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. We performed a multicenter, randomized, placebo-controlled trial of one year of use of impermeable bedding covers in the bedrooms of patients with rhinitis who were sensitized to house-dust mites to determine the effects on the signs and symptoms of disease.

Three participating university medical centers enrolled 279 patients with allergic rhinitis who were randomly assigned to receive impermeable or non-impermeable (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. 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. We also measured the concentrations of Dermatophagoides pteronyssinus (Der p1) and D. farinae (Der f1) in dust from patients' mattresses, bedroom floors, and living-room floors at base line and after 12 months as a measure of the efficacy of the intervention.

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.

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.

The effectiveness of avoidance of house-dust-mite allergen (Dermatophagoides pteronyssinus 1 [Der p1]) in the management of asthma is uncertain.

We conducted a double-blind, randomized, placebo-controlled study of allergen-impermeable bed covers involving 1122 adults with asthma. The primary outcomes were the mean morning peak expiratory flow rate over a four-week period during the run-in phase and at six months and the proportion of patients who discontinued inhaled corticosteroid therapy as part of a phased-reduction program during months 7 through 12. Der p1 was measured in mattress dust in a 10 percent random subsample of homes at entry and at 6 and 12 months.

The prevalence of sensitivity to dust-mite allergen was 65.4 percent in the group supplied with allergen-impermeable bed covers (active-intervention group) and 65.1 percent in the control group supplied with non-impermeable bed covers. The concentration of Der p1 in mattress dust was significantly lower in the active-intervention group at 6 months (geometric mean, 0.58 microg per gram vs. 1.71 microg per gram in the control group; P=0.01) but not at 12 months (1.05 microg per gram vs. 1.64 microg per gram; P=0.74). The mean morning peak expiratory flow rate improved significantly in both groups (from 410.7 to 419.1 liters per minute in the active-intervention group, P<0.001 for the change; and from 417.8 to 427.4 liters per minute in the control group, P<0.001 for the change). After adjustment for base-line differences (by analysis of covariance), there was no significant difference between the groups in the peak expiratory flow rate at six months (difference in means, active-intervention group vs. control group, -1.6 liters per minute [95 percent confidence interval, -5.9 to 2.7] among all patients [P=0.46] and -1.5 liters per minute [95 percent confidence interval, -6.9 to 3.9] among mite-sensitive patients [P=0.59]). There was no significant difference between the groups in the proportion in whom complete cessation of inhaled corticosteroid therapy was achieved (17.4 percent in the active-intervention group and 17.1 percent in the control group) or in the mean reduction in steroid dose, either among all patients or among mite-sensitive patients.

Allergen-impermeable covers, as a single intervention for the avoidance of exposure to dust-mite allergen, seem clinically ineffective in adults with asthma.

Although inhaled glucocorticosteroids are recommended for persistent asthma, their long-term effect on recent onset, mild, persistent asthma has yet to be established.

We did a randomised, double-blind clinical trial in 7241 patients in 32 countries to assess the effects of budesonide in patients who had had mild persistent asthma for less than 2 years and who had not had previous regular treatment with glucocorticosteroids. Patients aged 5-66 years received either budesonide or placebo once daily for 3 years in addition to their usual asthma medications. The daily budesonide dose was 400 g, or 200 g for children younger than 11 years. The primary outcome was time to first severe asthma-related event, and analysis was by intention to treat.

198 of 3568 patients on placebo and 117 of 3597 on budesonide had at least one severe asthma exacerbation; hazard ratio 0·56 (95% CI 0·45-0·71, p<0·0001). Patients on budesonide had fewer courses of systemic corticosteroids and more symptom-free days than did those on placebo. Compared with placebo, budesonide increased postbronchodilator forced expiratory volume in 1 s (FEV1) from baseline by 1·48% (p<0·0001) after 1 year and by 0·88% (p=0·0005) after 3 years (expressed as percent of the predicted value). The corresponding increase in prebronchodilator FEV1was 2·24% after 1 year and 1·71% after 3 years (p<0·0001 at both timepoints). The effect of treatment on all outcome variables was independent of the baseline lung function (prebronchodilator or postbron chodilator) or baseline medication. In children younger than 11 years, 3-year growth was reduced in the budesonide group by 1·34 cm. The reduction was greatest in the first year of treatment (0·58 cm) than years 2 and 3 (0·43 cm and 0·33 cm, respectively)

Long-term, once-daily treatment with low-dose budesonide decreases the risk of severe exacerbations and improves asthma control in patients with mild persistent asthma of recent onset.

This large study of >7000 patients (children and adults) from 32 countries, conducted over 5 years, gives us important information on the role of inhaled corticosteroids (ICS) in patients with mild persistent asthma.

In this study, once daily ICS:

• reduced the risk of exacerbations (including severe ones) and reduced the need for courses of oral steroids.

• increased the number of symptom-free days.

• produced a small benefit in FEV1 (post-bronchodilator)

• achieved these improvements with once daily dosage (budesonide 400mcg daily or 200mcg daily if <11 years of age)

• slowed growth by an average of 0.43 cm/year (although this unlikely to affect final height, it is a good reminder that the lowest effective dose should be used).

The study design is such that the benefits of ICS may have if anything been underestimated.

It is clear ICS can improve asthma control. The study doesn't provide good evidence for a long-term disease modifying effect (eg future asthma or irreversible airway disease).

In a long-term, prospective study, we set out to determine whether otitis media in the first 3 years of life persisting for periods currently considered developmentally threatening actually results in later impairments of children’s cognitive, language, speech, or psychosocial development; whether prompt insertion of tympanostomy tubes prevents or lessens any such impairments; and whether, irrespective of causality, associations exist between persistent early-life otitis media and later developmental impairments. This report describes findings in study participants at the age of 4 years.

We enrolled 6350 healthy infants from 2 to 61 days of age at urban hospitals and 2 small-town/rural and 4 suburban private pediatric practices. We regularly evaluated the children for the presence of middle-ear effusion (MEE) throughout their first 3 years of life by pneumatic otoscopy, supplemented by tympanometry; we monitored the validity of the otoscopic observations on an ongoing basis; and we treated children for otitis media according to specified guidelines. In the clinical trial component of the study, we randomly assigned 429 children who met specified minimum criteria regarding the persistence of MEE to undergo tympanostomy tube insertion either promptly or after a defined extended period if MEE remained present. In the associational component of the study, we selected a representative sample of 241 children who ranged from having no MEE to having MEE the cumulative duration of which fell just short of meeting randomization criteria for the clinical trial. In 397 (92.5%) of the children in the clinical trial and in 234 (97.1%) of the children in the representative sample, we assessed cognitive, language, speech, and psychosocial development at the age of 4 years, using formal tests, conversational samples, and parent questionnaires.

In children in the randomized clinical trial, there were no statistically significant differences in mean (±standard deviation) scores (higher denotes more favorable) favoring the early-treatment group over the late-treatment group on the General Cognitive Index of the McCarthy Scales of Children’s Abilities (97 ± 14 and 98 ± 14, respectively); the Peabody Picture Vocabulary Test–Revised, a measure of receptive language (90 ± 15 vs 92 ± 16); the Nonword Repetition Test, a measure of phonological memory (66 ± 12 vs 70 ± 12); the Number of Different Words, a measure of word diversity (150 ± 34 vs 150 ± 31); the Mean Length of Utterance in Morphemes, a measure of sentence length and grammatical complexity (3.4 ± 0.8 vs 3.4 ± 0.7); or the Percentage of Consonants Correct–Revised, a measure of speech-sound production (92 ± 5 vs 93 ± 5). There were also no significant differences in ratings (higher denotes less favorable) on the Parenting Stress Index–Short Form (Total Stress scores: 68 ± 18 vs 65 ± 17) or the Child Behavior Checklist (Total Problem T scores: 50 ± 10 vs 49 ± 10). In the associational component of the study, correlations between the children’s durations of MEE and their developmental outcomes were generally weak and, in most instances, nonsignificant. Exceptions, after adjustment for sociodemographic variables and for hearing thresholds at the time of developmental testing, consisted of a significant negative correlation between children’s cumulative durations of MEE in their first 3 years of life and scores on the McCarthy Verbal subscale, and significant positive correlations between durations of MEE and scores on 2 measures of parent–child stress. The percentage of variance in these scores explained by time with MEE beyond that explained by sociodemographic variables ranged from 1.6% to 3.3%. In both the randomized clinical trial and the associational component, sociodemographic variables seemed to be the most important factors influencing developmental outcomes, and in both components, the results at 4 years of age were consistent with the results that had been obtained at 3 years of age.

In otherwise healthy children who are younger than 3 years and have persistent MEE within the duration limits that we studied, prompt insertion of tympanostomy tubes does not measurably improve developmental outcomes at 4 years of age. In such children, persistent MEE within the duration limits that we studied is negligibly associated with and probably does not affect developmental outcomes at 4 years of age.

The New England Journal of Medicine -- April 19, 2001 -- Vol. 344, No. 16
Effect of Early or Delayed Insertion of Tympanostomy Tubes for Persistent Otitis Media on Developmental Outcomes at the Age of Three Years

Here is some more good evidence to support the watch and wait/ conservative approach to children with middle ear effusion.

In 2001, the Pittsburgh group reported a very big study the results of which support a watch and wait/ conservative approach to children with middle ear effusion. (N Engl J Med 2001;344:1179-87).

They now present their data on the longer term follow-up of these children and conclude: “In otherwise healthy children who are younger than 3 years and have persistent MEE within the duration limits that we studied, prompt insertion of tympanostomy tubes does not measurably improve developmental outcomes at 4 years of age.”

Tympanostomy tubes might produce short term behavioral or hearing benefits but appears they have no impact on longer-term developmental outcomes (the issue that parents are usually most concerned about).

Background. A main indication for the insertion of tympanostomy tubes in infants and young children is persistent otitis media with effusion, reflecting concern that this condition may cause lasting impairments of speech, language, cognitive, and psychosocial development. However, evidence of such relations is inconclusive, and evidence is lacking that the insertion of tympanostomy tubes prevents developmental impairment.

Methods. We enrolled 6350 healthy infants from 2 to 61 days of age and evaluated them regularly for middle-ear effusion. Before the age of three years 429 children with persistent effusion were randomly assigned to have tympanostomy tubes inserted either as soon as possible or up to nine months later if effusion persisted. In 402 of these children we assessed speech, language, cognition, and psychosocial development at the age of three years.

Results. By the age of three years, 169 children in the early-treatment group (82 percent) and 66 children in the late-treatment group (34 percent) had received tympanostomy tubes. There were no significant differences between the early-treatment group and the late-treatment group at the age of three years in the mean (±SD) scores on the Number of Different Words test, a measure of word diversity (124±32 and 126±30, respectively); the Percentage of Consonants Correct-Revised test, a measure of speech-sound production (85±7 vs. 86±7); the General Cognitive Index of McCarthy Scales of Children's Abilities (99±14 vs. 101±13); or on measures of receptive language, sentence length, grammatical complexity, parent-child stress, and behavior.

Conclusions. In children younger than three years of age who have persistent otitis media, prompt insertion of tympanostomy tubes does not measurably improve developmental outcomes at the age of three years. (N Engl J Med 2001;344:1179-87.)

How might pediatric health professionals apply the findings of these two studies? These surgical procedures have risks, known and unknown. In the short term they all involve a risk of well-described complications, including the very low risk of death from anesthesia and the risk of persistent bleeding among children who undergo adenotonsillectomy. Given the long history of tonsillectomy and adenoidectomy, we know more about their long-term risks than we do about the risks of tympanostomy-tube insertion. However, the risks of tympanostomy-tube insertion also appear to be fairly small, although some children have decreased rather than increased hearing after the tubes are inserted, and others have persistent otorrhea, requiring removal of the tubes. The tubes often lead to long-term anatomical changes in the tympanic membrane, especially tympanosclerosis, retraction, and changes in mobility. The clinical implications of these changes, however, are not well defined. What happens, for example, to hearing and the mobility of the tympanic membrane in middle-aged persons who had tubes inserted in childhood?

Perhaps most important, the study by Paradise et al. provides no evidence that the insertion of tubes improves developmental outcomes at the age of three years, although it does decrease the persistence of effusion and reduce short-term hearing loss. Clinicians will need to decide whether these benefits are enough to subject a child to surgery. The results of longer-term follow-up, especially to the age of five or six years, an age at which measures of development and behavior are more reliable, should make these decisions easier. In the meantime, the study by Paradise et al. indicates that children can have middle-ear effusion for more than three months without an apparent effect on development and behavior during the first three years of life.

To study the effectiveness of ventilation tubes on the language development in infants with persistent otitis media with effusion (OME). All existing studies addressed children 3 years of age or older. Currently, OME is detected and treated with ventilation tubes at a younger age. Because of the critical relationship between age, hearing, and language development, we conducted a study of the effects of ventilation tubes on language development in infants 1 to 2 years old with persistent OME.

A multicenter, randomized, controlled trial (embedded in a cohort) with 2 treatment arms: 1) treatment with ventilation tubes (VT group; n = 93); or 2) with a period of watchful waiting (WW group; n = 94). Hearing loss and expressive and comprehensive language were assessed every 6 months, while tympanometry and otoscopy were performed every 3 months. Other factors with potential influence on language development were also included: adenoidectomy, hospital, attending day care, sex, age at randomization, educational level of the mother, upper respiratory infections, and the native country of the parents and older siblings. The trial was designed to allow for the detection of a mean difference in language development of 3 months or more between children allocated to the VT and WW groups.

No relevant differences were found in expressive or comprehensive language between the 2 groups after adjustment for educational level of the mother, IQ of the child, and differences at baseline. A principal component analysis showed that in the VT group, the children with frequent complaints improved 1.6 months more in comprehensive language than those with no or some complaints. The children with favorable language stimulation, however, did not improve more than the children with less favorable stimulation. No differences were found for expressive language among the various clusters.The probability to improve >3 months in comprehensive language was .48 (95% confidence interval [CI]: .29-.68) for children with highly educated mothers versus .09 (95% CI: .02-.30) for children whose mothers had a low educational level. In the WW group, these changes were .30 (95% CI: .14-.53) and .14 (95% CI: .04-.35), respectively. The probability to improve >4 months in expressive language was .52 (95% CI: .32- .71) for children with highly educated mothers versus .06 (95% CI: .01-.31) for children whose mothers had a low educational level. In the WW group these changes were .42 (95% CI: .23-.64) and .11 (95% CI: .03-.35), respectively. In addition, there were delays in expressive language in both groups compared with their age expected values. The comprehensive language of the children who were effusion-free during the follow-up (n = 54) improved 1.5 months (95% CI: .2-3.2) more than that of the children who had persistent effusion during the entire follow-up (n = 28). No differences were found for expressive language development. Disregarding the intervention contrast, improvements in hearing seemed to be related to improvements in language development, especially in verbal comprehension.

In this study, we used the Reynell, Schlichting, and Lexi tests to study the relation between early persistent OME and language development. These tests are directly related to normal language, widely accepted, and validated. It cannot be ruled out that more specific measures such as auditory perception tests would have produced more differences between groups, but the focus was on general language development.A total of 10 children in the WW group received treatment with ventilation tubes during follow-up. A further 11 children dropped out during the trial. A sensitivity analysis with the 10 children who received ventilation tubes did not change the results, and baseline differences were not found between the 11 children who dropped out and those who completed the trial.

In the total group of infants with persistent OME, ventilation tubes did not have any incremental effect on language development. Beneficial effect of treatment in individual patients or subgroups of patients can, however, not be excluded.

• Autism is a behaviourally defined disorder, which is the endpoint of several organic aetiologies

• The number of children diagnosed as having autistic spectrum disorders is increasing for various reasons

• A diagnosis of autism can be reliably made at between 2 and 3 years of age

• Autism does not meet criteria for screening, but surveillance throughout the preschool years is recommended

• Diagnosis is by history taking, focusing on the developmental story and systematically inquiring for core behaviours, and by observation in several settings

To compare the safety and efficacy of anti-leukotrienes and inhaled glucocorticoids as monotherapy in people with asthma.

Systematic review of randomised controlled trials comparing anti-leukotrienes with inhaled glucocorticoids for 28 days or more in children and adults.

Rate of exacerbations that required treatment with systemic glucocorticoids.

13 trials (12 in adults, one in children) met the inclusion criteria; all were in people with mild and moderate asthma. Leukotriene receptor antagonists were compared with inhaled glucocorticoids at a daily dose equivalent to 400-450 µg beclometasone dipropionate. Patients treated with leukotriene receptor antagonists were 60% more likely to suffer an exacerbation requiring systemic glucocorticoids (relative risk 1.6, 95% confidence interval 1.2 to 2.2; number needed to treat 27, 13 to 81). A 130 ml greater improvement (80 ml to 170 ml) in forced expiratory volume in one second and a 19 l/min greater increase (14 l to 24 l) in morning peak expiratory flow rate were noted in favour of inhaled glucocorticoids. Differences in favour of inhaled glucocorticoids were also observed for nocturnal awakenings, use of rescue B2 agonists, and days without symptoms. Risk of side effects was no different between groups, but leukotriene receptor antagonists were associated a 2.5-fold increase risk of withdrawals due to poor asthma control (relative risk 2.5, 1.8 to 3.5).

Inhaled glucocorticoids doses equivalent to 400 µg/day beclometasone are more effective than leukotriene receptor antagonists in the treatment of adults with mild or moderate asthma. There is insufficient evidence to conclude on the efficacy of anti-leukotrienes in children.

In 2000 a Cochrane systematic review tentatively concluded that control of asthma was better in patients treated with inhaled glucocorticoids as single agents than with anti-leukotrienes

The 2002 Global Initiative for Asthma guidelines still classify the role of anti-leukotrienes as “under investigation”

Anti-leukotrienes as single agent are less effective than low doses of inhaled glucocorticoids for patients with mild and moderate persistent asthma

Several studies have demonstrated that acute otitis media (AOM) in children can be managed without antibiotics. Because children with AOM have traditionally been treated with antibiotics in the United States, there are concerns that parents may not be comfortable with their children being treated with pain control alone. Recently, Cates in England showed that antibiotic usage for AOM could be decreased by prescribing a safety-net antibiotic prescription (SNAP) to be filled if symptoms do not resolve with observation after 48 hours. It is not clear whether a SNAP will be acceptable to parents in other settings such as the United States. The objective of our study was to determine whether parents in the United States find a SNAP for AOM acceptable and whether antibiotic usage could be decreased by its use.

A pediatric practice-based research network in a midwestern community of 1.8 million was the setting for this study. The Cincinnati Pediatric Research Group (CPRG) includes practices in Ohio, Kentucky, and Indiana. Children who were between 1 and 12 years of age and presented to the offices of the CPRG with uncomplicated AOM were eligible for the study. Children were excluded when they had temperature >101.5°F, had an ear infection in the past 3 months, showed signs of another bacterial infection, or were toxic appearing. Families were given acetaminophen, ibuprofen, or topical otic anesthetic drops for pain control. They were also given a prescription for an antibiotic and instructed not to fill it unless symptoms either increased or did not resolve after 48 hours. The data were entered directly by investigators via an Internet site.

A total of 194 children were enrolled in 11 offices over 12 months; 175 (90%) completed the follow-up interview. The average child’s age was 5.0 years. Only 55 (31%) of the 175 who were contacted for follow-up had filled their antibiotic prescription. Compared with their previous experience, parents were overwhelmingly willing to treat AOM with pain medication alone (X² = 111). Seventy-eight percent (95% confidence interval: 71%–84%) of parents reported that the pain medication was effective. Sixty-three percent (95% confidence interval: 55%–70%) of parents reported that they would be willing to treat future AOM episodes without antibiotics and with pain medication alone.

A subset of parents find a safety-net prescription and pain control acceptable in the treatment of AOM, and antibiotic usage can be lowered with this strategy.

High rates of antibiotic prescribing to children contribute to antibiotic resistance in the community. The Centers for Disease Control and Prevention, in collaboration with other national and state level organizations, have actively promoted more judicious prescribing for children.

We sought to assess changes in the rate of antibiotic prescribing from 1996–2000 in 9 US health plans, patterns of diagnosis and treatment responsible for these trends, and changes in the use of first-line antimicrobial agents.

We analyzed claims data for dispensed medications and physician visits from 9 health plans. Each provided data on 25 000 children aged 3 months to <18 years enrolled between September 1, 1995, and August 31, 2000. Antibiotic dispensings were linked with an ambulatory visit claim to assign diagnosis. Antibiotic dispensings per person-year (antibiotics/p-y) were calculated for the age groups 3 months to <3 years, 3 years to <6 years, and 6 years to <18 years. The contribution of each diagnosis to changes in the overall rate of antibiotic use was determined. Generalized linear mixed models were used to test for trend and assess differences in rates by site.

From 1996–2000, antibiotic rates for children 3 months to <3 years decreased from 2.46 to 1.89 antibiotics/p-y (24%); for children 3 years to <6 years from 1.47 to 1.09 antibiotics/p-y (25%); and for children 6 to <18 years from 0.85 to 0.69 antibiotics/p-y (16%). The reduction varied among health plans from 6% to 39% for children 3 months to <3 years. A decrease in prescriptions for otitis media accounted for 59% of the total decrease, and was primarily accounted for by a decrease in the rate of diagnosis of this condition. The proportion of first-line penicillins increased from 49% to 53%, with health plans with the lowest initial rates increasing most.

Antibiotic prescribing decreased significantly between 1996 and 2000, concurrent with decreased frequency of diagnosis of potential bacterial infections, especially otitis media. Attention by public health and professional organizations and the news media to antibiotic resistance may have contributed to changes in diagnostic thresholds, resulting in more judicious prescribing.

To review the use of systemic corticosteroids to treat recurrent, acute asthma episodes in children, with a focus on the role of oral corticosteroids.

A comprehensive review of the literature was performed using the Medline database (January 1966–October 2002) and the Embase database (January 1980–August 2002).

The significant findings of 17 selected, controlled clinical trials of oral corticosteroids (OCSs) for acute exacerbations of asthma in children, compared with placebo or with other formulations of corticosteroids, can be summarized as follows: 1) OCSs are effective for the outpatient treatment of acute asthma, 2) pulmonary function tests may not be the best means of assessing the efficacy of OCSs for acute asthma, 3) early administration of OCSs for acute asthma reduces hospitalizations, 4) the critical factor for a positive outcome is early administration of the corticosteroid, and 5) OCSs are preferred for the outpatient treatment of acute asthma.

Early treatment of acute asthma symptoms with OCSs in children with a pattern of recurrent acute asthma may decrease the severity of acute asthma episodes and reduce the likelihood of subsequent relapses. Attention should be given to identifying these children and standardizing a treatment approach based on accepted, consistent definitions of what constitutes an asthma exacerbation and recurrence. A suggested protocol is described

This is a review of 17 controlled trials of oral steroids for acute exacerbations of asthma in children. It supports our current recommendation for early use of oral steroids in acute exaceerbations that are not responding quickly to inhaled bronchodilators. Oral steroids reduce the risk of hospitalisation, shorten the duration of exacerbation and reduce the risk of exacerbation relapse.

The treatment of infants with bronchiolitis is largely supportive. The role of bronchodilators 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.

We conducted a randomized, double-blind, controlled trial comparing nebulized single-isomer epinephrine with placebo in 194 infants admitted to four hospitals in Queens-land, Australia, with a clinical diagnosis of bronchiolitis. Three 4-ml doses of 1 percent nebulized epinephrine or three 4-ml doses of normal saline were administered at four-hour intervals after hospital admission. Observations were made at admission and just before, 30 minutes after, and 60 minutes after each dose. 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, the heart rate, and the respiratory-effort score and the time that supplemental oxygen was required.

There were no significant overall differences between the groups in the length of the hospital stay (P=0.16) or the time until the infant was ready for discharge (P=0.86). 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 (P=0.02). 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<0.001). 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=0.02 to P<0.001).

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.

There has been a lot of controversy and interest in the role of bronchodilators, particularly adrenaline, in the management of acute viral bronchiolitis. Many small and inconclusive studies have been published. This Australian study had the advantage of reasonable sample size. The weakness is the use of outcome measures related to length of hospital stay as this is a very noisy/dirty outcome measure, although the investigators did their best to allow for these difficulties. It suggests that adrenaline has no useful role in mild/moderate bronchiolitis but I don't believe it answers the question “can adrenaline reduce the risk of needing mechanical respiratory support in severe bronchiolitis?”

To compare clonidine with placebo added to ongoing psychostimulant therapy for the treatment of attention-deficit/hyperactivity disorder with comorbid oppositional defiant disorder or conduct disorder.

Children 6 to 14 years of age recruited through 2000 to 2001 were randomized to receive clonidine syrup 0.10 to 0.20 mg/day (n = 38) or placebo (n = 29) for 6 weeks. Primary outcome measures were the Conduct and Hyperactive Index subscales of the parent-report Conners Behavior Checklist. Side effects were monitored using physiological measures and the Barkley Side Effect Rating Scale.

Evaluable patient analysis showed that significantly more clonidine-treated children than controls were responders on the Conduct scale (21 of 37 versus 6 of 29; chi2(1) = 8.75, p <.01) but not the Hyperactive Index (13 of 37 versus 5 of 29). Compared with placebo, clonidine was associated with a greater reduction in systolic blood pressure measured standing and with transient sedation and dizziness. Clonidine-treated individuals had a greater reduction in a number of unwanted effects associated with psychostimulant treatment compared with placebo.

The findings support the continued use of clonidine in combination with psychostimulant medication to reduce conduct symptoms associated with attention-deficit/hyperactivity disorder. Treatment is well tolerated and unwanted effects are transient.

Clonidine and stimulants are commonly used concurrently for hyperactive and aggressive children, but without much published evidence of efficacy to support this practice. This Australian study, although relatively small, suggests there is an additional benefit of adding clonidine. It appears safe but the sample size is much too small to be sure.