Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P &lt; 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

EL USO DEL MEME EN LAS ELECCIONES DEL 4-M: ESTUDIO DE LAS ESTRATEGIAS ARGUMENTATIVAS Y DE PROYECCIÓN DE IMAGEN DE ISABEL AYUSO COMO CANDIDATA Y ALCALDESA DE MADRID

The present paper aims to delve deeper into the representation of women in public domains on 3.0 platforms. Specifically, emphasis will be placed on the multimodal discursive analysis in the pre-vote and post-election phase of Isabel Ayuso’s candidacy in the 4-M elections through the analysis of political memes. Among the strategies used by both politicians and users of social networks, the meme is characterized as the most powerful instrument when it comes to producing a message. At the same time is also a genre through which the political adversary is represented by means of communication rules that eradicate what is known as ‘pop communication’. In this context, we ask ourselves what is the representation of women in political domains in memes, what are the strategies used to represent their figure and if they undergo any change between the electoral campaign and post-electoral phases

Paremias e indumentaria en Refranes y Proverbios en Romance (1555) de Hernán Núñez. Análisis paremiológico, etnolingüístico y lingüístico de Luisa A. Messina Fajardo

Es reseña de:Paremias e indumentaria en Refranes y proverbios en Romance (1555) de Hernán Núñez. Análisis paremiológico, etnolingüístico y lingüísticoLuisa A. Messina Fajardo, Aracne, 201

EL USO DEL MEME EN LAS ELECCIONES DEL 4-M: ESTUDIO DE LAS ESTRATEGIAS ARGUMENTATIVAS Y DE PROYECCIÓN DE IMAGEN DE ISABEL AYUSO COMO CANDIDATA Y ALCALDESA DE MADRID

The present paper aims to delve deeper into the representation of women in public domains on 3.0 platforms. Specifically, emphasis will be placed on the multimodal discursive analysis in the pre-vote and post-election phase of Isabel Ayuso’s candidacy in the 4-M elections through the analysis of political memes. Among the strategies used by both politicians and users of social networks, the meme is characterized as the most powerful instrument when it comes to producing a message. At the same time is also a genre through which the political adversary is represented by means of communication rules that eradicate what is known as ‘pop communication’. In this context, we ask ourselves what is the representation of women in political domains in memes, what are the strategies used to represent their figure and if they undergo any change between the electoral campaign and post-electoral phases

El estudio del discurso político de mujeres: un enfoque para los estudiantes de Ciencias Políticas

The present paper aims to present a sample of exercises done for students of the Department of Political Sciences. We will try to carry out the study of the analysis discourse focusing on two different approaches: on one hand we will present a methodology approach with the aim to help students in the study of language for special purposes, and in particular political language; on the other hand we will try to analyse political women speech in order to discover the typical features of the above mentioned discourses and study the relation between political woman and her speech.En el presente estudio propone una muestra didáctica dirigida a estudiantes de la facultad de Ciencias Políticas. Se intentará desarrollar el estudio del análisis del discurso político a través de dos enfoques: por un lado, se ofrece una metodología para facilitar el aprendizaje de los lenguajes de especialidad, y del lenguaje político en particular; al mismo tiempo se pondrá la atención en los discursos políticos de mujeres a fin de ofrecer algunas reflexiones útiles para analizar el modo en que las políticas mencionan su feminidad y la relacionan con la imagen que dan de sí a través de sus discursos

Targeting of HSP70/HSF1 Axis Abrogates In Vitro Ibrutinib-Resistance in Chronic Lymphocytic Leukemia

none18The Btk inhibitor ibrutinib has significantly changed the management of chronic lymphocytic leukemia (CLL) patients. Despite its clinical efficacy, relapses occur, and outcomes after ibrutinib failure are poor. Although BTK and PLCγ2 mutations have been found to be associated with ibrutinib resistance in a fair percentage of CLL patients, no information on resistance mechanisms is available in patients lacking these mutations. The heat shock protein of 70 kDa (HSP70) and its transcription factor heat shock factor 1 (HSF1) play a role in mediating the survival and progression of CLL, as well as taking part in drug resistance in various cancers. We demonstrated that resveratrol and related phenols were able to induce apoptosis in vitro in leukemic cells from CLL untreated patients by acting on the HSP70/HSF1 axis. The same was achieved in cells recovered from 13 CLL patients failing in vivo ibrutinib treatment. HSP70 and HSF1 levels decreased following in vitro treatment, correlating to apoptosis induction. We suggest an involvement of HSP70/HSF1 axis in controlling resistance to ibrutinib in CLL cells, since their inhibition is effective in inducing in vitro apoptosis in cells from ibrutinib refractory patients. The targeting of HSP70/HSF1 axis could represent a novel rational therapeutic strategy for CLL, also for relapsing patients.restrictedFrezzato, Federica; Visentin, Andrea; Severin, Filippo; Pizzo, Serena; Ruggeri, Edoardo; Mouawad, Nayla; Martinello, Leonardo; Pagnin, Elisa; Trimarco, Valentina; Tonini, Alessia; Carraro, Samuela; Pravato, Stefano; Imbergamo, Silvia; Manni, Sabrina; Piazza, Francesco; Brunati, Anna Maria; Facco, Monica; Trentin, LivioFrezzato, Federica; Visentin, Andrea; Severin, Filippo; Pizzo, Serena; Ruggeri, Edoardo; Mouawad, Nayla; Martinello, Leonardo; Pagnin, Elisa; Trimarco, Valentina; Tonini, Alessia; Carraro, Samuela; Pravato, Stefano; Imbergamo, Silvia; Manni, Sabrina; Piazza, Francesco; Brunati, Anna Maria; Facco, Monica; Trentin, Livi