March 2013 Ann Daunic, PhD University of Florida Gainesville, Florida

CURRENT BEST EVIDENCE

lected group of study children, exible bronchoscopy and bronchoalveolar lavage (BAL) were undertaken at baseline. Main Results Cough resolution rate (48%) was signicantly higher in children who received amoxicillin clavulanate compared with those who received placebo (16%; P = .016). The absolute risk reduction was 0.32 (95% CI 0.08 to 0.56), with a number needed to treat of 3 (95% CI, 2, 12). Posttreatment, median verbal category descriptive score in the amoxicillin clavulanate group of 0.5 (IQR 0.0-2.0) was signicantly lower than in the placebo group, 2.25 (IQR 1.15-2.9; P = .02). Pretreatment BAL data were consistent with protracted bacterial bronchitis in the majority of children, with no signicant difference between groups. Conclusions A 2-week course of amoxicillin clavulanate will achieve cough resolution in a statistically signicant number of children with chronic wet cough. Commentary Chronic cough in children is associated with a high burden of recurrent doctor visits, parental stress and worry, and is known to impact a childs sleep, school performance, and ability to play. Although the majority of chronic cough illnesses appear to be due to viral infections, a subset of patients with prolonged wet cough may have bacterial etiology known as protracted bacterial bronchitis. The current practice guidelines, based on observational studies,1,2 recommend that a prolonged course (4-6 weeks) of antibiotics may be given for protracted bacterial bronchitis. Marchant et al conducted a randomized controlled trial to determine the efcacy of a two-week course of amoxicillin clavulanate therapy in treating chronic wet cough/presumed protracted bacterial bronchitis. The use of randomization with placebo control is a major strength of this study. A limitation of the study is the inclusion of all patients with chronic cough >3 weeks, resulting in patients with prolonged cough (3-8 weeks) and chronic cough (>8 weeks). Although statistically not signicant, the placebo group included patients with a shorter duration of cough (4-28 weeks) compared with the treatment group (8.5 59 weeks). Patients with a longer duration of cough may include a higher percentage of patients with bacterial infection. Among a subset of patients who underwent BAL prior to randomization, there was no signicant difference between the two groups in total cell count, neutrophil percentage, and bacterial growth. However, this subset of patients was undened (especially with respect to duration of cough) and may not be representative of the patients in the antibiotic and placebo groups. This randomized controlled study of antibiotic treatment for chronic wet cough/ presumed protracted bacterial bronchitis in children is a welcome addition to the literature on this topic. However, it must be emphasized that more work is needed to properly dene the various clinical and microbiological parameters of protracted bacterial bronchitis. Also, clinicians should recognize that an appropriate diagnostic work-up is necessary to exclude serious conditions prior to
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References
1. Sugai G, Horner RH. Responsiveness-to-intervention and school-wide positive behavior supports: Integration of multi-tiered system approaches. Exceptionality 2009;17:223-37. 2. Greenberg MT, Kusch e CA, Riggs N. The PATHS Curriculum: Theory and research on neuro-cognitive development and school success. In: Zins J, Weissberg R, Walber H, eds. Building school success on social and emotional learning. New York: Teachers College Press; 2004. 3. Daunic AP, Smith SW, Garvan CW, Barber BR, Becker MK, Peters CD, et al. Reducing developmental risk for emotional/behavioral problems: A randomized controlled trial examining the Tools for Getting Along curriculum. Journal of School Psychology 2012;50:149-66.

Children with chronic wet cough (presumed protracted bacterial bronchitis) respond to 14 days of amoxicillin clavulanate
Marchant J, Masters IB, Champion A, Petsky H, Chang AB. Randomised controlled trial of amoxycillin clavulanate in children with chronic wet cough. Thorax 2012;67: 689-93. Question Among children with chronic wet cough, presumed to be protracted bacterial bronchitis, dened as the presence of isolated chronic wet cough, resolution of cough with appropriate antibiotics and absence of an alternative cause for specic cough, what is the efcacy of antibiotic treatment, compared with placebo, in achieving resolution? Design Randomized controlled trial. Setting Outpatient referral site: Respiratory practice at the Royal Childrens Hospital, Brisbane, Australia. Participants Children (6 months - <18 years) with chronic (>3 weeks) cough and with doctor-observed moist/wet cough. Intervention A 2-week course of amoxicillin clavulanate or placebo. Outcomes Primary outcome was cough resolution, dened as an improvement in baseline cough score (>75% reduction in a validated cough score) at end of trial or cessation of coughing for a minimum period of 3 days within the trial period. Baseline cough score (0=no cough; 1=cough for one or two short periods only; 2=cough for more than two short periods; 3=frequent coughing but does not interfere with school and other activities; 4=frequent coughing which interferes with school and other activities; and 5=cannot perform most activities due to severe coughing) was the average score in the 2 days immediately before trial medication commencement (days 2 and 1). End of trial score was the average score of the 2 days immediately following completion of 14 days of medication (days 15 and 16). Secondary outcome measures were absolute change in cough score and change in cough score over the study period. In an undened, se-

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Vol. 162, No. 3 coughing. This rened rule had a sensitivity of 98.1% (95% CI, 97.0%-98.9%), specicity of 23.7% (21.7%-25.9%), -LR of 0.08 (0.05, 0.13), and a post test probability for a negative test of 5% (3%, 8%). Conclusions A validated and rened a clinical prediction rule was developed for pediatric appendicitis, identifying a population of children with suspected appendicitis who are at low but not zero risk for appendicitis. If applied, clinicians will need to balance the risks of missing a case of appendicitis with the increased risk of negative appendectomies and the potential long-term risks associated with exposure to ionizing radiation. Commentary Appendicitis is challenging to accurately diagnose in children.1 Computed tomography (CT) and ultrasound improve diagnostic accuracy, but also are costly, associated with radiation exposure, and not universally available. In this context, accurate clinical prediction rules would be valuable. Kharbanda et al present a well-executed validation of such a prediction rule. Using a robust methodology across multiple centers, the authors found their prediction rule performed nearly as well as identifying a low-risk patient pool in the validation study as the derivation study.2 A subsequent revision to the rule, now itself requiring validation, further improved the test characteristics, which begs the question: When is a prediction rule good enough? In the study by Kharbanda et al, nearly 2 in 5 children in the validation cohort were ultimately diagnosed with appendicitis. At the same time, missed appendicitis is the second most common cause of pediatric malpractice lawsuits in US emergency departments.3 Given this high baseline appendicitis risk in emergency department populations and the consequences of missed diagnoses, physicians in emergency departments will likely continue to back up their clinical impressions with radiology studies. This may be particularly true given the only moderate degree of inter-rater reliability demonstrated for the factors included in the prediction rule.4 Nonetheless, this validated tool is a welcome addition to the diagnostic armamentarium for pediatric appendicitis and may be useful to identify a pool of lower risk children who could be offered serial examinations as an alternative to radiology studies. David G. Bundy, MD, MPH Medical University of South Carolina Charleston, South Carolina

diagnosing and prescribing antibiotics for chronic wet cough/presumed protracted bacterial bronchitis. C. Lucy Park, MD University of Illinois at Chicago Chicago, Illinois

References
1. Darelid J, Lofgren S, Malmvall BE. Erythromycin treatment is benecial for longstanding Moraxella catarrhalis associated cough in children. Scand J Infect Dis 1993;25:323-9. 2. Gottfarb P, Brauner A. Children with persistent cough: outcome with treatment and role of Moraxella catarrhalis? Scand J Infect Dis 1994;26: 545-51.

Clinical prediction rule identies children at low risk for appendicitis

Kharbanda AB, Dudley NC, Bajaj L, Stevenson MD, Macias CG, Mittal MK, et al. Validation and renement of a prediction rule to identify children at low risk for acute appendicitis. Arch Pediatr Adolesc Med 2012;166:738-44. Question Among children with suspected appendicitis, what is the diagnostic accuracy of the clinical exam and basic lab tests, compared with pathological report or long-term follow-up, in diagnosing acute appendicitis? Design Prospective, multicenter, cross-sectional, diagnostic study. Setting 10 pediatric emergency departments across the US. Participants Children and adolescents aged 3 to 18 years who presented with suspected appendicitis. Intervention Low-Risk Appendicitis Rule (absolute neutrophil count > 6750/uL, nausea, maximal tenderness in the right lower quadrant) and Low-Risk Appendicitis Rule with renement (absolute neutrophil count > 6750/uL, maximal tenderness in the right lower quadrant, abdominal pain with walking/jumping or coughing). Outcomes The test performance of the Low-Risk Appendicitis Rule with and without renement to identify low-risk patients. Main 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%), specicity of 36.3% (33.9%-38.9%), negative likelihood ratio (-LR) of 0.12 (0.09, 0.17) and posttest probability for a negative test of 7% (5%, 10%). Theoretical application would have identied 573 (24.0%) as being at low risk, misclassifying 42 patients with appendicitis. The rened prediction rule resulted in a model that identied patients at low risk with: (1) an absolute neutrophil count of 6.75 103/ mL or less and no maximal tenderness in the right lower quadrant; or (2) an absolute neutrophil count of 6.75 103/mL or less with maximal tenderness in the right lower quadrant but no abdominal pain with walking/jumping or
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References
1. Bundy DG, Byerley JS, Liles EA, Perrin EM, Katznelson J, Rice HE. Does this child have appendicitis? JAMA 2007;298:438-51. 2. Kharbanda AB, Taylor GA, Fishman SJ, Bachur RG. A clinical decision rule to identify children at low risk for appendicitis. Pediatrics 2005; 116:709-16. 3. Selbst SM, Friedman MJ, Singh SB. Epidemiology and etiology of malpractice lawsuits involving children in US emergency departments and urgent care centers. Pediatr Emerg Care 2005;21:165-9.