Background: Evidence-based guidelines from the World Health Organization (WHO) have recommended a high (80%) fraction of inspired oxygen (FiO 2 ) to reduce surgical site infection in adult surgical patients undergoing general anaesthesia with tracheal intubation. However, there is ongoing debate over the safety of high FiO 2 . We performed a systematic review to define the relative risk of clinically relevant adverse events (AE) associated with high FiO 2 . Methods: We reviewed potentially relevant articles from the WHO review supporting the recommendation, including an updated (July 2018) search of EMBASE and PubMed for randomised and non-randomised controlled studies reporting AE in surgical patients receiving 80% FiO 2 compared with 30e35% FiO 2 . We assessed study quality and performed meta-analyses of risk ratios (RR) comparing 80% FiO 2 against 30e35% for major complications, mortality, and intensive care admission. Results: We included 17 moderateegood quality trials and two non-randomised studies with serious-critical risk of bias. No evidence of harm with high FiO 2 was found for major AE in the meta-analysis of randomised trials: atelectasis RR 0.91 [95% confidence interval (CI) 0.59e1.42); cardiovascular events RR 0.90 (95% CI 0.32e2.54); intensive care admission RR 0.93 (95% CI 0.7e1.12); and death during the trial RR 0.49 (95% CI 0.17e1.37). One non-randomised study reported that high FiO 2 was associated with major respiratory AE [RR 1.99 (95% CI 1.72e2.31)]. Conclusions: No definite signal of harm with 80% FiO 2 in adult surgical patients undergoing general anaesthesia was demonstrated and there is little evidence on safety-related issues to discourage its use in this population.

BackgroundLong-term inhaled corticosteroids (ICS) may reduce growth velocity and final height of children with asthma. We aimed to evaluate the association between ICS use of >12 months and growth.MethodsWe initially searched MEDLINE and EMBASE in July 2013, followed by a PubMed search updated to December 2014. We selected RCTs and controlled observational studies of ICS use in patients with asthma. We conducted random effects meta-analysis of mean differences in growth velocity (cm/year) or final height (cm) between groups. Heterogeneity was assessed using the I2 statistic.ResultsWe found 23 relevant studies (twenty RCTs and three observational studies) after screening 1882 hits. Meta-analysis of 16 RCTs showed that ICS use significantly reduced growth velocity at one year follow-up (mean difference -0.48 cm/year (95% CI -0.66 to -0.29)). There was evidence of a dose-response effect in three RCTs. Final adult height showed a mean reduction of -1.20 cm (95% CI -1.90 cm to -0.50 cm) with budesonide versus placebo in a high quality RCT. Meta-analysis of two lower quality observational studies revealed uncertainty in the association between ICS use and final adult height, pooled mean difference -0.85 cm (95% CI -3.35 to 1.65).ConclusionUse of ICS for >12 months in children with asthma has a limited impact on annual growth velocity. In ICS users, there is a slight reduction of about a centimeter in final adult height, which when interpreted in the context of average adult height in England (175 cm for men and 161 cm for women), represents a 0.7% reduction compared to non-ICS users.

ObjectivesWe aimed to assess the association between long-term use of inhaled corticosteroids (ICS) and bone adverse effects in patients with asthma.DesignSystematic review and meta-analysis of fracture risk and changes in bone mineral density with long-term ICS use in asthma.MethodsWe initially searched MEDLINE and EMBASE in July 2013, and performed an updated PubMed search in December 2014. We selected randomised controlled trials (RCTs) and controlled observational studies of any ICS (duration at least 12 months) compared to non-ICS use in patients with asthma. We conducted meta-analysis of ORs for fractures, and mean differences in bone mineral density. Heterogeneity was assessed using the I2 statistic.ResultsWe included 18 studies (7 RCTs and 11 observational studies) in the systematic review. Meta-analysis of observational studies did not demonstrate any significant association between ICS and fractures in children (pooled OR 1.02, 95% CI 0.94 to 1.10, two studies), or adults (pooled OR 1.09, 95% CI 0.45 to 2.62, four studies). Three RCTs and three observational studies in children reported on bone mineral density at the lumbar spine, and our meta-analysis did not show significant reductions with ICS use. Three RCTs and four observational studies in adults reported on ICS use and bone mineral density at the lumbar spine and femur, with no significant reductions found in the meta-analysis compared to control.ConclusionsICS use for ≥12 months in adults or children with asthma was not significantly associated with harmful effects on fractures or bone mineral density.

In view of the dose-response relationship seen between ICS use and important adverse effects such as fractures and pneumonia, clinicians needs to carefully balance the benefits of ICS versus the harms in older patients receiving long-term high-dose ICS.

3476 patients were treated. Incidence of any adverse events (AEs), serious AEs and investigator-defined drug-related AEs was similar across treatment groups within each trial. AEs reported by ≥5% of patients were similar across all treatment groups within each trial (Table). The number of cardiovascular AEs was small in all five studies and comparable between tiotropium Respimat ® and placebo. No deaths occurred in any trial. Conclusion: Once-daily tiotropium Respimat® is well tolerated and comparable with placebo in adult patients with symptomatic asthma receiving at least low-to high-dose ICS.