The Entrepreneurship Competence in the English Classroom. A Lesson Planning for Secondary Education

Education has evolved over the years. Initially, the concern was to convert traditional teaching into a more active one for students. However, although education is changing, students need to be trained to face the challenges of the 21st century adequately. To this end, secondary education should contemplate a competency-based education so that, through the transversality of competencies, students are able to apply the knowledge they acquire both inside and outside the classroom. For this reason, this document considers multilingual and entrepreneurial competences in a proposal for a lesson plan based on the videogame Minecraft. Likewise, the development of the same in the classroom of English as a foreign language is proposed not only for the development of the target language, but also to face the challenges that the didactic unit presents through cooperation, innovation and resolution.La educación ha ido evolucionando a lo largo de los años. Primeramente, la preocupación que existía era la de convertir la enseñanza tradicional en una más activa para los estudiantes. Sin embargo, a pesar de estar cambiando la educación, se necesita formar a los estudiantes para afrontar los retos que del siglo XXI de forma adecuada. Para ello, desde los institutos se debería de contemplar una educación competencial para que, mediante la transversalidad de las competencias, los alumnos sean capaces de aplicar los conocimientos que adquieren tanto dentro, como fuera del aula. Por este motivo, el presente documento contempla las competencias multilingüe y emprendedora en una propuesta didáctica basada en el videojuego Minecraft. Asimismo, se plantea el desarrollo de la misma en el aula de inglés como lengua extranjera no solo para el desarrollo de la lengua meta, sino también para promover la cooperación, la innovación y la resolución.Departamento de Didáctica de la Lengua y LiteraturaMáster en Profesor de Educación Secundaria Obligatoria y Bachillerato, Formación Profesional y Enseñanzas de Idioma

Producción escrita en el aula de ELE en los Países Bajos: condicionantes externos y propuestas metodológicas

La escritura posee un rol significativo en la enseñanza de español como lengua extranjera (ELE) debido a que es una destreza lingüística que forma parte de la comunicación y se caracteriza por su transmisión diacrónica. Sin embargo, la calidad del producto de dicha destreza está condicionada por factores externos que influyen, de forma positiva y negativa, en el entendimiento de las producciones escritas de los estudiantes de ELE. El presente trabajo no solo expone los factores externos influyentes que se han obtenido tras elaborar un estudio en una clase de ELE en los Países Bajos, sino que también exhibe una propuesta metodológica teórica que aborda las cuatro destrezas lingüísticas y estudia cómo podría mejorarse la calidad comunicativa escrita a través del control de dichos condicionantes externos que se extraen a lo largo del estudio.Writing possesses a significant role in the atmosphere of teaching Spanish as a foreign language because of its diachronic way of transmission. However, the quality of this skill depends on different external factors of learning that influence the understanding of the written texts that students of Spanish as a second language produce. This paper not only presents the external factors that have been obtained from a study of an SFL class in the Netherlands, but also it exhibits a theoretical methodological proposal that addresses the four linguistic skills. Additionally, it studies how written productions quality can be improved through the control of these external factors that are extracted throughout this study.Departamento de Lengua EspañolaMáster en Español como Lengua Extranjera: Enseñanza e Investigació

Estudio de la expresión del receptor de vitamina D en la ontogenia del testículo y en tumores de células de Leydig: posible interacción con el sistema histaminérgico

La vitamina D (VD), un esteroide pleiotrópico, ha sido relacionada con la función reproductiva masculina, pero aún no se ha estudiado la expresión de su receptor (RVD) en el desarrollo testicular. RVD regula la expresión de componentes del sistema histaminérgico, y la histamina (HA) modula la esteroidogénesis en células de Leydig (CL). Se ha relacionado a la deficiencia de VD con múltiples patologías, entre ellas cáncer. Los tumores de células de Leydig (TCL) son los más frecuentes del intersticio testicular, y al malignizar no responden a radio/quimioterapia. VD fue descripta como tratamiento para varios tumores, pero se desconoce su aplicación en TCL. Por lo expuesto, hemos estudiado la expresión de RVD en la ontogenia de testículo de rata, evaluando su correlación con los niveles de testosterona séricos (T) y el contenido de HA; y además evaluamos la expresión de RVD en testículo humano fetal, neonatal, prepuberal, TCL e hiperplasia de CL.En testículo de rata, se observó un aumento en la expresión de RVD en CL con la edad, en línea con el incremento de T, y en contraposición con la disminución del contenido de HA, lo cual fue consistente con la reducción en los niveles de la enzima que cataliza su síntesis, HDC. Esto sugiere que la VD podría ejercer una función en el desarrollo testicular normal, ya sea en forma directa sobre las CL o mediante la regulación de la expresión de componentes del sistema histaminérgico (HDC y/o receptores de HA).Por su parte, el TCL humano presentó sobreexpresión de RVD y HDC. Considerandoque las hormonas esteroideas se encuentran aumentadas en esta patología y funcionan como factores de crecimiento, si el calcitriol pudiera modular la esteroidogénesis podría tener una aplicación terapéutica.Vitamin D (VD) is a steroid hormone traditionally related to bone health. However, several authors have associated VD with reproduction and steroidogenesis in males. The presence of VD receptor (VDR) and the enzymes involved in its activation had been reported in several cell types of the testes. Until now, nobody has studied RVD expression during testicular development. In addition, VDR in association with its coactivators or co-repressors, regulates the expression of several genes, including those related to the histaminergic system. Previously, we demonstrated that histamine (HA) can modulate steroidogenesis in Leydig cells (LC) in a concentration-dependent manner. Also, we observed a decrease in the endogenous HA content, consistent with the previously described decrease of HDC (histidine decarboxylase, the enzyme responsible of HA synthesis) levels, during LC ontogeny. Epidemiologic studies strongly suggest that a relationship exists between VD deficiency and multiple pathologies, particularly cancer. Leydig cell tumors (LCT) are rare endocrine tumors ofunknown etiology, which originate in the testicular interstitium. The incidence worldwide is 1-3% in adults and 4% in prepubertal boys, but recent publications indicate that these figures have been increasing. While usually benign, approximately 10% of LCTin adults become malignant and do not respond to chemo or radiotherapy. It is imperative to deeply investigate the biology of LCT, to identify new therapeutic targets. The potential role of calcitriol (1α,25(OH)2-vitamin-D3) in cancer treatment has been described for several types of tumors, but it remains unexplored in LCT. Thus, as a first step, it is worth evaluating VDR expression in LCT.In view of the aforecited evidence, herein we studied VDR expression during the rat testicular ontogeny, evaluating a possible correlation withserum testosterone (T) levels in blood, endogenous levels of HAand the previously described HDC expression levels. We also analized VDR expression in human testes corresponding to three different stages of development (fetal, neonatal and juvenile), in LCTand in LC hyperplasia. Methods: Rat testes of different ages (7, 21, 35, 90 y 240 days), human fetal, neonatal and pre pubertal testes, a human LCT and a human LC hyperplasia; were used for detection of VDR by immunohistochemistry.Fil: Varela, María Luisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Abiuso, Adriana María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Berensztein, Esperanza Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Besio Moreno, Marcos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Knoblovits, Pablo. Hospital Italiano; ArgentinaFil: Suárez, Sebastián. Hospital Italiano; ArgentinaFil: Costanzo, P. R.. Hospital Italiano; ArgentinaFil: Mondillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Histidine decarboxylase inhibitors attenuate the pro angiogenic activity of Leydig tumor cells: Potential neoadjuvant therapy for the treatment of leydigiomas?

Los tumores de células de Leydig (TCL) son tumores endócrinos del intersticio testicular, cuya incidencia se encuentra en aumento. Los síntomas incluyen feminización o virilización en pacientes prepuberales, y pérdida de libido, disfunción eréctil, infertilidad y/o ginecomastia en adultos. Si bien son usualmente benignos, cuando malignizan en adultos no responden a radio y quimioterapia. Múltiples trabajos han reportado que la histidina decarboxilasa (HDC), enzima que cataliza la conversión de L-histidina en histamina (HA), tiene un rol importante en el desarrollo de tumores. A su vez, en nuestro laboratorio demostramos que la HA induce la proliferación de células de Leydig tumorales (CLT) murinas, mientras que la inhibición de HDC disminuye su proliferación y capacidad esteroidogénica. Además, observamos elevada expresión de HDC en TCL pediátricos vs. controles de distintos estadios de madurez sexual; y se ha descrito que ratones knock out para HDC poseen una angiogénesis incompleta. Para evaluar el rol de HDC en la modulación de la angiogénesis se empleó la línea de CLT de rata R2C, principal modelo utilizado en estudios de Leydigioma. También se realizaron estudios en TCL pediátricos. Los medios condicionados por las CLT R2C estimularon la angiogénesis tanto in vitro como in vivo (empleando HUVEC y analizando el grado de vascularización de membranas corioalantoideas de codorniz, respectivamente). El efecto in vitro se revirtió al tratar previamente las CLT R2C con α-metil-DL-histidinadihidrocloruro, inhibidor específico de HDC. A su vez, tanto la HA como los medios condicionados provenientes de TCL pediátricos, produjeron un aumento en la proliferación de las HUVEC. Nuestros resultados sugieren que las CLT producen HA y otros factores proangiogénicos, y que la inhibición selectiva de HDC atenúa la capacidad proangiogénica de las CLT. En base a estos resultados y evidencias previas del laboratorio, inhibidores específicos de HDC podrían ser utilizados como potencial terapia neoadyuvante en TCL.Leydig Cell tumors (LCT) are a rare group of endocrine tumors in the testicular interstitium. Between 1 and 3% of testicular malignances in adults and 4% in prepubertal children belong to LCT. An increasing incidence of this type of neoplasia has been reported recently all around the world. Particularly, a strong relationship between LCT and the use of anabolic steroids (which are commonly used nowadays) has been reported recently. In prepubertal boys, symptoms include feminization or virilization, depending on the major circulating steroid (estradiol or testosterone respectively). Adult patients show loss of libido, penile dysfunction, infertility and/or gynecomastia. Although the etiology still is unknown, several studies indicate that tumoral Leydig cells have an excessive production of insulin-like growth factor (IGF-1), as well as aromatase (CYP19) overexpression, which causes an enormous amount of estrogens (particularly estradiol, E2), and both factors play an important role in tumorigenesis. While usually benign, when LCT became malignant in adults they respond poorly to radio and chemotherapy. Likewise, it has been reported that both therapies increase the incidence of several tumors. All these data imply the need of new therapeutic targets to avoid the chirurgical dissection of the testes and the consequences of the hormonal therapies associated, which implicate not only the loss in reproductive function, but also psychological disorders. Several publications have reported that histidine decarboxylase (HDC), the only enzyme capable of catalyzing the conversion from L-histidine to histamine (HA) in mammals, has an important role in the development of several types of tumors, such as colorectal, breast and melanoma. At the same time, in our laboratory we have reported that HA induces cell proliferation of murine Leydig cells, and complementary, this cell proliferation decreases when inhibiting selectively HDC, as well as steroid synthesis (progesterone and E2). Also, we observed a higher expression of HDC in pediatric LCT (n = 3) than normal controls corresponding to different stages of sexual maturation (n = 9). It has been described that HDC knock out mice have an incomplete angiogenesis, and also that MA-10 Leydig cells HDC expression correlates with vascular endothelial growth factor (VEGF). The aim of this study is to improve our knowledge about the role of HDC in LCT biology, particularly, the angiogenesis modulation. We used the R2C Leydig cell line, the most used model for in vitro studies of Leydigioma, because it overexpresses CYP19 and constitutively produces high levels of IGF-1 and E2, as well as human LCT. R2C and pediatric LCT angiogenic capability was evaluated in vitro by measuring proliferation of human umbilical vein endothelial cells (HUVEC). In addition, we verified R2C cells angiogenic capability in vivo, using quail embryo vasculature (chorioallantoic membrane assay). Both models have been validated for the study of angiogenesis. Conditioned medium obtained from R2C cell culture stimulated angiogenesis in vitro (p <0.001) as well as in vivo (p <0.001). The in vitro effect was reverted with a previous treatment on the R2C cell culture using α-methyl-DL-histidine hydrochloride (α-MHD, 10 µM), a specific HDC activity inhibitor (p <0.001). Finally, human conditioned medium from pediatric LCT increased HUVEC proliferation (p <0.01). In the same way, the analyzed patients showed higher testosterone and estradiol levels than normal serum concentrations, which was in concordance to phenotypical features observed in presence of LCT. Our results indicate that tumoral Leydig cells (TLC) produce HA, as well as other angiogenic factors, and it could be stimulating the vascular endothelium. The selective inhibition of HDC attenuates the pro-angiogenic capability in TLC. Considering all these results and previous observations of our laboratory, specific inhibitors of HDC could be used, in the future, as a potential therapeutic target for the treatment of LCT.Fil: Abiuso, Adriana María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Varela, María Luisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Haro Durand, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Besio Moreno, Marcos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Ponzio, Roberto Oscar. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Rivarola, Marco Aurelio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Endocrinología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Endocrinología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Berensztein, Esperanza Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Endocrinología; ArgentinaFil: Mondillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Bacterial co-infection at hospital admission in patients with COVID-19

Objectives: We described the current incidence and risk factors of bacterial co-infection in hospitalized patients with COVID-19. Methods: Observational cohort study was performed at the Hospital Clinic of Barcelona (February 2020-February 2021). All patients with COVID-19 who were admitted for >48 hours with microbiological sample collection and procalcitonin (PCT) determination within the first 48 hours were included. Results: A total of 1125 consecutive adults met inclusion criteria. Co-infections were microbiologically documented in 102 (9.1%) patients. Most frequent microorganisms were Streptococcus pneumoniae (79%), Staphylococcus aureus (6.8%), and Haemophilus influenzae (6.8%). Test positivity was 1% (8/803) for blood cultures, 10.1% (79/780) for pneumococcal urinary antigen test, and 11.4% (15/132) for sputum culture. Patients with PCT higher than 0.2, 0.5, 1, and 2 ng/mL had significantly more co-infections than those with lower levels (p=0.017, p=0.031, p94%

Prevalence of submicroscopic malaria infection in immigrants living in Spain

BACKGROUND: The importance of submicroscopic malaria infections in high-transmission areas could contribute to maintain the parasite cycle. Regarding non-endemic areas, its importance remains barely understood because parasitaemia in these afebrile patients is usually below the detection limits for microscopy, hence molecular techniques are often needed for its diagnosis. In addition to this, the lack of standardized protocols for the screening of submicroscopic malaria in immigrants from endemic areas may underestimate the infection with Plasmodium spp. The aim of this study was to assess the prevalence of submicroscopic malaria in afebrile immigrants living in a non-endemic area. METHODS: A prospective, observational, multicentre study was conducted. Afebrile immigrants were included, microscopic observation of Giemsa-stained thin and thick blood smears, and two different molecular techniques detecting Plasmodium spp. were performed. Patients with submicroscopic malaria were defined as patients with negative blood smears and detection of DNA of Plasmodium spp. with one or both molecular techniques. Demographic, clinical, analytical and microbiological features were recorded and univariate analysis by subgroups was carried out with STATA v15. RESULTS: A total of 244 afebrile immigrants were included in the study. Of them, 14 had a submicroscopic malaria infection, yielding a prevalence of 5.7% (95% confidence interval 3.45-9.40). In 71.4% of the positive PCR/negative microscopy cases, Plasmodium falciparum alone was the main detected species (10 out of the 14 patients) and in 4 cases (28.6%) Plasmodium vivax or Plasmodium ovale were detected. One patient had a mixed infection including three different species. CONCLUSIONS: The prevalence of submicroscopic malaria in afebrile immigrants was similar to that previously described in Spain. Plasmodium vivax and P. ovale were detected in almost a third of the submicroscopic infections. Screening protocols for afebrile immigrants with molecular techniques could be useful for a proper management of these patients.This work was funded by projects PI14/01671, PI17/01791 and PI14CIII/00014, from the Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) and cofounded by the European Regional Development Fund, and approved by the Ethics Committee of our Institution. There was no funding from the PCR manufacturers; they did not play any role in data analysis or in the reporting of the results.S

Combined Treatment of Heterocyclic Analogues and Benznidazole upon Trypanosoma cruzi In Vivo

Chagas disease caused by Trypanosoma cruzi is an important cause of mortality and morbidity in Latin America but no vaccines or safe chemotherapeutic agents are available. Combined therapy is envisioned as an ideal approach since it may enhance efficacy by acting upon different cellular targets, may reduce toxicity and minimize the risk of drug resistance. Therefore, we investigated the activity of benznidazole (Bz) in combination with the diamidine prodrug DB289 and in combination with the arylimidamide DB766 upon T. cruzi infection in vivo. The oral treatment of T.cruzi-infected mice with DB289 and Benznidazole (Bz) alone reduced the number of circulating parasites compared with untreated mice by about 70% and 90%, respectively. However, the combination of these two compounds decreased the parasitemia by 99% and protected against animal mortality by 100%, but without providing a parasitological cure. When Bz (p.o) was combined with DB766 (via ip route), at least a 99.5% decrease in parasitemia levels was observed. DB766+Bz also provided 100% protection against mice mortality while Bz alone provided about 87% protection. This combined therapy also reduced the tissular lesions induced by T. cruzi infection: Bz alone reduced GPT and CK plasma levels by about 12% and 78% compared to untreated mice group, the combination of Bz with DB766 resulted in a reduction of GPT and CK plasma levels of 56% and 91%. Cure assessment through hemocultive and PCR approaches showed that Bz did not provide a parasitological cure, however, DB766 alone or associated with Bz cured ≥13% of surviving animals

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe