National patterns of aspirin use and Reye syndrome reporting, United States, 1980 to 1985

The number of cases of Reye syndrome reported annually to the Centers for Disease Control declined markedly between 1980 and 1985. In this article, we present pharmaceutical marketing research data that suggest sharp decreases in the use and purchase of children's aspirin between 1980 and 1985. These trends appear to correspond to the decrease in reporting of Reye syndrome cases. Additionally, analysis of physician mentions of aspiring and acetaminophen for treating flu and chickenpox showed statistically significant trends toward decreasing recommendations for the use of aspirin and significant trends toward increasing recommendations for use of acetaminophen. Trends in wholesale purchases of aspirin and acetaminophen by drug stores from 1979 through 1985 demonstrated a significant decline for the 81-mg children's aspirin tablet and an increase in purchases of children's acetaminophen products. Many factors may influence physician and parents' choice of analgesic/antipyretic medication, including information about Reye syndrome. Data suggest that a continuing decline in the use of aspirin for children may be accompanied by a continuing decline in the reported number of Reye syndrome cases.     

Severe Reye syndrome: report of 14 cases managed in a pediatric intensive care unit over 11 years]

Idiopathic Reye syndrome is a rare disease revealed by unexplained encephalopathy and microvesicular liver steatosis. Some clinical and epidemiological studies mainly performed in English speaking countries questioned the reality of Reye syndrome because numerous know inherited metabolic diseases, and some of them unrecognized, could mimick this disorder. We focused in our study on severe forms of Reye syndrome admitted to a pediatric intensive care unit. METHODS: Retrospective study over the last eleven years (1991-2001) included all the pediatric patients admitted to our tertiary referral center with the classical American Reye syndrome criteria (e.g. CDC). Extensive metabolic screening was performed in all cases, except for the ultimately dead patients. RESULT: Fourteen patients (mean age 52 months) were included. Fever always occurred before their admission and aspirin (n = 12) or acetaminophen (n = 7) was prescribed. Median Glasgow scale was 7 on admission. Mean amoniac plasma level was 320 mumol/L and alanine-aminotransferase peak plasma level 1475 +/- 1387 IU/L. Mechanical ventilation was started in ten children and six of them underwent continuous venovenous hemofiltration. Three patients ultimately died and 11 survived with a mean five years follow-up without relapses or neurological impairment. Any of them demonstrated inherited metabolic disease except for one infant with hereditary fructose intolerance. CONCLUSION: Unlike widespread opinion, severe Reye syndrome without identified metabolic disorders seems to not disappear in our country. Reye syndrome remains a potentially life threatening disease and raises for aggressive treatment of brain edema. If aspirin and Reye syndrome association are not formally documented in France, cautiousness must be kept in mind and all the aspirin adverse effects notifications should be addressed to the public drugs survey network.     

Reye syndrome associated with aspirin therapy for systemic lupus erythematosus

A 14-year-old girl in whom Reye syndrome developed during aspirin therapy for an inflammatory disorder proven to be systemic lupus erythematosus is reported. This case and similar cases of Reye syndrome in patients with juvenile rheumatoid arthritis suggest that an etiologic relationship exists between salicylate therapy and Reye syndrome in children with collagen vascular disorders.     

Tolmetin and salicylate therapy in acute rheumatic fever: Comparison of clinical efficacy and side-effects

BACKGROUND: The arthritis of rheumatic fever is very responsive to treatment with salicylates, but there are many adverse reactions, especially hepatotoxicity, due to aspirin (acetylsalicylic acid) therapy. These side-effects change the course and duration of rheumatic fever. Other non-steroidal anti-inflammatory drugs may be equally effective, although no reports are available. METHODS: We studied 72 patients with rheumatic fever who were admitted to Dr Sami Ulus Children's Hospital between 1995 and 1999. Twenty patients with arthritis were treated with tolmetin (25 mg/kg per day; group I) and 52 patients with arthritis and/or mild carditis were put on aspirin therapy (75-100 mg/kg per day) for 4-6 weeks (group II). Arthritis had disappeared at the same time in both the aspirin and tolmetin groups (P = 0.675). RESULTS: The erythrocyte sedimentation rates of patients upon admission, at the first week and at the end of therapy were not different in the two groups (P > 0.05). No adverse effect of tolmetin therapy was observed, whereas side-effects of salicylate were observed in 19 patients (36.5%) in the aspirin group. Hepatotoxicity, gastric irritation and salicylism were found in 16, four and three patients, respectively. Renal toxicity and Reye syndrome were not demonstrated. Because of these side-effects of aspirin, therapy had to be stopped for 10-20 days and the duration of hospitalization in this group was lengthened unnecessarily. CONCLUSION: Tolmetin was safe and effective treatment for arthritic rheumatic fever patients without carditis. Tolmetin can be used particularly in patients who cannot tolerate aspirin.     

Antipyretic use among children during the 1983 influenza season

We conducted a telephone survey in Houston in March 1983 to assess the level of aspirin use among children during the influenza season. We completed interviews of 200 households with 346 children aged 12 years or younger. Fifty-two percent of the 346 children experienced at least one acute illness in the preceding three months. Fever was measured with a thermometer in 114 ill children, 103 of whom had at least one measured temperature of 37.7 degrees C or greater. Fourteen percent of these 103 children received aspirin only, 61% received acetaminophen only, and 20% received both. Among a subgroup of 44 children with temperatures of at least 39.4 degrees C, 11% received aspirin only, 59% received acetaminophen only, and 27% received both. Only 60% of the 200 parents interviewed had heard of Reye's syndrome. Forty-two percent knew of the association between Reye's syndrome and aspirin use. The survey suggests that acetaminophen has replaced aspirin as the major antipyretic used by children in Houston. If the decline in aspirin use in Houston is representative of the population in the United States, and if aspirin is causally related to Reye's syndrome, the incidence of Reye's syndrome may decline.     

Association between antibiotic use and primary idiopathic intussusception

BACKGROUND: Intussusception is the leading cause of intestinal obstruction in young children. Antibiotics are the most frequently prescribed medication in the pediatric population and have common adverse effects on the gastrointestinal tract. OBJECTIVE: To determine whether a relationship exists between primary idiopathic intussusception and antibiotic drug use. DESIGN: Case-control study. PARTICIPANTS: Ninety-three case patients with intussusception and 353 injury controls younger than 4 years who were seen at the emergency department of the Children's Hospital of Alabama between January 1, 1996, and April 30, 2001, were included. Controls were matched to cases by quarter and year of time of diagnosis, age, and sex. MAIN OUTCOME MEASURES: Odds ratios and 2-sided 95% confidence intervals were estimated using conditional logistic regression. Prevalence of antibiotic use in an age-standardized, representative sample of US children from NHANES III (Third National Health and Nutrition Examination Survey) was used for external comparisons. RESULTS: Antibiotic use within 48 hours of diagnosis was found in 23 cases (25%) and 33 controls (9%) (odds ratio, 4.15; 95% confidence interval, 2.17-7.92; attributable risk, 18.7%). Antibiotic use among US children according to NHANES III was 10.7%. In cases, the beta-lactam class accounted for 78% of all medications used. Cephalosporin use was associated with more than a 20-fold increased risk of intussusception. CONCLUSION: An association between antibiotic drug use and intussusception was identified.     

Treatment of fever in childhood

Although the need for routine antipyretic therapy in children has often been questioned, there are no data to contra-indicate this. Not all fevers need to be treated but many physicians do so to relieve parental concern. The most commonly used antipyretic drugs are acetylsalicylic acid (ASA), paracetamol (acetaminophen) and dipyrone (metamizol). Paracetamol and ASA have been extensively evaluated but there are few clinical trials on dipyrone. In the last decade a strong statistical association has been observed between salicylates and Reye syndrome. Paracetamol is the most common cause of acute hepatic failure. Dipyrone has been associated with agranulocytosis. In the light of these findings the extensive use of antipyretics drugs has been seriously questioned.     

Preadmission antipyretics in Reye's syndrome.

The parents of 106 children who had had Reye''s syndrome and those of 185 comparison children who had febrile illnesses were interviewed in order to compare preadmission medication exposure rates in the two groups. Although comparable proportions of case and comparison patients had taken antipyretics in the three weeks before admission, a significant excess of cases (59% compared with 26% in the comparisons) had been given aspirin, whereas significantly more comparison children (49% compared with 25% in the cases) had taken paracetamol. There was an excess exposure to aspirin in children under 5 years of age; the excess observed in older patients just failed to reach significance. Separate analyses within Northern Ireland and England also showed a case-comparison difference. A significant correlation was shown between aspirin (but not paracetamol) exposure and the closeness with which cases conformed to the diagnostic criteria of Reye''s syndrome, measured by an artibrary score. The many difficulties of conducting and interpreting the findings of an epidemiological risk factor study of an association between aspirin and Reye''s syndrome are reviewed and emphasised. Inherent biases were present in this as in previous studies and it did not conform to the classical case-control design. Nevertheless the findings suggested that an association between Reye''s syndrome and preadmission aspirin may exist in some children.     

The changing clinical pattern of Reye's syndrome 1982-1990.

OBJECTIVE: To describe trends in the clinical pattern of Reye''s syndrome in the British Isles between 1982 and 1990; and to determine the relation between any changes and the June 1986 warnings against the use of aspirin in children. DESIGN: Development, and application to reported cases, of a scoring system designed such that patients showing the typical clinical and pathological features of ''classical'' Reye''s syndrome scored highly. The relations between ''Reye scores'' and a number of explanatory variables were explored using multivariable analysis. SETTING: British Isles. SUBJECTS: 445 cases fulfilling the Reye''s syndrome case definition reported to the surveillance scheme between January 1982 and December 1990. MAIN OUTCOME MEASURE: Individual ''Reye score''. RESULTS: Cases with high scores were more likely to have occurred in the 4 1/2 year period before June 1986 compared with the subsequent period (p < 0.006). Numbers of cases in the low and intermediate score categories declined by about 50% after June 1986, whereas those in the high category fell by 79%. High scorers were more likely to have received aspirin (p < 0.0001) and were older than intermediate and low scorers (p < 0.008). No relation was identified between score and season of onset. CONCLUSIONS: The decline in Reye''s syndrome after the aspirin warnings cannot be explained entirely, as has been proposed, by improved diagnosis of ''Reye-like'' inherited metabolic and other disorders: this would not account for the greater decline of the high scoring subgroup which also contained those cases most likely to resemble ''classical'' Reye''s syndrome and to have received aspirin. This study provides further evidence for the role of aspirin in a subset of cases meeting the standard diagnostic criteria for Reye''s syndrome and supports the need to consider this disorder as a heterogeneous group of conditions including Reye-like inherited metabolic disorders.     

Effectiveness of an Internet-based store-and-forward telemedicine system for pediatric subspecialty consultation

BACKGROUND: Pediatric subspecialists are often separated from the children who need them by distance, time, or socioeconomic factors. The Electronic Children's Hospital of the Pacific is an Internet-based store-and-forward pediatric consultation system established to overcome these barriers. OBJECTIVE: To characterize the use of the Electronic Children's Hospital of the Pacific and its impact on access to specialty care, the quality of the care provided, and cost savings. DESIGN: Prospective trial. SETTING: Twenty-two military treatment facilities in the Pacific. PARTICIPANTS: Primary care providers, pediatric consultants, and 5 reviewers. MAIN OUTCOME MEASURES: Consult response time, physician panel review, and evacuation cost avoidance. RESULTS: There were 267 cases from 16 sites. The mean +/- SD response time by a consultant was 32 +/- 8 hours. The panel review deemed that the initial diagnosis was changed or modified in 15% (39/267) of the cases, the diagnostic plan was changed or modified in 21% (57/267), and the treatment plan was changed or modified in 24% (64/267) (P < .01 for all). Routine air evacuations to a tertiary care medical center were avoided in 32 cases (12%), with an estimated cost savings of $185 408. CONCLUSIONS: The Electronic Children's Hospital of the Pacific improved the quality of patient care by providing expeditious specialty consultation. Significant cost avoidance in this military pediatric population was documented. Store-and-forward Internet-based teleconsultation is an effective means of providing pediatric subspecialty consultation to a population of underserved children.     

School-aged children with Kawasaki disease: high incidence of cervical lymphadenopathy and coronary artery involvement

OBJECTIVE: We describe 10 school-aged children with Kawasaki disease (KD) with a high incidence of cervical lymphadenopathy and coronary abnormality. METHODS: Based on a database of 1002 children with KD in Chang Gung Children's Hospital from January 1983 to March 2001, 10 (1%) school-aged patients (five boys, five girls) who met the diagnostic criteria of KD were included for analysis. RESULTS: Cervical lymphadenopathy was noted in all (100%) of these patients. Unilateral neck mass mimicking acute suppurative infections not responding to antibiotic therapy was the initial presentation in nine (90%) of the 10 patients. The mean interval between disease onset and diagnosis was 9.9 +/- 3.3 days (range, 6-15 days). Seven (70%) of these patients responded to one course of high-dose intravenous immunoglobulin (IVIG) therapy (2 g/kg) and oral aspirin (80-100 mg/kg per day), two (20%) required a second course of IVIG, and one (10%) responded to high-dose aspirin treatment only. Coronary artery abnormality (dilatation or aneurysm) was documented by echocardiography in seven (70%) patients (four boys, three girls). In six patients, the coronary artery abnormalities resolved in 1 year, while one patient had persistent right coronary artery aneurysm, which necessitated continued anticoagulant and low-dose aspirin therapy. CONCLUSION: The incidence of school-aged children among patients with KD is about 1% in our hospital. These patients are notable for the high incidence of initial manifestations of unilateral neck mass and coronary artery involvement. This disease should be listed as the differential diagnosis in school-aged children presenting with fever and neck mass that do not respond to antibiotic therapy.     

Reye syndrome: the Indian experience

All articles reporting cases of Reye syndrome in India were studied. The total number of reported cases is 71. Of these 54 are well-described and have been analysed with reference to their epidemiological, clinical and investigative features. The seasonal prevalence is early summer to the monsoon. Clinical and investigative features were similar to cases reported elsewhere. Mortality is high (87%). None of the patients had taken aspirin. The importance of Reye syndrome as a health problem and the need for wider surveillance of outbreaks of certain viral illnesses is dicussed.     

Reye syndrome and juvenile rheumatoid arthritis in Michigan

Reye syndrome (RS) is believed to occur infrequently among children receiving long-term aspirin therapy. We reviewed all cases of RS reported to the Michigan Department of Public Health during 1982 and 1983. Three of the 36 patients were receiving aspirin for the treatment of juvenile rheumatoid arthritis. All three patients had clinical courses characteristic of RS and two had supportive histologic findings on liver biopsy. The incidence of RS among children with juvenile rheumatoid arthritis is significantly greater than the incidence of RS among children who do not have juvenile rheumatoid arthritis. These findings support previous studies that showed that the use of aspirin during the antecedent illness may be a risk factor for the development of RS. Physicians should be aware of the potential for the development of RS among children who are receiving long-term aspirin therapy for the treatment of systemic inflammatory illnesses.     

Medium-chain acyl-CoA dehydrogenase deficiency in two siblings with a Reye-like syndrome

An increasing number of reports indicate that patients with some inherited metabolic diseases may have symptoms resembling those of Reye syndrome. We describe two siblings who developed a Reye-like syndrome at ages 16 and 18 months, respectively, after a viral illness and salicylate therapy. Both had fasting hypoglycemia and hypoketonemia. At the time of the acute episode and after ingestion of a medium-chain triglyceride load, one of them excreted large amounts of abnormal metabolites derived from the omega- and (omega-1)-oxidation of medium-chain fatty acids. Medium-chain acyl-CoA dehydrogenase activity was lower than 20% of control values in fibroblasts from both patients. This enzyme defect should be considered in children with a Reye-like syndrome with these distinctive manifestations.     

Diagnosis of urachal anomalies in infancy and childhood by contrast fistulography,ultrasound and CT

From 1981 to 1989 seventeen cases of pediatric patients with urachal remnants have been treated at the Fukuoka Municipal Children's Hospital (2 patent urachus, 5 urachal cyst, 9 urachal sinus, 1 urachal diverticulum). The cases of patent urachus were discovered in the neonates due to a urine discharge from the umbilicus; in the older children, cysts or sinuses accompanied by an infection led to the diagnosis of the urachal anomaly. In 8 of 11 cases, fistulography established the diagnosis. In 9 of 12 cases, ultrasound imaging was diagnostically successful, as was CT in all 3 cases that were given scans.     

宏基因组二代测序技术协助诊断3例无焦痂儿童恙虫病北大核心CSCD

目的对3例无焦痂恙虫病患儿的病原宏基因组二代测序技术(mNGS)检测结果进行分析,探讨其在临床的应用价值。方法回顾性分析。2018年6月至2019年10月温州医科大学附属第二医院、育英儿童医院收治的3例重症无焦痂儿童恙虫病的临床资料,2例为5岁男童,1例为6岁女童。3例患儿的外周血均进行mNGS检测。结果3例患儿经mNGS检测后均提示恙虫病东方体感染,且未并其他病原感染。例1死亡,例2和例3治愈出院。结论无焦痂恙虫病患儿早期诊断困难。对于临床感染性疾病,特别是早期无法确诊的疑难危重性感染性疾病,mNGS能够提供快速准确的病原学诊断支持,为精准治疗提供帮助。     

Primary cardiac arrhythmias in children

OBJECTIVES: Primary cardiac arrhythmias are much less common in children than adults. This study was performed to identify the characteristics of primary arrhythmias in pediatric patients in the Emergency Department (ED). METHODS: Retrospective review of ED visits of patients <18 years of age presenting between January 1991 and November 1996 with an Emergency Department diagnosis of primary cardiac arrhythmia. Secondary cardiac arrhythmias, ie, sinus tachycardia resulting from a fever, were excluded. Clinically significant arrhythmias were defined as those capable of altering cardiovascular stability. SITE: 26 Community Hospital EDs. RESULTS: A total of 2.3 million ED visits were reviewed and 320 arrhythmias in children were identified in 0.58 million patients under 18 years of age. The overall incidence of arrhythmias was 13.9 per 100,000 ED visits and 55.1 per 100,000 pediatric ED visits. The incidence of clinically significant arrhythmias was 5.7 per 100,000 ED visits and 22.5 per 100,000 patients <18 years of age. The mean patient age was 113 (+/-0.31) years with a peak in infancy and a second peak in late childhood and adolescence. The most common arrhythmias were: Sinus tachycardia: 160 (50%); Supraventricular tachycardia (SVT): 42 (13%); Nonspecific arrhythmia (NSA): 34 (10.6%); Bradycardia: 19 (6%); and Atrial fibrillation (a-fib): 15 (4.6%). The most common clinically significant arrhythmias by age group were: [table in text]. Nine patients had an additional diagnosis of Wolf-Parkinson-White syndrome, eight with Sinus tachycardia and one with SVT. There were four cardiac arrests noted all with ventricular fibrillation as the recorded arrhythmia. CONCLUSION: Primary arrhythmias are unusual ED presentations in children and atrial tachyarrhythmias are the most common rate and rhythm disturbance in this population.     

Neuroblastoma in adults: Incidence and survival analysis based on SEER data

PURPOSE: Clinical data on survival outcomes of adult patients (defined as 20 years of age and older) with neuroblastoma are scarce due to the rarity of the disease. Small single institution reports have described worse outcomes for adults than pediatric patients. MATERIALS/METHODS: Data from the public access Surveillance Epidemiology and End Results database were reviewed for a 30-year period between 1973 and 2002 for the diagnosis of neuroblastoma. Analyses compared frequency and survival rates of neuroblastoma among children and adults with particular focus on the incidence, case characteristics, and long-term survival of the adult patients. RESULTS: The observed 3- and 5-year survival rates were lowest among adult patients (45.9% and 36.3%, respectively), whereas infants fared best with 86.0% 3-year and 84.6% 5-year overall survival. There was a steady decline in the incidence of adult neuroblastoma from 0.47 cases per million per year in 1973-1977 to 0.12 cases per million per year in 1998-2002. When the long-term adult neuroblastoma survival was examined in detail for 1-, 3-, 5-, 7-, and 10-year follow-up periods, there was continuous decrease in survival during the first 7 years after the diagnosis with subsequent stabilization for both observed (OS) and relative survival (RS) rates. There was a notable trend towards improved outcome over the past three decades. CONCLUSIONS: Adults with neuroblastoma have significantly worse outcome than children. This may be due to tumor biology, more virulent clinical course, or possibly due to the fact that adults are less sensitive or have poor tolerance to pediatric chemotherapy regimens.     

Adverse pulmonary responses to aspirin and acetaminophen in chronic childhood asthma

Because aspirin (ASA) is often reported to have an adverse effect on pulmonary function in children with chronic asthma, acetaminophen is commonly used as an ASA substitute in these children. To study acetaminophen effects on pulmonary functions, double-blind, oral challenges of ASA (600 mg), acetaminophen (600 mg), or lactose were administered on separate days to 25 chronic asthmatics, ten boys and 15 girls, ranging in age from 8 to 18 years (mean age +/- 1 SD: 12.5 +/- 2.8 years). No patient had a past history of adverse reactions to either drug. Forced expiratory volume in 1 second (FEV1), peak expiratory flow rate (PEFR), maximal mid-expiratory flow rate (FEF25-75), forced vital capacity (FVC), maximal voluntary ventilation (MVV), and flow volume curves were measured at base line and 1/2, 1, 2, 3, and 4 hours after ingestion of drug or placebo. Persistent decreases from base line FEV1 (greater than 20%) or FEF25-75 (greater than 30%) occurred in four ASA- and two acetaminophen-challenged patients. One ASA-sensitive patient was placebo intolerant; another reacted to acetaminophen. The acetaminophen responses were of less intensity than the ASA responses. Analysis of group mean pulmonary function responses to ASA, acetaminophen, and lactose showed no significant difference among the three agents at any time. Aspirin should be used cautiously in asthmatic children. Acetaminophen appears to be an adequate, although not completely, innocuous ASA substitute.