Barbara J. Law

Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) prospective study of risk factors and outcomes in patients hospitalized with respiratory syncytial viral lower respiratory tract infection.

OBJECTIVEnTo provide information on disease attributable to respiratory syncytial viral lower respiratory tract infection (RSV LRI) and to quantify the morbidity associated with various risk factors.nnnDESIGNnProspective cohort study.nnnSUBJECTSnPatients hospitalized with RSV LRIs at seven centers were eligible for study if they were younger than 2 years of age, or hospitalized patients of any age if they had underlying cardiac or pulmonary disease or immunosuppression.nnnMEASUREMENTS AND RESULTSnEnrolled (n = 689) and eligible but not enrolled (n = 191) patients were similar in age, duration of illness and proportion with underlying illness, use of intensive care, and ventilation. Of the enrolled patients, 156 had underlying illness. The isolates from 353 patients were typeable: 102 isolates were subgroup A, 250 were subgroup B, and one isolated grouped with both antisera. The mean hospital stay attributable to respiratory syncytial virus (RSV) was 7 days; 110 patients were admitted to intensive care units, 63 were supported by mechanical ventilation, and 6 patients died. Regression models were developed for the prediction of three outcomes: RSV-associated hospital duration, intensive care unit admission, and ventilation treatment. In addition to previously described risk factors for an increased morbidity, such as underlying illness, hypoxia, prematurity and young age, three other factors were found to be significantly associated with complicated hospitalization: aboriginal race (defined by maternal race), a history of apnea or respiratory arrest during the acute illness before hospitalization, and pulmonary consolidation as shown on the chest radiograph obtained at admission. The RSV subgroup, family income, and day care attendance were not significantly associated with these outcomes.nnnCONCLUSIONSnHypoxia on admission, a history of apnea or respiratory arrest, and pulmonary consolidation should be considered in the management of children with RSV LRIs. Vaccine trials should target patients with underlying heart or lung disease or of aboriginal race.

Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of admission and management variation in patients hospitalized with respiratory syncytial viral lower respiratory tract infection

OBJECTIVEnTo describe differences in patients hospitalized with respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) at nine Canadian tertiary care hospitals. In addition, this study describes the variation in use of drug and other interventions.nnnMETHODSnData on patients hospitalized with RSV LRI and their outcomes were prospectively collected. Demographic data were obtained on enrollment by center study nurses. Data recorded daily included clinical assessment, oxygen saturation determination, and interventions (bronchodilators, steroids, ribavirin, antibiotics, intensive care, and mechanical ventilation) received during the day. Patients were divided into those with underlying diseases including congenital heart disease, chronic lung disease, immunodeficiency, or multiple congenital anomalies and those who were previously healthy. Mean RSV-associated length of stay and the proportion of patients receiving each intervention in each group were determined by hospital.nnnRESULTSnA total of 1516 patients were enrolled at nine hospitals during January 1 to June 30, 1993, and January 1 to April 30, 1994. Significant differences were observed among hospitals in the proportion of patients with underlying disease, postnatal age less than 6 weeks, hypoxia, and pulmonary infiltrate on chest radiograph. The mean length of stay varied among hospitals from 8.6 to 11.8 days and 4.6 to 6.7 days in compromised and previously healthy patients, respectively. Except for receipt of bronchodilators, compromised patients were significantly more likely to receive interventions than previously healthy patients. There was variation among hospitals in receipt of most interventions in compromised and previously healthy patients. This variation was statistically significant for previously healthy patients but not statistically significant in those with underlying disease, because the numbers of patients in the latter group were much smaller. The magnitude of the variation for each intervention, however, was not different between those with underlying disease compared with previously healthy patients.nnnCONCLUSIONnDifferences exist among tertiary pediatric hospitals in the nature of the patients admitted with RSV LRI. Variation occurred in the use of five interventions among the hospitals, regardless of whether the patient had underlying illness or was previously healthy. Given their current widespread use, high cost, and potential side effects, randomized clinical trials are needed to determine the efficacy of different drug treatments used to treat infants hospitalized with RSV.

Variable morbidity of respiratory syncytial virus infection in patients with underlying lung disease : a review of the PICNIC RSV database

OBJECTIVEnWe wished to compare outcomes of respiratory syncytial virus (RSV) infection in children with bronchopulmonary dysplasia (BPD) with those with other pulmonary disorders: cystic fibrosis, recurrent aspiration pneumonitis, pulmonary malformation, neurogenic disorders interfering with pulmonary toilet, and tracheoesophageal fistula.nnnMETHODSnChildren with RSV infection hospitalized at seven Canadian pediatric tertiary care hospitals in 1993 through 1994 and 9 hospitals in 1994 through 1995 were enrolled and prospectively followed. This study is a secondary analysis of data from this prospective cohort.nnnRESULTSnOf the 1516 patients enrolled the outcomes of 159 with preexisting lung disorders before RSV lower respiratory tract infection constitute this report. There were no significant differences among the 7 groups (BPD, cystic fibrosis, recurrent aspiration pneumonitis, pulmonary malformation, neurogenic disorders interfering with pulmonary toilet, tracheoesophageal fistula, other) for the morbidity measures: duration of hospitalization, intensive care unit (ICU) admission, duration of ICU stay, mechanical ventilation and duration of mechanical ventilation. Patients using home oxygen were more likely to be admitted to the ICU than those who had never or previously used home oxygen (current 57.1%, past 23.8%, never 33.3%, P = 0.03).nnnCONCLUSIONSnChildren with other underlying diseases have morbidity similar to those with BPD. Prophylactic interventions against RSV should also be studied in these groups.

Surveillance for Influenza Admissions Among Children Hospitalized in Canadian Immunization Monitoring Program Active Centers, 2003-2004

OBJECTIVES. Influenza is a common childhood infection that may result in hospitalization. Our objectives were to (1) determine characteristics of children hospitalized for influenza and disease manifestations and (2) obtain baseline data before implementation of new recommendations for routine immunization of young children and their caretakers against influenza. METHODS. All of the children hospitalized with laboratory-confirmed influenza at 9 Canadian tertiary care hospitals during the 2003–2004 influenza season were identified from virology laboratory reports, and their charts were reviewed. RESULTS. There were 505 children admitted because of influenza. Fifty-seven percent were <2 years old. Previously healthy children accounted for 58% of all of the cases. Pulmonary and neurologic disorders were the most common underlying chronic conditions. Fever and cough were the most frequent manifestations. Seizures occurred in 9% of cases. Serious complications included myocarditis (2), encephalopathy (6), and meningitis (1). There were 3 influenza-related deaths. Mean duration of hospitalization was 5.3 days. Twelve percent of children required ICU admission, and 6% required mechanical ventilation. Antibiotic therapy was administered in 77% of cases, and 7% received anti-influenza drugs. Information on influenza vaccination was available for 84 of 154 children identified as vaccine candidates. Twenty two had received vaccine, but only 7 children had been fully immunized >14 days before the onset of illness. CONCLUSIONS. Healthy young children and children with chronic conditions are at risk for serious illness with influenza. Ongoing surveillance is needed to evaluate the impact of changing immunization recommendations on the burden of influenza illness in children.

Respiratory syncytial virus infections in hospitalized Canadian children : regional differences in patient populations and management practices

Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization for respiratory tract infection during the first 2 years of life. The optimal approach to management remains controversial. During the 1991 to 1992 RSV season RSV-infected children admitted to eight Canadian tertiary care pediatric centers were followed to: (1) assess the morbidity and mortality attributable to RSV infection among hospitalized patients with and without known risk factors for severe disease; and (2) assess regional variation in the management of RSV infection. Of 529 RSV-infected patients 69% (363) had one or more of the risk factors for severe disease and the remaining 31% (166) had none. There were significant differences (P ≤ 0.01) between the high and low risk groups, respectively, for: intensive care unit admission (27%, 2%), assisted ventilation (14%, 0.6%), ribavirin therapy (20%, 2%), supplemental oxygen (75%, 34%), antibiotic therapy (69%, 58%) and length of hospital stay ≥ 7 days (39%, 6%). Among low risk patients, centers varied significantly (P ≤ 0.01) in the use of systemic corticosteroids (from 3 to 69% of patients), supplemental oxygen (13 to 74%), bronchodilators (68 to 93%) and ribavirin (0 to 10%). The observed regional variation in management of hospitalized children with RSV infection has implications for both the costs of hospital care and the conduct of multicenter trials of ribavirin and other therapies for RSV infection.

Serious adverse events associated with bacille calmette-guérin vaccine in Canada

Background: Targeted Bacille Calmette-Guérin (BCG) vaccination is offered to neonates in some First Nations and Inuit (FNI) communities in Canada. Serious adverse events associated with BCG vaccine prompted a review to assess causality. Methods: The Immunization Monitoring Program Active (IMPACT), a pediatric hospital-based active surveillance network, reported admissions for BCG-related adverse events between 1993 and April 2002. The Canadian Advisory Committee on Causality Assessment (ACCA) reviewed the reports to assess causality. Data between 1987 and September 2002 from the Vaccine-Associated Adverse Event Surveillance (VAAES) Program, a passive national reporting system, were also reviewed. Results: IMPACT identified 21 pediatric cases; 19 were Canadian-born, and 18 were FNI. Six disseminated BCG cases were identified; 5 were FNI infants who subsequently died. All had immunodeficiencies and concurrent infections. Other adverse events included 2 cases of osteomyelitis, BCG abscesses and lymphadenitis. ACCA reviewed the 21 cases and determined that 14 were very likely associated with the vaccine, including the 6 disseminated BCGs; 5 were probably associated and 1 was possibly associated with the vaccine; 1 was unclassifiable. The VAAES program identified 157 adverse events. No additional serious systemic adverse events (disseminated BCG or osteomyelitis) were identified. Conclusions: Serious BCG vaccine-associated complications continue to occur in Canada. The numbers of FNI children with disseminated disease was greater than expected from reported rates in the literature.

Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of aseptic meningitis.

BackgroundThe seasonality, clinical and radiographic features and outcome of aseptic meningitis have been described for regional outbreaks but data from a wider geographic area is necessary to delineate the epidemiology of this condition.MethodsA retrospective chart review was completed of children presenting with aseptic meningitis to eight Canadian pediatric hospitals over a two-year period.ResultsThere were 233 cases of proven enteroviral (EV) meningitis, 495 cases of clinical aseptic meningitis and 74 cases of possible aseptic meningitis with most cases occurring July to October. Headache, vomiting, meningismus and photophobia were more common in children ≥ 5 years of age, while rash, diarrhea and cough were more common in children < 5 years of age. Pleocytosis was absent in 22.3% of children < 30 days of age with proven EV meningitis. Enterovirus was isolated in cerebrospinal fluid (CSF) from 154 of 389 patients (39.6%) who had viral culture performed, and a nucleic acid amplification test for enterovirus was positive in CSF from 81 of 149 patients (54.3%). Imaging of the head by computerized tomography or magnetic resonance imaging was completed in 96 cases (19.7%) and 24 had abnormal findings that were possibly related to meningitis while none had changes that were definitely related to meningitis. There was minimal morbidity and there were no deaths.ConclusionThe clinical presentation of aseptic meningitis varies with the age of the child. Absence of CSF pleocytosis is common in infants < 30 days of age. Enterovirus is the predominant isolate, but no etiologic agent is identified in the majority of cases of aseptic meningitis in Canadian children.

Study of interobserver reliability in clinical assessment of RSV lower respiratory illness: A pediatric investigators collaborative network for infections in Canada (PICNIC) study

Randomized trials of ribavirin therapy have used clinical scores to assess illness severity. Little information on agreement for these findings between observers has been published. We decided to determine interobserver agreement for (1) a history for apnea or respiratory failure; (2) assessment of cyanosis, respiratory rate, retractions, and oximetry; and (3) determination of reason for hospitalization (requirement for medications, supportive care, underlying illness, poor home environment). At eight centers 137 RSV‐infected patients were assessed by two observers blinded to the assessments by others with no interventions made between assessments. Observations were categorized, and agreement was summarized as percentage of observed agreement, Pearson correlation, or as a κ statistic. Observed agreement for a history of either apnea or a respiratory arrest was at least 90% at all centers, with seven of the eight centers in total agreement. At all centers except one, the agreement on the reason why the patient remained in hospital was at least 80%. The observed agreement for assessing cyanosis was at least 94% at all eight centers. The correlation coefficient for respiratory rate varied from 0.42 to 0.97 across centers. The κ values for agreement beyond chance for retractions varied from 0.05 to 1.00. The κ values for oxygen saturation measures varied from 0.31 to 0.70. Although not statistically significant, there appeared to be more variation as the time between assessments increased. In conclusion, agreement for historical findings and assessment of cyanosis was high. However, there was wide variation in agreement in the other assessments. Training to ensure consistent and reproducible assessment by different examiners will be necessary if these findings are to be used as outcome variables in clinical trials. Pediatr Pulmonol. 1996;22;23–27.

Pediatric investigators collaborative network on infections in Canada (PICNIC): The politics and positives of a cooperative study group

‘DEPARTMENT OF PEDIATRICS AND CLINICAL EPIDEMIOLOGY AND HEALTH CARE RESEARCH PROGRAM, UNIVERSITY OF TORONTO, TORONTO, ONTARIO, M5G 1X8, *DEPARTMENT OF PEDIATRICS, UNIVERSITY OF BRITISH COLUMBIA, VANCOUVER, BRITISH COLUMBIA V6H 3N1, ‘DEPARTMENTS OF PEDIATRICS AND MEDICAL MICROBIOLOGY, UNIVERSITY OF MANITOBA, WINNIPEG, MANITOBA R3A lR9, AND 4D~~~~~~~~~ OF PEDIATRICS, UNIVERSITY OF OTTAWA, OTTAWA, ONTARIO, KlH 8Ll

Epiglottitis in Canada: A Multiregional Review

Epiglottitis is an acute, life threatening infection usually caused by Haemophilus influenzae type b. Although antibiotic therapy is an important part of management, the optimal route and duration is unknown. A multicentre retrospective review of 305 children with epiglottitis was carried out in order to relate antibiotic therapy to hospital course and outcome, as well as to examine regional variation in patient demographics, clinical presentation and course of disease. A standardized form was used to extract data from hospital records. Although management varied significantly among the six centres in terms of mean duration of intubation (46 to 81 h), intravenous antibiotic therapy (3.8 to 5.7 days) and hospital stay (5.3 to 8.4 days), there were no significant centre-related differences in epidemiology, clinical course or outcome of epiglottitis. An extraepiglottic focus of infection was present in 15% of patients and included three with septic arthritis and one with meningitis. The duration of fever in hospital and maximum recorded temperature in hospital were significantly greater for children with extraepiglottic infection compared to those with epiglottitis alone. The data presented in this review suggest that most children with epiglottitis have an uncomplicated course and respond rapidly to antimicrobial therapy following airway securement. A short period of intravenous and oral antibiotic therapy is likely adequate for most children with epiglottitis. A well designed multicentre prospective trial is still needed to determine the optimal duration of antibiotic therapy.