<i>The Cochrane Library</i> and safety of regular long‐acting beta<sub>2</sub>‐ agonists in children with asthma: an overview of reviews
Notice bibliographique
Résumé
Abstract Background: Two large randomized trials of regular salmeterol monotherapy in adults with asthma found an increased risk of asthma‐related mortality for salmeterol versus placebo or regular salbutamol. There are no similar large trials in children, and the safety of monotherapy with salmeterol or other long‐acting beta2‐agonists in children with asthma is unclear. Current guidelines recommend that regular long‐acting beta2‐agonist therapy should be given only in combination with regular inhaled corticosteroids. However, the safety of combination therapy in children with asthma is also unclear. Objectives: We used the paediatric trial results from Cochrane systematic reviews to assess the safety of regular long‐acting beta2‐agonist therapy, either as monotherapy or as combination therapy with inhaled corticosteroids, in children with asthma. Methods: We searched the Cochrane Database of Systematic Reviews in May 2012 for Cochrane reviews relating to the safety of regular formoterol and salmeterol, and ran updated searches for trials for each of the Cochrane reviews. We used odds ratios (ORs) to summarize the direct randomized evidence on safety from trials comparing regular formoterol or regular salmeterol as monotherapy versus placebo and then as combination therapy with inhaled corticosteroids versus the same dose of inhaled corticosteroids. We indirectly compared the safety of monotherapy and combination therapy by testing for differences between the pooled ORs for monotherapy and for combination therapy. We used ORs to summarize the direct randomized evidence on safety from trials comparing regular formoterol with regular salmeterol. We also compared the safety of regular formoterol and regular salmeterol indirectly by calculating an OR for the pooled results of trials assessing formoterol and the pooled results of trials assessing salmeterol, and then combined the direct and indirect evidence by calculating an overall OR for this comparison. Results: We identified four Cochrane reviews examining the safety of regular formoterol or salmeterol as either monotherapy or combination therapy. The reviews included 19 trials in children and we found two additional studies on salmeterol combination therapy, for a total of 21 trials in 7318 children. We identified two Cochrane reviews comparing the safety of formoterol with salmeterol, which included a single trial in 156 children. We found a statistically significant increase in the odds of suffering a nonfatal serious adverse event in children on formoterol monotherapy [OR = 2.48; 95% confidence interval (CI) = 1.27–4.83, I2 = 0%, five trials, N = 1335] and smaller nonsignificant increases in odds for salmeterol monotherapy (OR = 1.30; 95% CI = 0.82–2.05, I2 = 17%, five trials, N = 1333), formoterol combination therapy (OR = 1.60; 95% CI = 0.80–3.28, I2 = 32%, seven trials, N = 2788) and salmeterol combination therapy (OR = 1.20; 95% CI = 0.37–2.91, I2 = 0%, five trials, N = 1862). There was no significant difference between the pooled ORs of a serious adverse event on monotherapy (OR = 1.60; 95% CI = 1.10–2.33, 10 trials, N = 2668) and combination therapy (OR = 1.50; 95% CI = 0.82–2.75, 12 trials, N = 4650). However, there was an absolute increase of 21 children (95% CI = 4–45) suffering a severe adverse event of any cause for every thousand children treated over six months on monotherapy, compared with an absolute increase of three (95% CI = 1 fewer to 12 more) per 1000 children over three months on combination therapy. The evidence comparing the safety of regular salmeterol to regular formoterol was limited, and even when direct and indirect evidence were combined, the CI around the effect on serious adverse events was too wide to tell whether there was a difference in the comparative safety of formoterol and salmeterol (OR = 1.26; 95% CI = 0.37–4.32). Only one child died across all the trials, so the impact on mortality could not be assessed. Authors' conclusions: Although regular combination therapy is likely to be safer than monotherapy in children with asthma, the safety of regular combination therapy with formoterol or salmeterol in children remains uncertain, particularly in terms of mortality. The relative safety of formoterol and salmeterol is also unclear. There are currently large ongoing surveillance studies that may clarify the risks of combination therapy in children and adolescents with asthma. Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,010 | 0,056 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,002 |
| Méta-épidémiologie (sens large) | 0,011 | 0,010 |
| Bibliométrie | 0,014 | 0,016 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,004 | 0,003 |
| Science ouverte | 0,002 | 0,002 |
| Intégrité de la recherche | 0,003 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,008 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».