Some Agents are more Similar than Others:Customer Orientation of Frontline Robots and Employees

Purpose: The impact of frontline robots (FLRs) on customer orientation perceptions remains unclear. This is remarkable because customers may associate FLRs with standardization and cost-cutting, such that they may not fit firms that aim to be customer oriented. Design/methodology/approach: In four experiments, data are collected from customers interacting with frontline employees (FLEs) and FLRs in different settings. Findings: FLEs are perceived as more customer-oriented than FLRs due to higher competence and warmth evaluations. A relational interaction style attenuates the difference in perceived competence between FLRs and FLEs. These agents are also perceived as more similar in competence and warmth when FLRs participate in the customer journey's information and negotiation stages. Switching from FLE to FLR in the journey harms FLR evaluations. Practical implications: The authors recommend firms to place FLRs only in the negotiation stage or in both the information and negotiation stages of the customer journey. Still then customers should not transition from employees to robots (vice versa does no harm). Firms should ensure that FLRs utilize a relational style when interacting with customers for optimal effects. Originality/value: The authors bridge the FLR and sales/marketing literature by drawing on social cognition theory. The authors also identify the product categories for which customers are willing to negotiate with an FLR. Broadly speaking, this study’s findings underline that customers perceive robots as having agency (i.e. the mental capacity for acting with intentionality) and, just as humans, can be customer-oriented.</p

Immediate effects of dasatinib on the migration and redistribution of naïve and memory lymphocytes associated with lymphocytosis in chronic myeloid leukemia patients

Introduction: Dasatinib is a dual SRC/ABL tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML) that is known to have unique immunomodulatory effects. In particular, dasatinib intake typically causes lymphocytosis, which has been linked to better clinical response. Since the underlying mechanisms are unknown and SRC family kinases are involved in many cell motility processes, we hypothesized that the movement and migration of lymphocytes is modulated by dasatinib. Patients, Materials and Methods: Peripheral blood samples from CML patients treated with second-line dasatinib were collected before and 2 h after the first dasatinib intake, and follow-up samples from the same patients 3 and 6 months after the start of therapy. The migratory capacity and phenotype of lymphocytes and differential blood counts before and after drug intake were compared for all study time-points. Results: We report here for the first time that dasatinib intake is associated with inhibition of peripheral blood T-cell migration toward the homeostatic chemokines CCL19 and CCL21, which control the trafficking toward secondary lymphoid organs, mainly the lymph nodes. Accordingly, the proportion of lymphocytes in blood expressing CCR7, the chemokine receptor for both CCL19 and CCL21, decreased after the intake including both naïve CD45RA+ and central memory CD45RO+ T-cells. Similarly, naïve B-cells diminished with dasatinib. Finally, such changes in the migratory patterns did not occur in those patients whose lymphocyte counts remained unchanged after taking the drug. Discussion: We, therefore, conclude that lymphocytosis induced by dasatinib reflects a pronounced redistribution of naïve and memory populations of all lymphocyte subsets including CD4+ and CD8+ T-cells and B-cells

Deep-Sequencing Reveals Broad Subtype-Specific HCV Resistance Mutations Associated with Treatment Failure

[Abstract] 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) α-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.Ministerio de Economía y Empresa; IDI-20151125Ministerio de Ciencia, Innovación y Universidades; SAF SAF 2017-87846-

VDR gene polymorphisms on risk of osteoporotic hip fracture in an adult population spanish

La osteoporosis es una enfermedad esquelética compleja multifactorial con un fuerte componente genético, caracterizada por un deterioro en la microestructura ósea que causa fragilidad ósea y un incremento en el riesgo de fracturas osteoporóticas. El gen VDR podría estar fuertemente involucrado en el riesgo de fractura. El objetivo de este trabajo fue investigar la asociación entre polimorfismos del gen VDR y la susceptibilidad a fractura de cadera (FC). Se reclutaron 147 pacientes andaluces (102 con factores de riesgos de fracturas osteoporóticas y 45 con metabolismo óseo normal). El aislamiento de ADN se realizó a partir de 300 mL de sangre, genotipando 2 SNPs: BsmI y FokI mediante PCRRFLP (PCR-Restriction Fragment Length Polymorphism). Todas las fracturas fueron confirmadas por rayos-X mientras que el riesgo de fracturas a través de la escala FRAX y DMO. Los resultados se evaluaron estadísticamente, considerando significativo valores de p<0,05. La edad media de los pacientes fracturados fue de 68,5 años, cuyas frecuencias alélicas fueron 64.7% G y 68.6% C para BsmI y FokI, respectivamente. La prevalencia de estos SNPs en la población caso fueron: 43,3% GA, 43.3% GG y 13,7% AA para BsmI y 49,0% CC, 39,20% CT, 11,8% TT para FokI. Las frecuencias de los alelos y genotipos no mostraron diferencias entre pacientes con riesgo de fracturas y pacientes control. Las frecuencias están acorde con las demostradas en HapMap para población europeacaucásica. No se encontró ninguna asociación significativa entre estos SNPs y la susceptibilidad a las FC en la población adulta andaluza.Osteoporosis is a multifactorial complex skeletal disease with strong genetic component, characterized by a deterioration of bone microstructure that causes bone fragility and an increased risk of osteoporotic fractures. VDR gene could be strongly involved in the risk of fracture. The aim of this study was to investigate the association between VDR gene polymorphisms and susceptibility to hip fracture (HF). 147 Andalusian patients were recruited (102 with risk factors for osteoporotic fractures and 47 with normal bone metabolism). DNA isolation was performed from 300 mL of blood, genotyping 2 SNPs: BsmI and FokI by PCR-RFLP (PCR-Restriction Fragment Length Polymorphism). All fractures were confirmed by X-rays while the risk of fractures through FRAX level and BMD. The results were statistically evaluated, considering significant p-values <0.05. The average age of fractured patients was 68.5 years, whose allele frequencies were 64.7% G and 68.6% C for BsmI and FokI, respectively. Prevalence of these SNPs in the case population were: 43.3% GA, 43.3% GG and 13.7% AA BsmI and 49.0 % CC, 39.2% CT, 11.8% TT for FokI. The frequencies of alleles and genotypes showed no differences between patients with and without risk of hip fracture. The frequencies are agree to HapMap for European-Caucasian population. It was found no significant association between these SNPs and susceptibility to HF in the adult population of Andalusia

A multi-stakeholder multicriteria decision analysis for the reimbursement of orphan drugs (FinMHU-MCDA study)

Background: Patient access to orphan medicinal products (OMPs) is limited and varies between countries, reimbursement decisions on OMPs are complex, and there is a need for more transparent processes to know which criteria should be considered to inform these decisions. This study aimed to determine the most relevant criteria for the reimbursement of OMPs in Spain, from a multi-stakeholder perspective, and using multicriteria decision analysis (MCDA). Methods: An MCDA was developed in 3 phases and included 28 stakeholders closely related to the field of rare diseases (6 physicians, 5 hospital pharmacists, 7 health economists, 4 patient representatives and 6 members from national and regional health authorities). Initially [phase A], a bibliographic review was conducted to identify the potential reimbursement criteria. Then, a reduced advisory board (8 members) proposed, selected, and defined the final list of criteria that could be relevant for reimbursement. A discrete choice experiment (DCE) [phase B] was developed to determine the relevance and relative importance weight of such criteria according to the stakeholders’ preferences by choosing between pairs of hypothetical financing scenarios. A multinomial logit model was fitted to analyze the DCE responses. Finally [phase C], the advisory board review the results using a deliberative process. Results: Thirteen criteria were selected, related to 4 dimensions: patient population, disease, treatment, and economic evaluation. Nine criteria were deemed relevant for decision-making and associated with a higher relative importance: Health-related quality of life (HRQL) (23.53%), treatment efficacy (14.64%), availability of treatment alternatives (13.51%), disease severity (12.62%), avoided costs (11.21%), age of target population (7.75%), safety (seriousness of adverse events) (4.72%), quality of evidence (3.82%) and size of target population (3.12%). The remaining criteria had a < 3% relative importance: economic burden of disease (2.50%), cost of treatment (1.73%), cost-effectiveness (0.83%) and safety (frequency of adverse events) (0.03%). Conclusion: The reimbursement of OMPs in Spain should be determined by its effect on patient’s HRQL, the extent of its therapeutic benefit from efficacy and the availability of other therapeutic options. Furthermore, the severity of the rare disease should also influence the decision along with the potential of the treatment to avoid associated costs

Sofosbuvir/ledipasvir plus ribavirin achieves high SVR12 in genotype‐3 patients with compensated cirrhosis and similar to sofosbuvir plus daclatasvir: a multicentre real life cohort

Poster abstrac

Carbapenem-resistant Citrobacter spp. isolated in Spain from 2013 to 2015 produced a variety of carbapenemases including VIM-1, OXA-48, KPC-2, NDM-1 and VIM-2

Objectives: There is little information about carbapenemase-producing (CP) Citrobacter spp.We studied the molecular epidemiology and microbiological features of CP Citrobacter spp. isolates collected in Spain (2013-15). Methods: In total, 119 isolates suspected of being CP by the EUCAST screening cut-off values were analysed. Carbapenemases and ESBLs were characterized using PCR and sequencing. The genetic relationship among Citrobacter freundii isolates was studied by PFGE. Results: Of the 119 isolates, 63 (52.9%) produced carbapenemases, of which 37 (58.7%) produced VIM-1, 20 (31.7%) produced OXA-48, 12 (19%) produced KPC-2, 2 (3.2%) produced NDM-1 and 1 (1.6%) produced VIM- 2; 9 C. freundii isolates co-produced VIM-1 plus OXA-48. Fourteen isolates (22.2%) also carried ESBLs: 8 CTX-M-9 plus SHV-12, 2 CTX-M-9, 2 SHV-12 and 2 CTX-M-15. Fifty-seven isolates (90.5%) were C. freundii, 4 (6.3%) were Citrobacter koseri, 1 (1.6%) was Citrobacter amalonaticus and 1 (1.6%) was Citrobacter braakii. By EUCAST breakpoints, eight (12.7%) of the CP isolates were susceptible to the four carbapenems tested. In the 53 CP C. freundii analysed by PFGE, a total of 44 different band patterns were observed. Four PFGE clusters were identified: cluster 1 included eight isolates co-producing VIM-1 and OXA-48; blaVIM-1 was carried in a class 1 integron (intI-blaVIM-1 - aacA4-dfrB1-aadA1-catB2-qacE¿1/sul1) and blaOXA-48 was carried in a Tn1999.2 transposon. Conclusions: We observed the clonal and polyclonal spread of CP Citrobacter spp. across several Spanish geographical areas. Four species of Citrobacter spp. produced up to five carbapenemase types, including coproduction of VIM-1 plus OXA-48. Some CP Citrobacter spp. isolates were susceptible to the four carbapenems tested, a finding with potential clinical implications

Safety and Efficacy of Sofosbuvir plus Simeprevir in a Spanish Cohort of 622 Cirrhotic Patients Infected with Genotypes 1 or 4

Presentation Poste

Efficacy and safety of HCV-treatment with direct-acting antiviral agents interferon-free, in patients with severe renal impairment in clinical practice

Abstrac

Eliminación de la hepatitis C. Documento de posicionamiento de la Asociación Española para el Estudio del Hígado (AEEH)

La Asociación Española para el Estudio del Hígado (AEEH) está convencida de que la eliminación de la hepatitis C en España es posible siempre y cuando seamos capaces de emplear los recursos y las herramientas necesarias para la misma. Este documento refleja la posición de la AEEH respecto a la eliminación del virus de la hepatitis C (VHC), estableciendo una amplia serie de recomendaciones que se pueden agrupar en cinco categorías: 1) cribado del VHC en función de la edad, de la existencia de factores de riesgo clásicos de adquisición de la infección, búsqueda activa de pacientes diagnosticados con anterioridad y desarrollo de estrategias de microeliminación en poblaciones vulnerables; 2) simplificación del diagnóstico del VHC (diagnóstico en un solo paso y diagnóstico en el punto de atención del paciente); 3) simplificación del tratamiento de los pacientes y mejora de los circuitos asistenciales; 4) medidas de política sanitaria, y, finalmente, 5) establecimiento de indicadores de eliminación del VHC. The Spanish Association for the Study of the Liver (AEEH) is convinced that the elimination of hepatitis C virus (HCV) in Spain is possible as long as we are able to use the resources and tools necessary for it. This document reflects the position of the AEEH regarding the elimination of HCV, establishing a wide range of recommendations that can be grouped into five categories: 1) Screening of HCV according to age, of the existence of classic acquisition risk factors of infection, active search of previously diagnosed patients and development of microelimination strategies in vulnerable populations; 2) Simplification of HCV diagnosis (one-step diagnosis and diagnosis at the point of patient care); 3) Simplification of patient treatment and improvement of care circuits; 4) Health policy measures, and, finally, 5) Establishment of HCV elimination indicators