lymphocytes, and higher ALCs are more likely to have a positive test. The ALC was the best predictor of pertussis, and an ALC of less than 9400/microL excluded almost all infants without pertussis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/pec.0b013e31815f39b6DOI Listing
January 2008

Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis.

JAMA 2007 Jan;297(1):52-60

Department of Medicine, Children's Hospital Boston and Harvard Medical School, Boston, Mass 02115, USA.

Context: Children with cerebrospinal fluid (CSF) pleocytosis are routinely admitted to the hospital and treated with parenteral antibiotics, although few have bacterial meningitis. We previously developed a clinical prediction rule, the Bacterial Meningitis Score, that classifies patients at very low risk of bacterial meningitis if they lack all of the following criteria: positive CSF Gram stain, CSF absolute neutrophil count (ANC) of at least 1000 cells/microL, CSF protein of at least 80 mg/dL, peripheral blood ANC of at least 10,000 cells/microL, and a history of seizure before or at the time of presentation.

Objective: To validate the Bacterial Meningitis Score in the era of widespread pneumococcal conjugate vaccination.

Design, Setting, And Patients: A multicenter, retrospective cohort study conducted in emergency departments of 20 US academic medical centers through the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. All children aged 29 days to 19 years who presented at participating emergency departments between January 1, 2001, and June 30, 2004, with CSF pleocytosis (CSF white blood cells > or =10 cells/microL) and who had not received antibiotic treatment before lumbar puncture.

Main Outcome Measure: The sensitivity and negative predictive value of the Bacterial Meningitis Score.

Results: Among 3295 patients with CSF pleocytosis, 121 (3.7%; 95% confidence interval [CI], 3.1%-4.4%) had bacterial meningitis and 3174 (96.3%; 95% CI, 95.5%-96.9%) had aseptic meningitis. Of the 1714 patients categorized as very low risk for bacterial meningitis by the Bacterial Meningitis Score, only 2 had bacterial meningitis (sensitivity, 98.3%; 95% CI, 94.2%-99.8%; negative predictive value, 99.9%; 95% CI, 99.6%-100%), and both were younger than 2 months old. A total of 2518 patients (80%) with aseptic meningitis were hospitalized.

Conclusions: This large multicenter study validates the Bacterial Meningitis Score prediction rule in the era of conjugate pneumococcal vaccine as an accurate decision support tool. The risk of bacterial meningitis is very low (0.1%) in patients with none of the criteria. The Bacterial Meningitis Score may be helpful to guide clinical decision making for the management of children presenting to emergency departments with CSF pleocytosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.297.1.52DOI Listing
January 2007

Clinical features of bacterial conjunctivitis in children.

Acad Emerg Med 2007 Jan 21;14(1):1-5. Epub 2006 Nov 21.

Division of Pediatric Emergency Medicine, Alfred I. duPont Hospital for Children, Wilmington, DE, USA.

Objectives: Conjunctivitis is a common cause of primary care and emergency department (ED) visits. There is a paucity of data in recent literature on the prevalence of pediatric bacterial conjunctivitis, and there are no evidence-based clinical guidelines for empirical treatment. The study objective was to describe clinical features most predictive of bacterial conjunctivitis.

Methods: This was a prospective study in a children's hospital ED. Conjunctival swabs for bacterial culture were obtained from patients aged 1 month to 18 years presenting with red or pink eye and/or the diagnosis of conjunctivitis.

Results: A total of 111 patients were enrolled over one year. Patients had a mean (+/-SD) age of 33.2 (+/-37.5) months, and 55% were male. Eighty-seven patients (78%) had positive bacterial cultures. Nontypeable Haemophilus influenzae accounted for 82% (71/87), Streptococcus pneumoniae for 16% (14/87), and Staphylococcus aureus for 2.2% (2/87). Five clinical variables were significantly associated with a positive bacterial culture. Regression analysis revealed that the combination of a history of gluey or sticky eyelids and the physical finding of mucoid or purulent discharge had a posttest probability of 96% (95% confidence interval = 90% to 99%). Subjective scoring by physicians for a positive culture was 50.6%.

Conclusions: Conjunctivitis in children is predominantly bacterial, with nontypeable H. influenzae being the most common organism. A history of gluey or sticky eyelids and physical findings of mucoid or purulent discharge are highly predictive of bacterial infection. Based on the above data, empirical ophthalmic antibiotic therapy may be appropriate in children presenting with conjunctivitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1197/j.aem.2006.08.006DOI Listing
January 2007

The role of parental preferences in the management of fever without source among 3- to 36-month-old children: a decision analysis.

Pediatrics 2006 Apr;117(4):1067-76

Department of Pediatrics, University of California, San Francisco, CA 94118, USA.

Objectives: Recent analyses assessing the impact of the conjugate pneumococcal vaccine on the care of febrile children do not reflect the role parental preferences play in physicians' decisions. The objective of this study was to identify the management strategy that would best suit parents, on the basis of their values for possible outcomes of fever of > or =39 degrees C without source among well-appearing, 3- to 36-month-old children.

Methods: A decision analysis was performed to compare the benefits and outcomes of 3 management options (treat: blood culture and antibiotics for all children; test: blood culture and complete blood count for all children, with antibiotics for selected children; observe: no immediate intervention). A hypothetical cohort of 100,000 children with fever of > or =39 degrees C with no obvious source of infection was modeled for each strategy. Using this model, we identified the treatment option that would best suit each parent's preferences, on the basis of parental utilities (from a prior study) for various interventions and outcomes at vaccine efficacies of 0% (ie, no vaccine) and 95%. In addition, we performed survival analyses to assess the morbidity and mortality rates associated with each treatment strategy at various vaccine efficacies.

Results: At a vaccine efficacy of 0%, the majority of parents' preferences suggested the treat option, the strategy with the lowest mortality rate. At a vaccine efficacy of 95%, mortality rates were similar for all 3 management options (approximately 1 in 100,000), but parental preferences were still aligned with different options; 50% suggested observe, 42% suggested test, and 8% suggested treat.

Conclusions: Like physicians, parents have different approaches to risk. With the conjugate pneumococcal vaccine, risks of complications from fever without source are low regardless of treatment strategy. Rather than having a "one size fits all" approach, it is reasonable to incorporate parental preferences into the treatment decision.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2005-1865DOI Listing
April 2006

Assessing the benefit of radiation therapy after breast-conserving surgery for ductal carcinoma-in-situ.

J Clin Oncol 2005 Aug;23(22):5171-7

Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI 48109-0010, USA.

Purpose: To assess women's preferences regarding the trade-off between the risks and benefits of treatment with radiation therapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma-in-situ (DCIS).

Patients And Methods: Utilities were obtained from 120 patients and 210 nonpatients for eight relevant health states using standard gambles.

Results: Differences in utilities obtained from patient and nonpatient participants between health states were relatively similar. Reduction in the likelihood of local recurrence associated with RT did not result in higher utilities. Utilities for noninvasive recurrence were only lower after initial treatment with RT. Patient and nonpatient participants had the lowest utilities for invasive local recurrence, regardless of initial treatment or manner of salvage therapy. When comparing patient and nonpatient utilities directly, patients had higher utility for being without recurrence after initial RT and lower utility for invasive recurrence salvaged by mastectomy after initial BCS alone. None of the clinical or sociodemographic factors examined explained more than 5% of the variability in the patients' or nonpatients' utilities or their differences.

Conclusion: The principal benefit associated with adding RT to BCS for DCIS seems to be its ability to reduce invasive recurrences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2005.11.692DOI Listing
August 2005

Clinical course of urinary tract infections in infants younger than 60 days of age.

Pediatr Emerg Care 2004 Feb;20(2):85-88

The Children's Hospital of New York-Presbyterian, Columbia University, College of Physicians and Surgeons.

Objectives: Although often managed differently than older children, no study has specifically described the clinical course of urinary tract infections (UTIs) in young infants. Our objective was to determine the risk of progression of illness and the pattern of fever resolution in infants younger than 60 days of age with Gram-negative rod UTIs.

Methods: We completed a retrospective medical chart review. Patients younger than 60 days of age presenting to an urban, tertiary care pediatric hospital were included if they had single organism growth of Gram-negative rods in any amount from suprapubic aspiration samples or more than 10,000 cfu/mL from catheterized specimens. Significant progression of illness was defined as the need for transfer to an intensive care setting. Fever was defined as a rectal temperature of 38.0 degrees C or higher or an axillary temperature 37.0 degrees C or higher. Temperatures were assigned to blocks of 4 hours.

Results: Of 128 patients with available records, none were transferred from the general pediatric ward to the intensive care unit and 2 were transferred to a step-down unit for events potentially unrelated to the UTI. No patient had a positive repeat urine culture. For patients with fever, median time to fever resolution was within the 4 to 8 hour time block. Eighty-five percent of the febrile patients became afebrile within 24 hours and only 3.6% were febrile after 48 hours.

Conclusions: Progression of illness in infants with Gram-negative rod UTIs is unlikely. Fever resolution is rapid. If subsequent studies concur with our findings, outpatient therapy or short-stay unit admission may become a viable management strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.pec.0000113876.10140.9bDOI Listing
February 2004
-->