Background: Rare diseases (RDs) are a heterogeneous group of complex and low-prevalence conditions in which the time to establish a definitive diagnosis is often too long. In addition, for most RDs, few to no treatments are available and it is often difficult to find a specialized care team. Objectives: The project “acERca las enfermedades raras” (in English: “bringing RDs closer”) is an initiative primary designed to generate a consensus by a multidisciplinary group of experts to detect the strengths and weaknesses in the public healthcare system concerning the comprehensive care of persons living with a RD (PLWRD) in the region of Catalonia, Spain, where a Network of Clinical Expert Units (Xarxa d’Unitats de Expertesa Clínica or XUEC) was created and is being implemented since 2015. The additional primary aim was to propose recommendations to solve or improve the limitations found. Methods: A task force of 13 participants with multidisciplinary expertise on RDs completed a questionnaire and participated in two focus groups. A document was drafted with an item series of strengths and weaknesses of the healthcare system regarding the care of PLWRD, and a set of proposals or recommendations to overcome the problems identified. Results: The Catalan Government healthcare model of XUECs for the comprehensive care for RDs is currently valid and adapted to the needs of PLWRD and their families since its strategic optimal and operational framework, and it is aligned with the European Reference Networks (ERNs) thematic areas. The problems found in the current healthcare model were grouped into ten main areas: (1) the healthcare model for RDs; (2) coordination with primary healthcare providers and other tertiary and secondary hospitals; (3) access to and coordination with non-medical services; (4) the role of case manager in the XUEC; (5) genetic diagnosis; (6) undiagnosed patients; (7) treatments; (8) referring process, continuous follow-up, and transition from pediatric to adult centers; (9) research and education for professionals; and (10) associations of PLWRD and their families (patients’ advocacy). The need for more resources was currently detected as the common factor for most of them. Ten key recommendations to improve the healthcare system regarding RDs were postulated. Conclusions: Catalonia has established a unique healthcare model for RDs in Spain, with clear strengths and advantages. However, after analyzing them, the experts suggested that new governmental political and administrative decisions are needed to ensure the efficient implementation of a healthcare plan for PLWRD in Catalonia, which could be applied to other regions and nations worldwide.

Vitamin K-dependent proteins play a critical role in hemostasis. We have analysed the genetic and environmental correlations between measures of several vitamin K-dependent proteins in 21 Spanish extended families, including 397 individuals. Plasma functional levels of factors II, VII, IX, X, protein C and functional protein S were assayed in an automated coagulometer. Antigenic levels of total and free protein S were measured using an ELISA method. A maximum likelihood-based covariance decomposition analysis was used to assess the heritability of each trait and the genetic and environmental correlations between all possible pairs. All of the plasma levels had a significant genetic component (heritability) ranging from 22% to 52% of the phenotypic variance. Among the 28 possible pairs of genetic correlations, 18 were significant at a level of p <0.05 and six exhibited a p-value between 0.05 and 0.10. Positive environmental correlation was observed for 25 of the pairs (p <0.05). We conclude that genetic effects account for a large proportion of the observed phenotypic variation in vitamin K-dependent proteins. Some of the genes appear to pleiotropically influence all of these traits, since most pairs of phenotypes exhibit significant genetic correlation. However, since these phenotypes show a high degree of environmental correlation, it is also likely that the same environmental factors influence them co-jointly.

Increased plasma concentrations of various markers of endothelial damage have been observed in type 1 diabetic patients, particularly in those with microangiopathy. Objective. To evaluate the effect of nearnormalisation of glycaemic control on different markers of endothelial injury involved in haemostasis in poorly-controlled type 1 diabetic patients. Material and Methods. TFPI, thrombomodulin (TM), plasminogen activator inhibitor, tissue-type plasminogen activator and von Willebrand factor were measured in 14 poorly-controlled type 1 diabetic patients free of diabetes-related complications (8 men, 6 women; mean age 29.8 ± 9.9 years) before (baseline) and after 3 months of intensive therapy and in 14 sex-, age-and BMI-matched control subjects. Results. After a mean follow-up of 107 ± 49 days (56-210), Hb A_1c decreased from 11.2 ± 2.3 to 6.7 ± 0.7% (p <0.0001). TFPI activity at baseline was higher than in the control group (126.9 ± 34 vs 92.0 ± 13%, p <0.005) and decreased after good glycaemic control was achieved (p <0.005), becoming similar to that in the control group (91.0 ± 16.5%). The TFPI descent correlated with the variations observed in HbA_1c (p <0.05; r = 0.54). TM levels at baseline were significantly higher than in the control group (42.3 ± 9.1 vs 29.00 ± 10.9; p <0.005) and did not change. The remaining parameters studied were similar between patients and controls and did not change after glycaemic optimisation. Conclusions. Optimisation of glycaemic control normalises the increased activity of TFPI but not the higher TM levels observed in poorly-controlled type 1 diabetic patients without chronic complications.