Clinical research abstracts for pediatricians
Article Outline
Editor's Note: Journals reviewed for this issue: New England Journal of Medicine, Journal of the American Medical Association, British Medical Journal, The Lancet, Pediatric Infectious Diseases Journal, and Archives of Disease in Childhood
A multicenter, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis
Wainwright C, Altamirano L, Cheney M, Cheney J, Barber S, Price D, et al. N Engl J Med 2003;349:27-35
Context The role of bronchodilators in the treatment of infants with bronchiolitis is controversial. Most studies of the use of bronchodilators have enrolled small numbers of subjects and have examined only short-term outcomes, such as clinical scores.
Objectives To examine the effect of nebulized epinephrine on the length of the hospital stay among infants with bronchiolitis.
Design Randomized, double-blind, controlled trial.
Setting Four hospitals in Queensland, Australia.
Participants 194 infants admitted with a clinical diagnosis of bronchiolitis.
Interventions Nebulized single-isomer epinephrine (three 4-mL doses of 1% epinephrine) versus placebo (normal saline solution) administered at 4-hour intervals after hospital admission.
Main outcome measures The primary outcome measures were the length of the hospital stay and the time until the infant was ready for discharge. The secondary outcome measures were the degree of change in the respiratory rate, heart rate, and respiratory-effort score, and the time that supplemental oxygen was required.
Results There were no significant overall differences between the groups in the length of the hospital stay (58.8 h vs 69.5h, P
=.16) or the time until the infant was ready for discharge (46.5 h vs 47.7 h, P=.86). Among infants who required supplemental oxygen and intravenous fluids, the time until the infant was ready for discharge was significantly longer in the epinephrine group than in the placebo group (135.9 h vs 80.2 h, P=.02). The need for supplemental oxygen at admission had the greatest influence on the score for severity of illness, and strongly predicted the length of the hospital stay and the time until the infant was ready for discharge (P<.001). There were no significant changes in the respiratory rate, blood pressure, or respiratory-effort scores from before each treatment to after each treatment. The heart rate was significantly increased after each treatment with epinephrine (P=.02 to P<.001).
Conclusions The use of nebulized epinephrine did not significantly reduce the length of the hospital stay or the time until the infant was ready for discharge among infants admitted to the hospital with bronchiolitis.
Comment The role of bronchodilators in the treatment of bronchiolitis is controversial, with a recent review of the use of a β2 adrenergic agent (salbutamol) for bronchiolitis that showed short-term improvements in clinical scores, with no improvement in measures of oxygenation or in the rate of hospitalization.1 Since Wohl and Chernick's initial suggestion that epinephrine, because of its α-adrenergic activity, might be a better bronchodilator for use in patients with bronchiolitis,2 investigators have shown that the use of epinephrine reduces combined pulmonary and upper-airway resistance in admitted infants,3 results in more rapid discharge from the emergency department,4 and decreased hospital stay (compared with those treated with salbutamol alone).5
Wainwright et al suggest that the current results differ from previous work because of a type I error, that is, incorrect rejection of the null hypothesis due to a small number of subjects. This could be true; however, there are other factors that could influence the results they reported: (1) time of enrollment (infants were assigned to received treatment within 24 hours after admission to the hospital, and not in the emergency department); (2) patient age (previous work has shown a better effect in patients <6 months of age3., 5.; and (3) infants only received three treatments, at 4-hour intervals, and not during the total time they were admitted, as done in other studies.5
Nevertheless, if the goal is to discharge home earlier, the evidence does not support treatment with bronchodilators (salbutamol or epinephrine) in infants <12 months with acute bronchiolitis. However, epinephrine does reduce airway resistance, improves clinical score, and shortens hospital stay in younger infants (<6 months), so this medication should be used in this age group and to try to relieve respiratory distress in older infants. The speculation by Wohl and Chernick that α-adrenergic nose drops, particularly before feeding, could be an effective treatment,6 is an interesting hypothesis that could be tested by an appropriate clinical study.
Ignacio Sanchez, MD
Pediatric Pulmonology Section, Department of Pediatrics
Catholic University of Chile
Santiago, Chile
Evaluation of impermeable covers for bedding in patients with allergic rhinitis
Terreehorst I, Hake, Oosting AJ, Tempels-Pavlica Z, de Monchy JGR, Bruijnzeel-Koomen CAFM. N Engl J Med 2003;349:237-46
Context Encasing bedding in impermeable covers reduces exposure to house-dust mites, but the clinical benefit of this intervention as part of mite-avoidance measures for patients with allergic rhinitis is not known.
Objectives To determine the effects of one year of use of impermeable bedding covers in the bedrooms of patients with rhinitis who were sensitized to house-dust mites on the signs and symptoms of disease.
Design Randomized, placebo-controlled trial.
Setting Three university medical centers.
Participants 279 patients with allergic rhinitis.
Interventions Subjects were randomized to impermeable or nonimpermeable (control) covers for their mattress, pillow, and duvet or blanket. At the start of the study, all participants received information on general allergen-avoidance measures.
Main outcome measures The severity of rhinitis was measured on a rhinitis-specific visual-analogue scale and by means of a daily symptom score and nasal allergen provocation testing. The concentrations of Dermatophagoides pteronyssinus (Der p1) and D farinae (Der f1) in dust from patients' mattresses, bedroom floors, and living room floors at baseline and after 12 months were measured to assess the efficacy of the intervention.
Results A total of 232 patients completed the study. There was a significant reduction in Der p1 and Der f1 concentrations in the mattresses of the impermeable-cover group, whereas there was no significant reduction in the control group. However, there was no significant effect on the clinical outcome measures. Analyses of subgroups defined according to age, level of exposure, type, and severity of sensitization, or characteristics of the patient's home, had similar results.
Conclusions Mite-proof bedding covers, as part of a structured allergy-control program, reduced the level of exposure to mite allergens. Despite the success of the intervention, this single avoidance measure did not lead to a significant improvement of clinical symptoms in patients with allergic rhinitis.
Comment The treatment of allergic diseases requires a multidirectional approach, including pharmacotherapy to improve patients' symptoms, specific allergen immunotherapy to control the immunologic basis of allergic disease, and allergen avoidance to decrease specific allergen exposures. Terreehorst et al conducted a well-designed study to evaluate clinical improvement in patients, instituting dust mite allergen impermeable barriers for pillows and mattresses, one component of allergen avoidance. However, both the control and intervention groups also instituted other dust mite avoidance techniques, such as washing bedding in hot water weekly and employment of a routine schedule of home ventilation/heating. Thus, all subjects were using some dust avoidance techniques, which might also reduce exposures to other substances that influence allergies such as endotoxin, mold, and animal dander. Data from this study clearly show a statistically significant reduction in isolation of dust mite allergen from mattresses with impermeable covers, but do not show a significant difference in rhinitis symptom scores between the study and control populations. Although this study demonstrates no additional control of rhinitis symptoms when dust mite encasements are added to other interventions, it may mislead readers into thinking that environmental controls have little role in comprehensive allergy treatment. In addition, how well this information translates to the general pediatrician's practice is unclear. We suspect that in practical terms, when patients are not participating in a study, other dust mite avoidance techniques may not be strictly observed. The relative ease of using dust mite allergen-impermeable barriers may be a way to reduce dust mite allergens to levels that do impact clinical symptoms when compared with no avoidance techniques. A definitive “real-world” study with no intervention in the control population has not been performed.
Georgiana Sanders, MD, MS
Andrew Singer, MD
Division of Allergy and Clinical Immunology
University of Michigan
Ann Arbor, MI 48109
Effect of viewing smoking in movies on adolescent smoking initiation: A cohort study
Dalton MA, Sargent JD, Beach ML, Titus-Ernstoff L, Gibson JJ, Ahrens MB. Lancet 2003;362:281-5
Context Exposure to smoking in movies has been linked with adolescent smoking initiation in cross-sectional studies.
Objectives To determine whether exposure to smoking in movies predicts smoking initiation among adolescents.
Design Prospective cohort study.
Setting 14 schools in Vermont and New Hampshire.
Participants 3547 adolescents, aged 10 to 14 years, who reported in a baseline survey that they had never tried smoking.
Interventions Exposure to smoking in movies was estimated for individual respondents on the basis of the number of smoking occurrences viewed in unique samples of 50 movies, which were randomly selected from a larger sample pool of popular contemporary movies. We successfully recontacted 2603 (73%) students were recontacted 13 to 26 months later for a follow-up interview to determine whether they had initiated smoking.
Main outcome measures Rate of smoking initiation.
Results Overall, 10% (n=259) of students initiated smoking during the follow-up period. In the highest quartile of exposure to movie smoking, 17% (107) of students had initiated smoking, compared with only 3% (22) in the lowest quartile. After controlling for baseline characteristics, adolescents in the highest quartile of exposure to movie smoking were 2.71 (95% CI, 1.73-4.25) times more likely to initiate smoking compared with those in the lowest quartile. The effect of exposure to movie smoking was stronger in adolescents with nonsmoking parents than in those whose parents smoked. In this cohort, 52.2% (95% CI, 30.0-67.3) of smoking initiation can be attributed to exposure to smoking in movies.
Conclusions These results provide strong evidence that viewing smoking in movies promotes smoking initiation among adolescents.
Comment This longitudinal study by Dalton et al substantially strengthened the large and consistent scientific literature indicating that smoking in the movies stimulates children to smoke. Several cross-sectional and experimental studies indicated that exposure to smoking in movies increased the likelihood that adolescents would begin smoking.
As in the cross-sectional studies, Dalton et al found a clear dose–response relationship (Figure). The more on-screen smoking the children saw, the more likely they were to have started to smoke. This effect is stronger in children of nonsmoking parents than parents who smoke. Children of nonsmoking parents in the most exposed group are 4.1 times as likely to have started smoking compared with those in the lowest exposure group. This effect is substantially stronger than the increase of “only” 1.6 times among children of smoking parents.
Figure.
The more smoking adolescents see in movies, the more likely they are to start smoking. The effect is strongest for children of nonsmokers (black bars). (Graph courtesy of Dr. James Sargent, Dartmouth University.)
Smoking in the movies accounted for 52% of the children who started smoking, a stronger effect than traditional cigarette advertising. Applying these results nationwide means that 1070 children start to smoke every day because of the movies, 330 of whom will die as a result.
The existence of this dose–response relationship not only strengthens the scientific case, but it also means that steps to reduce the “dose,” particularly assigning an “R” rating for movies with smoking, will lead to less teen smoking. An “R” rating would cut the effect of smoking in movies by more than half.
Stanton A. Glantz
Center for Tobacco Control Research and Education
University of California, San Francisco
San Francisco, CA 94143
Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: Two randomized controlled trials
Dineen Wagner K, Ambrosini P, Rynn M, Wohlberg C, Yang R, Greenbaum MS, et al. JAMA 2003;290:1033-41
Context The efficacy, safety, and tolerability of selective serotonin reuptake inhibitors (SSRIs) in the treatment of adults with major depressive disorder (MDD) are well established. Comparatively few data are available on the effects of SSRIs in depressed children and adolescents.
Objectives To evaluate the efficacy and safety of sertraline compared with placebo in treatment of pediatric patients with MDD.
Design Two multicenter randomized, double-blind, placebo-controlled trials were conducted between December 1999 and May 2001 and were pooled a priori.
Setting 53 hospital, general practice, and academic centers in the United States, India, Canada, Costa Rica, and Mexico.
Participants 376 children and adolescents, aged 6 to 17 years with DSM-IV–defined MDD of at least moderate severity.
Interventions Patients were randomly assigned to receive a flexible dosage (50-200 mg/d) of sertraline (n=189) or matching placebo tablets (n=187) for 10 weeks.
Main outcome measures Change from baseline in the Children's Depression Rating Scale–Revised (CDRS-R) Best Description of Child total score and reported adverse events.
Results Sertraline-treated patients had statistically significantly greater improvement than placebo patients on the CDRS-R total score (mean change at week 10, −30.24 vs −25.83, respectively; P=.001; opverall mean change, −22.84 vs −20.19, respectively; P=.007). Based on a 40% decrease in the adjusted CDRS-R total score at study end point, 69% of sertraline-treated patients compared with 59% of placebo patients were considered responders (P=.05, number needed to treat=10). Sertraline treatment was generally well tolerated. Seventeen (9%) sertraline-treated patients and 5 (3%) placebo patients prematurely discontinued the study because of adverse events. Adverse events that occurred in at least 5% of sertraline-treated patients and with an incidence of at least twice that in placebo patients, included diarrhea, vomiting, anorexia, and agitation.
Conclusions The results of this pooled analysis demonstrate that sertraline is an effective and well-tolerated short-term treatment for children and adolescents with MDD.
Comment This study adds further evidence to an important, growing area that addresses the relative paucity of data for children and adolescents with mental health disorders. The study is well designed with clear information on methodology and limitations. As with many antidepressant trials, a very high rate of placebo response (59%) makes treatment effect size difficult to demonstrate. Sertraline does appear effective in this international, multicenter, pooled set of well-organized trials. However, clinicians need to consider the outcome used in this study to analyze whether change on the CDRS-R scale is clinically significant. In addition, the 10-week follow up period is shorter than the recommended duration of most antidepressants, which may extend to 6 months or beyond. Although the adverse event data are helpful, this study was not sufficiently powered to determine rare side effects or complications of therapy. Further studies and clinical surveillance are necessary to fully weigh any potential harms with benefits. Finally, this study is useful to determine the effects of pharmacotherapy; however, psychotherapy was not part of the treatment. Ultimately, clinicians will need more information on the relative benefits of each therapeutic modality and effects of combined treatment.
Jerry Rushton, MD, MPH
Indiana University
Indianapolis, IN 46202
Also noted
Belt-positioning booster seats and reduction in risk of injury among children in vehicle crashes
Durbin DR, Elliott MR, Winston FK. JAMA 2003;289:2835-40
The goal of this well-designed cohort study was to quantify the association of belt-positioning booster seats compared with seat belts alone and risk of injury among 4- to 7-year-old children. The odds of injury, adjusting for child, driver, crash, and vehicle characteristics, were 59% lower for children in belt-positioning boosters than in seat belts (odds ratio, 0.41; 95% CI, 0.20-0.86).
Neurobehavioral outcomes of school-age children born extremely low birth weight or very preterm in the 1990s
Anderson P, Doyle LW. JAMA 2003;289:3264-72
This study compared the cognitive, educational, and behavioral outcomes of extremely low birth weight (ELBW) or very preterm infants born in the 1990s with normal birth weight (NBW) controls. Cognitive and reading scores were significantly lower among the ELBW infants. In addition, attention difficulties, internalizing behavior problems, and immature adaptive skills were more common in the ELBW or very preterm cohort.
References
- . Bronchodilators for bronchiolitis. Cochrane Database Syst Rev. 2000;2:CD001266
- . State of the art: bronchiolitis. Am Rev Respir Dis. 1978;118:759–781
- . Effect of racemic epinephrine and salbutamol on clinical score and pulmonary mechanics in infants with bronchiolitis. J Pediatr. 1993;122:145–151
- . A randomized trial comparing the efficacy of epinephrine with salbutamol in the treatment of acute bronchiolitis. J Pediatr. 1995;126:1004–1007
- . Efficacy of nebulized epinephrine versus salbutamol in hospitalized infants with bronchiolitis. Pediatr Pulmonol. 2001;31:284–288
- . Treatment of acute bronchiolitis. N Engl J Med. 2003;349:82–83
PII: S0022-3476(03)00728-5
doi:10.1016/j.jpeds.2003.10.027
© 2004 Elsevier Inc. All rights reserved.
