Anupam B. Kharbanda

A clinical decision rule to identify children at low risk for appendicitis

Objective. Computed tomography (CT) has gained widespread acceptance in the evaluation of children with suspected appendicitis. Concern has been raised regarding the long-term effects of ionizing radiation. Other means of diagnosing appendicitis, such as clinical scores, are lacking in children. We sought to develop a clinical decision rule to predict which children with acute abdominal pain do not have appendicitis. Methods. Prospective cohort study was conducted of children and adolescents who aged 3 to 18 years, had signs and symptoms suspicious for appendicitis, and presented to the emergency department between April 2003 and July 2004. Standardized data-collection forms were completed on eligible patients. Two low-risk clinical decision rules were created and validated using logistic regression and recursive partitioning. The sensitivity, negative predictive value (NPV), and negative likelihood ratio of each clinical rule were compared. Results. A total of 601 patients were enrolled. Using logistic regression, we created a 6-part score that consisted of nausea (2 points), history of focal right lower quadrant pain (2 points), migration of pain (1 point), difficulty walking (1 point), rebound tenderness/pain with percussion (2 points), and absolute neutrophil count of >6.75 × 103/μL (6 points). A score ≤5 had a sensitivity of 96.3% (95% confidence interval [CI]: 87.5–99.0), NPV of 95.6% (95% CI: 90.8–99.0), and negative likelihood ratio of .102 (95% CI: 0.026–0.405) in the validation set. Using recursive partitioning, a second low-risk decision rule was developed consisting of absolute neutrophil count of <6.75 × 103/μL, absence of nausea, and absence of maximal tenderness in the right lower quadrant. This rule had a sensitivity of 98.1% (95% CI: 90.1–99.9), NPV of 97.5% (95% CI: 86.8–99.9), and negative likelihood ratio of 0.058 (95% CI: 0.008–0.411) in the validation set. Theoretical application of the low-risk rules would have resulted in a 20% reduction in CT. Conclusions. Our low-risk decision rules can predict accurately which children are at low risk for appendicitis and could be treated safely with careful observation rather than CT examination.

Performance of Ultrasound in the Diagnosis of Appendicitis in Children in a Multicenter Cohort

OBJECTIVES The objectives were to assess the test characteristics of ultrasound (US) in diagnosing appendicitis in children and to evaluate site-related variations based on the frequency of its use. Additionally, the authors assessed the test characteristics of US when the appendix was clearly visualized. METHODS This was a secondary analysis of a prospective, 10-center observational study. Children aged 3 to 18 years with acute abdominal pain concerning for appendicitis were enrolled. US was performed at the discretion of the treating physician. RESULTS Of 2,625 patients enrolled, 965 (36.8%) underwent abdominal US. US had an overall sensitivity of 72.5% (95% confidence interval [CI] = 58.8% to 86.3%) and specificity 97.0% (95% CI = 96.2% to 97.9%) in diagnosing appendicitis. US sensitivity was 77.7% at the three sites (combined) that used it in 90% of cases, 51.6% at a site that used it in 50% of cases, and 35% at the four remaining sites (combined) that used it in 9% of cases. US retained a high specificity of 96% to 99% at all sites. Of the 469 (48.6%) cases across sites where the appendix was clearly visualized on US, its sensitivity was 97.9% (95% CI = 95.2% to 99.9%), with a specificity of 91.7% (95% CI = 86.7% to 96.7%). CONCLUSIONS Ultrasound sensitivity and the rate of visualization of the appendix on US varied across sites and appeared to improve with more frequent use. US had universally high sensitivity and specificity when the appendix was clearly identified. Other diagnostic modalities should be considered when the appendix is not definitively visualized by US.

Race, Ethnicity, and Socioeconomic Status in Research on Child Health

An extensive literature documents the existence of pervasive and persistent child health, development, and health care disparities by race, ethnicity, and socioeconomic status (SES). Disparities experienced during childhood can result in a wide variety of health and health care outcomes, including adult morbidity and mortality, indicating that it is crucial to examine the influence of disparities across the life course. Studies often collect data on the race, ethnicity, and SES of research participants to be used as covariates or explanatory factors. In the past, these variables have often been assumed to exert their effects through individual or genetically determined biologic mechanisms. However, it is now widely accepted that these variables have important social dimensions that influence health. SES, a multidimensional construct, interacts with and confounds analyses of race and ethnicity. Because SES, race, and ethnicity are often difficult to measure accurately, leading to the potential for misattribution of causality, thoughtful consideration should be given to appropriate measurement, analysis, and interpretation of such factors. Scientists who study child and adolescent health and development should understand the multiple measures used to assess race, ethnicity, and SES, including their validity and shortcomings and potential confounding of race and ethnicity with SES. The American Academy of Pediatrics (AAP) recommends that research on eliminating health and health care disparities related to race, ethnicity, and SES be a priority. Data on race, ethnicity, and SES should be collected in research on child health to improve their definitions and increase understanding of how these factors and their complex interrelationships affect child health. Furthermore, the AAP believes that researchers should consider both biological and social mechanisms of action of race, ethnicity, and SES as they relate to the aims and hypothesis of the specific area of investigation. It is important to measure these variables, but it is not sufficient to use these variables alone as explanatory for differences in disease, morbidity, and outcomes without attention to the social and biologic influences they have on health throughout the life course. The AAP recommends more research, both in the United States and internationally, on measures of race, ethnicity, and SES and how these complex constructs affect health care and health outcomes throughout the life course.

Novel Serum and Urine Markers for Pediatric Appendicitis

OBJECTIVES The objective was to describe the association between two novel biomarkers, calprotectin and leucine-rich alpha glycoprotein-1 (LRG), and appendicitis in children. METHODS This was a prospective, cross-sectional study of children 3 to 18 years old presenting to a pediatric emergency department (ED) with possible appendicitis. Blood and urine samples were assayed for calprotectin and LRG via enzyme-linked immunosorbent assay (ELISA). Final diagnosis was determined by histopathology or telephone follow-up. Biomarker levels were compared for subjects with and without appendicitis. Recursive partitioning was used to identify thresholds that predicted appendicitis. RESULTS Of 176 subjects, mean (±SD) age was 11.6 (±4.0) years and 52% were male. Fifty-eight patients (34%) were diagnosed with appendicitis. Median plasma calprotectin, serum LRG, and urine LRG levels were higher in appendicitis versus nonappendicitis (p < 0.008). When stratified by perforation status, median plasma calprotectin and serum LRG levels were higher in nonperforated appendicitis versus nonappendicitis (p < 0.01). Median serum LRG, urine LRG, and plasma calprotectin levels were higher in perforated appendicitis compared to nonperforated appendicitis (p < 0.05). Urine calprotectin did not differ among groups. A serum LRG < 40,150 ng/mL, a urine LRG < 42 ng/mL, and a plasma calprotectin < 159 ng/mL, each provided a sensitivity and negative predictive value of 100% to identify children at low risk for appendicitis, but with specificities ranging from 23% to 35%. The standard white blood cell (WBC) count achieved 100% sensitivity at a higher specificity than both novel biomarkers. CONCLUSIONS Plasma calprotectin and serum/urine LRG are elevated in pediatric appendicitis. No individual marker performed as well as the WBC count.

The effect of abdominal pain duration on the accuracy of diagnostic imaging for pediatric appendicitis.

STUDY OBJECTIVE Advanced imaging with computed tomography (CT) or ultrasonography is frequently used to evaluate for appendicitis. The duration of the abdominal pain may be related to the stage of disease and therefore the interpretability of radiologic studies. Here, we investigate the influence of the duration of pain on the diagnostic accuracy of advanced imaging in children being evaluated for acute appendicitis. METHODS A secondary analysis of a prospective multicenter observational cohort of children aged 3 to 18 years with suspected appendicitis who underwent CT or ultrasonography was studied. Outcome was based on histopathology or telephone follow-up. Treating physicians recorded the duration of pain. Imaging was coded as positive, negative, or equivocal according to an attending radiologists interpretation. RESULTS A total of 1,810 children were analyzed (49% boys, mean age 10.9 years [SD 3.8 years]); 1,216 (68%) were assessed by CT and 832 (46%) by ultrasonography (238 [13%] had both). The sensitivity of ultrasonography increased linearly with increasing pain duration (test for trend: odds ratio=1.39; 95% confidence interval 1.14 to 1.71). There was no association between the sensitivity of CT or specificity of either modality with pain duration. The proportion of equivocal CT readings significantly decreased with increasing pain duration (test for trend: odds ratio=0.76; 95% confidence interval 0.65 to 0.90). CONCLUSION The sensitivity of ultrasonography for appendicitis improves with a longer duration of abdominal pain, whereas CT demonstrated high sensitivity regardless of pain duration. Additionally, CT results (but not ultrasonographic results) were less likely to be equivocal with longer duration of abdominal pain.

Discriminative accuracy of novel and traditional biomarkers in children with suspected appendicitis adjusted for duration of abdominal pain.

OBJECTIVES The objective was to assess the accuracy of novel and traditional biomarkers in patients with suspected appendicitis as a function of duration of symptoms. METHODS This was a prospective cohort study, conducted in a tertiary care emergency department (ED). The authors enrolled children 3 to 18 years old with acute abdominal pain of less than 96 hours and measured serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP), white blood cell (WBC) count, and absolute neutrophil count (ANC). Final diagnosis was determined by histopathology or telephone follow-up. Trends in biomarker levels were examined based on duration of abdominal pain. The accuracy of biomarkers was assessed with receiver operating characteristic (ROC) curves. Optimal cut-points and test performance characteristics were calculated for each biomarker. RESULTS   Of 280 patients enrolled, the median age was 11.3 years (interquartile range [IQR] = 8.6 to 14.8), 57% were male, and 33% had appendicitis. Median IL-6, median CRP, mean WBC count, and mean ANC differed significantly (p < 0.001) between patients with nonperforated appendicitis and those without appendicitis; median IL-8 levels did not differ between groups. In nonperforated appendicitis, median IL-6, WBC, and ANC levels were maximal at less than 24 hours of pain, while CRP peaked between 24 and 48 hours. In perforated appendicitis, median IL-8 levels were highest by 24 hours, WBC count and IL-6 by 24 to 48 hours, and CRP after 48 hours of pain. The WBC count appeared to be the most useful marker to predict appendicitis in those with fewer than 24 or more than 48 hours of pain, while CRP was the most useful in those with 24 to 48 hours of pain. CONCLUSIONS In this population, the serum levels and accuracy of novel and traditional biomarkers varies in relation to duration of abdominal pain. IL-6 shows promise as a novel biomarker to identify children with appendicitis.

Characteristics of Recurrent Utilization in Pediatric Emergency Departments

BACKGROUND AND OBJECTIVE: Nationally, frequent utilizers of emergency departments (EDs) are targeted for quality improvement initiatives. The objective was to compare the characteristics and ED health services of children by their ED visit frequency. METHODS: A retrospective study in 1 896 547 children aged 0 to 18 years with 3 263 330 visits to 37 EDs in 2011. The number of ED visits per child within 365 days of their first visit was counted. Patient characteristics (age, chronic condition) and ED care (medications, testing [laboratory and radiographic], and hospital admission) were assessed. We evaluated the relationship between patient characteristics and ED health services received with multivariable regression. RESULTS: Children with ≥4 ED visits (8%) accounted for 24% of all visits and 31% (

Interrater Reliability of Clinical Findings in Children With Possible Appendicitis

1.4 billion) of all costs. As visit frequency increased from 1 to ≥4, the percentage of children aged <1 year increased (12.1% to 33.2%) and the percentage of children without a chronic condition decreased (81.9% to 45.6%) (P < .001 for both). Children with ≥4 ED visits had a higher percentage of visits without medication administration (aside from acetaminophen or ibuprofen), testing, or hospital admission when compared with children with 1 visit (35.4% vs 29.0%; P < .001). Children with ≥4 ED visits who were aged <1 year (odds ratio: 3.8; 95% confidence interval: 3.7–3.9) and who were without a chronic condition (odds ratio: 3.1; 95% confidence interval: 3.0–3.1) had the highest likelihood of experiencing this type of visit. CONCLUSIONS: With a disproportionate share of pediatric ED cost and utilization, frequent utilizers, especially infants without a chronic condition, are the least likely to need medications, testing, and hospital admission.

The Presentation of Appendicitis in Preadolescent Children

OBJECTIVE: Our objective was to determine the interrater reliability of clinical history and physical examination findings in children undergoing evaluation for possible appendicitis in a large, multicenter cohort. METHODS: We conducted a prospective, multicenter, cross-sectional study of children aged 3–18 years with possible appendicitis. Two clinicians independently evaluated patients and completed structured case report forms within 60 minutes of each other and without knowing the results of diagnostic imaging. We calculated raw agreement and assessed reliability by using the unweighted Cohen κ statistic with 2-sided 95% confidence intervals. RESULTS: A total of 811 patients had 2 assessments completed, and 599 (74%) had 2 assessments completed within 60 minutes. Seventy-five percent of paired assessments were completed by pediatric emergency physicians. Raw agreement ranged from 64.9% to 92.3% for history variables and 4 of 6 variables had moderate interrater reliability (κ > .4). The highest κ values were noted for duration of pain (κ = .56 [95% confidence intervals .51–.61]) and history of emesis (.84 [.80–.89]). For physical examination variables, raw agreement ranged from 60.9% to 98.7%, with 4 of 8 variables exhibiting moderate reliability. Among physical examination variables, the highest κ values were noted for abdominal pain with walking, jumping, or coughing (.54 [.45–.63]) and presence of any abdominal tenderness on examination (.49 [.19–.80]). CONCLUSIONS: Interrater reliability of patient history and physical examination variables was generally fair to moderate. Those variables with higher interrater reliability are more appropriate for inclusion in clinical prediction rules in children with possible appendicitis.

Impact of Increasing Ondansetron Use on Clinical Outcomes in Children With Gastroenteritis

Purpose: We describe the clinical presentation of appendicitis in preadolescent children and differences in symptoms among age-stratified subgroups. Methods: This is a retrospective analysis of a prospectively collected de-identified data set of patients 3 years or older and patients younger than 12 years presenting to a pediatric emergency department during a 21-month period with symptoms suspicious for appendicitis. The rates of appendicitis, perforation, negative appendectomy, as well as sensitivities, specificities, and positive likelihood ratios for historical and clinical variables associated with appendicitis were calculated for the entire cohort and for 3 age-stratified subgroups. Results: Of 379 children, 121 (32%) had appendicitis, 75 (62%) were male, 24 (20%) had a perforated appendix, and 16 (12%) had a negative appendectomy. The perforation rate was highest (53%) in the youngest subset of patients (3-5.99 years). Patients with appendicitis presented with inability to walk (82%), maximal right lower quadrant tenderness (82%), nausea (79%), pain with percussion, hopping, coughing (79%), and anorexia (75%). Fewer patients with appendicitis presented with a history of vomiting (66%), fever (47%), or diarrhea (16%), and these findings were not associated with the diagnosis. The youngest subset of patients (3-5.99 years) presented to the emergency department with fever; however, within this age subset, there was no significant difference in temperatures between patients with and without appendicitis. Fever was an indicator for perforation. Psoas, Rovsing, and obturator signs were infrequent but very specific for appendicitis (0.86-0.98 depending on age). Conclusions: Nausea, right lower quadrant tenderness, inability to walk, and elevated white blood cell and neutrophil counts are sensitive indicators of appendicitis in preadolescent children. Although peritoneal signs are infrequently elicited, when present, they substantially increase the likelihood of appendicitis. Fever, vomiting, and diarrhea are not associated with appendicitis in preadolescent children.