Development and outcomes of a patient driven cystic fibrosis quality of care improvement project.

The Dutch CF Foundation (NCFS) developed a quality improvement program, to assess and improve quality of care in all CF centers in The Netherlands. Criteria to assess quality of care from the patient perspective were defined, and quality of care was assessed by patients via online surveys and site visits. Recommendations were addressed to all centers to improve quality of care. Most recommendations were related to communicational issues. All centers were given the quality mark of the patient organisation, although two of them needed extra time to meet the lower limit of the core set of criteria. After two years, over 75 % of the recommendations given to the centers were fully or partly implemented, showing a high efficacy of the program.

Long-term effectiveness of dual CFTR modulator treatment of cystic fibrosis.

Background: Although short-term efficacy of lumacaftor/ivacaftor and tezacaftor/ivacaftor is clearly established in clinical trials, data on long-term effectiveness is limited. This registry-based cohort study assessed real-world longitudinal outcomes of F508del-homozygous people with cystic fibrosis (pwCF) ≥12 years, up to 3 years after the introduction of dual cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Methods: Annual data (2010-2019) were retrieved from the Dutch Cystic Fibrosis Registry. Longitudinal trends of per cent predicted forced expiratory volume in 1 s (FEV1 % pred) decline, body mass index (BMI), BMI Z-score and intravenous antibiotic treatment duration before and after CFTR modulator initiation were assessed with linear and negative binomial mixed models. Results: We included 401 participants (41.9% female, baseline age 24.5 years (IQR 18.0-31.5 years), baseline mean±sd FEV1 70.5±23.4% pred). FEV1 decline improved from -1.36% pred per year to -0.48% pred per year after modulator initiation (change: 0.88% pred, 95% CI: 0.35-1.39%, p=0.001). This change was even 1.40% pred per year (95% CI: -0.0001-2.82%, p=0.050) higher in participants with baseline FEV1 <40% pred. In adults, annual BMI trend was not altered (change: 0.10 kg·m-2·year-1, 95% CI:-0.01-0.21, p=0.079). Annual BMI Z-score in children reversed from -0.08 per year before modulator treatment to 0.06 per year afterwards (change: 0.14 per year, 95% CI: 0.06-0.22, p<0.001). Intravenous antibiotic treatment duration showed a three-fold reduction in the first year after modulator initiation (incidence rate ratios (IRR): 0.28, 95% CI: 0.19-0.40, p<0.001), but the annual trend did not change in the subsequent years (IRR: 1.19, 95% CI: 0.94-1.50, p=0.153). Conclusion: Long-term effectiveness of dual CFTR modulator therapies on FEV1 decline, BMI and intravenous antibiotic treatment duration is less pronounced in a real-world setting than in clinical trials and varies considerably between pwCF and different baseline FEV1 levels.

Aligning patients' needs and research priorities towards a comprehensive CF research program.

The Dutch CF Foundation started to focus on scientific research thirteen years ago. The patient organization defined the patients perspective and unmet needs bottom-up, and through a structured process. The patients research priorities were matched with the research priorities of Dutch basic scientists and clinicians. The Dutch patient organization facilitated the process, in which mutual dependency between patients, scientists and clinicians is the keyword. The, at that time initiated dialogue, maintained. Subsequently a research program called "HIT CF" was composed and executed over five years. HIT CF was financially supported mainly by the patient community and some other stakeholders.

Newborn blood spot screening for cystic fibrosis with a four-step screening strategy in the Netherlands.

BACKGROUND: Newborn screening for cystic fibrosis (NBSCF) was introduced in the Dutch NBS program in 2011 with a novel strategy. METHODS: Dutch NBSCF consisted of four steps: immuno-reactive trypsin (IRT), Pancreatitis-associated Protein (PAP), DNA analysis by Inno-LiPa (35 mutations), extended gene analysis (EGA) as fourth step and as safety net. Only samples with two CFTR-variants were considered screen-positive, but samples with one disease-causing variant were considered also screen-positive from April 2013. The first 5 years of NBSCF were evaluated during a follow-up ranging from 2 to 6.8 years for sensitivity, specificity, positive predictive value (PPV), ratio of CF/Cystic Fibrosis Screen Positive infants with an Inconclusive Diagnosis (CFSPID) and median age at diagnosis, and were compared to other novel strategies for NBSCF and European Cystic Fibrosis Society (ECFS) Best Practice Standards of Care. RESULTS: NBSCF achieved a sensitivity of 90% (95% CI 82%-94%), specificity of 99.991% (95% CI 99.989%-99.993%), PPV of 63% (95% CI 55%-69%), CF/CFSPID ratio of 4/1, and median age at diagnosis of 22 days, if samples with two variants as well as samples with one disease-causing variant were considered screen-positive. CONCLUSION: The program achieved the goal to minimize the number of false positives and showed a favourable performance but sensitivity and CF/CFSPID ratio did not meet criteria of EFCS Best Standards of Care. Changed cut-off values for PAP and IRT and classification of R117H-7T/9T to non-pathogenic may improve sensitivity to ≥95% and CF/CFSPID ratio to 10/1. PPV is estimated to be around 60%.

Height Assessment in the Dutch-Origin Pediatric Cystic Fibrosis Population.

BACKGROUND: Height evaluation is an integral part of cystic fibrosis (CF) care. Height is compared with reference values by converting it to height-for-age (HFA) z scores. However, HFA z scores do not adjust for genetic potential (ie, target height [TH]), which could result in an incorrect estimation of the height. MATERIALS AND METHODS: To evaluate the magnitude of this potential problem, we assessed the agreement between HFA and HFA-adjusted-for-TH (HFA/TH) z scores in 474 Dutch children with CF. RESULTS: In this study sample, HFA z scores were -0.07 (95% confidence interval, -0.02 to -0.12) lower than HFA/TH z scores. When HFA and HFA/TH z scores were subdivided into 4 categories (≥0, <0 and ≥-1, <-1 and ≥-2, and ≤-2), a moderate agreement was found. HFA z scores were classified lower than HFA/TH z scores in 21% of the measurements and higher in 15% of the measurements. CONCLUSION: In clinical routine, height evaluation based on HFA may result in underestimation or overestimation of height growth, which may induce inappropriate nutrition interventions.