21 research outputs found

    Infliximab versus second intravenous immunoglobulin for treatment of resistant Kawasaki disease in the USA (KIDCARE): a randomised, multicentre comparative effectiveness trial

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    Background Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease, 10–20% of patients have recrudescent fever as a sign of persistent inflammation and require additional treatment. We aimed to compare infliximab with a second infusion of IVIG for treatment of resistant Kawasaki disease. Methods In this multicentre comparative effectiveness trial, patients (aged 4 weeks to 17 years) with IVIG resistant Kawasaki disease and fever at least 36 h after completion of their first IVIG infusion were recruited from 30 hospitals across the USA. Patients were randomly assigned (1:1) to second IVIG (2 g/kg over 8–12 h) or intravenous infliximab (10 mg/kg over 2 h without premedication), by using a randomly permuted block randomisation design with block size of two or four. Patients with fever 24 h to 7 days following completion of first study treatment crossed over to receive the other study treatment. The primary outcome measure was resolution of fever at 24 h after initiation of study treatment with no recurrence of fever attributed to Kawasaki disease within 7 days post-discharge. Secondary outcome measures included duration of fever from enrolment, duration of hospitalisation after randomisation, and changes in markers of inflammation and coronary artery Z score. Efficacy was analysed in participants who received treatment and had available outcome values. Safety was analysed in all randomised patients who did not withdraw consent. This clinical trial is registered with ClinicalTrials.gov, NCT03065244. Findings Between March 1, 2017, and Aug 31, 2020, 105 patients were randomly assigned to treatment and 103 were included in the intention-to-treat population (54 in the infliximab group, 49 in the second IVIG group). Two patients randomised to infliximab did not receive allocated treatment. The primary outcome was met by 40 (77%) of 52 patients in the infliximab group and 25 (51%) of 49 patients in the second IVIG infusion group (odds ratio 0·31, 95% CI 0·13–0·73, p=0·0076). 31 patients with fever beyond 24 h received crossover treatment: nine (17%) in the infliximab group received second IVIG and 22 (45%) in second IVIG group received infliximab (p=0·0024). Three patients randomly assigned to infliximab and two to second IVIG with fever beyond 24h did not receive crossover treatment. Mean fever days from enrolment was 1·5 (SD 1·4) for the infliximab group and 2·5 (2·5) for the second IVIG group (p=0·014). Mean hospital stay was 3·2 days (2·1) for the infliximab group and 4·5 days (2·5) for the second IVIG group (p<0·001). There was no difference between treatment groups for markers of inflammation or coronary artery outcome. 24 (44%) of 54 patients in the infliximab group and 33 (67%) of 49 in the second IVIG group had at least one adverse event. A drop in haemoglobin concentration of at least 2g/dL was seen in 19 (33%) of 58 patients who received IVIG as either their first or second study treatment (three of whom required transfusion) and in three (7%) of 43 who received only infliximab (none required transfusion; p=0·0028). Haemolytic anaemia was the only serious adverse events deemed definitely or probably related to study treatment, and was reported in nine (15%) of 58 patients who received IVIG as either their first or second study treatment and none who received infliximab only. Interpretation Infliximab is a safe, well tolerated, and effective treatment for patients with IVIG resistant Kawasaki disease, and results in shorter duration of fever, reduced need for additional therapy, less severe anaemia, and shorter hospitalisation compared with second IVIG infusion

    Pediatric Perioperative Pulmonary Arterial Hypertension: A Case-Based Primer

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    The perioperative period is an extremely tenuous time for the pediatric patient with pulmonary arterial hypertension. This article will discuss a multidisciplinary approach to preoperative planning, the importance of early identification of pulmonary hypertensive crises, and practical strategies for postoperative management for this unique group of children

    Recurrent Kawasaki Disease: A Case Report of Three Separate Episodes at &gt;4-Year Intervals

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    Kawasaki disease (KD) is a self-limited systemic vasculitis, most often occurring in children 1&#8315;5 years old. It has a 2% recurrence rate and is associated with coronary aneurysms (CA), which can develop within two weeks of onset. A 25% increased risk is noted in patients who are recalcitrant to treatment. We describe a patient with recurrence of KD three times, approximately four years apart. A 10-year-old female with two previous episodes of KD, at 11 months and five years of age), in which she met five out of five criteria for KD and had no coronary involvement, presented with 15 days of fever, conjunctivitis and mucocutaneous changes. Infectious work-up was negative, and she was diagnosed with incomplete KD meeting three out of five criteria. An echocardiogram (ECHO) on day 12 revealed dilation of the right coronary artery (RCA) and left coronary artery (LCA). Treatment with intravenous immunoglobulin (IVIG) and high-dose aspirin was started at an outside hospital. After transfer, serial ECHOs showed evolving coronary aneurysms, left anterior descending (LAD) z-score + 8.2 and RCA z-score + 4.0. She received 10 mg/kg infliximab (day 18) and began clopidogrel. A cardiac MRI (day 20) demonstrated progression of the LAD aneurysm, with a z-score + 13, and warfarin was started. To our knowledge, this is the first report of recurrent KD occurring three times at ~5 year intervals

    Variation in Pharmacologic Management of Patients with Kawasaki Disease with Coronary Artery Aneurysms

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    OBJECTIVE: To evaluate practice variation in pharmacologic management in the International Kawasaki Disease Registry (IKDR). STUDY DESIGN: Practice variation in intravenous immunoglobulin (IVIG) therapy, anti-inflammatory agents, statins, beta-blockers, antiplatelet therapy, and anticoagulation was described. RESULTS: We included 1627 patients from 30 IKDR centers with maximum coronary artery aneurysm (CAA) z scores 2.5-4.99 in 848, 5.0-9.99 in 349, and ≥10.0 (large/giant) in 430 patients. All centers reported IVIG and acetylsalicylic acid (ASA) as primary therapy and use of additional IVIG or steroids as needed. In 23 out of 30 centers, (77%) infliximab was also used; 11 of these 23 centers reported using it in \u3c10% of their patients, and 3 centers used it in \u3e20% of patients. Nonsteroidal anti-inflammatory agents were used in \u3e10% of patients in only nine centers. Beta-blocker (8.8%, all patients) and abciximab (3.6%, all patients) were mainly prescribed in patients with large/giant CAAs. Statins (2.7%, all patients) were mostly used in one center and only in patients with large/giant CAAs. ASA was the primary antiplatelet modality for 99% of patients, used in all centers. Clopidogrel (18%, all patients) was used in 24 centers, 11 of which used it in \u3e50% of their patients with large/giant CAAs. CONCLUSIONS: In the IKDR, IVIG and ASA therapy as primary therapy is universal with common use of a second dose of IVIG for persistent fever. There is practice variation among centers for adjunctive therapies and anticoagulation strategies, likely reflecting ongoing knowledge gaps. Randomized controlled trials nested in a high-quality collaborative registry may be an efficient strategy to reduce practice variation
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