12 research outputs found
Clinically Suspected Myocarditis Temporally Related to COVID-19 Vaccination in Adolescents and Young Adults: Suspected Myocarditis After COVID-19 Vaccination
Background:
Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth.
Methods:
We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings. Myocarditis cases were classified as confirmed or probable on the basis of the Centers for Disease Control and Prevention definitions.
Results:
We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1–20.3; interquartile range [IQR], 14.5–17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0–22; IQR, 1–3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0–10; IQR, 2–3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50–15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25–1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction <55% on echocardiogram. Of 97 patients who underwent cardiac MRI at a median 5 days (range, 0–88; IQR, 3–17) from symptom onset, 75 (77.3%) had abnormal findings: 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria. Among 26 patients with left ventricular ejection fraction <55% on echocardiogram, all with follow-up had normalized function (n=25).
Conclusions:
Most cases of suspected COVID-19 vaccine myocarditis occurring in persons <21 years have a mild clinical course with rapid resolution of symptoms. Abnormal findings on cardiac MRI were frequent. Future studies should evaluate risk factors, mechanisms, and long-term outcomes
Infliximab versus second intravenous immunoglobulin for treatment of resistant Kawasaki disease in the USA (KIDCARE): a randomised, multicentre comparative effectiveness trial
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
US Mortality Attributable to Congenital Heart Disease Across the Lifespan From 1999 Through 2017 Exposes Persistent Racial/Ethnic Disparities
Background: Congenital heart disease (CHD) accounts for ≈40% of deaths in US children with birth defects. Previous US data from 1999 to 2006 demonstrated an overall decrease in CHD mortality. Our study aimed to assess current trends in US mortality related to CHD from infancy to adulthood over the past 19 years and determine differences by sex and race/ethnicity.
Methods: We conducted an analysis of death certificates from 1999 to 2017 to calculate annual CHD mortality by age at death, race/ethnicity, and sex. Population estimates used as denominators in mortality rate calculations for infants were based on National Center for Health Statistics live birth data. Mortality rates in individuals ≥1 year of age used US Census Bureau bridged-race population estimates as denominators. We used joinpoint regression to characterize temporal trends in all-cause mortality, mortality resulting directly attributable to and related to CHD by age, race/ethnicity, and sex.
Results: There were 47.7 million deaths with 1 in 814 deaths attributable to CHD (n=58 599). Although all-cause mortality decreased 16.4% across all ages, mortality resulting from CHD declined 39.4% overall. The mean annual decrease in CHD mortality was 2.6%, with the largest decrease for those \u3e65 years of age. The age-adjusted mortality rate decreased from 1.37 to 0.83 per 100 000. Males had higher mortality attributable to CHD than females throughout the study, although both sexes declined at a similar rate (≈40% overall), with a 3% to 4% annual decrease between 1999 and 2009, followed by a slower annual decrease of 1.4% through 2017. Mortality resulting from CHD significantly declined among all races/ethnicities studied, although disparities in mortality persisted for non-Hispanic Blacks versus non-Hispanic Whites (mean annual decrease 2.3% versus 2.6%, respectively; age-adjusted mortality rate 1.67 to 1.05 versus 1.35 to 0.80 per 100 000, respectively).
Conclusions: Although overall US mortality attributable to CHD has decreased over the past 19 years, disparities in mortality persist for males in comparison with females and for non-Hispanic Blacks in comparison with non-Hispanic Whites. Determining factors that contribute to these disparities such as access to quality care, timely diagnosis, and maintenance of insurance will be important moving into the next decade
US Mortality Attributable to Congenital Heart Disease Across the Lifespan From 1999 Through 2017 Exposes Persistent Racial/Ethnic Disparities
Background: Congenital heart disease (CHD) accounts for ≈40% of deaths in US children with birth defects. Previous US data from 1999 to 2006 demonstrated an overall decrease in CHD mortality. Our study aimed to assess current trends in US mortality related to CHD from infancy to adulthood over the past 19 years and determine differences by sex and race/ethnicity.
Methods: We conducted an analysis of death certificates from 1999 to 2017 to calculate annual CHD mortality by age at death, race/ethnicity, and sex. Population estimates used as denominators in mortality rate calculations for infants were based on National Center for Health Statistics live birth data. Mortality rates in individuals ≥1 year of age used US Census Bureau bridged-race population estimates as denominators. We used joinpoint regression to characterize temporal trends in all-cause mortality, mortality resulting directly attributable to and related to CHD by age, race/ethnicity, and sex.
Results: There were 47.7 million deaths with 1 in 814 deaths attributable to CHD (n=58 599). Although all-cause mortality decreased 16.4% across all ages, mortality resulting from CHD declined 39.4% overall. The mean annual decrease in CHD mortality was 2.6%, with the largest decrease for those \u3e65 years of age. The age-adjusted mortality rate decreased from 1.37 to 0.83 per 100 000. Males had higher mortality attributable to CHD than females throughout the study, although both sexes declined at a similar rate (≈40% overall), with a 3% to 4% annual decrease between 1999 and 2009, followed by a slower annual decrease of 1.4% through 2017. Mortality resulting from CHD significantly declined among all races/ethnicities studied, although disparities in mortality persisted for non-Hispanic Blacks versus non-Hispanic Whites (mean annual decrease 2.3% versus 2.6%, respectively; age-adjusted mortality rate 1.67 to 1.05 versus 1.35 to 0.80 per 100 000, respectively).
Conclusions: Although overall US mortality attributable to CHD has decreased over the past 19 years, disparities in mortality persist for males in comparison with females and for non-Hispanic Blacks in comparison with non-Hispanic Whites. Determining factors that contribute to these disparities such as access to quality care, timely diagnosis, and maintenance of insurance will be important moving into the next decade
Outcomes After SARS-CoV-2 Vaccination Among Children With a History of Multisystem Inflammatory Syndrome
This case series evaluates the outcomes following COVID-19 vaccination in patients previously diagnosed with multisystem inflammatory syndrome in children at children’s hospitals in Texas and Italy
Atrial septal defect closure is associated with improved clinical status in patients ≤ 10 kg with bronchopulmonary dysplasia
Abstract Patients with bronchopulmonary dysplasia (BPD) have shown clinical improvement after secundum atrial septal defect (ASD) closure. We sought to determine if this post‐ASD closure improvement is secondary to the expected course in BPD patients or related to the closure itself. A novel BPD‐ASD score was created to assess patients' clinical status (higher score = worse disease) and applied to 10 BPD‐ASD inpatients weighing ≤ 10 kg who underwent ASD closure. The score and its subcomponents were retrospectively calculated serially ranging from 8 weeks pre‐ to 8 weeks post‐intervention, and pre‐ and post‐intervention score slopes were created. These slopes were compared using mixed regression modeling with an interaction term. There was a significant difference in pre‐ versus post‐intervention slope with the most score drop the first week post‐intervention (−2.1 + /− 0.8, p = 0.014). The mean score also dropped through weeks 2 (slope −0.8 + /− 0.8, p = 0.013) and 4 (slope −1.0 + /− 0.5, p = 0.001) post‐intervention. There was a significant difference in pre‐ and post‐intervention slopes for diuretics (p = 0.018) and the combined score of respiratory support, FiO2 need, and respiratory symptoms (p = 0.018). This study demonstrated significant improvement in BPD‐ASD score, diuretic need, and respiratory status after ASD closure in BPD‐ASD patients ≤ 10 kg that was outside of the natural course of BPD. Our study was limited by its small, single‐center, retrospective nature. Future studies should be performed in a larger multicenter population to both validate the scoring system and compare to non‐intervention infants
Examination of Adverse Reactions After COVID-19 Vaccination Among Patients With a History of Multisystem Inflammatory Syndrome in Children
Importance: Data are limited regarding adverse reactions after COVID-19 vaccination in patients with a history of multisystem inflammatory syndrome in children (MIS-C). The lack of vaccine safety data in this unique population may cause hesitancy and concern for many families and health care professionals.
Objective: To describe adverse reactions following COVID-19 vaccination in patients with a history of MIS-C.
Design, setting, and participants: In this multicenter cross-sectional study including 22 North American centers participating in a National Heart, Lung, and Blood Institute, National Institutes of Health-sponsored study, Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children (MUSIC), patients with a prior diagnosis of MIS-C who were eligible for COVID-19 vaccination (age ≥5 years; ≥90 days after MIS-C diagnosis) were surveyed between December 13, 2021, and February 18, 2022, regarding COVID-19 vaccination status and adverse reactions.
Exposures: COVID-19 vaccination after MIS-C diagnosis.
Main outcomes and measures: The main outcome was adverse reactions following COVID-19 vaccination. Comparisons were made using the Wilcoxon rank sum test for continuous variables and the χ2 or Fisher exact test for categorical variables.
Results: Of 385 vaccine-eligible patients who were surveyed, 185 (48.1%) received at least 1 vaccine dose; 136 of the vaccinated patients (73.5%) were male, and the median age was 12.2 years (IQR, 9.5-14.7 years). Among vaccinated patients, 1 (0.5%) identified as American Indian/Alaska Native, non-Hispanic; 9 (4.9%) as Asian, non-Hispanic; 45 (24.3%) as Black, non-Hispanic; 59 (31.9%) as Hispanic or Latino; 53 (28.6%) as White, non-Hispanic; 2 (1.1%) as multiracial, non-Hispanic; and 2 (1.1%) as other, non-Hispanic; 14 (7.6%) had unknown or undeclared race and ethnicity. The median time from MIS-C diagnosis to first vaccine dose was 9.0 months (IQR, 5.1-11.9 months); 31 patients (16.8%) received 1 dose, 142 (76.8%) received 2 doses, and 12 (6.5%) received 3 doses. Almost all patients received the BNT162b2 vaccine (347 of 351 vaccine doses [98.9%]). Minor adverse reactions were observed in 90 patients (48.6%) and were most often arm soreness (62 patients [33.5%]) and/or fatigue (32 [17.3%]). In 32 patients (17.3%), adverse reactions were treated with medications, most commonly acetaminophen (21 patients [11.4%]) or ibuprofen (11 [5.9%]). Four patients (2.2%) sought medical evaluation, but none required testing or hospitalization. There were no patients with any serious adverse events, including myocarditis or recurrence of MIS-C.
Conclusions and relevance: In this cross-sectional study of patients with a history of MIS-C, no serious adverse events were reported after COVID-19 vaccination. These findings suggest that the safety profile of COVID-19 vaccination administered at least 90 days following MIS-C diagnosis appears to be similar to that in the general population
The Kawasaki Disease Comparative Effectiveness (KIDCARE) trial: A phase III, randomized trial of second intravenous immunoglobulin versus infliximab for resistant Kawasaki disease.
Background
Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease (KD), the most common cause of acquired heart disease in children, 10–20% of patients are IVIG-resistant and require additional therapy. This group has an increased risk of coronary artery aneurysms (CAA) and there has been no adequately powered, randomized clinical trial in a multi-ethnic population to determine the optimal therapy for IVIG-resistant patients.
Objectives
The primary outcome is duration of fever in IVIG-resistant patients randomized to treatment with either infliximab or a second IVIG infusion. Secondary outcomes include comparison of inflammatory markers, duration of hospitalization, and coronary artery outcome. An exploratory aim records parent-reported outcomes including signs, symptoms and treatment experience.
Methods
The KIDCARE trial is a 30-site randomized Phase III comparative effectiveness trial in KD patients with fever ≥36 h after the completion of their first IVIG treatment. Eligible patients will be randomized to receive either a second dose of IVIG (2 g/kg) or infliximab (10 mg/kg). Subjects with persistent or recrudescent fever at 24 h following completion of the first study treatment will cross-over to the other treatment arm. Subjects will exit the study after their first outpatient visit (5–18 days following last study treatment). The parent-reported outcomes, collected daily during hospitalization and at home, will be compared by study arm.
Conclusion
This trial will contribute to the management of IVIG-resistant patients by establishing the relative efficacy of a second dose of IVIG compared to infliximab and will provide data regarding the patient/parent experience of these treatments