Elaine E. L. Wang

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.

Induction of labor compared with expectant management for prelabor rupture of the membranes at term

BACKGROUNDnAs the interval between rupture of the fetal membranes at term and delivery increases, so may the risk of fetal and maternal infection. It is not known whether inducing labor will reduce this risk or whether one method of induction is better then another.nnnMETHODSnWe studied 5041 women with prelabor rupture of the membranes at term. The women were randomly assigned to induction of labor with intravenous oxytocin; induction of labor with vaginal prostaglandin E2 gel; or expectant management for up to four days, with labor induced with either intravenous oxytocin or vaginal prostaglandin E2 gel if complications developed. The primary outcome was neonatal infection. Secondary outcomes were the need for cesarean section and womens evaluations of their treatment.nnnRESULTSnThe rates of neonatal infection and cesarean section were not significantly different among the study groups. The rates of neonatal infection were 2.0 percent for the induction-with-oxytocin group, 3.0 percent for the induction-with-prostaglandin group, 2.8 percent for the expectant-management (oxytocin) group, and 2.7 percent for the expectant-management (prostaglandin) group. The rates of cesarean section ranged from 9.6 to 10.9 percent. Clinical chorioamnionitis was less likely to develop in the women in the induction-with-oxytocin group than in those in the expectant-management (oxytocin) group (4.0 percent vs. 8.6 percent, P<0.001), as was postpartum fever (1.9 percent vs. 3.6 percent, P=0.008). Women in the induction groups were less likely to say they liked nothing about their treatment than those in the expectant-management groups.nnnCONCLUSIONSnIn women with prelabor rupture of the membranes at term, induction of labor with oxytocin or prostaglandin E2 and expectant management result in similar rates of neonatal infection and cesarean section. Induction of labor with intravenous oxytocin results in a lower risk of maternal infection than does expectant management. Women view induction of labor more positively than expectant management.

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.

Association of Ureaplasma urealyticum colonization with chronic lung disease of prematurity: Results of a metaanalysis

OBJECTIVESnWe performed a metaanalysis to determine whether there is an association between Ureaplasma urealyticum and chronic lung disease of prematurity (CLD); most studies involved small sample sizes, and the reported lack of statistical significance could have been due to inadequate power.nnnMETHODSnArticles were identified from the literature through a search of MEDLINE, Excerpta Medica, and Reference Update, with the search terms Ureaplasma urealyticum, CLD, and bronchopulmonary dysplasia. The search was initially conducted in June 1994 and updated in March 1995. Abstracts were identified through a hand search of proceedings from two meetings for the years 1987 through 1994. Summary data on frequency of CLD in U. urealyticum-colonized and uncolonized babies were independently determined by the three authors. Preterm and term neonates were included. Colonization required recovery of U. urealyticum from a respiratory or surface specimen. The presence of CLD at 28 or 30 days was determined.nnnRESULTSnSeventeen publications comprising 13 full publications and 4 abstracts were included in the analysis. The estimates for relative risk (RR) exceeded one in all studies, although the lower confidence interval included one in seven studies. The RR for the development of CLD in colonized neonates was 1.72 (95% confidence interval, 1.5 to 1.96) times that for uncolonized neonates. The RR was not significantly different for abstracts versus full publications; studies focusing on extremely premature, low birth weight neonates versus studies including all neonates; and studies in which only endotracheal aspirates were used to define colonization versus others. The RR since surfactant use was somewhat lower than in studies in which receipt of surfactant was unknown.nnnCONCLUSIONSnThis metaanalysis supports a significant association between U. urealyticum colonization and subsequent development of CLD. A randomized, controlled trial showing a reduction in CLD through the use of an antibiotic effective against U. urealyticum would provide further support of a causative role for this agent.

Reliability of the chest radiograph in the diagnosis of lower respiratory infections in young children.

OBJECTIVEnThis study was conducted to determine the reliability of detecting features and making diagnoses of lower respiratory infections from chest radiograms in young infants.nnnMETHODSnForty chest radiograms of infants younger than 6 months of age admitted with lower respiratory tract infection to a tertiary care pediatric hospital were independently reviewed on two separate occasions by three pediatric radiologists blinded to the patients clinical diagnoses. For each radiograph the radiologists noted whether a feature was present, absent or equivocal on a standardized form. The features examined were hyperinflation, peribronchial thickening, perihilar linear opacities, atelectasis and consolidation. On the same form each radiologist indicated whether the radiograph was normal or showed airways and/or airspace disease. Within and between observer agreement were calculated by the average weighted kappa statistic.nnnRESULTSnWithin observer agreement for the radiologic features of hyperinflation, peribronchial wall thickening, perihilar linear opacities, atelectasis and consolidation were 0.85, 0.76, 0.87, 0.86 and 0.91, respectively. The between observer kappa results for these features were 0.83, 0.55, 0.82, 0.78 and 0.79, respectively. The within and between observer kappa statistics for interpretation of the radiographic features were best for airspace disease (within, 0.92; between, 0.91), and lower for normal (within, 0.80; between, 0.66) radiogram and for airways disease (within, 0.68; between, 0.48). The presence of consolidation was highly correlated with a diagnosis of airspace disease by all three radiologists.nnnCONCLUSIONSnClinicians basing the diagnosis of lower respiratory infections in young infants on radiographic diagnosis should be aware that there is variation in intraobserver and interobserver agreement among radiologists on the radiographic features used for diagnosis. There is also variation in how specific radiologic features are used in interpreting the radiogram. However, the cardial finding of consolidation for the diagnosis of pneumonia appears to be highly reliable.

Epidemiological Features of Pertussis in Hospitalized Patients in Canada, 1991- 1997: Report of the Immunization Monitoring Program—Active (IMPACT)

To assess the morbidity associated with the continued high levels of pertussis, we studied all children <2 years of age who were admitted to the 11 Immunization Monitoring Program--Active (IMPACT) centers, which constitute 85% of Canadas tertiary care pediatric beds. In the 7 years preceding implementation of acellular pertussis vaccine, a total of 1,082 pertussis cases were reported, of which 49.1% were culture-confirmed. The median age of the patients was 12.4 weeks; 78.9% of cases were in children <6 months of age. Complications of pertussis were common: pneumonia was reported in 9.4% of cases, new seizures in 2.3%, and encephalopathy in 0.5%. There were 10 deaths (0.9%), all in children < or =6 months of age. Duration of hospitalization was longer (9.3 days vs. 4.9 days; P = .001) and intensive care was required more frequently (19.2% vs. 4.9%; P = .001) in infants under <6 months of age than in those > or =6 months. Pertussis continues to cause significant morbidity and occasional mortality in Canada, particularly in young infants.

Economic evaluation of respiratory syncytial virus infection in Canadian children: A Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study

OBJECTIVESnTo quantify the cost and distribution of health care resources consumed annually in management of Canadian children from birth to 4 years of age with respiratory syncytial virus (RSV) infection.nnnSTUDY DESIGNnEstimates of direct medical expenditures (in 1993 U.S. dollars) were collected from a prospective cohort study of hospitalized children with RSV and from national and provincial databases.nnnRESULTSnThe annual cost of RSV-associated illness was almost

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

18 million. The largest component of direct expenditures (62%) was for inpatient care for the estimated 0.7% of all infected children ill enough to require admission. Physician fees comprised only 4% of inpatient expenses. Expenditures for ambulatory patients accounted for 38% of direct costs.nnnCONCLUSIONSnThe greatest reductions in the economic cost of RSV infections will be found in interventions that reduce duration of or prevent hospital stay. Costs for management of RSV infection in children in the Canadian health care system are considerably less than charges reported in the United States.

Canadian Acute Respiratory Illness and Flu Scale (CARIFS): Development of a valid measure for childhood respiratory infections

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.

Respiratory syncytial virus vaccine: a systematic overview with emphasis on respiratory syncytial virus subunit vaccines

Although acute respiratory infection (ARI) is the most frequent clinical syndrome in childhood, there is no validated measure of its severity. Therefore a parental questionnaire was developed: the Canadian Acute Respiratory Illness Flu Scale (CARIFS). A process of item generation, item reduction, and scale construction resulted in a scale composed of 18 items covering three domains; symptoms (e.g., cough); function (e.g., play), and parental impact (e.g., clinginess). The validity of the scale was evaluated in a study of 220 children with ARI. Construct validity was assessed by comparing the CARIFS score with physician, nurse, and parental assessment of the childs health. Data were available from 206 children (94%). The CARIFS correlated well with measures of the construct (Spearmans correlations between 0.36 and 0.52). Responsiveness was shown, with 90% of children having a CARIFS score less than a quarter of its initial value, by the tenth day.