Cost-effectiveness of a community pharmacist intervention in patients with depression: a randomized controlled trial (PRODEFAR study)

Background: Non-adherence to antidepressants generates higher costs for the treatment of depression. Little is known about the cost-effectiveness of pharmacist's interventions aimed at improving adherence to antidepressants. The study aimed to evaluate the cost-effectiveness of a community pharmacist intervention in comparison with usual care in depressed patients initiating treatment with antidepressants in primary care. Methods: Patients were recruited by general practitioners and randomized to community pharmacist intervention (87) that received an educational intervention and usual care (92). Adherence to antidepressants, clinical symptoms, Quality-Adjusted Life-Years (QALYs), use of healthcare services and productivity losses were measured at baseline, 3 and 6 months. Results: There were no significant differences between groups in costs or effects. From a societal perspective, the incremental cost-effectiveness ratio (ICER) for the community pharmacist intervention compared with usual care was 1,866 for extra adherent patient and 9,872 per extra QALY. In terms of remission of depressive symptoms, the usual care dominated the community pharmacist intervention. If willingness to pay (WTP) is 30,000 per extra adherent patient, remission of symptoms or QALYs, the probability of the community pharmacist intervention being cost-effective was 0.71, 0.46 and 0.75, respectively (societal perspective). From a healthcare perspective, the probability of the community pharmacist intervention being cost-effective in terms of adherence, QALYs and remission was of 0.71, 0.76 and 0.46, respectively, if WTP is 30,000. Conclusion: A brief community pharmacist intervention addressed to depressed patients initiating antidepressant treatment showed a probability of being cost-effective of 0.71 and 0.75 in terms of improvement of adherence and QALYs, respectively, when compared to usual care. Regular implementation of the community pharmacist intervention is not recommended.

Evaluation of a pharmacist intervention on patients initiating pharmacological treatment for depression: a randomized controlled superiority trial

Major depression is associated with high burden, disability and costs. Non-adherence limits the effectiveness of antidepressants. Community pharmacists (CP) are in a privileged position to help patients cope with antidepressant treatment. The aim of the study was to evaluate the impact of a CP intervention on primary care patients who had initiated antidepressant treatment. Newly diagnosed primary care patients were randomised to usual care (UC) (92) or pharmacist intervention (87). Patients were followed up at 6 months and evaluated three times (Baseline, and at 3 and 6 months). Outcome measurements included clinical severity of depression (PHQ-9), health-related quality of life (HRQOL) (Euroqol-5D) and satisfaction with pharmacy care. Adherence was continuously registered from the computerised pharmacy records. Non-adherence was defined as refilling less than 80% of doses or having a medication-free gap of more than 1 month. Patients in the intervention group were more likely to remain adherent at 3 and 6 months follow-up but the difference was not statistically significant. Patients in the intervention group showed greater statistically significant improvement in HRQOL compared with UC patients both in the main analysis and PP analyses. No statistically significant differences were observed in clinical symptoms or satisfaction with the pharmacy service. The results of our study indicate that a brief intervention in community pharmacies does not improve depressed patients' adherence or clinical symptoms. This intervention helped patients to improve their HRQOL, which is an overall measure of patient status.

Effect of Maraviroc Intensification on HIV-1-Specific T Cell Immunity in Recently HIV-1-Infected Individuals

Background The effect of maraviroc on the maintenance and the function of HIV-1-specific T cell responses remains unknown. Methods Subjects recently infected with HIV-1 were randomized to receive anti-retroviral treatment with or without maraviroc intensification for 48 weeks, and were monitored up to week 60. PBMC and in vitro-expanded T cells were tested for responses to the entire HIV proteome by ELISpot analyses. Intracellular cytokine staining assays were conducted to monitor the (poly)-functionality of HIV-1-specific T cells. Analyses were performed at baseline and week 24 after treatment start, and at week 60 (3 months after maraviroc discontinuation). Results Maraviroc intensification was associated with a slower decay of virus-specific T cell responses over time compared to the non-intensified regimen in both direct ex-vivo as well as in in-vitro expanded cells. The effector function profiles of virus-specific CD8+ T cells were indistinguishable between the two arms and did not change over time between the groups. Conclusions Maraviroc did not negatively impact any of the measured parameters, but was rather associated with a prolonged maintenance of HIV-1-specific T cell responses. Maraviroc, in addition to its original effect as viral entry inhibitor, may provide an additional benefit on the maintenance of virus-specific T cells which may be especially important for future viral eradication strategies.

Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals

Background The MPER region of the HIV-1 envelope glycoprotein gp41 is targeted by broadly neutralizing antibodies. However, the localization of this epitope in a hydrophobic environment seems to hamper the elicitation of these antibodies in HIV infected individuals. We have quantified and characterized anti-MPER antibodies by ELISA and by flow cytometry using a collection of mini gp41-derived proteins expressed on the surface of 293T cells. Longitudinal plasma samples from 35 HIV-1 infected individuals were assayed for MPER recognition and MPER-dependent neutralizing capacity using HIV-2 viruses engrafted with HIV-1 MPER sequences. Results Miniproteins devoid of the cysteine loop of gp41 exposed the MPER on 293T cell membrane. Anti-MPER antibodies were identified in most individuals and were stable when analyzed in longitudinal samples. The magnitude of the responses was strongly correlated with the global response to the HIV-1 envelope glycoprotein, suggesting no specific limitation for anti-MPER antibodies. Peptide mapping showed poor recognition of the C-terminal MPER moiety and a wide presence of antibodies against the 2F5 epitope. However, antibody titers failed to correlate with 2F5-blocking activity and, more importantly, with the specific neutralization of HIV-2 chimeric viruses bearing the HIV-1 MPER sequence; suggesting a strong functional heterogeneity in anti-MPER humoral responses. Conclusions Anti-MPER antibodies can be detected in the vast majority of HIV-1 infected individuals and are generated in the context of the global anti-Env response. However, the neutralizing capacity is heterogeneous suggesting that eliciting neutralizing anti-MPER antibodies by immunization might require refinement of immunogens to skip nonneutralizing responses.

Estratigrafía secuencial de sistemas deltaicos en cuencas de antepaís: ejemplos de Montserrat, Sant Llorenç del Munt, Montserrat y Roda (Paleogeno, cuenca de Antepaís surpirenaica).

After the sedimentological study of the Sant Llorenc del Munt, Montserrat and Roda deltaic systems, a stratigraphic subdivision based on three different scale transgressiveregressive sequences has been developed. This subdivision has been established on the coastal facies belts from the deduced shoreline (and associated facies belts) migration. These transgressive-regressive sequences are formed by a lower transgressive part with a deepening-upwards trend and a retrogradational staclung pattern and an upper regressive part, with shallowing-upwards trend and a progradational stacking pattern. The lowest scale sequences (metrical) have been named 'fundamental sequences'. A series of 'composite sequences', intermediate scale (decametric to hectometric), have been defined afier the study of the staclung pattem of the fundamental sequences. After the study of the stacking pattem of composite sequences there have been defined a series of large-scale (decametric to kilometric) 'composite megasequences'.

A new multidisciplinary home care telemedicine system to monitor stable chronic human immunodeficiency virus-infected patients: a randomized study.

Background: Antiretroviral therapy has changed the natural history of human immunodeficiency virus (HIV) infection in developed countries, where it has become a chronic disease. This clinical scenario requires a new approach to simplify follow-up appointments and facilitate access to healthcare professionals. Methodology: We developed a new internet-based home care model covering the entire management of chronic HIV-infected patients. This was called Virtual Hospital. We report the results of a prospective randomised study performed over two years, comparing standard care received by HIV-infected patients with Virtual Hospital care. HIV-infected patients with access to a computer and broadband were randomised to be monitored either through Virtual Hospital (Arm I) or through standard care at the day hospital (Arm II). After one year of follow up, patients switched their care to the other arm. Virtual Hospital offered four main services: Virtual Consultations, Telepharmacy, Virtual Library and Virtual Community. A technical and clinical evaluation of Virtual Hospital was carried out. Findings: Of the 83 randomised patients, 42 were monitored during the first year through Virtual Hospital (Arm I) and 41 through standard care (Arm II). Baseline characteristics of patients were similar in the two arms. The level of technical satisfaction with the virtual system was high: 85% of patients considered that Virtual Hospital improved their access to clinical data and they felt comfortable with the videoconference system. Neither clinical parameters [level of CD4 + T lymphocytes, proportion of patients with an undetectable level of viral load (p = 0.21) and compliance levels 90% (p = 0.58)] nor the evaluation of quality of life or psychological questionnaires changed significantly between the two types of care. Conclusions: Virtual Hospital is a feasible and safe tool for the multidisciplinary home care of chronic HIV patients. Telemedicine should be considered as an appropriate support service for the management of chronic HIV infection.

Psicoterapia positiva grupal en cáncer. Hacia una atención psicosocial integral del superviviente de cáncer

Objetivo: Las enfermedades graves como el cáncer pueden vivirse como experiencias traumáticas y/o como impulso para realizar cambios vitales positivos (ej. crecimiento postraumático). El programa de psicoterapia positiva grupal para supervivientes de cáncer que realizamos integra ambos elementos, trauma y crecimiento. Los objetivos del programa no son sólo la reducción de emociones negativas (malestar emocional o sintomatología postraumática) sino el trabajo con emociones positivas y la facilitación de crecimiento postraumático. Método: Los elementos de trabajo psicoterapéutico que han mostrado evidencia en la consecución de estos objetivos y que componen los módulos de este programa son: favorecer la expresión y procesamiento emocional, entrenar habilidades de regulación emocional y estrategias de afrontamiento, trabajo con elementos facilitadores del crecimiento postraumático y confrontación con los aspectos existenciales y espirituales que surgen tras el diagnóstico y tratamiento oncológico. Además de estos aspectos psicoterapéuticos, complementamos el programa con otros factores relevantes en la adaptación psicosocial tras la enfermedad como: el fomento de estilos de vida saludables, la adherencia a los tratamientos oncológicos, la reinserción laboral y los comportamientos solidarios. Resultados: Los resultados preliminares del programa muestran mayor reducción de sintomatología postraumática y mayor crecimiento postraumático en el programa de psicoterapia positiva en el seguimiento a 3 meses al compararlo con un programa anterior centrado únicamente en la reducción de malestar emocional.

Efectos de la primera visita de consejo genético sobre la percepción de riesgo y el malestar emocional

Objetivo: Analizar los efectos que provoca la primera visita de consejo genético para cáncer hereditario sobre la percepción de riesgo, y el malestar emocional en pacientes que acuden por primera vez a la Unidad de Consejo Genético (UCG) por historia familiar de cáncer de mama, ovario o colon hereditario. Método: Se evaluó la percepción de riesgo de padecer cáncer (al año, a 10 años, y a lo largo de toda la vida), y la intensidad del malestar emocional (evaluada como la ansiedad, tristeza y preocupación por la salud experimentadas durante la última semana) en tres ocasiones: inmediatamente antes de la primera visita de consejo genético (CG), inmediatamente después de la misma, y al cabo de 2-3 semanas. Resultados: El malestar emocional previo a la visita se producía en aproximadamente un 30% de los pacientes, siendo mayor en las personas que no realizaban actividad laboral. Si bien la visita de CG reducía el malestar emocional en muchos casos, ocurría lo contrario en algunos pacientes inmediatamente después de la misma (un 34% se sentía más ansioso, un 32% se sentía más triste, y un 23% se sentía más preocupado), y ello guardaba relación con la preocupación por los hijos (tanto si se tenían como si se pretendía tenerlos en el futuro). No obstante, este malestar se reducía en las 2-3 semanas posteriores. La visita de CG reducía la percepción de riesgo de padecer cáncer a lo largo de toda la vida (p< .01), no existiendo diferencias en función del tipo de cáncer. Conclusiones: Esta primera visita reduce la sobreestimación del riesgo de padecer cáncer que los pacientes tienen antes de la misma, pero, en aproximadamente un tercio de los mismos, no reduce los niveles de malestar emocional, observándose, incluso, un incremento de éste que va disminuyendo durante las semanas posteriores a la visita. Son necesarios más estudios que permitan determinar si este incremento es una consecuencia inevitable del inicio del proceso de CG, o si puede reducirse modificando algún aspecto del protocolo que se aplica en la primera visita.

p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes

It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (K562) with inducible p21 expression and human primary keratinocytes with adenoviral-mediated p21 expression, we carried out microarray-based gene expression profiling. We found that p21 rapidly and strongly repressed the mRNA levels of a number of genes involved in cell cycle and mitosis. One of the most strongly down-regulated genes was CCNE2 (cyclin E2 gene). Mutational analysis in K562 cells showed that the N-terminal region of p21 is required for repression of gene expression of CCNE2 and other genes. Chromatin immunoprecipitation assays indicated that p21 was bound to human CCNE2 and other p21-repressed genes gene in the vicinity of the transcription start site. Moreover, p21 repressed human CCNE2 promoter-luciferase constructs in K562 cells. Bioinformatic analysis revealed that the CDE motif is present in most of the promoters of the p21-regulated genes. Altogether, the results suggest that p21 exerts a repressive effect on a relevant number of genes controlling S phase and mitosis. Thus, p21 activity as inhibitor of cell cycle progression would be mediated not only by the inhibition of CDKs but also by the transcriptional down-regulation of key genes.

The fossil crown wasp Electrostephanus petiolatus Brues in Baltic Amber (Hymenoptera, Stephanidae): designation of a neotype, revised classification,and a key to amber Stephanidae.

The fossil crown wasp Electrostephanus petiolatus Brues comb. rev.(Stephanidae, Electrostephaninae) is re-described from a single male preserved in middle Eocene Baltic Amber. The holotype was lost or destroyed around the time of World War II and subsequent interpretations of its identity have been based solely on the brief descriptive comments provided by Brues in his original account. The new specimen matches the original description and illustration provided by Brues in every detail and we hereby consider them to be conspecific, selecting the specimen as a neotype for the purpose of stabilizing the nomenclature for this fossil species. This neotype exhibits a free first metasomal tergum and sternum, contrary to the assertion of previous workers who indicated these to be fused. Accordingly, this species does indeed belong to the genus Electrostephanus Brues rather than to Denaeostephanus Engel & Grimaldi (Stephaninae). Electrostephanus petiolatus is transferred to a new subgenus, Electrostephanodes n. subgen. , based on its elongate pseudo- petiole and slender gaster, but may eventually warrant generic status as the phylogenetic placement of these fossil lineages continues to be clarifi ed. A revised key to the Baltic amber crown wasps is provided.

Palinomorfos del Triásico superior resedimentados en los materiales marinos eocenos de Sant LlorenÇ del Munt (Cuenca del Ebro, NE EspaÑa)

El complejo de abanico costero de Sant Lloren$ del Munt se encuentra en el margen sureste de la cuenca del Ebro, en el noroeste de España. Durante el Paleógeno, este margen de la cuenca estuvo sometido a unas condiciones de tipo transpresivo durante las que se desarrollaron una serie de pliegues, cabalgarnientos y failas de desgarre. Esta estructuración dió lugar a un bloque tectónicamente elevado constituido por materiales del zócalo paleozoico y la cobertera mesozoica que alimentaba una serie de abanicos aluviales y costeros, como el de Sant Lloren$ del Munt, que se desarrollaron en el borde de la cuenca del Ebro. El complejo de Sant Lloren$ del Munt presenta depósitos tanto subaereos como submarinos bien desarrollados, donde se han podido diferenciar cinco principales asociaciones de facies : abanico aluvial proximal, abanico aluvial distal/llanura de abanico costero, frente deltaico, talud deltaico/offshore y plataforma carbonática. Se han tomado 32 muestras de las facies marinas del Bartoniense para el estudio de su contenido palinológico y en 19 de éstas se han encontrado granos de polen triásicos. La mayor parte de las muestras con porcentajes altos de palinomorfos triásicos se corresponden con facies detríticas ligadas a períodos con importantes aportes sedimentarios. Se ha determinado la presencia de más de 15 palinomorfos triásicos diferentes, la mayoría de los cuales nunca han sido encontrados en las muestras tomadas en los materiales triásicos que afloran en areas relativamente cercanas a la aquí estudiada. Se han encontrado palinomorfos típicos del Kamiense y Nonense (Tnásico superior). Los materiales del Triásico superior debieron aflorar extensamente durante el Bartoniense en el actual Valles occidental. El área fuente del complejo de Sant Lloren$ del Munt estuvo constituida tanto por materiales del zócalo paleozoico como de la cobertera Triásica, alcanzando esta última un desarrollo mucho más importante de lo que se había deducido hasta el momento. Existe una relación entre los tramos de las secuencias (fundamentales y compuestas), el contenido en palinomorfos triásicos resedimentados y el grado de conservación del polen. Existe también una relación entre el tipo de facies y el contenido en palinomorfos triásicos resedimentados.

CBS: an open platform that integrates predictive methods and epigenetics information to characterize conserved regulatory features in multiple Drosophila genomes.

Background: Information about the composition of regulatory regions is of great value for designing experiments to functionally characterize gene expression. The multiplicity of available applications to predict transcription factor binding sites in a particular locus contrasts with the substantial computational expertise that is demanded to manipulate them, which may constitute a potential barrier for the experimental community. Results: CBS (Conserved regulatory Binding Sites, http://compfly.bio.ub.es/CBS) is a public platform of evolutionarily conserved binding sites and enhancers predicted in multiple Drosophila genomes that is furnished with published chromatin signatures associated to transcriptionally active regions and other experimental sources of information. The rapid access to this novel body of knowledge through a user-friendly web interface enables non-expert users to identify the binding sequences available for any particular gene, transcription factor, or genome region. Conclusions: The CBS platform is a powerful resource that provides tools for data mining individual sequences and groups of co-expressed genes with epigenomics information to conduct regulatory screenings in Drosophila.

Architectural characterization of a delta-front reservoir analogue combining ground penetrating radar and electrical resistivity tomography: Roda Sandstone (Lower Eocene, Graus-Tremp basin, Spain)

Three-dimensional reconstruction of reservoir analogues can be improved combining data from different geophysical methods. Ground Penetrating Radar (GPR) and Electrical Resistivity Tomography (ERT) data are valuable tools, since they provide subsurface information from internal architecture and facies distribution of sedimentary rock bodies, enabling the upgrading of depositional models and heterogeneity reconstruction. The Lower Eocene Roda Sandstone is a well-known deltaic complex widely studied as a reservoir analogue that displays a series of sandstone wedges with a general NE to SW progradational trend. To provide a better understanding of internal heterogeneity of a 10m-thick progradational delta-front sandstone unit, 3D GPR data were acquired. In addition, common midpoints (CMP) to measure the sandstone subsoil velocity, test profiles with different frequency antennas (25, 50 and 100MHz) and topographic data for subsequent correction in the geophysical data were also obtained. Three ERT profiles were also acquired to further constrain GPR analysis. These geophysical results illustrate the geometry of reservoir analogue heterogeneities both depositional and diagenetic in nature, improving and complementing previous outcrop-derived data. GPR interpretation using radar stratigraphy principles and attributes analysis provided: 1)tridimensional geometry of major stratigraphic surfaces that define four units in the GPR Prism, 2) image the internal architecture of the units and their statistical study of azimuth and dips, useful for a quick determination of paleocurrent directions. These results were used to define the depositional architecture of the progradational sandbody that shows an arrangement in very-high-frequency sequences characterized by clockwise paleocurrent variations and decrease of the sedimentary flow, similar to those observed at a greater scale in the same system. This high-frequency sequential arrangement has been attributed to the autocyclic dynamics of a supply-dominated delta- front where fluvial and tidal currents are in competition. The resistivity models enhanced the viewing of reservoir quality associated with cement distribution caused by depositional and early diagenetic processes related to the development of transgressive and regressive systems tracts in igh-frequency sequences.

Proporción de carga asistencial generada por la diabetes mellitus en las consultas de enfermería de atención primaria de salut

Objetivo La mayoría de enfermos con diabetes mellitus tipo 2 (DM2) se controla en atención primaria de salud (APS). La atención y educación proporcionadas por enfermería son clave para controlar la glucemia y prevenir las complicaciones macro y microangiopáticas de la DM. El objetivo de este trabajo es conocer la proporción de carga asistencial atribuible a la DM en consultas de enfermería de APS. Material y método Estudio observacional, analítico y transversal. Durante 2 semanas consecutivas se registraron datos de todos los enfermos que acudieron a 15 consultas de enfermería de APS ubicadas en 14 Áreas Básicas de Salud (ABS) de la provincia de Barcelona. Las variables de estudio fueron: edad, sexo, situación laboral, motivo de consulta, duración de la visita, presencia de DM y, en los enfermos diabéticos, el tipo de tratamiento. La recogida de datos se realizó en 2 períodos. El primero entre noviembre del año 2003 y enero del 2004 y el segundo en abril de 2005. Se realizó un análisis descriptivo de estas variables con un intervalo de confianza del 95% y la asociación entre variables mediante el programa SPSS v.11.1. Resultados Tenía DM el 29% de los pacientes. La DM es el primer motivo de consulta (29,1%), aumenta con la edad y llega al 40% en mayores de 65 años. La duración media de una visita por DM es de 14,59 min, un 30,8% más elevada que la duración media del resto de los problemas de salud. Globalmente, las mujeres consultan más que los varones (56,6%) excepto en DM, curas y hábito tabáquico. Conclusiones La DM es el problema de salud que genera más demanda y consume más tiempo de enfermería en la APS. Esta realidad y el futuro que se prevé con relación al incremento de la prevalencia de DM exigen considerar nuevas estrategias organizativas y formativas, y establecer criterios para mejorar la gestión de recursos y promover estrategias educativas más efectivas.

Proporción de carga asistencial generada por la diabetes mellitus en las consultas de enfermería de atención primaria de salut

Objetivo La mayoría de enfermos con diabetes mellitus tipo 2 (DM2) se controla en atención primaria de salud (APS). La atención y educación proporcionadas por enfermería son clave para controlar la glucemia y prevenir las complicaciones macro y microangiopáticas de la DM. El objetivo de este trabajo es conocer la proporción de carga asistencial atribuible a la DM en consultas de enfermería de APS. Material y método Estudio observacional, analítico y transversal. Durante 2 semanas consecutivas se registraron datos de todos los enfermos que acudieron a 15 consultas de enfermería de APS ubicadas en 14 Áreas Básicas de Salud (ABS) de la provincia de Barcelona. Las variables de estudio fueron: edad, sexo, situación laboral, motivo de consulta, duración de la visita, presencia de DM y, en los enfermos diabéticos, el tipo de tratamiento. La recogida de datos se realizó en 2 períodos. El primero entre noviembre del año 2003 y enero del 2004 y el segundo en abril de 2005. Se realizó un análisis descriptivo de estas variables con un intervalo de confianza del 95% y la asociación entre variables mediante el programa SPSS v.11.1. Resultados Tenía DM el 29% de los pacientes. La DM es el primer motivo de consulta (29,1%), aumenta con la edad y llega al 40% en mayores de 65 años. La duración media de una visita por DM es de 14,59 min, un 30,8% más elevada que la duración media del resto de los problemas de salud. Globalmente, las mujeres consultan más que los varones (56,6%) excepto en DM, curas y hábito tabáquico. Conclusiones La DM es el problema de salud que genera más demanda y consume más tiempo de enfermería en la APS. Esta realidad y el futuro que se prevé con relación al incremento de la prevalencia de DM exigen considerar nuevas estrategias organizativas y formativas, y establecer criterios para mejorar la gestión de recursos y promover estrategias educativas más efectivas.