CroniCare: Platform for the Design and Implementation of Follow-Up, Control and Self-Management Interventions for Chronic and Multimorbidity Patients Based on Mobile Technologies.

The project proposes to facilitate the design and evaluation of interventions based on mobile technologies and information systems in order to improve the capacity for self-management, empowerment and control of chronic and multimorbidity patients. The system allows to create customizable apps according to the needs of primary care and specialized care. The project includes an evaluation of the impact of the care model, as well as the effectiveness and efficiency of the intervention through a study with 124 multimorbidity patients.

Genetic contribution of endoplasmic reticulum aminopeptidase 1 polymorphisms to liver fibrosis progression in patients with HCV infection.

The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive immune responses, trimming peptides and loading onto HLA class I molecules. Coding single nucleotide polymorphisms within ERAP1 are associated with autoimmune diseases, viral infections, and cancer development. Our purpose was to analyze the influence of ERAP1 variants on fibrogenesis in hepatitis C virus (HCV)-infected patients. A range of ERAP1 polymorphisms were genotyped in 722 unrelated Caucasian patients diagnosed with chronic HCV from two Spanish cohorts. Patients were classified according to their fibrosis stage. Paraffin-embedded tissue microarrays were constructed to assess ERAP1 expression (HCV = 38; alcoholic = 20) by immunohistochemistry. A statistical algorithm was applied to derive a fibrogenesis prediction model. The ERAP1 variants rs30187/T (K528, pc < 0.001) and rs27044/G (Q730, pc < 0.001) were related with severe fibrosis. These results were validated in the two independent cohorts. Furthermore, patients with the rs30187/T allele had stronger ERAP1 protein expression than those with the rs30187/C (p < 0.05). The statistical model showed that patients with rs30187 C/T and T/T genotypes took 15.58 years (median) to develop advanced fibrosis, but this value was 32.08 years in patients carrying C/C genotype (p < 0.005). ERAP1 variants may influence the clinical course of fibrogenesis in HCV-infected patients. These polymorphisms could be exploited as constitutive new markers of fibrosis evolution. The results highlight the possibility of using modulators of ERAP1 to generate a protective immune response against chronic HCV infection. KEY MESSAGES: What is known Several ERAP1 polymorphisms are associated with autoimmune diseases and cancer. ERAP1 trims peptides to HLA class I presentation. What is new here ERAP1 polymorphisms are associated with fibrogenesis. The ERAP1 polymorphisms genotype could help us in clinical management of patients. Potential translational impact The use of modulators of ERAP1 could generate a protective response depending on SNPs.

Optimisation in the multidisciplinary approach to patients with hepatitis C in the era of direct-acting antivirals. / Optimización en el abordaje multidisciplinar del paciente con hepatitis C en la era de los antivirales de acción directa.

The advents of current direct-acting antiviral treatments has revolutionised the therapeutic approach to hepatitis C, increasing cure rates to above 90% and substantially simplifying treatment, which translates into benefits for patients, clinicians and the health system. These new drugs allow cure to be achieved, irrespective of the patient's characteristics, with tolerability similar to that of placebo and few drug reactions with concomitant medication. This in turn improves patients' quality of life and wellbeing. Moreover, these drugs allow multidisciplinary optimisation of the approach to patients with hepatitis C, thus reducing both short- and long-term costs. All these factors facilitate treatment universality, with treatments that are less influenced by specific factors and that allow better results to be obtained in a larger number of patients. Elimination of hepatitis C is now a real possibility. Supplement information: This article is part of a supplement entitled "The value of simplicity in hepatitis C treatment", which is sponsored by Gilead. © 2019 Elsevier España, S.L.U. All rights reserved.

Acute hepatitis due to hepatitis A virus during the 2017 epidemic expansion in Asturias. Spain. / Hepatitis aguda por virus de la hepatitis A durante la expansión epidémica de 2017 en Asturias.

INTRODUCTION: Since June 2016, there has been an increase in cases of acute hepatitis A (AHA) in several European countries, mainly affecting men who have sex with men (MSM). The aim was to know the characteristics of AHA diagnosed in recent months, comparing them with a previous series. PATIENTS AND METHODS: All cases of AHA diagnosed in adults between November 2016 and December 2017 (G-I; n=108) were prospectively collected and compared with a series also prospectively collected between January 2004 and September 2016 (G-II; n=49), analysing clinical and epidemiological characteristics. RESULTS: Compared with group II, in group I there was a greater proportion of males (95.4 vs. 81.6%; p=0.005), of MSM (63.9 vs. 22.4%; p<0.001), of cases with positive luetic serology (20.4 vs 2%; p=0.001) and of severe acute hepatitis (15 vs. 4%; p=0.043). CONCLUSIONS: AHA diagnosed in recent months in our environment mainly affect MSM and have a more serious presentation with respect to what was observed in a historical series, highlighting the need to increase the vaccination rate against the hepatitis A virus.

Effectiveness and safety of elbasvir/grazoprevir therapy in patients with chronic HCV infection: Results from the Spanish HEPA-C real-world cohort.

In randomized controlled trials of patients with chronic HCV infection, elbasvir/grazoprevir (EBR/GZR) demonstrated high cure rates and a good safety profile. This study assessed the effectiveness and safety of EBR/GZR, with and without ribavirin, in a real-world HCV patient cohort. HEPA-C is a collaborative, monitored national registry of HCV patients directed by the Spanish Association for the Study of the Liver and the Networked Biomedical Research Centre for Hepatic and Digestive Diseases. Patients entered into HEPA-C between December 2016 and May 2017, and treated with EBR/GZR with at least end-of-treatment response data, were included. Demographic, clinical and virologic data were analysed, and adverse events (AEs) recorded. A total of 804 patients were included in the study. The majority were male (57.9%), with a mean age of 60 (range, 19-92) years. Genotype (GT) distribution was GT 1, 86.8% (1a, 14.3%; 1b, 72.5%); GT 4, 13.2% and 176 patients (21.9%) were cirrhotic. Overall, among 588 patients with available data, 570 (96.9%) achieved sustained virologic response at 12 weeks post-treatment (SVR12). SVR12 rates by genotype were GT 1a, 97.7%; GT 1b, 98.6%; and GT 4, 98.1%. No significant differences in SVR12 according to fibrosis stage were observed. Eighty patients experienced an AE, resulting in treatment discontinuation in three. In this large cohort of patients with chronic HCV managed in a real-world setting in Spain, EBR/GZR achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with a similarly good safety profile.

Eight weeks of Paritaprevir/r/Ombitasvir + Dasabuvir in HCV genotype 1b with mild-moderate fibrosis: Results from a real-world cohort.

BACKGROUND & AIMS: The interferon-free regimen paritaprevir/ritonavir, ombitasvir + dasabuvir (PTV/r/OBV/DSV) has shown high efficacy in patients with hepatitis C virus (HCV) genotype 1b infection when administered for 8 or 12 weeks, but data regarding the 8-week treatment are scarce. The aim of our study was to assess the efficacy and safety of the 8-week administration of PTV/r/OBV/DSV in a real-world cohort. METHODS: We performed a multicentre observational study from Spanish Hepa-C database including patients receiving 8 weeks of PTV/r/OBV/DSV (October 2016-November 2017). Those with advanced fibrosis, with non-genotype 1b or who were treatment-experienced were excluded. RESULTS: A total of 211 patients were registered from 23 Spanish centres; eleven were excluded. At baseline, 42.5% (n = 85) were male, median (range) age was 57 (23-86), ALT was 45 (11-494) IU/mL, viral load was 6.1 (3.3-8.2) log10 IU/mL, and 74.5% had mild liver fibrosis (F0-F1) and 25.5% moderate fibrosis (F2). At the end of treatment (EOT), HCV viral load was undetectable in 100% (200/200). Seven patients relapsed after treatment discontinuation. Sustained virological response (SVR12) rates by intention-to-treat analysis were 96% (192/200). Regarding treatment safety, 2 patients developed ALT elevation >5x ULN, but there were no treatment discontinuations. One patient died 7 weeks after EOT. CONCLUSION: Treatment with PTV/r/OBV/DSV in genotype 1b-infected treatment-naive patients with mild-moderate fibrosis shows excellent efficacy and safety in real life, similarly to clinical trials. Clinicaltrials.gov, number: NCT03122132.

Barriers to HCV treatment in the era of triple therapy: a prospective multi-centred study in clinical practice.

BACKGROUND & AIMS: (i) To describe the demographic, clinical, virological and histological characteristics of the patients undergoing evaluation for indication of triple therapy against hepatitis C virus genotype 1, and to identify the reasons why candidate patients are excluded; and (ii) to evaluate the characteristics of the healthcare environment related to treatment. METHODS: Observational, prospective and multi-centred study involving 16 hospitals of Spain. Data were collected on 1122 patients receiving attention in the outpatient clinics between June and December 2012. RESULTS: Of the 1122 patients evaluated, 769 were finally included in this study; 27% (211/769) had contraindications to the therapy. Of those without contraindications, 54% (301/558) did not receive the treatment, and so, only about a third of the patients (33%-257/769) underwent therapy. The reasons for not initiating therapy were as follows: patient refusal (30%), mild disease/awaiting new treatments (34%), restrictions by the health service (30%), other reasons (6%). In univariate analyses, the probability of receiving treatment was related to: age <60 years, male gender, high education level, advanced fibrosis, having had previous treatment, being assessed in a centre of excellence. In multivariate analyses, the factors independently related to the probability of receiving treatment were as follows: high education level of the patients (P = 0.004), advanced fibrosis (P < 0.001) and centres of excellence (P = 0.009). CONCLUSION: Despite the high efficacy of triple therapy, only a small proportion of patients receive the treatment. The causes related to non-treatment depend on patient factors, disease stage and characteristics of the health-service provision.

Diversity of killer cell immunoglobulin-like receptor (KIR) genotypes and KIR2DL2/3 variants in HCV treatment outcome.

The aim of this study was to analyse the distribution of KIR haplotypes and the KIR2DL2/3 alleles in chronic HCV-infected patients in order to establish the influence on the response to pegylated interferon plus ribavirin classical treatment. The alleles study of previously associated KIR2DL2/3 showed that KIR2DL2*001 was more frequent in non-SVR (NSVR) (42.2% vs. 27.5%, p<0.05) and KIR2DL3*001 was associated with sustained viral response (SVR) (41.6% vs. 61.2%, p<0.005). The KIR2DL3*001-HLA-C1 association was also significant (24.5% vs. 45.7%, p<0.001). From the frequencies of KIR obtained, 35 genotypes were assigned on the basis of previous studies. The centromeric A/A genotype was more frequent in SVR (44.1% vs. 34.5%, p<0.005) and the centromeric B/B genotype was found to be significantly more frequent in NSVR (20.9% vs. 11.2%, p<0.001). The logic regression model showed the importance of KIR genes in predicting the response to combined treatment, since the positive predictive value (PPV) was improved (from 55.9% to 75.3%) when the analysis of KIR was included in addition to the IFNL3 rs12979860 polymorphism. The study of KIR receptors may be a powerful tool for predicting the combined treatment response in patients with chronic HCV infection in association with the determination of IFNL3 polymorphism.

Morphology matches mtDNA lineages in the southern smooth snake (Coronella girondica) from Iberia.

The rise of molecular techniques in the study of evolutionary histories has resulted in a gradual abandonment of morphological characters as the only sources of phylogenetic inference. However, morphological characters may be valuable for phylogenetic reconstruction, especially for tracking adaptive changes across phylogeographic groups defined by genetic markers. We examined the discriminative power of morphological characters between four mitochondrial clades covering almost the entire distribution area of the smooth snake Coronella girondica in the Western Mediterranean. We detected three characters showing sexual dimorphism (relative tail length, number of ventral and of subcaudal scale counts) and, more interestingly, two characters (number of subcaudal and of dorsal rows) displaying interclade differences. Almost all C. girondica examined had 21 dorsal rows except those from a narrow coastal belt in the south-eastern Iberian Peninsula, which had 19 dorsal rows. The distribution of these specimens matches a mitochondrial clade that originated approximately 1.4-2.0 million years ago. Both of these morphological characters support a Betic lineage with a rather well-defined contact zone with the other Iberian lineage, which has been maintained even without the existence of current geographic barriers. The long-term survival of the Betic lineage throughout the Pleistocene climatic oscillations suggests a systematic revision within C. girondica.

Sobreexposición de los pacientes en hospitales docentes: la experiencia en un servicio de medicina / Superexposição de pacientes em hospitais de ensino: experiência em um serviço de medicina / Patient overexposure in teaching hospitals: the experience in a medical service facility

Introducción: la enseñanza práctica de la medicina en hospitales ha llevado a la sobrepoblación de estudiantes y muchas veces al agotamiento de los pacientes. Percibimos que a los docentes clínicos se les produce un conflicto de intereses: respeto por la condición del enfermo frente a enseñanza. Planteamos que si estudiantes y docentes conocen la percepción que de ellos tienen los pacientes, es posible crear un clima que permita el aprendizaje y descubrira la persona que hay detrás de cada cuadro clínico. Objetivos: conocer la reacción que provocan los alumnos en los enfermos y precisar si hay un máximo prudente de entrevistas por paciente. Se entrevistó una cohorte de enfermos de un servicio de medicina comprobando que ellos: 1) identifican la relación estudiante-paciente como de beneficio mutuo; 2) piensan que el límite de entrevistaslo establece cada enfermo; 3) saben que pueden negarse a cooperar; 4) que esto último no los predispone negativamente. Conclusiones: 1) la oportunidad de entrevistar o no a un paciente la establece él mismo; 2) es indispensable solicitar el consentimiento informado en docencia; 3) el rol del docente es de observador activo del binomio estudiante paciente fomentando en los alumnos virtudes propias de la convivencia e interviniendo si peligra la confianza o confidencialidad debidas.

Introduction: Practical training in medicine at hospitals has led to an overpopulation of students and, oftentimes, to patient exhaustion. The authors believe professors in a clinical environment face a conflict of interests: respect for the patient's condition versus teaching. It is suggested that a climate conducive to learning and discovery of the person behind each set of clinical symptoms can be created if students and teachers know how they are perceived by patients. Objectives: To understand the reaction students provoke in patients and to indicate whether there is a prudent maximum amount of interviews per patient. A cohort of patients at a medical service facility was interviewed. The results of those interviews indicate: 1) patients identify the student-patient relationship as one of mutual benefit; 2) they believe the limit on interviews should be set by each patient, 3) patients know they can refuse to cooperate; and 4) doing so does not predispose them negatively. Conclusions: 1) The opportunity to interview a patient, or not, is determined by the patient. 2) It is essential to seek informed consent in teaching. 3) The teacher's role is that of an active observer of the studentpatient duo, promoting the virtues of coexistence among students and intervening if due trust or confidentiality are compromised.

Introdução: o ensino prático da medicina nos hospitais conduziu a superlotação de alunos e, muitas vezes, até a exaustão dos pacientes. Os professores clínicos afrontam um conflictode interesses clínicos: o respeito pela condição do paciente versus ensino. Sugerimos que se os estudantes e professores conhecer a percepção que deles têm os pacientes, pode criar-se um clima de aprendizado que permita descobrir a pessoa por trás de cada quadro clínico. Objetivos: conhecer a reação dos doentes à frente dos estudantes e indicar se é máximo da entrevistas-paciente é pertinente. Se entrevistou uma coorte de pacientes de um serviço médico, verificando que: 1) identificam que a relação aluno-paciente é de benefício mútuo, 2) acreditam que o limite de entrevistas o determina cada paciente, 3) sabem que podem se recusar a cooperar, 4) que o último não predispô-los negativamente. Conclusões: 1) a oportunidade de entrevistar um paciente ou não depende deste, 2) é essencial obter o consentimento informado pelo ensino, 3) o papel do professor é um observador ativo do binómio aluno-paciente a fim de promover nos alunos virtudes de convivência, intervindo somente se a confiança ou a confidencialidade estão comprometidas.

The prevalence of peptic ulcer not related to Helicobacter pylori or non-steroidal anti-inflammatory drug use is negligible in southern Europe.

BACKGROUND AND AIM: Helicobacter pylori is the major cause of peptic ulcer disease, but the proportion of H. pylori-negative peptic ulcers seems to be increasing in developed countries. We investigated the frequency of H. pylori-negative peptic ulcer without intake of nonsteroidal anti-inflammatory drugs (NSAIDs) in a Mediterranean European country. MATERIALS AND METHODS: We prospectively collected consecutive patients with an endoscopically verified active peptic ulcer over 6 months from different areas of Spain. Helicobacter pylori infection was assessed by rapid urease test and histologic examination (corpus and antral biopsies). A (13)C-urea breath test was performed if H. pylori was not detected with the invasive test. Patients were considered H. pylori-negative if all three tests were negative. NSAID use was determined by structured data collection. RESULTS: Of 754 consecutive peptic ulcer patients, 16 (2.1%) were H. pylori-negative and had not used NSAIDs before the diagnosis. Of the 472 patients who had duodenal ulcers, 95.7% (n = 452) were H. pylori-positive and only 1.69% (n = 8) were negative for both H. pylori infection and NSAID use; 193 patients had benign gastric ulcers and 87% (n = 168) of them were infected by H. pylori (p <.001 vs. duodenal ulcers). NSAID intake was more frequent in gastric ulcer patients (52.8%) than in duodenal ulcer patients (25.4%; p <.001). Consequently, the frequency of H. pylori-negative gastric ulcer in patients not using NSAID was 4.1% (n = 8). CONCLUSION: Peptic ulcer disease is still highly associated with H. pylori infection in southern Europe, and only 1.6% of all duodenal ulcers and 4.1% of all gastric ulcers were not associated with either H. pylori infection or NSAID use.