Ivacaftor: Five-year outcomes in the West of Scotland cystic fibrosis population.

INTRODUCTION: Ivacaftor has shown to be effective in patients with cystic fibrosis (CF) with a G551D mutation. OBJECTIVES: This work aims to evaluate ivacaftor's effectiveness and safety in the real world, over 5 years, in the West of Scotland CF population. METHODS: We evaluated ivacaftor's effect on pulmonary function, body mass index (BMI), hospital bed occupancy, and adverse effects in patients ≥6 years with at least one G551D mutation. RESULTS: Statistically significant increases from baseline were observed in mean per cent predicted forced expiratory volume in 1 s (FEV1 ) at year 1 (which was maintained at years 2 and 5) and BMI over 5 years in our adolescent/adult cohort. Improvements were observed in per cent predicted FEV1 within the paediatric cohort with a suggestion of a plateau effect. The increase in paediatric BMI z-score was nonstatistically significant. There was a reduction in the number of pulmonary exacerbations requiring intravenous antibiotics and hospital bed occupancy. Ivacaftor was well tolerated. CONCLUSION: Ivacaftor was effective in our population.

Once daily combined inhaled steroid and ultra long-acting bronchodilator prescribing in pediatric asthma: a dual Center retrospective cohort study.

OBJECTIVE: A high proportion of children and adolescents who have "difficult" or therapy-resistant asthma, are found to have poor adherence to maintenance therapies. Such individuals are thus difficult asthmatics (for reasons of poor adherence) rather than being young people with true difficult asthma. In our centers, once daily ICS/ULABA (Relvar™) is considered if there is an increase in reported interval symptoms, asthma attacks requiring hospital attendance or rescue oral prednisolone, or persistently low lung function despite reported regular use of a twice daily ICS/LABA preparation. In the majority of these young people, a clinical history of overt non-adherence or a clinical suspicion of covert non-adherence will be noted. METHODS: The aim of our retrospective cohort study was to assess the clinical effectiveness of Relvar™ in a selected adolescent asthma population. RESULTS: In a pre-selected group of adolescents with likely poor prior adherence to inhaled therapies, a change to Relvar™ (once daily combined ICS/ULABA) led to improvements in asthma control, as assessed by ED attendances and oral steroid burden. CONCLUSIONS: A prospective study to verify these findings and also explore the effects on quality of life, asthma control, and adherence is warranted.

Impact of newborn screening on outcomes and social inequalities in cystic fibrosis: a UK CF registry-based study.

BACKGROUND: Newborn bloodspot screening (NBS) for cystic fibrosis (CF) was introduced across the UK in 2007 but the impact on clinical outcomes and health inequalities for children with CF is unclear. METHODS: We undertook longitudinal analyses of UK CF registry data on over 3000 children with CF born between 2000 and 2015. Clinical outcomes were the trajectories of percent predicted forced expiratory volume in one second (%FEV1) from age 5, weight for age and body mass index (BMI) SD-scores from age one, and time to chronic Pseudomonas aeruginosa (cPA) infection. Using mixed effects and time-to-event models we assessed the association of NBS with outcomes and potential interactions with childhood socioeconomic conditions, while adjusting for confounders. RESULTS: NBS was associated with higher average lung function trajectory (+1.56 FEV1 percentage points 95% CI 0.1 to 3.02, n=2216), delayed onset of cPA, and higher average weight trajectory intercept at age one (+0.16 SD; 95% CI 0.07 to 0.26, n=3267) but negative rate of weight change thereafter (-0.02 SD per year; 95% CI -0.03 to -0.00). We found no significant association of NBS with BMI or rate of change of lung function. There was no clear evidence of an impact of NBS on health inequalities early in life. CONCLUSIONS: Children diagnosed with CF by NBS in the UK have better lung function and increased early weight but NBS does not appear to have narrowed early health inequalities.

The impact of 12†months treatment with ivacaftor on Scottish paediatric patients with cystic fibrosis with the G551D mutation: a review.

We reviewed the impact of ivacaftor on Scottish paediatric patients with cystic fibrosis ≥6 years of age after 12 months of treatment. Statistically significant improvements in FEV1 and body mass index and a reduction in sweat chloride, all comparable with previously published data were observed. The findings also suggested reduced use of intravenous antibiotics and oral antibiotics. No significant adverse effects were observed but a possible association with cataract formation could not be excluded. This review suggests that, in the short term at least, ivacaftor is effective and safe in paediatric patients ≥6 years of age with G551D.

A retrospective analysis of longitudinal changes in bone mineral content in cystic fibrosis.

BACKGROUND: We aimed to describe the longitudinal changes in bone mineral content and influencing factors, in children with cystic fibrosis (CF). METHODS: One hundred children (50 females) had dual X-ray absorptiometry (DXA) performed. Of these, 48 and 24 children had two to three scans, respectively over 10 years of follow-up. DXA data were expressed as lumbar spine bone mineral content standard deviation score (LSBMCSDS) adjusted for age, gender, ethnicity and bone area. Markers of disease, anthropometry and bone biochemistry were collected retrospectively. RESULTS: Baseline LSBMCSDS was >0.5 SDS in 13% children, between -0.5; 0.5 SDS, in 50% and ≤-0.5 in the remainder. Seventy-eight percent of the children who had baseline LSBMCSDS >-0.5, and 35% of the children with poor baseline (LSBMCSDS<-0.5), showed decreasing values in subsequent assessments. However, mean LS BMC SDS did not show a significant decline in subsequent assessments (-0.51; -0.64; -0.56; p=0.178). Lower forced expiratory volume in 1 s percent (FEV1%) low body mass index standard deviation scores (BMI SDS) and vitamin D were associated with reduction in BMC. CONCLUSIONS: Bone mineral content as assessed by DXA is sub-optimal and decreases with time in most children with CF and this study has highlighted parameters that can be addressed to improve bone health.

Reduced fetal growth in methadone-maintained pregnancies is not fully explained by smoking or socio-economic deprivation.

AIM: To determine if reduced fetal growth in infants of opioid-dependent mothers prescribed methadone maintenance in pregnancy is explained by cigarette smoking or socio-economic deprivation. DESIGN: Retrospective cohort study. SETTING: Inner-city maternity unit in Scotland. PARTICIPANTS: A total of 366 singleton infants of methadone-prescribed opioid-dependent mothers compared with the Scottish birth population (n=103 366) as a whole. MEASUREMENTS: Primary outcome measures were birth weight and head circumference. FINDINGS: In infants of methadone-prescribed opioid-dependent mothers mean birth weight was 259 g [95% confidence interval (CI) 214-303 g; P<0.0001] less, and mean head circumference 1.01 cm (95% CI 0.87-1.15 cm; P<0.0001) less than in controls, allowing for gestation, cigarette smoking, area deprivation, infant sex and maternal age and parity. This represents an adjusted difference of -0.61 (95% CI -0.52--0.71; P<0.0001) Z-score in mean birth weight and -0.77 (95% CI -0.66--0.89; P<0.0001) Z-score in mean head circumference. CONCLUSIONS: Reduced fetal growth in infants of opioid-dependent mothers prescribed methadone maintenance in pregnancy is not fully explained by cigarette smoking, area deprivation, maternal age or parity.

Postnatal weight loss in substitute methadone-exposed infants: implications for the management of breast feeding.

It is widely accepted that maternal drug-exposed infants demonstrate excessive early weight loss, but this has not previously been quantified. Among 354 term, substitute methadone-exposed infants, median maximal weight losses were 10.2% and 8.5% for breast- and formula-fed infants, respectively (p=0.003). Weight loss was less in small for gestational age compared to appropriately grown infants (p<0.001). There was no association between maximal weight loss and plasma sodium concentration (p=0.807). Relative to non-drug exposed infants, weight loss was more marked in formula-fed infants, 48% of whom demonstrated weight loss in excess of the 95th centile (compared to 23% of exclusively breastfed infants; p<0.001). Median weight loss nadir was on day 5, excepting those infants exclusively breastfed (day 4). These data suggest that excessive neonatal weight loss among breastfed infants of drug-misusing mothers does not necessarily reflect poorly established lactation and may help to guide management of breast feeding in this population.