ABSTRACT. Objective. Although dornase alfa is a widely used, aerosolized, mucolytic agent in patients with cystic fibrosis (CF), its efficacy in relation to the timing of physiotherapy has not been tested. We sought to determine whether dornase alfa is more efficacious when it is administered 30 minutes before versus 30 minutes after physiotherapy/positive expiratory pressure (PEP) therapy in clinically stable children.Methods. Using a crossover, randomized, doubleblind, and placebo-controlled trial, we undertook a 6-week study of the efficacy of dornase alfa in relation to the timing of physiotherapy at home. There were 2 treatment orders. Dornase alfa before ؉ placebo after physiotherapy/PEP for 2 weeks was followed by a 2-week washout and then the reverse order placebo before and dornase alfa after physiotherapy/PEP for the final 2 weeks. The second treatment order reversed the placebo and dornase alfa therapy for the first and last 2-week blocks. The main outcome measures used included the change in predicted percentage of forced expiratory volume in 1 second (FEV 1 ), a composite quality of wellbeing score (QWB), and a measure of aerobic fitness (maximal oxygen consumption, [VO 2max ]), determined using shuttle testing.Results. Fifty-two patients who had CF (27 female) with mild to moderate suppurative lung disease, were a mean ؎ SD age of 10.7 ؎ 3.2 years, had Shwachman scores of 86 ؎ 11.8, had predicted FEV 1 of 83% ؎ 18%, had quality of well-being score of 0.76 ؎ 0.08, and had VO 2max of 42.6 ؎ 6.3 ml/kg per min were enrolled. Fifty patients completed the study. Intention-to-treat analysis was used. Nonsignificant mean (95% confidence interval) differences in FEV 1 ABBREVIATIONS. CF, cystic fibrosis; FEV 1 , forced expiratory volume in 1 second; PEP, positive expiratory pressure; VO 2max , maximal oxygen consumption; QWB, quality of well-being score; CI, confidence interval; FEF , mid expiratory flow rate. P hysiotherapy and systemic and nebulized antibiotics have been the cornerstones of treatment in cystic fibrosis (CF) for many years. [1][2][3] The introduction of the nebulized mucolytic agent dornase alfa (Pulmozyme [Hoffman-La Roche, Dee Why, Sydney, Australia]) in the 1990s proved to be an innovative adjunct to the management of lung disease in terms of reduced pulmonary exacerbations, improved lung function, and quality-of-life measures. 3-5 Dornase alfa use varies from country to country, on the basis of patient preference, physician prescribing practices, measured benefit in an individual, and health funding arrangements. In Australia, most recent figures indicate that dornase alfa is used by 22.1% of school-aged children (5-18 years), all of whom have demonstrated a Ͼ10% improvement in forced expiratory volume in 1 second (FEV 1 ) after 4 weeks of therapy. 6 However, despite the evaluation of dornase alfa in Ͼ15 years of clinical trials, there is no evidence as to whether dornase alfa is more efficacious when delivered before or after physiotherapy. As has been shown in adults who are prescri...

ObjectiveTo identify, summarise and evaluate evidence on the correlation between perceived and actual neighbourhood safety (personal and road danger) and diverse forms of outdoor active mobility behaviour (ie, active play, exercise, and travel) among primary-school-aged children.DesignA systematic review of evidence from observational studies exploring children’s active mobility behaviour and safety.Data sourcesSix electronic databases were searched: Google Scholar, PubMed, Scopus, Science Direct, ProQuest and Web of Science from study inception until July 2020.Data extraction and synthesisStudy selection and quality assessment were conducted independently by two reviewers. We expanded on a quality assessment tool and adopted a vote-counting technique to determine strength of evidence. The outcomes were categorised by individual, family and neighbourhood levels.ResultsA total of 29 studies were included, with a majority of cross-sectional design. Higher parental perceived personal safety correlated with increased children’s active mobility behaviour, but most commonly in active travel (eg, independent walking or cycling to a local destination). Increased concerns regarding road danger correlated with a decrease in each type of children’s active behaviour; active travel, play and exercise. However, these correlations were influenced by child’s sex/gender, age, car ownership, neighbourhood types, across time, and proximity to destination. Limited or inconclusive evidence was found on correlate of children’s outdoor active mobility behaviour to ‘stranger danger’, children’s perceived personal safety, race/ethnicity, socioeconomic status or measured safety.ConclusionChildren are restricted by perception of safety. Encouraging children’s active travel may require future strategies to address characteristics relevant to types of the neighbourhood that promote a high sense of personal safety. Children and parents may embrace other types of active mobility behaviour if road danger is mitigated. Sex/gender and age-specific interventions and redesign of public places could lead to child-friendly cities. Future studies may benefit from adopting validated measurement methods and fill existing research gaps.

No abstract