WITHDRAWN: Immunoglobulin for preventing respiratory syncytial virus infection.

BACKGROUND: Respiratory Syncytial virus, the most important cause of lower respiratory tract infections in infants and young children in industrialized countries, is associated with increased morbidity in premature infants with or without bronchopulmonary dysplasia as well as those with congenital heart disease. Because of observations that lower rates of disease occur immediately after birth, presumably due to vertical transmission of maternal antibody, and animal studies where protection from pneumonia was observed through administration of immune globulin, the efficacy of passive prophylaxis in premature infants has been studied. OBJECTIVES: This meta-analysis was performed to assess the effects of polyclonal respiratory syncytial virus hyperimmune globulin or monoclonal antibody in preventing RSV hospitalization, receipt of intensive care, mechanical ventilation, and mortality in those with underlying prematurity, bronchopulmonary dysplasia, or congenital heart disease. SEARCH STRATEGY: We searched the Cochrane Acute Respiratory Infections trials register and MEDLINE in March, 1999. In addition, abstracts on these topics were sought from the Pediatric Academies Meetings and the Intersciences Conference on Antimicrobial Agents and Chemotherapy for the years 1994 to 1997, inclusive. SELECTION CRITERIA: Randomized, controlled trials of prevention of RSV using immune globulin, respiratory syncytial virus immune globulin, or monoclonal RSV antibody in children with prematurity, bronchopulmonary dysplasia or congenital heart disease. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted data and assessed study quality. Only incidences could be pooled because data for durations was summarized in a manner that did not allow combining results across the studies. MAIN RESULTS: Four studies with a total of 2598 subjects were included in the main analysis. All were randomized controlled trials. Two trials were not blinded. Three studies examined RSV hyperimmune globulin and one examined monoclonal RSV antibody. A study of a different monoclonal RSV antibody could not be included because it has not been presented or published. The pooled Peto Odds Ratios favoring prophylaxis were 0.48 (95% CI 0.37, 0.64), 0.47 (0.29, 0.77), and 0.99 (0.48, 2.07) for incidence of hospitalization, incidence of ICU admission, and incidence of mechanical ventilation, respectively. The numbers needed to prevent one hospitalization and one ICU admission are 17 and 50 respectively. AUTHORS' CONCLUSIONS: RSVIG is effective in preventing RSV hospitalizations and admission to the intensive care unit, but not in preventing mechanical ventilation. There was a non-significant trend towards a higher mortality in children given RSVIG.

Bcl-xL is phosphorylated in malignant cells following microtubule disruption.

The oncogenic protein Bcl-2 functions as a potent inhibitor of programmed cell death. This survival activity has been shown in some settings to be influenced by the Bcl-2 phosphorylation state. It has been demonstrated that treatment with microtubule-targeted agents results in phosphorylation of both Raf-1 kinase and Bcl-2. The Bcl-2-related family member Bcl-xL also exhibits a death suppressive activity, but its potential for phosphorylation following exposure to drugs that interact with microtubules has not been evaluated. Several tumor cell lines with low or undetectable levels of Bcl-2 protein expression were found to express Bcl-xL. A more slowly migrating Bcl-xL band was observed on immunoblots after cells were treated with microtubule-targeted agents. The appearance of this band was responsive to dose and was absent when the cell lysates were treated with lambda protein phosphatase. Using a Bcl-xL-specific monoclonal antibody, the phosphorylated form of Bcl-xL was immunoprecipitated from cells treated with paclitaxel and metabolically labeled with 32P-labeled inorganic orthophosphate. Herein, we report that Bcl-xL is phosphorylated in malignant cells after incubation with agents that target tubulin, including paclitaxel, vincristine, vinblastine, colchicine, and nocodazole. Moreover, paclitaxel-resistant ovarian carcinoma cell lines that have mutations in tubulin failed to exhibit phosphorylation of Bcl-xL after paclitaxel exposure, but they did demonstrate Bcl-xL phosphorylation in the presence of other tubulin-targeting agents. As observed for Bcl-2, phosphorylation of Bcl-xL was accompanied by phosphorylation of Raf-1. Interestingly, phosphorylation of these three proteins failed to occur or was much less pronounced when cells grown at high density were challenged with drug. Also, reduced Raf-1 expression, observed after treatment of cells with geldanamycin prior to and during incubation with the microtubule-active drugs, correlated with diminished Bcl-xL phosphorylation. Taken together, these results suggest that Bcl-xL, like Bcl-2, is phosphorylated by agents that disrupt microtubule architecture. By analogy with Bcl-2, this phosphorylation may play a critical role in modulating Bcl-xL function and may be an important determinant of microtubule-directed chemotherapeutic efficacy in human tumors.

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

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 child's health. Data were available from 206 children (94%). The CARIFS correlated well with measures of the construct (Spearman's 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.

Assessment of lymph node size in hemophiliac children: observer agreement and association with serologic status to human immunodeficiency virus I.

Lymphadenopathy is an important component of a wide variety of different illnesses including the acquired immunodeficiency syndrome and acquired immunodeficiency syndrome-related conditions. In this study two pairs of observers independently examined the lymph nodes of hemophiliacs younger than 18 years of age to determine the level of agreement of assessments of lymph node mass (the product of the number and mean diameter of lymph nodes). Spearman correlation coefficients for the first and second pairs of observers were 0.75 (P less than 0.001) and 0.66 (P less than 0.005), respectively. The range of lymph node mass was quite different for controls (2.8 to 3.8), human immunodeficiency virus I (HIV)-seronegative hemophiliacs (4 to 5.7) and HIV-seropositive hemophiliacs (10.3 to 15.6). The HIV serologic status could be predicted by lymph node mass. In this group of hemophiliacs, if the lymph node mass was less than 5 cm, the probability of being HIV-seropositive was 0.14. The corresponding probabilities if the lymph node mass was in the range 5 to 9.99, 10 to 14.99, 15 to 19.99 and 20 or greater were 0.33, 0.8, 0.67 and 1.00, respectively. Thus there is adequate agreement between observers in assessing the lymph node mass and there is a direct relationship between lymph node mass and evidence of infection with HIV.

False positivity of Legionella serology in patients with cystic fibrosis.

Respiratory deterioration accounts for the morbidity and mortality observed in patients with cystic fibrosis. The role of Legionella in this deterioration was determined in a 2-year prospective study of 49 patients with cystic fibrosis and 19 sibling controls. Sera were obtained from participants on enrollment and at quarterly intervals. Legionella antibodies were measured in parallel using an indirect fluorescent assay. No seroconversions were observed. Eleven of 49 patients with cystic fibrosis (22%) were seropositive compared to none of 19 siblings (P less than 0.05). Six of the 11 patients demonstrated high titers (greater than or equal to 1:512) that persisted throughout the study. Absorption with pools of various Pseudomonas species reduced the antibody titers such that only 3 remained positive after absorption. Legionella was not found to be an important cause of clinical deterioration during this study. The results of the absorption studies suggest that high titers to Legionella in this population are due to cross-reacting antibodies.

Hepatitis B and human immunodeficiency virus infection in street youths in Toronto, Canada.

Hepatitis B and human immunodeficiency virus are transmitted by venereal contact or by the sharing of used needles during drug use. A questionnaire was administered to street youths admitting to prostitution and to a group denying prostitution, as well as to sexually active adolescents who lived with their family and were attending an adolescent medical clinic. The age, gender, race, number of sexual partners, condom use, illicit drug use, anal intercourse and admission to prostitution were recorded for each of the subjects. Serology was obtained for hepatitis B markers and human immunodeficiency virus antibody. Multiple regression analysis was performed to determine the factors which might predict hepatitis B serologic status. A single subject, who admitted to prostitution, was found to be human immunodeficiency virus-seropositive. Seven of 43 (16%) admitted prostitutes compared with 1 of 44 (2%) other street youth and none of 27 controls demonstrated anti-hepatitis B surface antibodies. The higher rate of seropositivity in admitted prostitutes was statistically significant (P less than 0.0097). Two seropositive prostitutes had IgM hepatitis B core antibody suggesting recent infection. Two factors, number of partners (P less than 0.0007) and practice of anal intercourse (P less than 0.05), were identified in the multiple regression analysis as predictive of seropositivity. Thus adolescents who live on the street are at increased risk for becoming infected with hepatitis B virus. The difficulty in ensuring vaccine coverage in this population would support calls for including hepatitis B vaccination as part of childhood immunization.

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

OBJECTIVE: This study was conducted to determine the reliability of detecting features and making diagnoses of lower respiratory infections from chest radiograms in young infants. METHODS: Forty 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. RESULTS: Within 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. CONCLUSIONS: Clinicians 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.

Role of Ureaplasma urealyticum and other pathogens in the development of chronic lung disease of prematurity.

A prospective cohort study enrolling 107 infants weighing less than 1250 g was conducted between September 1, 1986, and November 15, 1987 in order to determine the role of microorganisms on the development of chronic lung disease (CLD). Ureaplasma urealyticum was isolated significantly more frequently from gastric aspirates and nasopharyngeal or endotracheal aspirates from 43 infants developing CLD than from 56 who did not (51% vs. 16%; P less than 0.005). Infants developing CLD, defined by radiographic and blood gas abnormalities, were significantly younger (26 vs. 29 weeks; P less than 0.0001), weighed significantly less (830 vs. 1050 g; P less than 0.0001) and required more ventilatory support (37 vs. 10 were being ventilated and 42 vs. 26 received oxygen supplementation on Day 7) compared with those who did not develop CLD. Viruses were isolated in association with U. urealyticum in two infants developing CLD and in one infant who did not develop CLD. Mycoplasma hominis was isolated from three infants who were colonized with U. urealyticum and developed CLD. Chlamydia trachomatis was not recovered from any patients. From a discriminant analysis it was found that U. urealyticum contributed to the development of CLD along with the effect of ventilatory support, gestational age and severity of initial respiratory disease. The effect of interventions directed against U. urealyticum on the development of CLD deserves further study.

Variable morbidity of respiratory syncytial virus infection in patients with underlying lung disease: a review of the PICNIC RSV database. Pediatric Investigators Collaborative Network on Infections in Canada.

OBJECTIVE: We 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. METHODS: Children 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. RESULTS: Of 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). CONCLUSIONS: Children with other underlying diseases have morbidity similar to those with BPD. Prophylactic interventions against RSV should also be studied in these groups.

Ribavirin for respiratory syncytial virus lower respiratory tract infection. A systematic overview.

OBJECTIVE: To systematically review the evidence evaluating the efficacy of aerosolized ribavirin for the treatment of infants with respiratory syncytial virus lower respiratory tract infection. DESIGN: A computerized search of MEDLINE from 1975 to the present, a review of the reference lists of each retrieved article, and contact with experts. PATIENTS: infants with documented respiratory syncytial virus lower respiratory tract infection who were the subjects of 8 double-blind randomized placebo-controlled trials. METHODS: Two independent reviewers assessed study quality and extracted data on the study populations, the drug regimens, and clinically relevant outcome measurements. RESULTS: Ribavirin does not significantly reduce mortality rate (relative risk [RR] = 0.42, 95% confidence interval [CI] = 0.13, 1.44) or lower the probability of respiratory deterioration (RR = 0.42, 95% CI = 0.16, 1.34) when meta-analysis is used to pool the outcomes of 3 trials, although strong trends in the direction of benefit are present. No study found ribavirin to shorten length of hospitalization. Results on length of ventilation and oxygen supplementation are conflicting. CONCLUSIONS: Use of ribavirin in infants with respiratory syncytial virus lower respiratory tract infection is not supported by evidence of significant benefit. However, previous studies lack sufficient power to rule out a potential reduction in mortality rate or respiratory deterioration. A large randomized controlled trial of ribavirin for ventilated and other high-risk patients is needed.

Testing models predicting severity of respiratory syncytial virus infection on the PICNIC RSV database. Pediatric Investigators Collaborative Network on Infections in Canada.

OBJECTIVES: To determine the sensitivity and specificity of published prognostic models to predict morbidity resulting from lower respiratory tract disease caused by respiratory syncytial virus in an independent pediatric population and to assess the accuracy of single risk factors in predicting adverse outcome. DESIGN: All articles obtained from a MEDLINE search that used the terms prognosis or sequelae and respiratory syncytial virus, and from the references of these articles, were reviewed. Studies were included if risk factors and outcomes were defined and if information was available in a database of prospectively enrolled patients with respiratory syncytial virus infections. A probability of adverse outcome was assigned to each patient in the cohort using prognostic models described in the articles. A test was considered positive if the probability of the adverse outcome was 5% or more. PATIENTS: Six hundred eighty-nine patients hospitalized with respiratory syncytial virus in seven tertiary care centers across Canada were prospectively enrolled in the Pediatric Investigators Collaborative Network on Infections in Canada database. MAIN OUTCOME MEASURES: The sensitivity and specificity of single predictors and of models in predicting severe disease were determined. RESULTS: The sensitivity of single predictors varied from 17% to 46%. A model that used age and oxygen saturation at admission in previously well infants had a sensitivity of 98% and a specificity of 47% when predicting intensive care unit admission. Another model that included age at hospitalization, gestational age, presence of an underlying condition, and respiratory syncytial virus subtype used to predict the outcome of a high severity index had a sensitivity of 77% and a specificity of 76%. When the above model was modified by exclusion of viral subgroup, sensitivity increased to 94%, but specificity decreased to 46%. CONCLUSION: Previously described prognostic models were generalizable to an independent study population.

Underlying causes of recurrent pneumonia in children.

OBJECTIVES: To determine the relative frequency of underlying factors for recurrent pneumonia and the proportion of patients in whom the underlying illness diagnosis was known prior to pneumonia recurrence. METHODS: Retrospective medical record review for a 10-year period from January 1987 through December 1997 at The Hospital for Sick Children in Toronto, Ontario, a tertiary care pediatric hospital. Recurrent pneumonia was defined as at least 2 pneumonia episodes in a 1-year period or at least 3 during a lifetime. RESULTS: Of 2952 children hospitalized with pneumonia, 238 (8%) met criteria for recurrent pneumonia. An underlying illness diagnosis was identified in 220 (92%). Of these, the underlying illness was diagnosed prior to pneumonia in 178 (81%), with the first episode in 25 (11%), and during recurrence in 17 (8%). Underlying illnesses included oropharyngeal incoordination with aspiration syndrome (114 cases [48%]), immune disorder (24 [10%]), congenital cardiac defects (22 [9%]), asthma (19 [8%]), pulmonary anomalies (18 [8%]), gastroesophageal reflux (13[5%]), and sickle cell anemia (10 [4%]). Clinical clues to diagnosis were recurrent infections at other locations and failure to thrive in the cases of an immune disorder, recurrences involving the same location in those with underlying pulmonary pathology, the association of respiratory symptoms with feeding in those with gastroesophageal reflux, or recurrent wheezing in asthmatic children. CONCLUSIONS: Recurrent pneumonia occurs in fewer than one tenth of all children hospitalized with pneumonia. Most of them have a known predisposing factor. The most common cause was oropharyngeal incoordination.

Efficacy of bronchodilator therapy in bronchiolitis. A meta-analysis.

OBJECTIVE: To determine if bronchodilators are efficacious in treating bronchiolitis. DATA SOURCES: A search of bibliographic databases (MEDLINE, Excerpta Medica, and Reference Update) for bronchiolitis and albuterol or ipratropium bromide, or adrenergic agents or bronchodilator agents. Reference lists were also used. STUDY SELECTION: Randomized, placebo-controlled trials of bronchodilator treatment in bronchiolitis were selected by 2 investigators. Fifteen of 89 identified publications met the selection criteria. DATA EXTRACTION: Investigators independently abstracted data for 3 outcomes: clinical score, oxygen saturation, and hospitalization. Clinical score was measured as a dichotomous variable (score +/- improved) or continuous variable (average score). DATA SYNTHESIS: For primary analysis, data were pooled from 8 trials of children with first-time wheezing. The effect size for average score was -0.32 (95% confidence interval [CI], -0.54 to -0.11; P < .01), favoring treatment; the relative risk for score +/- improved was 0.76 (95% CI, 0.60 to 0.95; P = .02), favoring treatment. Bronchodilators had no effect on hospitalization (relative risk, 0.85; 95% CI, 0.47 to 1.53; P = .58), but co-interventions may have been administered prior to this outcome. The results for oxygen saturation were too varied to allow pooling of the results. Secondary analyses were performed on 4 outpatient trials of children with first-time wheezing, 7 trials in which only nebulized beta-agonists were used, and on all 15 trials identified. The results were similar, but the data varied more. CONCLUSION: Bronchodilators produce modest short-term improvement in clinical features of mild or moderately severe bronchiolitis.

Child care center staff contribute to physician visits and pressure for antibiotic prescription.

OBJECTIVE: To determine whether child care center (CCC) providers contribute to unnecessary physician referrals and antibiotic prescriptions in young children with upper respiratory tract infections. DESIGN: A survey using a structured telephone questionnaire between May 3, 1998, and July 27, 1998. PARTICIPANTS: Child care center providers from randomly selected licensed Ontario CCCs accepting diapered children. MAIN OUTCOME MEASURES: Knowledge, attitudes, and practices concerning physician referral; exclusion; and antibiotic use for children with upper respiratory tract infections. Indications for exclusion were compared with published Canadian guidelines. RESULTS: Contact was made with 42 eligible CCCs to obtain the requisite number of 36 participants (participation rate, 86%). Of the 36 centers, staff reported advising that children visit a physician for colored nasal discharge in 28 (78%), for productive cough in 23 (64%), and for unusual behavior in 9 (25%). Also of the 36 centers, staff reported excluding children for colored nasal discharge in 20 (56%), for productive cough in 16 (44%), and for unusual behavior in 15 (42%). Antibiotics were thought useful for nonspecific upper respiratory tract infections to prevent the spread of infection in 9 (26%), to speed up recovery in 7 (21%), and to prevent bacterial infection in 13 (38%) of 34 centers. In the previous 6 months, 25 (69%) of 36 staff members reported making an exception to exclusion because a child had an antibiotic prescription. CONCLUSIONS: Many children are referred by CCC staff to physicians contrary to established guidelines. As staff must act on behalf of parents, a low threshold for referral is not unreasonable. However, this survey confirms that CCC staff recommend children to receive antibiotics and exclude children inappropriately. These practices are based on incomplete knowledge. Research on appropriate management of upper respiratory tract infections by CCC staff is needed. Education to correct specific knowledge deficits should be initiated.

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 kappa 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 kappa values for agreement beyond chance for retractions varied from 0.05 to 1.00. The kappa 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.

Computers and connectivity in Illinois emergency departments.

UNLABELLED: Although the Internet has been described as "ubiquitous," little is known about the extent to which physicians have access to the Internet while providing clinical care. OBJECTIVE: To assess the extent of Internet connectivity within the clinical area of every ED within the state of Illinois. METHODS: This was a prospective observational study. Each Illinois ED listed in a published directory was called by telephone, and a responsible party was identified to provide information regarding the type and size of the ED, patient demographics, the types of personal computers (PCs) available in the ED (if any), the types of operating systems used, the availability of access to the World Wide Web (Web), and the highest speed at which an Internet connection could be established. Responses regarding the presence and types of PCs and the types of operating systems used were assessed using one-factor chi-square. Univariate and multivariate predictors of the type of PC used, the presence or absence of Web access, and the highest speed of Internet access were evaluated using optimal discriminant analysis and nonlinear classification tree analysis, respectively. RESULTS: One hundred ninety-eight of the 199 EDs in the state of Illinois (99.5%) completed the survey. Of the responding EDs, 50.5% had PCs, but only 17.6% had Web access. When Web access was available, it was most often available through a high-speed Internet connection that was faster than a dial-up modem. Most departments (68.1%) with PCs used the Windows 95 or Windows 98 operating systems. A majority (62.5%) used the Netscape browser exclusively. Larger EDs (more than six ED beds) in rural or suburban areas were more likely to have a PC compared with smaller EDs (six or fewer beds). Large EDs (more than 12 ED beds) in private tertiary care or academic hospitals were most likely to have Web access. CONCLUSIONS: Although half of Illinois EDs have PCs, only one in six has access to the Internet; thus, most emergency physicians do not have ready access to the Web from the site where they deliver clinical care.

Ribavirin for respiratory syncytial virus infection of the lower respiratory tract.

OBJECTIVES: Respiratory syncytial virus (RSV) is a common cause of pneumonia in infants. Ribavirin is the only antiviral therapy available against RSV. The objective of this review was to assess the effects of aerosolized ribavirin for infants with RSV lower respiratory tract infection. SEARCH STRATEGY: We searched MEDLINE from 1975 to 1999, we scanned reference lists of articles, and we contacted experts in the field. SELECTION CRITERIA: Randomized trials comparing ribavirin with placebo in infants and children with RSV infection and lower respiratory tract infection. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. Unpublished data were requested from authors when necessary. MAIN RESULTS: Ten trials were included. All trials enrolled infants below the age of six months. In four trials with 158 patients, mortality with ribavirin was 5.8% compared with 9.7% with placebo (odds ratio 0.58, 95% confidence interval 0.18 to 1.85). In three trials with 116 patients the probability of respiratory deterioration with ribavirin was 7.1% compared with 18.3% with placebo (odds ratio 0.37, 95% confidence interval 0.12 to 1.18). In three studies with 104 patients the weighted mean difference in days of hospitalization was 1.9 fewer days with ribavirin (95% confidence interval +0.9 to -4.6) and the difference in days of ventilation was 1.2 fewer days with ribavirin (95% confidence interval -0.2 to -3.4). REVIEWER'S CONCLUSIONS: Trials of ribavirin for RSV lack sufficient power to provide reliable estimates of the effects. The cumulative results of three small trials show that ribavirin reduces length of mechanical ventilator support and may reduce days of hospitalization. A large randomized controlled trial of ribavirin for ventilated and other high-risk patients is indicated.

Immunoglobulin for preventing respiratory syncytial virus infection.

BACKGROUND: Respiratory Syncytial virus, the most important cause of lower respiratory tract infections in infants and young children in industrialized countries, is associated with increased morbidity in premature infants with or without bronchopulmonary dysplasia as well as those with congenital heart disease. Because of observations that lower rates of disease occur immediately after birth, presumably due to vertical transmission of maternal antibody, and animal studies where protection from pneumonia was observed through administration of immune globulin, the efficacy of passive prophylaxis in premature infants has been studied. OBJECTIVES: This meta-analysis was performed to assess the effects of polyclonal respiratory syncytial virus hyperimmune globulin or monoclonal antibody in preventing RSV hospitalization, receipt of intensive care, mechanical ventilation, and mortality in those with underlying prematurity, bronchopulmonary dysplasia, or congenital heart disease. SEARCH STRATEGY: We searched the Cochrane Acute Respiratory Infections trials register and MEDLINE in March, 1999. In addition, abstracts on these topics were sought from the Pediatric Academies Meetings and the Intersciences Conference on Antimicrobial Agents and Chemotherapy for the years 1994 to 1997, inclusive. SELECTION CRITERIA: Randomized, controlled trials of prevention of RSV using immune globulin, respiratory syncytial virus immune globulin, or monoclonal RSV antibody in children with prematurity, bronchopulmonary dysplasia or congenital heart disease. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted data and assessed study quality. Only incidences could be pooled because data for durations was summarized in a manner that did not allow combining results across the studies. MAIN RESULTS: Four studies with a total of 2598 subjects were included in the main analysis. All were randomized controlled trials. Two trials were not blinded. Three studies examined RSV hyperimmune globulin and one examined monoclonal RSV antibody. A study of a different monoclonal RSV antibody could not be included because it has not been presented or published. The pooled Peto Odds Ratios favoring prophylaxis were 0.48 (95% CI 0.37, 0.64), 0.47 (0.29, 0. 77), and 0.99 (0.48, 2.07) for incidence of hospitalization, incidence of ICU admission, and incidence of mechanical ventilation, respectively. The numbers needed to prevent one hospitalization and one ICU admission are 17 and 50 respectively. REVIEWER'S CONCLUSIONS: RSVIG is effective in preventing RSV hospitalizations and admission to the intensive care unit, but not in preventing mechanical ventilation. There was a non-significant trend towards a higher mortality in children given RSVIG.

Bronchodilators for bronchiolitis.

OBJECTIVES: Bronchiolitis is an acute, highly communicable lower respiratory tract infection. Bronchodilators are commonly used in the management of bronchiolitis in North America, but not in the United Kingdom. The objective of this review was to assess the effects of bronchodilators for bronchiolitis. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Reference Update, reference lists of articles, and the files of two of the authors up to June 1998. SELECTION CRITERIA: Randomised trials comparing bronchodilators with placebo in the treatment of bronchiolitis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Unpublished data were requested from authors when necessary. MAIN RESULTS: In eight trials with 394 children, 46% demonstrated an improved clinical score with bronchodilators compared to 75% with placebo (odds ratio for no improvement 0.29, 95% confidence interval 0.19 to 0.45). However, the inclusion of studies that enrolled people with recurrent wheezes may have biased these results in favour of bronchodilators. Bronchodilator recipients did not show improvement in measures of oxygenation, the rate of hospitalisation (18% versus 26%, odds ratio 0.70, 95% confidence interval 0.36 to 1.35) or duration of hospitalisation (weighted mean difference 0.12, 95% confidence interval -0.3 to 0.5). REVIEWER'S CONCLUSIONS: Bronchodilators produce modest short-term improvement in clinical scores. This small benefit must be weighed against the costs of these agents.

Glucocorticoids for acute viral bronchiolitis in infants and young children.

BACKGROUND: Systemic glucocorticoids have been widely prescribed for use in infants and young children with acute viral bronchiolitis but the actual benefit of this intervention requires clarification. OBJECTIVES: To systematically review the evidence on the effectiveness of systemic glucocorticoids for the treatment of infants and young children with acute viral bronchiolitis. SEARCH STRATEGY: Multiple strategies were incorporated to maximize identification of suitable studies. The following databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2003); MEDLINE (January 1966 to September 2003); Current Contents (1998 to 2000); EMBASE (January 1990 to September 2003); and Sci Search. Handsearches through cited references and contacts with experts were also used. SELECTION CRITERIA: Only randomised controlled trials (RCT) were eligible for inclusion. Studies were included if participants were diagnosed with acute viral bronchiolitis and treated with systemic (oral, intramuscular or intravenous) corticosteroids. Three reviewers independently selected potentially relevant articles. Four reviewers evaluated these studies, determined eligibility and assessed the methodological quality of each RCT. DATA COLLECTION AND ANALYSIS: The primary outcome of interest was length of hospital stay (LOS). Secondary outcomes were: respiratory rate, haemoglobin oxygen saturation, and hospital admission and revisit rates. Data were extracted independently by the four reviewers and the results compiled and compared. Two reviewers reassessed studies to clarify points of discrepancy in the data extraction and database entry processes. Missing data were requested from the authors or calculated from other data presented in the study report. MAIN RESULTS: There was complete agreement on the inclusion of 13 trials and the exclusion of five studies. Two main study recruitment groups were identified: a) infants and young children within the first 48 hours of hospitalisation (10 trials), and b) outpatient infants and young children who were randomised from the emergency department and who may nor may not have required hospital admission (three trials).A total of 1,198 children aged 0 to 30 months were treated with the equivalent of 0.5 to 10 mg/kg of systemic prednisone for two to seven days. Outcomes of interest were not measured in each RCT. In the pooled analysis of seven trials, there was a decrease in LOS in treated children of 0.38 days (95% confidence interval (CI) -0.81 to 0.05), indicating no significant difference between treatment groups. In the pooled analysis of eight trials, the day three clinical score measured: a standard mean difference (SMD) of -0.20 (95% CI -0.73 to 0.32), indicating no difference between treatment groups. Subgroup analyses for base LOS and clinical score outcomes were performed on infants who were a) less than 12 months of age, b) all respiratory syncytial virus (RSV) positive, c) treated with less than 6 mg/kg of prednisone equivalent throughout the illness and d) first-time wheezers. These were limited by the small number of studies in each subgroup. Hospital admission rates were examined in three trials and no difference was seen between treatment groups (odds ratio (OR) 1.05 (95% CI 0.23 to 4.87). Readmission rates were reported in six studies; with no significant differences between treatment groups. Hospital revisit rates were reported in three studies, with a significant difference between treatment groups reported in one study only. The respiratory rate and haemoglobin oxygen saturation were reported descriptively in six RCTs; no differences were found between groups. Co-interventions (oxygen, supportive fluids and bronchodilators) were used similarly between treatment groups in all RCTs. REVIEWERS' CONCLUSIONS: No benefits were found in either LOS or clinical score in infants and young children treated with systemic glucocorticoids as compared to placebo. There were no differences in these outcomes between treatment groups; either in the pooled groups; either in the pooled analysis or in any of the sub analyses. Among the three studies evaluating hospital admission rates following the initial hospital visit there was no difference between treatment groups. There were no differences found in respiratory rate, haemoglobin oxygen saturation, hospital revisit or readmission rates. Subgroup analyses were significantly limited by the low number of studies in each comparison. Marked study heterogeneity and occasionally conflicting direction of benefit between trials suggests that these results should be interpreted with caution. Specific data on the harm of corticosteroid therapy in this patient population are lacking. Available evidence suggests that corticosteroid therapy is not of benefit in this patient group.