KIWI (NCT01705145) was a 24-week, single-arm, pharmacokinetics, safety, and efficacy study of ivacaftor in children aged 2 to 5 years with cystic fibrosis (CF) and a CFTR gating mutation. Here, we report the results of KLIMB (NCT01946412), an 84-week, open-label extension of KIWI. Children received age- and weight-based ivacaftor dosages for 84 weeks. The primary outcome was safety. Other outcomes included sweat chloride, growth parameters, and measures of pancreatic function. All 33 children who completed KIWI enrolled in KLIMB; 28 completed 84 weeks of treatment. Most adverse events were consistent with those reported during KIWI. Ten (30%) children had transaminase elevations >3 × upper limit of normal (ULN), leading to 1 discontinuation in a child with alanine aminotransferase >8 × ULN. Improvements in sweat chloride, weight, and body mass index z scores and fecal elastase-1 observed during KIWI were maintained during KLIMB; there was no further improvement in these parameters. Ivacaftor was generally well tolerated for up to 108 weeks in children aged 2 to 5 years with CF and a gating mutation, with safety consistent with the KIWI study. Improvements in sweat chloride and growth parameters during the initial 24 weeks of treatment were maintained for up to an additional 84 weeks of treatment. Prevalence of raised transaminases remained stable and did not increase with duration of exposure during the open-label extension.

Genetic results of uncertain clinical significance are being returned to parents following newborn screening, representing a paradigm change in how society considers health and illness. ‘Cystic Fibrosis screen positive, inconclusive diagnosis’ (CFSPID) is a designation given to newborns with a positive screening result for, but not a definitive diagnosis of, cystic fibrosis. We explored the psychological impact of receiving a CFSPID result on parents. Five semi-structured interviews were conducted with eight parents whose children have CFSPID. Interpretative phenomenological analysis identified these themes: “The way we were told”: ‘diagnosis as a traumatic event’ focused on how parents were distressed and dissatisfied by the initial screening result communication, ‘Facing and challenging traditional ideas about health and illness’ explored the emerging problem of how CFSPID does not fit the commonly accepted medical model, and ‘Making certainty out of uncertainty’ explored the varying strategies parents developed to adapt to the uncertainty regarding their child’s prognosis. Findings suggest that CFSPID results caused parents’ distress, initiated with the first communication of the result and persisting thereafter. Our data suggests approaches to the delivery of CFSPID results that may reduce the impact. Work is needed to close the gap between healthcare advances and societies commonly held medical model.

Physical activity (PA) is associated with reduced hospitalisations and maintenance of lung function in patients with Cystic Fibrosis (CF). PA is therefore recommended as part of standard care. Despite this, there is no consensus for monitoring of PA and little is known about perceptions of PA monitoring among children and young people with CF. Therefore, the research aimed to explore patients’ perceptions of PA and the acceptability of using PA monitoring devices with children and young people with CF. An action research approach was utilised, whereby findings from earlier research phases informed subsequent phases. Four phases were utilised, including patient interviews, PA monitoring, follow-up patient interviews and health care professional (HCP) interviews. Subsequently, an expert panel discussed the study to develop recommendations for practice and future research. Findings suggest that experiences of PA in children and young people with CF are largely comparable to their non-CF peers, with individuals engaging in a variety of activities. CF was not perceived as a barrier per se, although participants acknowledged that they could be limited by their symptoms. Maintenance of health emerged as a key facilitator, in some cases PA offered patients the opportunity to ‘normalise’ their condition. Participants reported enjoying wearing the monitoring devices and had good compliance. Wrist-worn devices and devices providing feedback were preferred. HCPs recognised the potential benefits of the devices in clinical practice. Recommendations based on these findings are that interventions to promote PA in children and young people with CF should be individualised and involve families to promote PA as part of an active lifestyle. Patients should receive support alongside the PA data obtained from monitoring devices. PA monitoring devices appear to be an acceptable method for objective assessment of PA among children and young people with CF and their clinicians. Wrist-worn devices, which are unobtrusive and can display feedback, were perceived as most acceptable. By understanding the factors impacting PA, CF health professionals will be better placed to support patients and improve health outcomes.

Although the communication pathways of Newborn Bloodspot Screening (NBS) are a delicate task, these pathways vary across different conditions and are often not evidence-based. The ReSPoND interventions were co-designed by healthcare professionals alongside parents who had received a positive NBS result for their child. To calculate the cost of these co-designed strategies and the existing communication pathways, we interviewed 71 members of the clinical and laboratory staff of the 13 English NBS laboratories in the English National Health Service. Therefore, a scenario analysis was used to compare the cost of the existing communication pathways to the co-designed strategies delivered by (i) home-visits and (ii) telecommunications. On average, the existing communication pathway cost £447.08 per infant (range: £237.12 to £628.51) or £234,872.75 (£3635.99 to £1,932,986.23) nationally. Implementing the new interventions relying on home-visits exclusively would cost on average £521.62 (£312.84 to £646.39) per infant and £297,816.03 (£4506.37 to £2,550,284.64) nationally, or £447.19 (£235.79 to £552.03) and £231,342.40 (£3923.7 to £1,922,192.22) if implemented via teleconsultations, respectively. The new strategies delivered are not likely to require additional resources compared with current practice. Further research is needed to investigate whether this investment represents good value for money for the NHS budget.