Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) a-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions

¿Ha cambiado la actividad asistencial de la neurología pediátrica en 11 años?

Resumen: Introducción: Pensamos que en la última década ha existido un aumento en la demanda de atención de neurología pediátrica (NP) por parte de la población pero también con un cambio cualitativo en las patologías que se atienden.Por este motivo planteamos realizar un segundo registro (2013) y analizar si existían o no diferencias con el efectuado en el año 2002. Métodos: Se realiza un registro prospectivo de actividad asistencia de NP en el Hospital Universitario de Getafe en 2013 y se compara con otro registro prospectivo previo realizado en 2002. Resultados: Se ha pasado de 1.300 consultas a 1.982 (incremento del 52,46%) y de 32,6 consultas/1.000 niños al año a 57,48 (76,32% de aumento).La actividad en consulta supone el 92,2% de toda la asistencia neuropediátrica del 2013; actualmente el trastorno por déficit de atención e hiperactividad (TDAH) es la patología más frecuente (27,6% en 2013/8,1% en 2002). Aunque las cefaleas siguen siendo muy frecuentes han disminuido (19% en 2013/22% en 2002). Como primeras consultas la cefalea sigue siendo la más frecuente en 2013 (32,1%), seguida del TDAH (19,1%). En régimen de hospitalización la epilepsia continúa siendo el diagnóstico más frecuente (30,3% en 2013/36,7% en 2002). Conclusiones: La NP continúa siendo una actividad básicamente ambulatoria, con un incremento considerable en los últimos años. Este aumento se debe fundamentalmente a los trastornos del neurodesarrollo y muy especialmente al TDAH. Podríamos decir que el TDAH es a la NP lo que la demencia a la neurología general. Abstract: Introduction: We believe that the demand for paediatric neurology (PN) care has increased over the past decade, and that reasons for requesting consultations have also changed. The objective of this study is to complete a registry study to profile the demand for PN care in 2013 and compare results to those from a study performed in 2002. Methods: A prospective registry of PN healthcare activities was completed at Hospital Universitario de Getafe in 2013. Results were compared with those from a prospective registry study conducted in 2002. Results: The number of visits increased from 1,300 in 2002 to 1,982 in 2013 (a 52.46% increase), and from 32.6 visits per 1,000 children to 57.48 (a 76.32% increase). Outpatient consultations accounted for 92.2% of all PN consultations in 2013. Currently, attention deficit-hyperactivity disorder (ADHD) is the most frequent diagnosis (27.6% in 2013 vs. 8.1% in 2002). Although the percentage of headache consultations has decreased (19% in 2013 vs. 22% in 2002), headache was still the most common reason for an initial visit in 2013 (32.1%), followed by ADHD (19.1%). Epilepsy remains the most frequent diagnosis in hospitalised patients (30.3% in 2013 vs. 36.7% in 2002). Conclusions: PN is fundamentally an outpatient activity that has increased considerably in recent years. This increase is mainly due to neurodevelopmental disorders, especially ADHD. We might state that the role of ADHD in PN is comparable to that of dementia in general neurology. Palabras clave: Actividad asistencial, Gestión sanitaria, Neurología infantil, Neurología pediátrica, Neurodesarrollo, TDAH, Keywords: Medical care, Healthcare administration, Child neurology, Paediatric neurology, Neurodevelopment, ADH