ABSTRACT
BACKGROUND: In times of genotype guided therapy options, a total of 3.2 % of people with CF (pwCF) in the German CF Registry[1] only have one or no CFTR-variant detected after genetic analysis. Additionally, genetic data in the Registry can be documented as free text and can therefore be prone to error. In order to allow the greatest possible amount of pwCF access to modern therapies, we conducted a re-evaluation of free text entries and established a custom-whole-CFTR-locus NGS-approach for all pwCF who remained without genetic confirmation afterwards. METHODS: To this end, we assembled 731 free text variants of 655 pwCF in the German CF Registry. All variants were evaluated using ClinVar, HGMD and CFTR1/2, corrected in the Registries' database and uploaded to ClinVar. PwCF whose diagnosis remained uncertain as well as additional pwCF or pwCFTR-RD that were assembled through a nationwide call for testing of unclear cases were offered genetic analysis. Samples were analysed using a target-capture based NGS-custom-design-panel covering the entire CFTR-locus. RESULTS: Evaluation of free text variants led to the discovery of 43 variants not formerly reported in the context of CF. The Registries' dropdown list was extended by 497 variants and over 500 pwCF were provided with their most up-to-date genotype. Samples of 47 pwCF/pwCFTR-RD were sequenced via NGS with an overall success rate of 61.7 %, resulting in implementation of entire CFTR-genotyping into routine diagnostics. CONCLUSION: Entire CFTR-genotyping can greatly increase the genetic diagnostic rate of pwCF/pwCFTR-RD and should be considered after inconspicuous CFTR screening panels in CFTR-diagnostics.
ABSTRACT
OBJECTIVES: Globally, the COVID-19 pandemic has a major impact on healthcare provision. The effects in primary care are understudied. This study aimed to explore changes in consultation numbers and patient management during the COVID-19 pandemic, and to identify challenges for patient care. DESIGN: Survey of paediatric primary care practices on consultation numbers and patient management changes, and semistructured interviews to identify challenges for patient care. Surveys and interviews were partially linked in an explanatory sequential design to identify patient groups perceived to be at higher risk for worse care during the pandemic. SETTING: In and around Düsseldorf, a densely populated area in Western Germany. The primary care facilities are spread over an area with approximately 2 million inhabitants. PARTICIPANTS: Primary care in Germany is provided through practices run by self-employed specialist physicians that are contracted to offer services to patients under public health insurance which is compulsory to the majority of the population. The sample contained 44 paediatric primary care practices in the area, the response rate was 50%. RESULTS: Numbers of consultations for scheduled developmental examinations remained unchanged compared with the previous year while emergency visits were strongly reduced (mean 87.3 less/week in March-May 2020 compared with 2019, median reduction 55.0%). Children dependent on developmental therapy and with chronic health conditions were identified as patient groups receiving deteriorated care. High patient numbers, including of mildly symptomatic children presenting for health certificates, in combination with increased organisational demands and expected staff outages are priority concerns for the winter. CONCLUSIONS: Primary care paediatricians offered stable service through the early pandemic but expected strained resources for the upcoming winter. Unambiguous guidance on which children should present to primary care and who should be tested would help to allocate resources appropriately, and this guidance needs to consider age group specific issues including high prevalence of respiratory symptoms, dependency on carers and high contact rates.
