Recruitment in randomized clinical trials: The MeMeMe experience.

INTRODUCTION: Recruitment is essential for the success of clinical trials. We are conducting a randomized clinical trial to test the effect of a Mediterranean dietary intervention with or without 1700 mg/day of metformin for the prevention of age-related chronic diseases, the MeMeMe trial (Trial registration number: EudraCT number: 2012-005427-32 ClinicalTrials.gov ID: NCT02960711). MeMeMe recruiting experience, highlighting strengths, limitations encountered and results is reported. PATIENTS AND METHODS: Statistical analysis focused on the reasons for withdrawal according to the recruitment method ("active" versus "passive" criterion) and the time of withdrawal. Logistic regression models were used to explore the associations between the risk of withdrawal and sex, recruitment method, randomization arm, and with markers of compliance to the intervention, such as one-year change in body weight. RESULTS: Out of 2035 volunteers, 660 (32.4%) were recruited "actively" and 1375 (67.6%) "passively". Among people who dropped out of the trial after randomization, there were 19.5% for the "active" and 22.0% for the "passive" method (p = 0.28). The risk of withdrawal was significantly higher in women (OR:1.91; 95% CI:1.17-3.12; p = 0.01), in volunteers older at recruitment (OR:1.25; 95% CI:1.07-1.45; p = 0.004), and in those with a higher BMI at baseline (OR:1.23; 95% CI:1.07-1.43; p = 0.004). Volunteers who lost at least 2 kg (the median weight change) in the first year of intervention were significantly less (53%) likely to withdraw from the trial (OR:0.48; 95% CI:0.30-0.75; p = 0.001). CONCLUSION: Our findings suggest that the "passive" recruitment method was more effective than the "active" one to advance recruitment. The benefits of "passive" recruitment hardly outweighed the drawbacks. TRIAL REGISTRATION: Trial registration number: EudraCT number: 2012-005427-32. ClinicalTrials.gov ID: NCT02960711.

A management system for randomized clinical trials: A novel way to supply medication.

BACKGROUND: Randomized controlled clinical trials require management effort, involving huge organizational, economic and informatics investments. Information technology offers opportunities to approach clinical trial methodology in new ways. However, there are only a few reports of computerized data and drug management systems. OBJECTIVE: This paper describes a novel software created specifically for the management of a randomized trial of diet and metformin in people with metabolic syndrome (the Me.Me.Me. trial). METHODS: Me.Me.Me. is an ongoing phase III randomized controlled trial in healthy people with metabolic syndrome to test the hypothesis that comprehensive lifestyle changes and/or metformin can prevent age-related chronic non-communicable diseases. To manage all the phases of the trial, we created a software which is a state pattern machine, user friendly, web-based, able to maintain the correct balance between randomization groups, and structured in various levels of security in order to guarantee the participant's privacy and compliance with the study protocol. The software achieves budget savings: drug management is not based on patients' packs, but on the actual need for drugs according to each participant's "state", with strict guidelines for the handling and supply of medication. RESULTS: The trial is ongoing and recruitment will close on August 31, 2018. To date, 11737 bottles of metformin/placebo have been dispensed to 1054 randomized participants, with drug savings of 29.5%. CONCLUSIONS: A software which takes into account the "state" of participant might be a powerful resource for developing and managing clinical trials, helping avoid poor treatment allocation, and wastage of drugs and money. ME.ME.ME. TRIAL: EUDRACT no. 2012-005427-32. ClinicalTrials.gov Identifier: NCT02960711.

[Defining abuse: a difficult and controversial task]. / Définir la maltraitance : contours d'une caractérisation urgente et disputée.

Defining abuse: a difficult and controversial task. To offer a comprehensive definition of abuse is difficult, for the understanding of this phenomenon varies considerably from one author to the next. However, certain common characteristics are proposed in this paper: the victim's vulnerability, a specific, trustful, relationship to the perpetrator, and the fact that a power relationship is at stake. Abuse can be also clarified by using two lines of distinction, between conscious and unconscious behaviors, and between individual and collective practices. Those distinctions however, which help clarify the pertinent answers in each type of situation, do not always make the resolution any easier. For all the situations, what's more, four necessary steps are to be followed, which can be summarized by the following terms: recognizing, reporting, responding and questioning.

Définir la maltraitance : contours d'une caractérisation urgente et disputée. La maltraitance souffre d'une définition incertaine, qui en rend la compréhension partagée et la mesure difficile. Certains éléments distinctifs sont ici proposés pour la caractériser : la vulnérabilité de la victime, son lien de confiance avec l'auteur de la maltraitance, et la dimension d'abus de pouvoir que la situation comporte. En outre, la maltraitance peut être classée en distinguant les actes individuels des pratiques collectives, et les actes posés consciemment de ceux qui ne le sont pas. Ces distinctions clarifient les réponses pertinentes, sans pour autant les rendre aisées à mettre en oeuvre. De manière transversale, pour toutes les situations, quatre impératifs s'imposent : reconnaître, signaler, répondre et questionner.

A randomized controlled trial of Mediterranean diet and metformin to prevent age-related diseases in people with metabolic syndrome.

PURPOSE: Age-related non-communicable chronic diseases (ArCDs) are the leading cause of mortality. The major metabolic risk factor for their development is the metabolic syndrome (MetS), defined as a clustering of risk factors of metabolic origin such as abdominal obesity, high blood pressure, dyslipidemia and high fasting glycemia. There is increasing observational and experimental evidence that improving diet and the use of metformin (a calorie-restriction mimetic drug) may modify the risk of developing MetS and ArCD. We designed a phase III randomized controlled trial (the Me.Me.Me trial) to evaluate the effect of a comprehensive lifestyle intervention (including moderate physical activity and a Mediterranean-macrobiotic diet) and the effect of treatment with metformin in the prevention of ArCDs in healthy people with MetS. This report describes the scientific protocol of this trial. METHODS: The design of the study is 2 × 2 factorial with 2,000 volunteers to be randomized into 4 equal groups of 500 each, which are allocated to the following treatments: metformin (1,700 mg/day) + active lifestyle intervention, placebo + active lifestyle intervention, metformin (1,700 mg/day) alone, and placebo alone. The metformin/placebo component of the study is double blind. The study is planned for a term of 5 years. RESULTS: The Me.Me.Me. trial is ongoing and recruitment of participants is underway. No patient has completed the 5 years of follow-up. CONCLUSIONS: We believe that the results of the trial will clarify the importance of lifestyle for primary prevention and the role of metformin as a potential chemopreventive agent. The trial is registred on ClinicalTrials.gov with the identification NCT02960711.

[Compassionate care, emergence of a notion in the light and shade of the care environment]. / La bientraitance, naissance d'une notion dans le clair-obscur des espaces de soins.

Compassionate care is a recent notion. It is based on a shared culture which focuses on promoting the rights of vulnerable people, integral to the quality of professionals' life at work. Tangible and part of day-to-day practice, it requires room to be set aside for discussion and ethical considerations, essential for ensuring the long-lasting creativity of caregivers, at the source of their mobilisation.

[Proposals for a new health democracy in institutions]. / Propositions pour une nouvelle démocratie sanitaire en institution.

Dignity, or rather a lack thereof, in healthcare institutions, often becomes apparent through a situation where the patient, or sometimes the nurse, is not given due respect. It is important to promote a real democratic culture, an authentic collective dialogue. This article presents the basis of a fundamental notion.

Electrochemical gas sensors based on paper-supported room-temperature ionic liquids for improved analysis of acid vapours.

A prototype of a fast-response task-specific amperometric gas sensor based on paper-supported room-temperature ionic liquids (RTILs) is proposed here for improved analysis of volatile acid species. It consists of a small filter paper foil soaked with a RTIL mixture containing an ionic liquid whose anion (acetate) displays a basic character, upon which three electrodes are screen printed by carbon ink profiting from a suitable mask. It takes advantage of the high electrical conductivity and negligible vapour pressure of RTILs and of their easy immobilization into a porous and inexpensive supporting material such as paper. The performance of this device, used as a wall-jet amperometric detector for flow injection analyses of headspace samples in equilibrium with aqueous solutions at controlled concentrations, was evaluated for phenol and 1-butanethiol vapours which were adopted as model acid gaseous analytes. The results obtained showed that the quite high potentials required for the detection of these analytes are lowered significantly, thanks to the addition of the basic acetate RTIL. In such a way, overlap with the medium discharge is avoided, and the possible adverse effect of interfering species is minimised. The sensor performance was quite satisfactory (detection limits, ca. 0.3 µM; dynamic range, ca. 1-200 µM, both referred to solution concentrations; correlation coefficients in the range 0.993-0.997; repeatability, ± 6% RSD; long-term stability, 9%); thus suggesting the possible use of this device for manifold applications.

[What are the different prospects for positive treatment?]. / Quels destins possibles pour la bientraitance?

While the concept of positive treatment is undeniably fashionable, the manner in which it is replacing the concept of mistreatment raises questions. What is the significance of this semantic development and what should be deduced from this new term with regard to the effective development of professional practices? Three different prospects appear to await the term positive treatment: incarnating a figure of denial, acting as an asset, or infinitely more preferable, bringing about a questioning of professional practices. But this third prospect is not without its challenges: it cannot exist without managerial involvement focusing on the ethical requirements of positive treatment in terms of respect for people in care.

[Are we free to discuss the living-donor issue?]. / Peut-on parler d'un libre arbitre du donneur vivant?

A gift does not take place in a neutral context: every act of giving sets up a complex system of more or less constraining obligations. In the donation of an organ, it is particularly difficult to distinguish between decisions made under pressure and those made freely. This distinction is of capital importance if we admit that a donation is ethically acceptable on;y if the decision to donate is made on free and autonomous grounds. thus the duty of the transplantation team to satisfy themselves that the donor is able to make a rational decision on the basis of his free will, without moral pressure from the family. In particular, the potential donor should receive clear and understandable information about the implications of the donation. Finally, to ensure that these conditions are met, the motivation of the donor should be scrutinized and evaluated by a physician as well as a psychologist.