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- Axelsson, Inge, 1947-, et al.
(author)
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Inhaled corticosteroids in children with persistent asthma : effects of different drugs and delivery devices on growth
- 2019
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In: Cochrane Database of Systematic Reviews. - : John Wiley & Sons. - 1469-493X. ; :6
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Research review (peer-reviewed)abstract
- Background: Inhaled corticosteroids (ICS) are the most effective treatment for children with persistent asthma. Although treatment with ICS is generally considered to be safe in children, the potential adverse effects of these drugs on growth remains a matter of concern for parents and physicians.Objectives: To assess the impact of different inhaled corticosteroid drugs and delivery devices on the linear growth of children with persistent asthma.Search methods: We searched the Cochrane Airways Trials Register, which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, Embase, CINAHL, AMED and PsycINFO. We handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials.gov and manufacturers' clinical trial databases, or contacted the manufacturer, to search for potential relevant unpublished studies. The literature search was initially conducted in September 2014, and updated in November 2015, September 2018, and April 2019.Selection criteria: We selected parallel‐group randomized controlled trials of at least three months' duration. To be included, trials had to compare linear growth between different inhaled corticosteroid molecules at equivalent doses, delivered by the same type of device, or between different devices used to deliver the same inhaled corticosteroid molecule at the same dose, in children up to 18 years of age with persistent asthma.Data collection and analysis: At least two review authors independently selected studies and assessed risk of bias in included studies. The data were extracted by one author and checked by another. The primary outcome was linear growth velocity. We conducted meta‐analyses using Review Manager 5.3 software. We used mean differences (MDs) and 95% confidence intervals (CIs ) as the metrics for treatment effects, and the random‐effects model for meta‐analyses. We did not perform planned subgroup analyses due to there being too few included trials.Main results: We included six randomized trials involving 1199 children aged from 4 to 12 years (per‐protocol population: 1008), with mild‐to‐moderate persistent asthma. Two trials were from single hospitals, and the remaining four trials were multicentre studies. The duration of trials varied from six to 20 months.One trial with 23 participants compared fluticasone with beclomethasone, and showed that fluticasone given at an equivalent dose was associated with a significant greater linear growth velocity (MD 0.81 cm/year, 95% CI 0.46 to 1.16, low certainty evidence). Three trials compared fluticasone with budesonide. Fluticasone given at an equivalent dose had a less suppressive effect than budesonide on growth, as measured by change in height over a period from 20 weeks to 12 months (MD 0.97 cm, 95% CI 0.62 to 1.32; 2 trials, 359 participants; moderate certainty evidence). However, we observed no significant difference in linear growth velocity between fluticasone and budesonide at equivalent doses (MD 0.39 cm/year, 95% CI ‐0.94 to 1.73; 2 trials, 236 participants; very low certainty evidence).Two trials compared inhalation devices. One trial with 212 participants revealed a comparable linear growth velocity between beclomethasone administered via hydrofluoroalkane‐metered dose inhaler (HFA‐MDI) and beclomethasone administered via chlorofluorocarbon‐metered dose inhaler (CFC‐MDI) at an equivalent dose (MD ‐0.44 cm/year, 95% CI ‐1.00 to 0.12; low certainty evidence). Another trial with 229 participants showed a small but statistically significant greater increase in height over a period of six months in favour of budesonide via Easyhaler, compared to budesonide given at the same dose via Turbuhaler (MD 0.37 cm, 95% CI 0.12 to 0.62; low certainty evidence).Authors' conclusions: This review suggests that the drug molecule and delivery device may impact the effect size of ICS on growth in children with persistent asthma. Fluticasone at an equivalent dose seems to inhibit growth less than beclomethasone and budesonide. Easyhaler is likely to have less adverse effect on growth than Turbuhaler when used for delivery of budesonide. However, the evidence from this systematic review of head‐to‐head trials is not certain enough to inform the selection of inhaled corticosteroid or inhalation device for the treatment of children with persistent asthma. Further studies are needed, and pragmatic trials and real‐life observational studies seem more attractive and feasible.
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| 3. |
- Zhang, Linjie, et al.
(author)
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Acellular vaccines for preventing whooping cough in children
- 2014
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In: Cochrane Database of Systematic Reviews. - 1469-493X. ; :9
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Research review (peer-reviewed)abstract
- Background Routine use of whole-cell pertussis (wP) vaccines was suspended in some countries in the 1970s and 1980s because of concerns about adverse effects. Following this action, there was a resurgence of whooping cough. Acellular pertussis (aP) vaccines, containing purified or recombinant Bordetella pertussis (B. pertussis) antigens, were developed in the hope that they would be as effective, but less reactogenic than the whole-cell vaccines. This is an update of a Cochrane review first published in 1999, and previously updated in 2012. In this update, we included no new studies. Objectives To assess the efficacy and safety of acellular pertussis vaccines in children and to compare them with the whole-cell vaccines. Search methods We searched CENTRAL (2013, Issue 12), MEDLINE (1950 to January week 2, 2014), EMBASE (1974 to January 2014), Biosis Previews (2009 to January 2014) and CINAHL (2009 to January 2014). Selection criteria We selected double-blind randomised efficacy and safety trials of aP vaccines in children up to six years old, with active follow-up of participants and laboratory verification of pertussis cases. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias in the studies. Differences in trial design precluded a meta-analysis of the efficacy data. We pooled the safety data from individual trials using a random-effects meta-analysis model. Main results We included six efficacy trials with a total of 46,283 participants and 52 safety trials with a total of 136,541 participants. Most of the safety trials did not report the methods for random sequence generation, allocation concealment and blinding, which made it difficult to assess the risk of bias in the studies. The efficacy of multi-component (>= three) vaccines varied from 84% to 85% in preventing typical whooping cough (characterised by 21 or more consecutive days of paroxysmal cough with confirmation of B. pertussis infection by culture, appropriate serology or contact with a household member who has culture-confirmed pertussis), and from 71% to 78% in preventing mild pertussis disease (characterised by seven or more consecutive days of cough with confirmation of B. pertussis infection by culture or appropriate serology). In contrast, the efficacy of one-and two-component vaccines varied from 59% to 78% against typical whooping cough and from 41% to 58% against mild pertussis disease. Multi-component acellular vaccines are more effective than low-efficacy whole-cell vaccines, but may be less effective than the highest-efficacy whole-cell vaccines. Most systemic and local adverse events were significantly less common with aP vaccines than with wP vaccines for the primary series as well as for the booster dose. Authors' conclusions Multi-component (>= three) aP vaccines are effective in preventing whooping cough in children. Multi-component aP vaccines have higher efficacy than low-efficacy wP vaccines, but they may be less efficacious than the highest-efficacy wP vaccines. Acellular vaccines have fewer adverse effects than whole-cell vaccines for the primary series as well as for booster doses.
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