Predictors of severe illness in children with multisystem inflammatory syndrome after SARS-CoV-2 infection: a multicentre cohort study

Background:SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in disease severity over time.Methods:We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar. 1, 2020, and Mar. 7, 2021. Using multivariable analyses, we evaluated whether admission date and other characteristics were associated with ICU admission or cardiac involvement.Results:Of 232 children with MIS-C (median age 5.8 yr), 130 (56.0%) were male and 50 (21.6%) had comorbidities. Seventy-three (31.5%) patients were admitted to the ICU but none died. We observed an increased risk of ICU admission among children aged 13–17 years (adjusted risk difference 27.7%, 95% confidence interval [CI] 8.3% to 47.2%), those aged 6–12 years (adjusted risk difference 25.2%, 95% CI 13.6% to 36.9%) or those with initial ferritin levels greater than 500 μg/L (adjusted risk difference 18.4%, 95% CI 5.6% to 31.3%). Children admitted to hospital after Oct. 31, 2020, had numerically higher rates of ICU admission (adjusted risk difference 12.3%, 95% CI −0.3% to 25.0%) and significantly higher rates of cardiac involvement (adjusted risk difference 30.9%, 95% CI 17.3% to 44.4%). At Canadian sites, the risk of ICU admission was significantly higher for children admitted to hospital between December 2020 and March 2021 than those admitted between March and May 2020 (adjusted risk difference 25.3%, 95% CI 6.5% to 44.0%).Interpretation:We observed that age and higher ferritin levels were associated with more severe MIS-C. We observed greater severity of MIS-C later in the study period. Whether emerging SARS-CoV-2 variants pose different risks of severe MIS-C needs to be determined.

Multisystem inflammatory syndrome in children (MIS-C)¹ manifests as immune dysregulation after SARS-CoV-2 infection.² The syndrome has no pathognomonic features. Thus, the diagnostic criteria of the Royal College of Paediatrics and Child Health (RCPCH), the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) differ, but they all include fever, evidence of systemic inflammation and involvement of at least 1 organ or system.³Our primary objective was to assess initial clinical or laboratory features that predict severe illness in MIS-C. We also sought to explore changes in overall disease severity and cardiac involvement over time as it was the impression of many investigators that severity of MIS-C increased through pandemic waves.     

Five hundred patients with myocardial infarction monitored within one hour of symptoms.

Of 2886 patients monitored during acute myocardial infarction, 500 were observed within one hour of the onset of symptoms. Half of the early admission group were admitted in response to emergency 999 calls and 435 of them travelled in resuscitation ambulances, where surveillance for arrhythmias was instituted. Pulmonary oedema occurred in 130 patients (26%), cardiogenic shock supervened in 60 (12%), and 115 (23%) died in hospital. Ventricular fibrillation was observed in 98 patients (20%). Forty two of them survived to be discharged, including 20 of the 24 with primary fibrillation which had occurred first in hospital. In only one case did primary ventricular fibrillation occur after the first 10 hours of onset of illness. Sinus bradycardia, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation were all observed more frequently in patients admitted within one hour after the onset of symptoms than in those admitted later. An element of selection is inevitable when early admission is encouraged by the existence of a resuscitation ambulance system; this will depend in part on the early recognition of risk and the geographical location of the attack. These factors may bias the group towards relatively high risk. Nevertheless, prompt admission after myocardial infarction should improve survival by permitting successful management both of ventricular fibrillation and of other arrhythmias which may influence short term and long term prognosis.     

Amitriptyline and Imipramine Poisoning in Children

The increasing number of children admitted to this hospital with poisoning by tricyclic antidepressants is causing concern. Of 60 children admitted between January 1966 and July 1973, half were admitted in the last 18 months. In 60% of these patients the tricyclic compounds had been prescribed for nocturnal enuresis. One child aged 2 years and 4 months died of imipramine poisoning. It is imperative that all children with poisoning by tricyclic compounds, irrespective of the dosage, are admitted to hospital for continuous cardiac monitoring. Cardiac arrhythmias induced in children by amitriptyline and imipramine are prominent and dangerous.In the earlier years of this survey the antidepressants taken by children had usually been prescribed for adults, but recently they have been increasingly prescribed as a treatment for enuresis in children themselves. Medicine for a trivial complaint is unlikely to be regarded by parents as potentially dangerous and practitioners should therefore warn them accordingly; if, indeed, the transient effect of these potentially dangerous drugs upon the average case of bed-wetting in childhood can be justified.     

Canadian Thalidomide Experience

Data are presented on 115 children, including three sets of twins, born in Canada in 1961 and 1962 with congenital malformations associated with the use of thalidomide by their mothers in early pregnancy. The epidemiological method is described. Of the 115 children, 74 were alive at the time of reporting, 41 of these being severely handicapped; 8 had been stillborn; 33 had died. Limb involvement was usually bilateral, affecting the upper limbs alone in 42 cases, and the upper and lower limbs in 41. Of 112 mothers, only 60 had had the drug prescribed by the physician providing maternity care; 87 were estimated to have first taken the drug before their last menstrual period or within 56 days thereafter. A plea is made for the development of better methods of collecting information on the occurrence of congenital malformations, with the aid of practising physicians.     

Incidences of fatal postoperative pulmonary embolism after prophylaxis with dextran 70 and low-dose heparin: an international multicentre study.

A total of 4352 patients were admitted to a prospective'' randomised multicentre trial comparing the prophylactic efficacy of dextran 70 and low-dose heparin against fatal pulmonary embolism after elective operations for general, orthopaedic, urological, and gynaecological conditions. Out of 3984 patients correctly admitted, 1993 were allocated to receive dextran 70 and 1991 to receive low-dose heparin. Withdrawal of prophylaxis because of bleeding or technical difficulties occurred more often in the heparin group, but allergic reactions were more common in the dextran group. Of the 75 patients who died within 30 days after operation, 38 had been given dextran and 37 low-dose heparin. Necropsy was performed in 33 and 32 of these cases respectively. In six patients in each group pulmonary embolism was the sole or a contributory cause of death. Of these, five patients in the dextran group and two in the heparin group had received a full course of prophylaxis. There was no statistically significant difference between the two treatment groups in the incidence of fatal pulmonary embolism after a full course of prophylaxis.     

Inoperable aortic stenosis in the elderly: benefit from percutaneous transluminal valvuloplasty.

Eight patients with severe symptomatic calcific aortic stenosis were considered to be unsuitable for valve replacement. Four were admitted with pulmonary oedema and three in cardiogenic shock and one had angina at rest. With the use of echocardiographic and radiographic guidance percutaneous transluminal aortic valvuloplasty was carried out. Aortic gradients were reduced by an average of 40%. All four patients who presented with cardiac failure improved immediately and remained well six months later. The patient with angina was symptom free at nine months. Two of the three patients who presented in cardiogenic shock improved immediately and were well nine and three months later. The other patient died four hours after the procedure. Doppler echocardiographic studies showed a slight initial increase in aortic incompetence, but this did not worsen and valvar gradients remained improved three and six months later. Percutaneous valvuloplasty of the aortic valve is an effective therapeutic option in patients with severe calcific aortic stenosis who are unfit for surgery. Its role as an alternative to surgery has not been considered and should be investigated in a controlled clinical trial.     

Duration of Last Attack in 998 Fatal Cases of Coronary Artery Disease and its Relation to Possible Cardiac Resuscitation

All the deaths attributed to coronary artery disease and occurring in Belfast during one year were studied.The frequency distributions of the cases by interval of time between onset of the last attack and death are given for those not admitted to hospital, for those admitted to hospital, and for those already in hospital for some other cause of illness.Sixty per cent. of all the deaths occurred outside hospital. This indicates that the problem of cardiac resuscitation in coronary artery disease is to a considerable extent an extra-hospital one.Twenty-seven per cent. of the men and 22% of the women died within 15 minutes, but the median period of survival was 3 hours 30 minutes for men and 6 hours 18 minutes for women.The median time interval from the onset of the attack to sending for medical aid was 1 hour 17 minutes for men and 1 hour 6 minutes for women, and from summoning medical aid to sending for the ambulance 59 minutes for men and 1 hour 26 minutes for women. Ninety-six per cent. of the ambulance journeys to the patient were accomplished in less than 20 minutes.It was found among men, but not among women, that the duration of survival tended to be longer in older patients and in second or subsequent attacks.Of the 596 who did not gain admission to hospital 229 (23% of all the 998 patients) were known to have survived for more than half an hour after the onset of the fatal attack; 182 (18%) survived for more than one hour; and 143 (14%) survived for more than two hours. It is among these that there would appear to be special scope for the cardiac ambulance, providing that medical aid is sought and the ambulance is summoned without delay.     

Incidence of congenital hypothyroidism: retrospective study of neonatal laboratory screening versus clinical symptoms as indicators leading to diagnosis.

Filter paper blood samples taken routinely from 100 239 newborn infants were radioimmunoassayed five years later for plasma thyrotrophin concentrations. In 32 cases (0.03%) these were found to be raised. Thirty one of these children were traced and subjected to follow up examination by a paediatrician and a psychologist. Of the 31 children, 15 were found to have been receiving treatment for congenital hypothyroidism since a median of 5 months of age (diagnosed group). Of the 16 others, seven children were found to have raised serum thyrotrophin concentrations and were classified as hypothyroid (undiagnosed group). The remaining nine children were euthyroid. Children in the diagnosed group had a mean Griffiths developmental quotient of 87 (control value 103; p less than 0.01), and five out of 13 showed impaired neurological development. Of the remainder, those in the undiagnosed group had a mean developmental quotient of 100 and those in the euthyroid group a mean developmental quotient of 107. In this study achieving a detection rate of congenital hypothyroidism of one in 3000 in a neonatal screening programme resulted in overdiagnosis of about a quarter of patients considered to have true positive findings. This was outweighed, however, by the early identification of all infants with the disease.     

儿童哮喘与肺炎支原体感染关系的探讨

目的:探讨儿童哮喘发作与肺炎支原体(MP)感染之间的关系,并分析合并MP感染的患儿的临床表现。方法:将79例2-14岁急性哮喘发作的患儿依据病史分做两组:第一次哮喘发作的35人(始发哮喘组),已经有哮喘病史的44人(复发哮喘组)。采用被动冷凝集法检测两组患儿肺炎支原体抗体(MP-IgM)。结果:始发哮喘组和复发哮喘组分别有16例(45.7%)和10例(22.7%)患儿MP-IgM阳性(P0.05)。始发哮喘组与复发哮喘组MP-IgM阳性的患儿发热和肺部啰音发生率明显高于MP-IgM阴性的患儿(P0.05),血清IgE水平也明显高于MP-IgM阴性的患儿(P0.05)。结论:MP感染与儿童哮喘发作关系密切,合并MP感染的哮喘患儿发热或肺部啰音发生率明显高于未合并MP感染的哮喘患儿。     

Vomiting as a diagnostic aid in acute ischaemic cardiac pain.

The incidence of vomiting before the administration of analgesics was studied in 109 patients admitted to hospital as emergencies with prolonged ischaemic cardiac pain. In transmural myocardial infarction (58 patients) the incidence was 43% (anterior infarction 58%, inferior infarction 41%). Of the 23 patients with myocardial necrosis but without transmural infarction (that is, those with diffuse or subendocardial necrosis) and the 28 with coronary insufficiency but no necrosis, only one patient in each group experienced vomiting. When vomiting occurs early in association with cardiac pain transmural infarction may be expected in 90% of patients.     

The Role of Surgery in the Treatment of Transposition of the Great Vessels

In 28 infants and children with complete transposition of the great vessels, atrial septal defects were created utilizing an open technique with inflow caval occlusion and moderate hypothermia. Of the 12 infants for whom operation was necessary during the first two weeks of life only two survived, suggesting that this technique is not adequate for infants at this age. Only four of the 16 children operated on between the ages of two weeks and three years failed to survive. Two of these died because of pre-existing non-cardiac conditions. Seven children with associated systemic-to-pulmonary shunts survived; the open technique may be preferable in this particular group. Despite the initial improvement afforded by this procedure, three sudden late deaths occurred. For this reason, and because of the danger of early development of pulmonary vascular disease, total operative correction of the malformation should be performed early.     

City-wide screening for urinary abnormalities in schoolgirls

Screening for urinary tract infection was carried out in 23,427 schoolgirls, aged 5 to 14 years, using Uricult and, for hematuria, glycosuria and proteinuria using Hema-combistix. Cultures of 10⁵ colonies per ml. or more on two occasions were obtained in 2.3% and a positive culture was confirmed by the family physician using standard culture techniques in 82.7% of cases, giving an overall incidence of infection of 1.9%. Fifty-eight percent of these children had no previous history of any urinary tract symptoms. Of the infected group 9.5% had pyelonephritic scarring, 58.7% chronic cystitis and 58.7% urethral stenosis. Two additional cases had unilateral ureteropelvic junction obstruction with hydronephrosis. Reflux occurred in 26.6% of those investigated by voiding cystogram. In 58% of cases the urinary tract infection was not accompanied by significant proteinuria, hematuria or pyuria.Proteinuria was detected on two occasions in 1.6% of the children and confirmed by the family physician in 33% of cases, giving an overall incidence of 0.5%. In this group 9.2% had evidence of pyelonephritic scarring without a positive urine culture.Hematuria was detected on two occasions in 0.6% of the children and was confirmed by the family physician in 53%, giving an overall incidence of 0.3%. Only one case with pyelonephritic scarring was seen in this group.Of the 25 cases with pyelonephritic changes only six had been previously diagnosed radiologically.Four previously unrecognized diabetics were also detected.     

Malaria in Britain: 1977-86

The incidence of malaria in Britain as reported to the Malaria Reference Laboratory during the past decade has increased by 51%, from 1529 to 2309 cases, and infection with Plasmodium falciparum has increased from one fifth to one third of all cases. The case fatality rate for P falciparum infections declined from 2·7% to 0·5%. Of the 67 persons who died, 54 were of British origin, nine of Asian descent, and four African. Sixteen had taken chemoprophylaxis; of these, nine had taken pyrimethamine alone.The pattern of infection shows that resident ethnic minority groups, temporary residents from west Africa, and tourists who visit Kenya are particularly at high risk. The calculated attack rates suggest that men, children, and young adults are at greater risk of malaria than women and older people. Rates are highest in immigrants who have settled in Britain who visit relatives: 316 and 331 per 100 000 for Africa and Asia respectively, 120 and 39 in tourists to those same regions, and 228 and 38 in business travellers to those regions.     

Meta-analysis of trials of prophylactic antibiotics for children with measles: inadequate evidence.

OBJECTIVE: To assess whether antibiotics should be given to all children with measles in communities with a high case fatality rate. DESIGN: Meta-analysis of randomised controlled trials that compared routine antibiotic prophylaxis with no antibiotic treatment or selective treatment of pneumonia or sepsis. SUBJECTS: Six trials of children admitted to hospital with measles: five in Glasgow, London, or New York between 1939 and 1954; and one in India in 1967. MAIN OUTCOME MEASURES: Incidence of pneumonia or sepsis, and mortality. RESULTS: All but one of the trials were unblinded, and randomisation was either not described or was by alternate allocation. In four studies, the incidence of pneumonia or sepsis in the control group was similar to that in the antibiotic prophylaxis group; in the other two studies, the incidence of pneumonia or sepsis was unusually high in the control group so these children had a higher complication rate than the antibiotic group. Four of the 764 children given antibiotics died compared with one of the 637 controls (exact odds ratio 4.0, mid-P corrected 95% confidence interval 0.5 to 101.6). CONCLUSION: The quality of the trials reviewed was poor, and they provide weak evidence for giving antibiotics to all children with measles. Available evidence suggests that, when mortality from measles is high, all children with measles should be treated with vitamin A but antibiotics should be given only if a child has clinical signs of pneumonia or other evidence of sepsis.     

Assessment of cardiac risk 10 days after uncomplicated myocardial infarction.

A total of 188 patients with uncomplicated acute myocardial infarction (long-term Norris prognostic index 3.2) were rapidly mobilised, underwent a symptom-limited exercise test around the day of discharge from hospital (day 10), and returned to work at a median of six weeks after the acute event. The incidence of cardiac death six months, one year, and three years after infarction was 2.7%, 4.5%, and 7.3% respectively, and the corresponding figures for recurrent heart attacks were 3.4%, 8.2%, and 18.5% respectively. The risk of recurrence of heart attack was predicted by three variables assessed at discharge--namely, a history of classical effort angina (p less than 0.01), radiological heart failure (p less than 0.05), and angina induced by the exercise test (p less than 0.05). The presence of any of these risk factors defined a group of patients with a sevenfold risk of recurrent heart attacks within six months of the initial acute infarct. It is concluded that these risk factors identify a group of patients with a high risk of recurrence early after infarction, in whom vigorous secondary prophylaxis is desirable.     

Abnormalities of the Urinary Tract in Association with Congenital Cardiovascular Disease

The incidence of urinary tract abnormalities in a group of infants and children with congenital cardiovascular disease was determined by assessing roentgenograms of the abdomen taken following angiocardiographic studies. The urinary tracts of 400 of these patients were so outlined, but in 50 others the tracts could not be outlined. In 21 of the latter the urinary tracts were assessed at autopsy.Of these 421 children, nine (approximately 2%) had serious urinary tract disease, and 15 (approximately 3.5%) had anomalies which were of no clinical significance.The incidence of four renal anomalies—bifid collecting system, rotated kidney, horsehoe kidney and ectopic kidney—was compared with that in another group of patients without cardiovascular disease. No significant difference was found in the incidence of these four anomalies in the two groups.     

Pertussis immunisation and serious acute neurological illness in children.

The first 1000 cases notified to the National Childhood Encephalopathy Study were analysed. The diagnoses included encephalitis/encephalopathy, prolonged convulsions, infantile spasms, and Reye''s syndrome. Eighty-eight of the children had had a recent infectious disease, including 19 with pertussis. Only 35 of the notified children (3.5%) had received pertussis antigen within seven days before becoming ill. Of 1955 control children matched for age, sex, and area of residence, 34 (1.7%) had been immunised with pertussis vaccine within the seven days before the date on which they became of the same age as the corresponding notified child. The relative risk of a notified child having had pertussis immunisation within that time interval was 2.4 (p less than 0.001). Of the 35 notified children, 32 had no previous neurological abnormality. A year later two had died, nine had developmental retardation, and 21 were normal. A significance association was shown between serious neurological illness and pertussis vaccine, though cases were few and most children recovered completely.     

Penoscrotal extramammary Paget's disease: a review of 33 cases in a 20-year experience

Extramammary Paget's disease in men most frequently involves the penoscrotal area. The uncertainty of the outcome and of the relationship to the underlying adnexal carcinoma and associated internal malignancy still exists. From 1982 to 2001, 33 patients with penoscrotal extramammary Paget's disease were treated and followed up. Therapeutic modalities included carbon dioxide laser ablation (two patients) and local wide excision (31 patients). Split-thickness skin graft (22 patients), local scrotal flap (six patients), and primary closure (three patients) were utilized to reconstruct the penoscrotal defects after local wide excision. An underlying adnexal carcinoma occurred in seven of 33 patients (21.2 percent). The incidence of associated internal malignancy was 9.1 percent (three of 33 patients), including one concurrently and two nonconcurrently associated malignancies. Eight of 33 patients had local recurrence, representing an incidence of 24.2 percent. Three patients (9.1 percent) had distant metastasis and ultimately died of metastatic carcinoma. Of these patients, 31 were grouped according to the degrees of involvement: limited to the epidermis (group 1, n = 14), involvement of the adnexal gland and/or hair follicle (group 2, n = 10), and the presence of an underlying adnexal carcinoma (group 3, n = 7). Local wide excision with subsequent reconstruction by split-thickness skin graft was favored in this series. Patients with an underlying adnexal carcinoma or pathological invasion of the dermis (group 2 or 3) had a worse prognosis than patients without. From this study, it is difficult to address the particular relationship between the outcome and the associated internal malignancy.     

Head injuries in childhood: a 2-year survey.

A retrospective study was conducted of the 880 children with head injuries consecutively admitted to the Children''s Hospital of Eastern Ontario in Ottawa from July 1976 to June 1978. It confirmed a boy:girl ratio of about 2:1, with a peak of 3.5:1 around 7 years of age. The largest number of head injuries was in children under 1 year of age. Injuries were most common in summer and spring, and most were caused by falls. The most common place for head injuries was in the home, but the single most common cause of injuries was bicycle accidents, which were responsible for 12% of all the head injuries. Skull fractures were found in 30% of all the patients. Of the 34 patients with severe head injuries 8 (24%) died, 9 (26%) had a moderate residual disability and 17 (50%) made a good recovery. There were no other deaths, so the mortality for the entire group of 880 patients was 0.9%.