Intervención para valorar la Inercia Terapéutica en el tratamiento de la hipertensión arterial

La Inercia Terapéutica fue definida por Phillips como los fallos del médico en la iniciación o intensificación del tratamiento cuando está indicado. Se trata de una actitud conservadora del clínico, en la cual no modifica el tratamiento a pesar de saber que no se están alcanzando los objetivos terapéuticos. La Inercia Terapéutica es un grave problema que afecta a toda la sanidad en general y de difícil solución, ya que se precisa de una mayor formación de los profesionales, mayor concienciación de estos en la aplicación de gulas y consensos en Hipertensión Arterial, pero sobre todo hace falta incentivación de los profesionales y disposición de tiempo en el manejo de sus consultas. Si analizamos la Inercia Terapéutica que se produce en España se observa que en estudios transversales oscila entre el 51 y el 84,6%, mientras que en estudios longitudinales varía entre el 40,3 y el 82,5%. Estos últimos se asemejan más a la práctica diaria del clínico. Además se produce Inercia Terapéutica en más de un 80% de pacientes hipeitensos no controlados, lo que nos indica la gran relevancia de este fenómeno en la práctica habitual de los profesionales sanitarios. En la bibliografía existen pocos estudios que valoren intervenciones con el objetivo de disminuir la Inercia Terapéutica. Por ello es relevante valorar que intervenciones tienen capacidad de disminuirla en la práctica clínica habitual. OBJETIVOS DEL ESTUDIO OBJETIVO PRINCIPAL Valorar si la consulta de enfermería es una estrategia eficaz para disminuir la Inercia Terapéutica en el tratamiento farmacológico de la Hipertensión Arterial. OBJETIVOS ESPECÍFICOS Conocer el porcentaje de Inercia Terapéutica cometido en el tratamiento farmacológico de la Hipertensión Arterial en consultas de Atención Primaria. Valorar la existencia de diferentes variables que pueden influir en la Inercia Terapéutica y la influencia de ésta en el control de las cifras de Presión Arterial. METODOLOGÍA El estudio se ha desarrollado en el ámbito de la Atención Primaria en diferentes áreas de salud de la provincia de Huelva. Han participado 206 pacientes diagnosticados de HTA leve-moderada, según los criterios del Consenso ESC-ESH 2007, distribuidos en dos grupos de intervención y con un seguimiento de 6 meses por cada paciente. Participaron 30 de los 110 médicos de las 11 áreas básicas de salud a Jas que se les propuso el estudio. Cada médico seleccionó a 7 pacientes de forma consecutiva a medida que detectaba un paciente hipertenso en su consulta que cumplía los criterios de inclusión y ninguno de exclusión. Para el cálculo del tamaño muestra! se ha utilizado la metodología para estudios que obtienen como resultados principales proporciones y necesitan de un análisis mediante contraste bilateral. Se ha considerado de valor clínico el observar diferencias del 26% de Inercia Terapéutica entre los grupos y una prevalencia de Inercia Terapéutica estimada de un 65% en el grupo de control. Se consideró linas posibles pérdidas del 10%, resultando en cada uno de los 2 grupos una muestra de 103 individuos. Por lo tanto, la muestra final fue de 206 pacientes. Se realizó una aleatorización a los médicos participantes mediante clúster, siendo asignados sus pacientes al grupo que le haya correspondido. La aleatorización se realizó de forma centralizada, mediante tablas de números aleatorios y por una persona ajena al seguimiento de los pacientes. PLAN DE TRABAJO El estudio tuvo una duración de 12 meses, con un periodo de inclusión de 6 meses. Tras la aleatorización de los médicos se obtuvieron dos grupos: Grupo control (GC): Los pacientes recibieron la intervención que habitualmente su médico de Atención Primaria aplica en la consulta en el manejo del paciente hipertenso y NO estaban anteriormente en seguimiento en la consulta de enfermería. Grupo Intetvención o Consulta de Enfermería (GCE): Los pacientes recibieron la intervención habitual de su médico de Atención Primaria, y además, fueron remitidos a un seguimiento mediante la consulta de enfermería para control de las cifras de Presión Arterial. En dicha consulta estos pacientes recibieron la intervención habitual que su profesional de enfermería desarrolla habitualmente con sus pacientes hipertensos. Se realizó una visita inicial y otra a los 2, 4 y 6 meses. En esta consulta había una hoja de derivación a consulta médica para ser utilizada en el caso de que el paciente presentara cifras de Presión Arterial elevadas, según protocolo del centro y a criterio del profesional de enfermería. Se realizaron 3 visitas médicas, la Visita de Inclusión o Inicial, una Visita de Seguimiento prevista realizarse en el centro de salud a los 3 meses y la Visita Final a los 6 meses de la Visita de Inclusión. VARIABLES Y ANÁLISIS ESTADÍSTICO Se estudió el número total de individuos, retiradas y sus causas, edad y sexo, número de enfermedades y fármacos consumidos, Factores de Riesgo Cardiovascular asociados, Presiones Arteriales medias clínicas con sus desviaciones estándar y las diferencias obtenidas entre cada dos visitas consecutivas y entre la visita inicial y la final. Se calculó el grado de control de la Hipertensión Arterial, considerándose controlada cuando las cifras de Presión Arterial Sistòlica y Presión Arterial Diastólica medias clínicas eran inferiores a 140 y 90 inmHg respectivamente. Se definió Inercia Terapéutica en cada visita mediante el cociente: (Número de pacientes a los que no se les ha modificado el tratamiento farmacológico / Número de pacientes con cifras medias de Presión Arterial clínica superiores a 140 y/o 90 mmHg) multiplicado por 100. Se calculó la Inercia Terapéutica por visitas clínicas a los 3 y 6 meses. Considerándose la Inercia Terapéutica por visitas la variable principal. Se dividió a la muestra en dos grupos según la Inercia Terapéutica cometida, pacientes con Inercia Terapéutica y pacientes sin Inercia Terapéutica. Se valoraron las diferencias existentes en variables que podrían influir en la Inercia Terapéutica realizándose un análisis bivariante y multivariante con regresión logística de dichas variables. Se calculó el grado de control de la Presión Arterial en relación con la Inercia Terapéutica cometida, es decir, grupo de pacientes sin Inercia Terapéutica y grupo de pacientes con Inercia Terapéutica. Se calculó la reducción del riesgo absoluto (RRA = diferencia entre el porcentaje de Inercia Terapéutica cometida en el Grupo Consulta de Enfermería y en el Grupo Control), la reducción del riesgo relativo (RRR = RRA dividido por el porcentaje de Inercia Terapéutica en el Grupo Control) y el número de pacientes que se necesitaba tratar para evitar un caso de Inercia Terapéutica (NNT = I/RRA). Se han evaluado todas las variables mediante el paquete informático estadístico SPSS 11.5 para Windows y posteriormente se calcularon y se compararon primero de forma global y después por grupos de intervención. Se analizó la relación entre la Presión Arterial y el grado de control de la Presión Arterial con la Inercia Terapéutica. Se valoró la correlación entre Inercia Terapéutica y las cifras de Presión Arterial mediante un análisis de regresión lineal múltiple. Se utilizaron los test de Chi cuadrado, t de Student y McNemar test para la comparación de variables cualitativas y cuantitativas para datos apareados y no apareados. Se consideró significativa una p<0.05 y se calcularon los intervalos de confianza (IC) al 95%. RESULTADOS Un total de 184 pacientes terminaron el estudio. Siendo evaluables 92 pacientes de cada grupo de intervención. La edad media global fue de 62,8 afíos, el 58,5% eran mujeres con una edad media de 63,4 años, y el 41,5% hombres con una edad media de 62 afíos. Por grupos de intervención, la edad en el Grupo Consulta de Enfermería fue de 62 años y 63,7 años en el Grupo Control. Padecían una media de 2,9 enfermedades y consumían una media de 4,1 fármacos diariamente incluyendo otros fármacos no indicados para la HTA, no existiendo en ambos diferencia por sexo. No se observó diferencia significativa entre los Factores de Riesgo Cardiovascular estudiados, excepto en las dislipemias, presentándose esta en el 33,8% en el Grupo Control de Enfermería y en el 49,3% en el Grupo Control. Las Presiones Arteriales medias han obtenido un descenso significativo entre las iniciales y finales, con unos descensos de 18,7 mmHg para la Presión Arterial Sistòlica y de 9,6 mmHg para la Presión Arterial Diastólica. Fueron estadísticamente significativos los descensos producidos entre el inicio y el final del estudio de las Presiones Arteriales medias Sistólicas y las Presiones de Pulso, siendo este descenso superior en el Grupo Consulta de Enfermería. El porcentaje de individuos controlados al finalizar fue del 60,6%. Se observó que el porcentaje de individuos controlados y respondedores aumentan a medida que avanzan las visitas (p<0,001). Cuando se refiere al grado de control de las cifras de Presión Arterial en cada visita, de forma global y en función del grupo de intervención, se observó diferencias significativas, con un mayor control en la visita final en el grupo de intervención. La Inercia Terapéutica que se produjo en la Visita 2 fue del 15,5% en el grupo de intervención y del 38% en el grupo control, en la Visita Final fue del 25,23% y 46,07% para el grupo de intervención y grupo control respectivamente. La Inercia Terapéutica que se cometió en los hipertensos no controlados del grupo de intervención fue del 22,9% en la Visita 2 y del 54,5% en la Visita Final, siendo mayor en el grupo control (57,5% en la Visita 2 y del 76,5% en la Visita Final). Siendo esta diferencia significativa en la Visita 2 (p^0,04). Se distribuyó la muestra en pacientes con y sin Inercia Terapéutica: en 49 pacientes se produjo Inercia Terapéutica y en 133 no. Se analizó la posible influencia de diferentes variables sobre la Inercia Terapéutica. Tras el análisis bivariante sólo se observaron diferencias en dos variables que obtienen significación estadística: cuanto menor es el número de enfermedades padecidas (RR 95% por enfermedades padecidas, p=0,002) y cuanto más bajo es el número de fármacos consumidos (RR 95 % por fármacos consumidos, p<0,001), mayor es la Inercia Terapéutica. El porcentaje de pacientes controlados fue del 38,51% en el grupo sin Inercia Terapéutica y del 18,36% en grupo con Inercia Terapéutica al final del estudio (p<0,05). Se observa como en el grupo sin Inercia Terapéutica la Presión Arterial Sistòlica en la Visita Final es menor que en el grupo con Inercia Terapéutica (p<0,05). La reducción del riesgo absoluto al final de la intervención fue del 22,5%. La reducción del riesgo relativo fue del 59% y el número necesario de pacientes a tratar fue de 4,44. Sería necesario tratar con esta intervención a 4 pacientes para evitar un caso de Inercia Terapéutica. CONCLUSIONES La consulta de enfermería es una estrategia eficaz para disminuir los casos de Inercia Terapéutica cometidas por los médicos de Atención Primaria en el tratamiento farmacológico de la Hipertensión Arterial. El porcentaje de Inercia Terapéutica es alto, en este estudio va desde un 15,5% hasta un 46,07%, en función de la visita y el grupo al que se haga referencia. El número de fármacos consumidos (número de comprimidos/día) y el número de enfermedades padecidas influye en la Inercia Terapéutica, ésta es mayor a medida que se consumen menos fármacos y se padecen menos enfermedades. Una menor Inercia Terapéutica se traduce en un mejor control de la Hipertensión Arterial.Therapeutic Inertia has been defined by Phillips as the failure of the physician to start or to intensify treatment when it is indicated. It is a conservative attitude on the part of the clinician, in which the treatment is not modified despite the fact that it is not achieving the therapeutic objectives. Therapeutic Inertia is a serious problem that affects all healthcare and which is difficult to resolve, as this requires better training for healthcare professionals and a greater awareness in the application of guidelines and consensuses in High Blood Pressure. Above all, it is incentives for healthcare professionals and the availability of time in the management of their consultations that are lacking. If we analyse the therapeutic inertia that occurs in Spain, we see that transversal studies put it at between 51% and 84,6%, while longitudinal studies put it at between 40,3% and 82,5%. The latter are more similar to everyday clinical practice. Furthermore, therapeutic inertia occurs in more than 80% of non-controlled hypertensive patients, which indicates the great importance of this phenomenon in the normal practice of healthcare professionals. There are few studies in the literature that evaluate interventions with the aim of reducing therapeutic inertia. It is for this reason that it is pertinent to evaluate whether interventions have the capacity to reduce it in normal clinical practice. OBJECTIVES OF THE STUDY PRIMARY OBJECTIVE To evaluate whether a nursing consultation is an effective strategy to reduce Therapeutic Inertia in the pharmacological treatment of High Blood Pressure. SPECIFIC OBJECTIVES To measure the prevalence of Therapeutic Inertia occurring in the pharmacological treatment of High Blood Pressure in primary-care consultations. To evaluate the existence of different variables that could influence Therapeutic Inertia and the influence of Therapeutic Inertia on Blood Pressure figures. METHODOLOGY The study was carried out in a primary care environment in the various healthcare districts of the province of Huelva, in south-western Spain. 206 patients with mild to moderate HBP, according to the criteria of the ESC/ESH 2007 Guidelines, took part. They were divided into two treatment groups, with 6 months’ follow-up for each patient. Of the 110 doctors in the eleven healthcare districts to who the study was proposed, 30 took part. Each doctor selected 7 patients consecutively as they detected hypertensive patients in their practice who met the inclusion criteria and none of the exclusion criteria. The methodology that was used for the calculation of sample size was that for studies that obtain proportions as principal results and that need a two-tailed test. An observation of a 26% difference in therapeutic inertia between the groups was considered to be clinically significant, and the prevalence of Therapeutic Inertia in the control group was estimated at 65%. Possible losses to follow-up of 10% were considered, giving a sample of 103 individuals for each of the two groups. Therefore the final sample size was 206 patients. A cluster randomisation was carried out to the participating doctors, with a doctor’s patients being assigned to the group to which he/she corresponded. The randomisation was carried out centrally using random-number tables by a person who was not involved in the follow-up of patients. WORKPLAN The study lasted 12 months, with an inclusion period of 6 months. Two groups were obtained after the randomisation of the doctors; Control group (CG): The patients received the treatment that their primary-care doctor usually applies in the practice for the management of hypertensive patients and were NOT previously seen in appointments with a nurse. Treatment group or nursing-consultation group (NCG): The patients received their primary-care doctor’s normal treatment and, in addition, were followed up through appointments with a nurse to monitor blood pressure figures. In these appointments, these patients received the normal treatment practiced by their nurse with his/her hypertensive patients normally. An initial visit and visits at 2, 4 and 6 months were carried out. For these appointments, a medical referral form was available to be used for patients who presented high blood pressure figures according to the health centre’s protocol and the judgement of the nurse. Three medical visits were carried out: the initial or inclusion visit, a follow-up visit at the health centre after 3 months, and a final visit 6 months after the inclusion visit. VARIABLES AND STATISTICAL ANALYSIS The variables studied were: the total number of individuals, drop-outs and their reasons, age and gender, number of illnesses and medicines taken, associated Cardiovascular Risk Factors, clinical mean Blood Pressures and their standard deviations and the differences in blood pressure between two consecutive visits and the initial and final visit. The degree of control of Blood Pressure was calculated, considering BP to be controlled when the clinical mean systolic and diastolic pressures were lower than 140 mmHg and 90 mmHg respectively. Therapeutic Inertia was defined at each visit by the ratio: (Number of patients whose pharmacological treatment was not changed / Number of patients with mean clinical blood pressure figures higher than 140 mmHg and/or 90 mmHg) multiplied by 100. The Therapeutic Inertia was calculated for the clinical visits at 3 and 6 months. The therapeutic Inertia at the visits was considered to be the principal variable. The sample was divided into two groups depending on the therapeutic inertia that occurred: patients with Therapeutic Inertia and patients without Therapeutic Inertia. The differences in variables that could influence Therapeutic Inertia were evaluated by carrying out a bivariate and multivariate analysis with logistic regression of said variables. The degree of control of blood pressure was calculated in relation to the Therapeutic Inertia that occurred, i.e. for the group of patients without therapeutic inertia and for the group of patients with Therapeutic Inertia. The absolute risk reduction (ARR = difference between the rates of therapeutic inertia in the nursing-consultation group and in the control group), the relative risk reduction (RRR ~ ARR divided by the rate of therapeutic inertia in the control group) and the number of patient who would need to be treated to avoid one case of therapeutic inertia (NNT = 1/ARR). All the variables were evaluated using the statistical software package SPSS 11.5 for Windows and were then calculated and compared, first overall and then by treatment groups. Tiie relationship between Blood Pressure and the degree of control of Blood Pressure with Therapeutic Inertia was analysed. The correlation between Therapeutic Inertia and Blood Pressure figures was evaluated using multiple linear regression analysis. The Chi-squared test, Student’s Mest and McNemar's test were used for the comparison of qualitative and quantitative variables for paired and unpaired data. A p<0,05 was considered significant and confidence intervals (Cl) were calculated at 95%. RESULTS A total of 184 patients finished the study, 92 patients from each treatment group could be evaluated. The overall mean age was 62,8 years; there were 58,5% women with a mean age of 63,4 years and 41,5% men with a mean age of 62 years. By treatment groups, the mean age of the Nursing-Consultation Group was 62 years and that of the Control Group 63.7 years. Patients suffered from an average of 2,9 illnesses and took an average of 4,1 medicines every day, including other medicines not indicated for HBP: there was no difference between genders. There was no significant difference between the cardiovascular risk factors studied except for dyslipidaemia, which was presented by 33,8% of patients in the nursing- consultation group and 49,3% of patients in the control group. The mean Blood Pressures showed a significant reduction between the initial and final visits, with drops of 18.7 mmHg in systolic pressure and 9,6 mmHg in diastolic pressure. The drops achieved between the start and the end of the study were statistically significant for the mean systolic pressures and the pulse pressures, with this drop being higher in the Nursing-Consultation Group. The proportion of individuals controlled at the end of the study was 60,6%. It was observed that the proportion of responding and controlled individuals increased as the study went on (p<0,001). Significant differences were observed in terms of the degree of control of the blood pressure figures at each visit, over all and as a function of treatment group, with greater control at the final visit in the treatment group. The Therapeutic Inertia level at visit 2 was 15,5% in the treatment group and 38% in the control group; for the final visit it was 25,23% and 46,07% for the treatment group and the control group respectively. The Therapeutic Inertia level in non-controlled hypertensive patients in the treatment group was 22,9% at visit 2 and 54,5% at the final visit, and was higher in the control group (57,5% at visit 2 and 76,5% at the final visit). This difference was significant for visit 2 (p=0,04). The sample was divided into patients with and without Therapeutic Inertia: there were 49 patients with Therapeutic Inertia and 133 without. The possible influence of various variable on Therapeutic Inertia was analysed. After two-tailed analysis, statistically significant differences were only observed in two variables: Therapeutic Inertia is higher with a higher number of illnesses suffered (95% RR for illness suffered, p=0,002) and with a lower number of medicines taken (95% RR for medicines taken, p<0,001). The proportion of patients controlled at the end of the study was 38,51% in the group without Therapeutic Inertia and 18,36% in the group with Therapeutic Inertia (p<0,05). The systolic blood pressure was observed to be lower in the group without Therapeutic Inertia than in the group with Therapeutic Inertia (p<0,05). The absolute risk reduction at the end of the treatment was 22,5%. The relative risk reduction was 59% and the number of patients needing to be treated was 4,44.

Melatonin as a Coadjuvant in the Treatment of Patients with Fibromyalgia

Fibromyalgia syndrome (FMS) is a chronic widespread pain syndrome that is accompanied by fatigue, sleep disturbances, anxiety, depression, lack of concentration, and neurocognitive impairment. As the currently available drugs are not completely successful against these symptoms and frequently have several side effects, many scientists have taken on the task of looking for nonpharmacological remedies. Many of the FMS-related symptoms have been suggested to be associated with an altered pattern of endogenous melatonin. Melatonin is involved in the regulation of several physiological processes, including circadian rhythms, pain, mood, and oxidative as well as immunomodulatory balance. Preliminary clinical studies have propounded that the administration of different doses of melatonin to patients with FMS can reduce pain levels and ameliorate mood and sleep disturbances. Moreover, the total antioxidant capacity, 6-sulfatoxymelatonin and urinary cortisol levels, and other biological parameters improve after the ingestion of melatonin. Recent investigations have proposed a pathophysiological relationship between mitochondrial dysfunction, oxidative stress, and FMS by looking at certain proteins involved in mitochondrial homeostasis according to the etiopathogenesis of this syndrome. These improvements exert positive effects on the quality of life of FMS patients, suggesting that the use of melatonin as a coadjuvant may be a successful strategy for the management of this syndrome

Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception

Purpose: Lack of diagnostic and prognostic biomarkers in hepatocellular carcinoma impedes stratifying patients based on their risk of developing cancer. The aim of this study was to evaluate phenotypic and genetic heterogeneity of circulating epithelial cells (CECs) based on asialoglycoprotein receptor 1 (ASGR1) and miR-122-5p expression as potential diagnostic and prognostic tools in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Methods: Peripheral blood samples were extracted from LC and HCC patients at different disease stages. CECs were isolated using positive immunomagnetic selection. Genetic and phenotypic characterization was validated by double immunocytochemistry for cytokeratin (CK) and ASGR1 or by in situ hybridization with miR-122-5p and CECs were visualized by confocal microscopy. Results: The presence of CECs increased HCC risk by 2.58-fold, however, this was only significant for patients with previous LC (p = 0.028) and not for those without prior LC (p = 0.23). Furthermore, the number of CECs lacking ASGR1 expression correlated significantly with HCC incidence and absence of miR-122-5p expression (p = 0.014; r = 0.23). Finally, overall survival was significantly greater for patients at earlier cancer stages (p = 0.018), but this difference was only maintained in the group with the presence of CECs (p = 0.021) whereas progression-free survival was influenced by the absence of ASGR1 expression. Conclusion: Identification and characterization of CECs by ASGR1 and/or miR- 122-5p expression may be used as a risk-stratification tool in LC patients, as it was shown to be an independent prognostic and risk-stratification marker in LC and early disease stage HCC patients.Regional Ministry of Health of AndalusiaMinistry of Economy, Competitiveness, Enterprises and Universities PC-0522-2016 PC-0267-2017 PC-0033-2017Health Institute Carlos III (ISCIII) DOC_01682 CD18/0012

Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception

Purpose: Lack of diagnostic and prognostic biomarkers in hepatocellular carcinoma impedes stratifying patients based on their risk of developing cancer. The aim of this study was to evaluate phenotypic and genetic heterogeneity of circulating epithelial cells (CECs) based on asialoglycoprotein receptor 1 (ASGR1) and miR-122-5p expression as potential diagnostic and prognostic tools in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Methods: Peripheral blood samples were extracted from LC and HCC patients at different disease stages. CECs were isolated using positive immunomagnetic selection. Genetic and phenotypic characterization was validated by double immunocytochemistry for cytokeratin (CK) and ASGR1 or by in situ hybridization with miR-122-5p and CECs were visualized by confocal microscopy. Results: The presence of CECs increased HCC risk by 2.58-fold, however, this was only significant for patients with previous LC (p = 0.028) and not for those without prior LC (p = 0.23). Furthermore, the number of CECs lacking ASGR1 expression correlated significantly with HCC incidence and absence of miR-122-5p expression (p = 0.014; r = 0.23). Finally, overall survival was significantly greater for patients at earlier cancer stages (p = 0.018), but this difference was only maintained in the group with the presence of CECs (p = 0.021) whereas progression-free survival was influenced by the absence of ASGR1 expression. Conclusion: Identification and characterization of CECs by ASGR1 and/or miR- 122-5p expression may be used as a risk-stratification tool in LC patients, as it was shown to be an independent prognostic and risk-stratification marker in LC and early disease stage HCC patients

Reflecting on gender, power and empowerment through art. An educational tool for facili-tators, art educators and young people

En este manual, el lector y la lectora encontrarán cinco itinerarios temáticos que ofrecen la posibilidad de analizar cómo la cultura en general, y los museos en particular, interpretan el pasado. Las actividades proporcionan herramientas para comprender qué perspectivas se privilegian, y convierten a los y las participantes en visitantes activos y críticos para interpretar el pasado o el presente. Cada capítulo ofrece itinerarios que han sido diseñados para ser utilizados en museos específicos o en un aula mediante la proyección de las imágenes. Cada itinerario se compone de cinco pasos organizados en torno a: una obra de arte, información sobre la obra y dos actividades relacionadas con el tema específico. Estas actividades pueden tener lugar en el espacio del museo o fuera de él creando el marco para un diálogo entre el espectador o espectadora y la obra, por un lado, y entre pares, por otro (ya sean miembros de un grupo de visitantes, una persona o un grupo de apoyo que quiera desarrollar un mejor conocimiento de los sistemas de poder en relación con los roles de género en la sociedad).In this manual, the reader will find five thematic itineraries. They offer the possibility of analysing how culture at large, and museums specifically, interpret the past. The activities provide tools to understand what perspectives are privileged, and turn participants into active and critical visitors to interpret the past or the present. Each chapter offers itineraries that have been designed to be used either in specific museums or in a classroom by projecting the images. Each itinerary is composed of five steps organised around: a work of art, information about the work, and two activities related to the specific theme. These activities can take place in the museum space or outside the museum. They create the framework for a dialogue between the viewer and the work on one hand, and between peers on the other hand (be it members of a visitor’s group, a person or a support group who would like to develop better knowledge of the powers at stake regarding gender roles in society).Depto. de Didáctica de las Lenguas, Artes y Educación FísicaFac. de EducaciónTRUEComisión EuropeaErasmus+pu

Prevalence and Associated Factors of Low Bone Mineral Density in the Femoral Neck and Total Hip in Axial Spondyloarthritis: Data from the CASTRO Cohort

Studies on osteoporosis in axial spondyloarthritis (axSpA) have focused on the lumbar segment, and few studies have assessed bone mineral density (BMD) in the hip and femoral neck in these patients. The aim of this study was to evaluate the prevalence of low BMD and osteopenia in the total hip or femoral neck and the factors associated with these conditions in axSpA patients. This was a single-centre, observational, cross-sectional study among consecutive patients with axSpA according to the ASAS criteria from the CASTRO registry. All patients underwent total hip and femoral neck DXA BMD measurements. Low BMD was defined as a Z-score less than −1, and osteopenia was defined as a T-score less than −1. Multivariate logistic and generalised linear regressions were used to evaluate factors independently associated with low BMD and osteopenia in the hip or femoral neck and those associated with variability in BMD, respectively. A total of 117 patients were included, among which 30.8% were female and the mean age was 45 years. A total of 36.0% of patients had low BMD (28.1% in the total hip and 27.4% in the femoral neck), and 56.0% of patients had osteopenia (44.7% in the total hip and 53.8% in the femoral neck). A multivariate logistic regression showed that age, radiographic sacroiliitis and ASAS-HI were independently associated with low BMD in the total hip or femoral neck. Factors that were independently associated with osteopenia were Body Mass Index, disease duration, radiographic sacroiliitis and ASAS-HI. In conclusion, 36% of the patients with axSpA had low BMD in the total hip or femoral neck. A younger age and radiographic sacroiliitis were the most important factors associated with decreased BMD

IL11 involvement in inflammatory and pro-fibrotic alterations via STAT3-WNT5A signaling activation by SARS-CoV-2 accessory proteins

1 p.-6 fig.SARS-CoV-2, the cause of the COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome. Their roles during infection are still not completely understood and several of them have been mutating into the different variants of the virus. WNT5A dysregulation signaling has been implicated in the development of various pathological conditions in humans such as inflammation and fibrosis. Interleukin-6 (IL6) family members induce WNT5A expression in various cell types, highlighting a critical role for WNT5A in immune responses. Expression of Interleukin-11 (IL11), a member of IL6 cytokine family, correlates with the extent of fibrosis and its signaling induced fibroblast activation via TGFβ. In this study, A549 were transduced with lentivirus expressing individual viral accessory proteins ORF6, ORF8,ORF9b or ORF9c from SARS-CoV-2 (Wuhan-Hu-1 isolate) and their interaction with cellular responses were analyzed. Firstly, transcriptomic analysis revealed that both WNT5A and IL11 were significantly up-regulated in all transduced cells. Some IL11 signaling-related genes, such as STAT3 or TGFβ, were differentially expressed. IPA software analysis showed that both WNT5A and IL11 were involved in pulmonary fibrosis idiopathic disease. Subsequently, bioinformatics and functional assays revealed that these four accessory proteins were implicated in both inflammatory and fibrotic responses. While overexpression of ORF8 and ORF9c appear to trigger a STAT3-dependent cellular response mediated by IL11, ORF6 and ORF9b seem to provoke a cell profibrotic response mediated by TGFb through WNT5A. Our results suggest that ORF6, ORF8, ORF9b and ORF9c could be involved in inflammatory and fibrotic responses in SARS-CoV-2 infection. Thus, these accessory proteins could be targeted by new therapies for COVID-19 disease.This research work was funded by the European Commission – NextGenerationEU(Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI+ Salud Global), Junta de Andalucía (CV20-20089) and Spanish Ministry of Science project PID2021-123399OB-I00.Peer reviewe

Emergency department direct discharge compared to short-stay unit admission for selected patients with acute heart failure: analysis of short-term outcomes

Short stay unit (SSU) is an alternative to conventional hospitalization in patients with acute heart failure (AHF), but the prognosis is not known compared to direct discharge from the emergency department (ED). To determine whether direct discharge from the ED of patients diagnosed with AHF is associated with early adverse outcomes versus hospitalization in SSU. Endpoints, defined as 30-day all-cause mortality or post-discharge adverse events, were evaluated in patients diagnosed with AHF in 17 Spanish EDs with an SSU, and compared by ED discharge vs. SSU hospitalization. Endpoint risk was adjusted for baseline and AHF episode characteristics and in patients matched by propensity score (PS) for SSU hospitalization. Overall, 2358 patients were discharged home and 2003 were hospitalized in SSUs. Discharged patients were younger, more frequently men, with fewer comorbidities, had better baseline status, less infection, rapid atrial fibrillation and hypertensive emergency as the AHF trigger, and had a lower severity of AHF episode. While their 30-day mortality rate was lower than in patients hospitalized in SSU (4.4% vs. 8.1%, p < 0.001), 30-day post-discharge adverse events were similar (27.2% vs. 28.4%, p = 0.599). After adjustment, there were no differences in the 30-day risk of mortality of discharged patients (adjusted HR 0.846, 95% CI 0.637-1.107) or adverse events (1.035, 0.914-1.173). In 337 pairs of PS-matched patients, there were no differences in mortality or risk of adverse event between patients directly discharged or admitted to an SSU (0.753, 0.409-1.397; and 0.858, 0.645-1.142; respectively). Direct ED discharge of patients diagnosed with AHF provides similar outcomes compared to patients with similar characteristics and hospitalized in a SSU

SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling

SARS-CoV-2, the cause of the COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome. Their roles during infection are still not completely understood. In this study, transcriptomics analysis revealed that both WNT5A and IL11 were significantly up-regulated in A549 cells expressing individual accessory proteins ORF6, ORF8, ORF9b or ORF9c from SARS-CoV-2 (Wuhan-Hu-1 isolate). IL11 is a member of the IL6 family of cytokines. IL11 signaling-related genes were also differentially expressed. Bioinformatics analysis disclosed that both WNT5A and IL11 were involved in pulmonary fibrosis idiopathic disease and functional assays confirmed their association with profibrotic cell responses. Subsequently, data comparison with lung cell lines infected with SARS-CoV-2 or lung biopsies from patients with COVID-19, evidenced altered profibrotic gene expression that matched those obtained in this study. Our results show ORF6, ORF8, ORF9b and ORF9c involvement in inflammatory and profibrotic responses. Thus, these accessory proteins could be targeted by new therapies against COVID-19 disease