Nonsteroidal Anti-Inflammatory Drugs: A survey of practices and concerns of pediatric medical and surgical specialists and a summary of available safety data

<p>Abstract</p> <p>Objectives</p> <p>To examine the prescribing habits of NSAIDs among pediatric medical and surgical practitioners, and to examine concerns and barriers to their use.</p> <p>Methods</p> <p>A sample of 1289 pediatricians, pediatric rheumatologists, sports medicine physicians, pediatric surgeons and pediatric orthopedic surgeons in the United States and Canada were sent an email link to a 22-question web-based survey.</p> <p>Results</p> <p>338 surveys (28%) were completed, 84 were undeliverable. Of all respondents, 164 (50%) had never prescribed a selective cyclooxygenase-2 (COX-2) NSAID. The most common reasons for ever prescribing an NSAID were musculoskeletal pain, soft-tissue injury, fever, arthritis, fracture, and headache. Compared to traditional NSAIDs, selective COX-2 NSAIDs were believed to be as safe (42%) or safer (24%); have equal (52%) to greater efficacy (20%) for pain; have equal (59%) to greater efficacy (15%) for inflammation; and have equal (39%) to improved (44%) tolerability. Pediatric rheumatologists reported significantly more frequent abdominal pain (81% vs. 23%), epistaxis (13% vs. 2%), easy bruising (64% vs. 8%), headaches (21% vs. 1%) and fatigue (12% vs. 1%) for traditional NSAIDs than for selective COX-2 NSAIDs. Prescribing habits of NSAIDs have changed since the voluntary withdrawal of rofecoxib and valdecoxib; 3% of pediatric rheumatologists reported giving fewer traditional NSAID prescriptions, and while 57% reported giving fewer selective COX-2 NSAIDs, 26% reported that they no longer prescribed these medications.</p> <p>Conclusions</p> <p>Traditional and selective COX-2 NSAIDs were perceived as safe by pediatric specialists. The data were compared to the published pediatric safety literature.</p

Recurrent refractory Kawasaki disease

Background: Kawasaki disease is a common childhood vasculitis. Unrelenting fever after treatment with intravenous immunoglobulin (IVIG) occurs in 10-15% of patients and is associated with a greater risk of developing coronary aneurysms. Aim: Describe a very unique case of recurrent and refractory Kawasaki disease. Case report: A 3 year old boy presented with 3 days of fever, rash, pharyngeal and gingival erythema, and swollen extremities. Laboratory investigations revealed leukocytosis, C–reactive protein 25.8 mg/dl, and erythrocyte sedimentation rate 100 mm/hr. Echocardiography disclosed diffuse dilatation of all proximal coronary arteries. The child received IVIG (2g/kg) and aspirin (100 mg/kg/d) with no response. IVIG was repeated, followed by methylprednisolone 30 mg/kg for 3 days, but the child remained febrile. Infliximab (5 mg/kg) was thereupon employed with prompt defervescence. Low-dose aspirin was continued, as well as clopidogrel. Echocardiographic findings remained stable. Six months after the initial episode, the child again presented with fever, irritability, sore throat and nuchal rigidity. Physical examination revealed cracked, swollen lips, oropharyngeal erythema, posterior cervical lymphadenopathy, and rash. Desquamation of the distal extremities was observed some days later. Aneurysms were detected, involving the left and right main coronary arteries, as well as the left anterior descending coronary. Magnetic resonance angiography of the chest and abdomen revealed no other involved vessels. The child again received IVIG, pulse methylprednisolone, and infliximab, but remained febrile and developed significant arthritis, requiring daily prednisolone. He is now asymptomatic. Conclusions: Currently, recurrent and refractory Kawasaki disease still represents a therapeutic challenge

Evidence for Periciliary Liquid Layer Depletion, Not Abnormal Ion Composition, in the Pathogenesis of Cystic Fibrosis Airways Disease

The pathogenesis of cystic fibrosis (CF) airways infection is unknown. Two hypotheses, "hypotonic [low salt]/defensin" and "isotonic volume transport/mucus clearance," attempt to link defects in cystic fibrosis transmembrane conductance regulator–mediated ion transport to CF airways disease. We tested these hypotheses with planar and cylindrical culture models and found no evidence that the liquids lining airway surfaces were hypotonic or that salt concentrations differed between CF and normal cultures. In contrast, CF airway epithelia exhibited abnormally high rates of airway surface liquid absorption, which depleted the periciliary liquid layer and abolished mucus transport. The failure to clear thickened mucus from airway surfaces likely initiates CF airways infection. These data indicate that therapy for CF lung disease should not be directed at modulation of ionic composition, but rather at restoring volume (salt and water) on airway surfaces

Development of a Novel Renal Activity Index of Lupus Nephritis in Children and Young Adults

OBJECTIVE: Noninvasive estimation of the degree of inflammation seen on kidney biopsy with lupus nephritis (LN) remains difficult. The objective of this study was to develop a Renal Activity Index for Lupus (RAIL) that, based solely on laboratory measures, accurately reflects histologic LN activity. METHODS: We assayed traditional LN laboratory tests and 16 urine biomarkers (UBMs) in children (n = 47) at the time of kidney biopsy. Histologic LN activity was measured by the National Institutes of Health activity index (NIH-AI) and the tubulointerstitial activity index (TIAI). High LN-activity status (versus moderate/low) was defined as NIH-AI scores >10 (versus ≤10) or TIAI scores >5 (versus ≤5). RAIL algorithms that predicted LN-activity status for both NIH-AI and TIAI were derived by stepwise multivariate logistic regression, considering traditional biomarkers and UBMs as candidate components. The accuracy of the RAIL for discriminating by LN-activity status was determined. RESULTS: The differential excretion of 6 UBMs (neutrophil gelatinase-associated lipocalin, monocyte chemotactic protein 1, ceruloplasmin, adiponectin, hemopexin, and kidney injury molecule 1) standardized by urine creatinine was considered in the RAIL. These UBMs predicted LN-activity (NIH-AI) status with >92% accuracy and LN-activity (TIAI) status with >80% accuracy. RAIL accuracy was minimally influenced by concomitant LN damage. Accuracies between 71% and 85% were achieved without standardization of the UBMs. The strength of these UBMs to reflect LN-activity status was confirmed by principal component and linear discriminant analyses. CONCLUSION: The RAIL is a robust and highly accurate noninvasive measure of LN activity. The measurement properties of the RAIL, which reflect the degree of inflammatory changes as seen on kidney biopsy, will require independent validation

Histo-Blood Group Gene Polymorphisms as Potential Genetic Modifiers of Infection and Cystic Fibrosis Lung Disease Severity

The pulmonary phenotype in cystic fibrosis (CF) is variable; thus, environmental and genetic factors likely contribute to clinical heterogeneity. We hypothesized that genetically determined ABO histo-blood group antigen (ABH) differences in glycosylation may lead to differences in microbial binding by airway mucus, and thus predispose to early lung infection and more severe lung disease in a subset of patients with CF. infection in the severe or mild groups. Multivariate analyses of other clinical phenotypes, including gender, asthma, and meconium ileus demonstrated no differences between groups based on ABH type. infection, nor was there any association with other clinical phenotypes in a group of 808 patients homozygous for the ΔF508 mutation