Depressive mixed state: Evidence for a new form of depressive state in type I and II bipolar patients

Katia M’Bailara1, Donatienne Van den Bulke2, Nicolas Demazeau2, Jacques Demotes-Mainard3, Chantal Henry11EA4139 Laboratoire de psychologie, Université Victor Segalen, Bordeaux Cedex, France; 2Centre Hospitalier Charles Perrens, Bordeaux Cedex, France; 3INSERM-DRCT, ECRIN, Paris, FranceBackground: A high proportion of unipolar and bipolar type II patients can present a depressive mixed state (DMX). This state is defined by an association of a major depressive episode with at least two specific hypomanic symptoms. This state seems underdiagnosed and this could have treatment implications. The aims of our study were: (i) to investigate the frequency of DMX in type I and II bipolar patients hospitalized for a severe or resistant depressive episode and (ii) to assess the therapeutic response in naturalistic conditions.Methods: Forty-two consecutive bipolar patients referred by psychiatrists for a severe or resistant depressive episode were assessed using the French version of the Mini International Neuropsychiatric Interview 5.0 (MINI 5.0), which assesses the suicide risk and provides DSM-IV diagnosis. The intensity of mood episodes was evaluated using the MADRS and Bech-Rafaelsen Mania Scale. One group of patients included patients presenting only depressive symptoms (ie, pure major depressive episode (MDE)), and the second group included patients with a major depressive episode and at least two specific hypomanic symptoms (DMX).Results: Twenty-one patients (50%) had a pure MDE and 21 patients (50%) had a DMX. The treatment leading to recovery was very different in the two groups. Antidepressants were effective (77%) in MDE patients, whereas antipsychotics were effective (81%) in DMX. 38% of patients with a MDE also received a mood stabilizer versus 86% in the group of DMX. Five MDE patients (24%) and one DMX patient required electroconvulsive therapy. The suicidal ideations did not differ between the two groups (p = 0.7).Conclusions: Some mood episodes in bipolar patients (type I and II) are characterised by depressive and hypomanic symptoms but do not meet criteria for mixed episode as defined by DSM-IV. These episodes are often diagnosed as depressive states, but are worsened by antidepressants and often considered as resistant depression. They rapidly respond to antimanic treatment. New categories of mood disorders should take into account this particular mixed state.Keywords: bipolar depression, mixed state, depressive mixed state, resistant depressio

Disclosure of investigators' Recruitment performance in multicenter clinical trials: a further step for research transparency

Transparency: A Fundamental Social Obligation for Clinical Research .After 60 years devoted to enhancing the methodology and ethics in clinical research, the last decade has been crucial to the scientific community in refining the transparency on conducting clinical trials (CTs), from their inception to the publication of results. A myriad of articles have been published on the design, conduct, conflicts of interest, reporting, and publication of CTs..

Methods for Stratification and Validation Cohorts: A Scoping Review

Personalized medicine requires large cohorts for patient stratification and validation of patient clustering. However, standards and harmonized practices on the methods and tools to be used for the design and management of cohorts in personalized medicine remain to be defined. This study aims to describe the current state-of-the-art in this area. A scoping review was conducted searching in PubMed, EMBASE, Web of Science, Psycinfo and Cochrane Library for reviews about tools and methods related to cohorts used in personalized medicine. The search focused on cancer, stroke and Alzheimer's disease and was limited to reports in English, French, German, Italian and Spanish published from 2005 to April 2020. The screening process was reported through a PRISMA flowchart. Fifty reviews were included, mostly including information about how data were generated (25/50) and about tools used for data management and analysis (24/50). No direct information was found about the quality of data and the requirements to monitor associated clinical data. A scarcity of information and standards was found in specific areas such as sample size calculation. With this information, comprehensive guidelines could be developed in the future to improve the reproducibility and robustness in the design and management of cohorts in personalized medicine studies

Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries

<p>Abstract</p> <p>Background</p> <p>In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe.</p> <p>Methods</p> <p>We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries.</p> <p>Results</p> <p>Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised.</p> <p>Conclusion</p> <p>The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.</p

A European multi-language initiative to make the general population aware of independent clinical research: the European Communication on Research Awareness Need project

BACKGROUND: The ECRAN (European Communication on Research Awareness Needs) project was initiated in 2012, with support from the European Commission, to improve public knowledge about the importance of independent, multinational, clinical trials in Europe. METHODS: Participants in the ECRAN consortium included clinicians and methodologists directly involved in clinical trials; researchers working in partnership with the public and patients; representatives of patients; and experts in science communication. We searched for, and evaluated, relevant existing materials and developed additional materials and tools, making them freely available under a Creative Commons licence. RESULTS: The principal communication materials developed were: 1. A website ( http://ecranproject.eu ) in six languages, including a Media centre section to help journalists to disseminate information about the ECRAN project 2. An animated film about clinical trials, dubbed in the 23 official languages of the European Community, and an interactive tutorial 3. An inventory of resources, available in 23 languages, searchable by topic, author, and media type 4. Two educational games for young people, developed in six languages 5. Testing Treatments interactive in a dozen languages, including five official European Community languages 6. An interactive tutorial slide presentation testing viewers' knowledge about clinical trials CONCLUSIONS: Over a 2-year project, our multidisciplinary and multinational consortium was able to produce, and make freely available in many languages, new materials to promote public knowledge about the importance of independent and international clinical trials. Sustained funding for the ECRAN information platform could help to promote successful recruitment to independent clinical trials supported through the European Clinical Research Infrastructure Network

Therapeutic hypothermia for acute ischaemic stroke. Results of a European multicentre, randomised, phase III clinical trial

Introduction: We assessed whether modest systemic cooling started within 6 hours of symptom onset improves functional outcome at three months in awake patients with acute ischaemic stroke. Patients and methods: In this European randomised open-label clinical trial with blinded outcome assessment, adult patients with acute ischaemic stroke were randomised to cooling to a target body temperature of 34.0–35.0°C, started within 6 h after stroke onset and maintained for 12 or 24 h, versus standard treatment. The primary outcome was the score on the modified Rankin Scale at 91 days, as analysed with ordinal logistic regression. Results: The trial was stopped after inclusion of 98 of the originally intended 1500 patients because of slow recruitment and cessation of funding. Forty-nine patients were randomised to hypothermia versus 49 to standard treatment. Four patients were lost to follow-up. Of patients randomised to hypothermia, 15 (31%) achieved the predefined cooling targets. The primary outcome did not differ between the groups (odds ratio for good outcome, 1.01; 95% confidence interval, 0.48–2.13; p = 0.97). The number of patients with one or more serious adverse events did not differ between groups (relative risk, 1.22; 95% confidence interval, 0.65–1.94; p = 0.52). Discussion: In this trial, cooling to a target of 34.0–35.0°C and maintaining this for 12 or 24 h was not feasible in the majority of patients. The final sample was underpowered to detect clinically relevant differences in outcomes. Conclusion: Before new trials are launched, the feasibility of cooling needs to be improved

[ECRIN (European clinical research infrastructures network), a pan-European infrastructure for clinical research].

International audienceClinical research plays a key role both in the development of innovative health products and in the optimisation of medical strategies, leading to evidence-based practice and healthcare cost containment. ECRIN is a distributed ESFRI-roadmap pan-European infrastructure designed to support multinational clinical research, making Europe a single area for clinical studies, taking advantage of its population size to access patients, and unlocking latent scientific providing services to multinational. Servicing of multinational trials started during the preparatory phase, and ECRIN has applied for ERIC status in 2011. In parallel, ECRIN has also proposed an FP7 integrating activity project to further develop, upgrade and expand the ECRIN infrastructure built up during the past FP6 and FP7 projects, facilitating an efficient organization of clinical research in Europe, with ECRIN developing generic tools and providing generic services for multinational studies, and supporting the construction of pan-European disease-oriented networks that will in turn act as ECRIN users. This organization will improve Europe's attractiveness for industry trials, boost its scientific competitiveness, and result in better healthcare for European citizens. The three medical areas supported in this project (rare diseases, medical devices, and nutrition) will serve as pilots for other biomedical research fields. By creating a single area for clinical research in Europe, this structure will contribute to the implementation of the Europe flagship initiative 2020 'Innovation Union', whose objectives include defragmentation of research and educational capacities, tackling the major societal challenges (starting with healthy aging), and removing barriers to bringing ideas to the market

Towards a European Clinical Research Infrastructures Network: The ECRIN Programme

On the basis of the interconnection of national networks of clinical research centres (CRCs) and clinical trials units (CTUs), the European Clinical Research Infrastructures Network (ECRIN) programme aims to develop an infrastructure allowing for bottom-up harmonisation of the support and training for, and practice of, clinical research, and to provide public sponsors for biotechnology small and medium-sized companies (SMEs) with support for translational research and multicentre clinical studies in Europe. This will be achieved through an application to the next FP6 "Integrated Infrastructure Initiatives" call. However, prior work is required to improve the reciprocal knowledge of partners in the ECRIN consortium and, as a first step, country-specific workshops will be organised by national networks in order to address the organisation of CRC/CTUs and national networks, and their interaction with the national environment of clinical research; this will enable in-depth discussion addressing the bottlenecks hampering transnational studies