Analysis of the genotypic profile and its relationship with the clinical manifestations in people with cystic fibrosis: study from a rare disease registry.

BACKGROUND: Cystic fibrosis (CF) has a vast and heterogeneous mutational spectrum in Europe. This variability has also been described in Spain, and there are numerous studies linking CFTR variants with the symptoms of the disease. Most of the studies analysed determinate clinical manifestations or specific sequence variants in patients from clinical units. Others used registry data without addressing the genotype-phenotype relationship. Therefore, the objective of this study is to describe the genetic and clinical characteristics of people with CF and to analyse the relationship between both using data from the rare disease registry of a region in southeastern Spain. METHODS: A cross-sectional study was carried out in people with a confirmed diagnosis of CF registered in the Rare Diseases Information System (SIER) of the Region of Murcia (Spain). The patients were classified into two genotypes according to the functional consequence that the genetic variants had on the CFTR protein. RESULTS: There were 192 people diagnosed with CF reported in the Region of Murcia as of 31 December 2018. Seventy-six genotypes and 49 different variants were described, with c.1521_1523delCTT (p. Phe508del) being the most common in 58.3% of the CF patients and 37.0% of the alleles. In addition, 67% of the patients were classified as a high-risk genotype, which was associated with a lower percentage of FEV1 (OR: 5.3; 95% CI: 1.2, 24.4), an increased risk of colonization by Pseudomonas aeruginosa (OR: 7.5; 95% CI: 1.7, 33.0) and the presence of pancreatic insufficiency (OR: 28.1; 95% CI: 9.3, 84.4) compared to those with a low-risk genotype. CONCLUSIONS: This is the first study in Spain that describes the mutational spectrum and its association with clinical manifestations in patients with CF using data from a rare disease registry. The results obtained allow planning for the health resources needed by people with this disease, thus contributing to the development of personalized medicine that helps to optimize health care in CF patients.

The interoperability between the Spanish version of the International Classification of Diseases and ORPHAcodes: towards better identification of rare diseases.

BACKGROUND: Rare diseases present a wide spectrum of clinical manifestations and severity levels and are often poorly known and underrepresented, making them difficult to classify. Diagnoses are usually coded using the International Classification of Diseases (ICD), with its different versions. In Spain, the ICD-10-ES (stem from the ICD-10-CM-Clinical Modification) is used throughout the National Healthcare System since 2016, indistinctively including rare diseases that often lack a specific code. Orphanet aims to provide high-quality resources on rare diseases. The goal was to interrelate the Orphanet classification with the ICD-10-ES in order to engage a tool to track rare diseases diagnosis and characterize the improvement space for the identification of rare diseases patients in the Spanish Healthcare System. METHODS: 5775 disorder level ORPHAcodes were mapped to ICD-10-ES codes by comparing the descriptors associated in both classifications. ORPHAcodes were then clustered based on their assigned ICD-10-ES chapter and the redundancy of each individual ICD-10-ES code was calculated by counting the ORPHAcodes they mapped to. Three groups were established: Group 1 (1 ORPHAcode per ICD-10-ES), Group 2 (between 2-49 ORPHAcodes per ICD-10-ES) and Group 3 (≥ 50 ORPHAcodes per ICD-10-ES). RESULTS: Equivalences to 1700 ICD-10-ES codes were established for 5664 ORPHAcodes. The ORPHAcodes distribution within the ICD-10-ES showed an aggregation in the "Q" (> 40%), "G" (> 14%), and "E" (12%) chapters. The availability of ICD-10-ES codes to map ORPHAcodes reached its lowest at the "G" and "Q" chapters with less than 0.2 ICD-10-ES codes available per ORPHAcode. Global ICD-10-ES codes redundancy analysis revealed that only 1055 of the equivalences pertain to group 1. Group 2 contained 3358 equivalences with 634 ICD-10-ES codes while 1322 equivalences were group 3 (11 ICD-10-ES). Within ICD-10-ES chapters, "G" and "Q" contained over 30% and 45% of their own equivalences in the highest redundancy level (group 3) respectively, but under 10% one to one equivalences each (group 1). CONCLUSIONS: ICD-10-ES codes have not enough specificity to identify rare diseases. Direct mapping between ICD and ORPHAcodes or the integration of ORPHAcodes at the healthcare system for diagnoses codification would enable better detection and epidemiological analysis of rare diseases.

Negative pleural suction in thoracic trauma patients: A randomized controlled trial.

BACKGROUND: The study aimed to establish the benefits of using chest tubes with negative pleural suction against trapped water in patients with penetrating or blunt chest trauma who underwent tube thoracostomy, in terms of the incidence of complications, such as persistent air leak, clotted hemothorax, empyema, and duration of stay. METHODS: Patients who underwent tube thoracostomy because of traumatic pneumothorax, hemothorax, or hemopneumothorax were randomly assigned into one of two groups: in Group 1, the three-bottle drainage system was connected to a negative suction; in Group 2, no suction was given. Patients who required mechanical ventilation or emergency surgery (thoracotomy or thoracoscopy) either at the time of admission to the institution or immediately after the tube thoracostomy, patients who had histories of thoracic procedures or chronic pulmonary diseases (chronic obstructive pulmonary disease, diffuse interstitial lung disease), and patients with multiple injuries with severe traumatic brain injury and a Glasgow Coma Scale (GCS) score less than 8 of 15 were excluded from the study. Hospital stay, duration of tube thoracostomy, prolonged fistula, and other clinical variables were compared. RESULTS: One hundred ten patients were included, 56 in the group with suction and 54 in the group without suction. There were no differences in the demographic characteristics of each group. There were no differences between the groups in terms of hospital stay (p = 0.22), duration of tube thoracostomy (p = 0.35) (3 days in each group), or complications. However, the probability of air leak presence in time was greater for the Group 1 patients with negative suction versus the Group 2 patients (p = 0.023). CONCLUSION: The use of negative pleural suction did not demonstrate advantages over the three-bottle chest drainage system without suction in patients with uncomplicated traumatic pneumothorax, hemothorax, or hemopneumothorax. LEVEL OF EVIDENCE: Therapeutic study, level II.