Urine proteomics for discovery of improved diagnostic markers of Kawasaki disease

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. Absence of definitive diagnostic markers limits the accuracy of clinical evaluations of suspected KD with significant increases in morbidity. In turn, incomplete understanding of its molecular pathogenesis hinders the identification of rational targets needed to improve therapy. We used high-accuracy mass spectrometry proteomics to analyse over 2000 unique proteins in clinical urine specimens of patients with KD. We discovered that urine proteomes of patients with KD, but not those with mimicking conditions, were enriched for markers of cellular injury such as filamin and talin, immune regulators such as complement regulator CSMD3, immune pattern recognition receptor muclin, and immune cytokine protease meprin A. Significant elevations of filamin C and meprin A were detected in both the serum and urine in two independent cohorts of patients with KD, comprised of a total of 236 patients. Meprin A and filamin C exhibited superior diagnostic performance as compared to currently used markers of disease in a blinded case-control study of 107 patients with suspected KD, with receiver operating characteristic areas under the curve of 0.98 (95% confidence intervals [CI] of 0.97–1 and 0.95–1, respectively). Notably, meprin A was enriched in the coronary artery lesions of a mouse model of KD. In all, urine proteome profiles revealed novel candidate molecular markers of KD, including filamin C and meprin A that exhibit excellent diagnostic performance. These disease markers may improve the diagnostic accuracy of clinical evaluations of children with suspected KD, lead to the identification of novel therapeutic targets, and allow the development of a biological classification of Kawasaki disease

Detection of occult pneumonia in a pediatric emergency department

BACKGROUND: Many children undergo chest radiography (CXR) in their evaluation of a febrile illness. Pneumonia without signs of respiratory distress or ausculatory findings has been previously described (termed occult pneumonia [OP]). OBJECTIVE: The objectives of this study were to determine the incidence of OP among children who have CXR performed and to identify clinical predictors of OP. METHODS: A prospective observational study of children undergoing CXR for possible pneumonia was conducted. Standardized data forms were completed before the CXR. Univariate analysis and recursive partitioning were used to identify predictors of OP. RESULTS: Of 1866 patients enrolled, 308 had no evidence of respiratory distress or lower respiratory tract findings and were studied for OP. Twenty-one patients had radiographic OP (6.8%; 95% confidence interval [CI], 4.0%-10.6%). Age, height of fever, duration or quality of cough, and pulse oximetry were not associated with OP. A decision rule based on fever for 1 day or longer or with a combination of fever for less than 1 day but worsening cough identifies patients at greater risk for OP (likelihood ratio, 1.47; 95% CI, 1.21-1.77). No patient with fever for less than 1 day and without any cough or without worsening cough had pneumonia (likelihood ratio, 0.40; 95% CI, 0.19-0.84). CONCLUSIONS: Occult pneumonia was identified in 1 of 15 patients undergoing CXR without respiratory distress or ausculatory findings. Obtaining a CXR for the detection of OP in children without cough and with fever for less than 1 day in duration should be discouraged

Errors of Medical Interpretation and Their Potential Clinical Consequences: A Comparison of Professional Versus Ad Hoc Versus No Interpreters

Study objective: To compare interpreter errors and their potential consequences in encounters with professional versus ad hoc versus no interpreters. Methods: This was a cross-sectional error analysis of audiotaped emergency department (ED) visits during 30 months in the 2 largest pediatric EDs in Massachusetts. Participants were Spanish-speaking limited-English-proficient patients, caregivers, and their interpreters. Outcome measures included interpreter error numbers, types, and potential consequences. Results: The 57 encounters included 20 with professional interpreters, 27 with ad hoc interpreters, and 10 with no interpreters; 1,884 interpreter errors were noted, and 18% had potential clinical consequences. The proportion of errors of potential consequence was significantly lower for professional (12%) versus ad hoc (22%) versus no interpreters (20%). Among professional interpreters, previous hours of interpreter training, but not years of experience, were significantly associated with error numbers, types, and potential consequences. The median errors by professional interpreters with greater than or equal to 100 hours of training was significantly lower, at 12, versus 33 for those with fewer than 100 hours of training. Those with greater than or equal to 100 hours of training committed significantly lower proportions of errors of potential consequence overall (2% versus 12%) and in every error category. Conclusion: Professional interpreters result in a significantly lower likelihood of errors of potential consequence than ad hoc and no interpreters. Among professional interpreters, hours of previous training, but not years of experience, are associated with error numbers, types, and consequences. These findings suggest that requiring at least 100 hours of training for interpreters might have a major impact on reducing interpreter errors and their consequences in health care while improving quality and patient safety. [Ann Emerg Med. 2012;60:545-553.

Measuring complications of serious pediatric emergencies using ICD‐10

ObjectiveTo create definitions for complications for 16 serious pediatric conditions using the International Classification of Diseases, 10th Revision, Clinical Modification or Procedure Coding System (ICD‐10‐CM/PCS), and to assess whether complication rates are similar to those measured with ICD‐9‐CM/PCS.Data SourcesThe Healthcare Cost and Utilization Project State Emergency Department and Inpatient Databases from five states between 2014 and 2017 were used to identify cases and assess complication rates. Incidences were calculated using population counts from the 5‐year American Community Survey.Data Collection/Extraction MethodsPatients were identified by the presence of a diagnosis code for one of the 16 serious conditions. Only the first encounter for a given condition by a patient was included. Encounters resulting in transfer were excluded as the presence of complications was unknown.Study DesignWe defined complications using data elements routinely available in administrative databases including ICD‐10‐CM/PCS codes. The definitions were adapted from ICD‐9‐CM/PCS using general equivalence mappings and refined using consensus opinion. We included 16 serious conditions: appendicitis, bacterial meningitis, compartment syndrome, new‐onset diabetic ketoacidosis (DKA), ectopic pregnancy, empyema, encephalitis, intussusception, mastoiditis, myocarditis, orbital cellulitis, ovarian torsion, sepsis, septic arthritis, stroke, and testicular torsion. Using data from children under 18 years, we compared incidences and complication rates across the ICD‐10‐CM/PCS transition for each condition using interrupted time series.Principal FindingsThere were 61 314 ED visits for a serious condition; the most common was appendicitis (n = 37 493). Incidence rates for each condition were not significantly different across the ICD‐10‐CM/PCS transition for 13/16 conditions. Three differed: empyema (increased 42%), orbital cellulitis (increased 60%), and sepsis (increased 26%). Complication rates were not significantly different for each condition across the ICD‐10‐CM/PCS transition, except appendicitis (odds ratio 0.62, 95% CI 0.57‐0.68), DKA (OR 3.79, 95% CI 1.92‐7.50), and orbital cellulitis (OR 0.53, 95% CI 0.30‐0.95).ConclusionsFor most conditions, incidences and complication rates were similar before and after the transition to ICD‐10‐CM/PCS codes, suggesting our system identifies complications of conditions in administrative data similarly using ICD‐9‐CM/PCS and ICD‐10‐CM/PCS codes. This system may be applied to screen for cases with complications and in health services research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167093/1/hesr13615-sup-0003-FigureS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167093/2/hesr13615_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167093/3/hesr13615-sup-0001-Authormatrix.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167093/4/hesr13615.pd

Clinical predictors of pneumonia among children with wheezing

OBJECTIVE: The goal was to identify factors associated with radiographically confirmed pneumonia among children with wheezing in the emergency department (ED) setting. METHODS: A prospective cohort study was performed with children RESULTS: A total of 526 patients met the inclusion criteria; the median age was 1.9 years (interquartile range: 0.7-4.5 years), and 36% were hospitalized. A history of wheezing was present for 247 patients (47%). Twenty-six patients (4.9% [95% confidence interval [CI]: 3.3-7.3]) had radiographic pneumonia. History of fever at home (positive likelihood ratio [LR]: 1.39 [95% CI: 1.13-1.70]), history of abdominal pain (positive LR: 2.85 [95% CI: 1.08-7.54]), triage temperature of \u3eor=38 degrees C (positive LR: 2.03 [95% CI: 1.34-3.07]), maximal temperature in the ED of \u3eor=38 degrees C (positive LR: 1.92 [95% CI: 1.48-2.49]), and triage oxygen saturation of \u3c92% (positive LR: 3.06 [95% CI: 1.15-8.16]) were associated with increased risk of pneumonia. Among afebrile children (temperature of \u3c38 degrees C) with wheezing, the rate of pneumonia was very low (2.2% [95% CI: 1.0-4.7]). CONCLUSIONS: Radiographic pneumonia among children with wheezing is uncommon. Historical and clinical factors may be used to determine the need for chest radiography for wheezing children. The routine use of chest radiography for children with wheezing but without fever should be discouraged