Questionnement éthique sur la posture du médecin-chercheur

International audienceÀ l’occasion d’un projet de recherche clinique réalisé dans le cadre de mon travail de thèse de science et de ma pratique de recherche clinique en médecine, j’ai été confronté au refus d’un patient de participer à un protocole. Ce refus n’était pas le premier auquel j’étais confronté, mais il m’a surpris et m’a fait m’interroger sur ma pratique en tant que chercheur et sur ma manière d’introduire la problématique de la recherche dans mon exercice de médecin addictologue

Interindividual variability in the occurrence of medical complications of alcohol use disorder : clinical biomarkers and development of plasma biomarkers

Il existe une variabilité interindividuelle dans la survenue des complications médicales de la dépendance à l'alcool, y compris à l'occasion de l'évènement physiologique que constitue le sevrage en alcool. L'objectif de cette thèse était l'identification de biomarqueurs de la variabilité interindividuelle de la survenue de complications médicales neurologiques et cardiologiques du trouble de l'usage de l'alcool et notamment de la période du sevrage en alcool. Nous avons employé une méthodologie observationnelle analytique transversale, à partir de plusieurs bases de données. Premièrement, nous avons utilisé des données préexistantes, issues du soin dans un service de médecine des addictions parisien et d'une recherche antérieure, sur lesquelles nous avons testé nos hypothèses de recherche. Deuxièmement, nous avons constitué une collection originale de données biologiques plasmatique, chez 52 patients, portant sur l'exploration de quatre biomarqueurs plasmatiques de souffrance cérébrale comme biomarqueurs de la neurotoxicité de l'alcool, du sevrage ou des complications neurologiques associées. Les résultats ont été publiés dans quatre articles de recherche anglophone et un cinquième est en cours de soumission. Dans un premier article, nous présenterons l'identification du BNP comme un biomarqueur de l'effort cardiaque lors du sevrage. Dans un deuxième, nous détaillerons nos hypothèses et l'absence d'association statistique significative sur la dépendance à l'alcool et des mutations génétiques comme facteur de risque d'épisode de douleur thoracique lors de l'usage de cocaïne. Dans un troisième, nous présenterons nos observations sur la prévalence de 28% de la carence en vitamine C chez les patients admis en sevrage en alcool et de son association au dépistage d'un trouble cognitif par le test MoCA. Dans un quatrième, nous détaillerons notre identification de trois biomarqueurs plasmatiques de souffrance cérébrale comme biomarqueurs d'encéphalopathie de Wernicke et de neurotoxicité durant le sevrage en alcool. Et enfin, dans un cinquième, nous illustrerons l'usage d'un biomarqueur associé à la technique de l'entretien motivationnel dans le renforcement de la capacité d'agir du patient. La mise en évidence de ces biomarqueurs s'intègre dans une perspective d'évolution de la prise en charge médicale, dont le renforcement motivationnel, ainsi que dans une perspective d'augmentation des connaissances scientifiques permettant de mettre au point de futurs protocoles de recherche interventionnels pharmacologiques utilisant ces biomarqueurs comme potentielles cibles intermédiaires. Ces résultats préliminaires seront poursuivi dans l'objectif de valider l'utilisation des biomarqueurs plasmatiques identifiés dans ce travail.There is interindividual variability in the occurrence of medical complications of alcohol dependence, including during the physiological event that constitutes alcohol withdrawal. The objective of this thesis was to identify biomarkers of interindividual variability in the occurrence of neurological and cardiological complications of alcohol use disorder and especially during the alcohol withdrawal process. We used an observational analytical cross-sectional methodology, based on several databases. Firstly, we used pre-existing data, from care in a Parisian addiction medicine department and from a previous research, on which we have tested our research hypotheses. Secondly, we constituted an original collection of plasma biological data, on 52 patients, exploring four plasma biomarkers of brain damage as biomarkers of neurotoxicity related to alcohol, withdrawal or associated neurological complications. The results have been published in four research articles and a fifth is currently being submitted. In the first article, we present the identification of BNP as a biomarker of cardiac stress during alcohol withdrawal. In a second, we describe our hypotheses and the non-significant statistical association of alcohol dependence and genetic mutations as a risk factor for cocaine associated chest pain. In a third, we present our findings on the prevalence of 28% for vitamin C deficiency in hospitalized patients undergoing alcohol withdrawal and its association with the screening of a cognitive impairment by the MoCA. In a fourth, we discuss our identification of three plasma biomarkers of brain damage as biomarkers of Wernicke's encephalopathy and neurotoxicity during alcohol withdrawal. And finally, in a fifth, we illustrate the use of a biomarker associated with the technique of motivational interviewing in the empowerment of the patient. The identification of these biomarkers is part of the evolution of medical management, including motivational reinforcement, as well as an increase in scientific evidence for the development of future pharmacological interventional research protocols using these biomarkers as potential intermediate criteria. These preliminary results will be continued with the objective of validating the use of plasma biomarkers identified in this work

Ascorbic Acid Deficiency Prevalence and Associated Cognitive Impairment in Alcohol Detoxification Inpatients: A Pilot Study

Malnutrition has been reported in alcohol use disorder patients as having a possible influence on cognitive function. The aim of this study was to analyse the prevalence of ascorbic acid (AA) deficiency in inpatients admitted for alcohol detoxification and the associated factors, including cognitive impairment in the early period of abstinence. A retrospective chart review was conducted. The AA level was categorised into three groups: deficiency (AAD) (<2 mg/L), insufficiency (AAI) (2–5 mg/L) and normal level. The cognitive impairment was screened using the Montreal Cognitive Assessment (MoCA). Ninety-six patients were included (74 men; mean age 49.1 years (±11.5)). Twenty-seven AAD (28.1%) and twenty-two AAI (22.9%) were observed. In multivariate analysis, risk factors for AAD versus normal AA level were men (OR 17.8, 95%CI (1.63–194)), compensated cirrhosis (OR 9.35, 95%CI (1.60–54.6)) and street homelessness (OR 5.76, 95%CI (1.24–26.8) versus personal housing). The MoCA score was available for 53 patients (mean MoCA score: 25.7 (±3.3)). In multivariate analysis, the natural logarithm of AA (β = 1.18, p = 0.037) and sedative use disorder (β = −2.77, p = 0.046) were associated with the MoCA score. AAD and AAI are frequent in inpatients admitted for alcohol detoxification. A low level of AA was associated with cognitive impairment in the early period of abstinence

Early Predictors of Trajectories of Tobacco Use Level from Adolescence to Young Adulthood: A 16-Year Follow-Up of the TEMPO Cohort Study (1999–2015)

International audiencePurpose: Individual and family characteristics early on in life are associated with adolescent smoking; however, their role with regard to long-term tobacco smoking trajectories into young adulthood is not well-known, which is what we set out to study using data from a longitudinal community-based cohort.Methods: We used data from 2,025 youths in France (12–26 years at baseline, 16 years of follow-up), participating in the longitudinal TEMPO cohort study. First, we modeled smoking trajectories from adolescence onwards using Group-Based Trajectory Modeling, by using the declared consumption of cigarettes at different ages. Second, among trajectories of smokers, associations with individual and family characteristics in childhood and adolescence were studied using multinomial logistic regression.Results: We observed 5 smoking trajectories: non-smokers (62.3%), 3 groups of persistent smokers with different levels of tobacco use (low, intermediate, high), and a group characterized by high-level smoking followed by cessation. Among participants who were lifetime smokers (n = 763), the trajectory of tobacco use was associated with early substance use initiation, academic attainment, grade retention, and parental smoking. Early tobacco and cannabis use initiation predicted high-level tobacco use, whether it persisted (OR 2.29, 95% CI 1.23–4.28) or not (OR 2.99, 95% CI 1.59–5.63). Grade retention and parental smoking predicted persistent smoking of intermediate (respectively OR 1.53, 95% CI 1.03–1.92; OR 1.74, 95% CI 1.03–2.92) or high level use (respectively OR 1.74, 95% CI 1.07–2.85; OR 1.70, 95% CI 0.91–3.18). Poor academic attainment predicted all 3 smoking trajectories, especially persistent high-level smoking (no high school degree: OR 5.29, 95% CI 1.65–16.97, vocational degree: OR 1.94, 95% CI 0.99–3.80).Conclusions: Tobacco smoking trajectories from adolescence to adulthood are associated with early substance use initiation, parental smoking, and academic difficulties

Use and knowledge of contraceptive methods by patients in two substance use disorders treatment centers in Paris

Abstract Background Studies on contraceptive use by patients with substance use disorders (SUD) show a concerning low use of contraception. Mainly conducted in USA, they could be irrelevant to patients attending European SUD treatment centers, especially since these studies mostly investigate women suffering from social exclusion, severe material deprivation andopiates use with frequent high-risk drug use and sexual behaviors including sex trade, frequently not currently attending treatment centers. The purpose of this study is to describe contraceptive use by patients, both male and female, since contraception can not only be considered as a female problem, with severe SUD in two free clinics in Paris, France. Methods An anonymous self-report questionnaire was distributed to literate patients followed in two generalist substance use disorders treatment centers in hospitals of Paris, France: Espace Murger and Centre Cassini, during 5 weeks between February and March 2016. Results Out of the 78 respondents (with an age mean 40.7 years, in which women are represented as 48.1%, and 29.7% of them have children), 53 have had at least one sexual partner in the last 6 months. Contraception was “always” used by 55.3% of sexually active patients, “sometimes” by 19.1%, and “not” used by 25.5%. Male condoms were the main contraceptive method. The use of intrauterine devices was low, contrarily to what is observed in the French general population. However, the knowledge of contraceptive methods was common. Conclusions In this population, with a high prevalence of at risk sexual behavior, the use of contraceptive methods is lower than in French general population. During standard care for SUD, contraception and desire to be a parent should be discussed and patients empowered to make their own choices. Lack of knowledge does not seem to be a hindrance to the use of contraception, but other sociological, psychological, or medical factors may limit contraceptive access and long-term use, especially for the long-acting reversible contraception methods. It is necessary to further develop this reflection by discussing the individual contraceptive choices with the patients themselves to clarify the nature of these constraints and maybe provide several contraceptive methods within the SUD care settings

Opinion of health professionals and drug users before the forthcoming opening of the first drug consumption room in Paris: a quantitative cross-sectional study

Abstract Background On the brink of the opening of the first French drug consumption room in Paris, the general opinion of the local involved health care professionals and drug users was not known. The objective of this study was to determine their expectations and to search for influencing factors. Method We carried out a quantitative cross-sectional study. A multiple choice questionnaire was proposed to the surrounding willing general practitioners (GPs) and pharmacists, to the emergency doctors of Lariboisière hospital, and to the professionals of the harm reduction facilities and their drug users (PWUD). For each question, there was a choice between seven answers, from “− 3” (very negative impact) to “+ 3” (very positive impact). The influence of the characteristics of each group on its mean answers was explored by Mann-Whitney, Kruskal-Wallis, and Spearman’s tests. Results The median expectations among the groups of responding GPs (N = 62), other health care professionals (N = 82), and PWUD (N = 57) were mainly positive. They thought that the drug consumption room (DCR) would improve the health of PWUD, reduce their at-risk behaviors, would not increase drug use or drug dealing in the neighborhood, and would reduce nuisance in the public space. Only the group of GPs expressed that the DCR could decrease the quietness of the neighborhood, and only the group of PWUD had higher expectations that the DCR would decrease the number of arrests and the number of violent behavior. GPs’ expectations were significantly better in terms of health improvement of PWUD and reducing their precariousness if they had a previous experience in addiction medicine (Mann-Whitney, p = 0.004 and p = 0.019), with a longer practice (Spearman’s rho, p = 0.021 and p = 0.009), and if they were currently prescribing opioid substitution treatments (Mann-Whitney, p = 0.030 and p = 0.002). Among non-GPs, those who were working in addiction medicine centers had significantly better expectations than pharmacists, and the professionals of the local emergency department had intermediate expectations. Conclusions Health care professionals and drug users had a positive opinion of the to-be-created Parisian drug consumption room. Experience in addiction medicine influenced positively health professionals’ expectations

UNINTENDED PREGNANCY PREVENTION IN WOMEN USING PSYCHOACTIVE SUBSTANCES: A SYSTEMATIC REVIEW

International audienceThis systematic review seeks to evaluate the efficacy of interventions aimed at preventing unintended pregnancies in women using psychoactive substances. Seven electronic databases (Medline, EMBASE, CINAHL, Web of Science Core Collection, PsycINFO, Cochrane CENTRAL database) were searched in October 2017. Twenty-two articles met our inclusion criteria. Interventions based on behavior change theory yielded an increase in the initiation of effective contraception as compared with provision of written information materials. The effect was more pronounced when the intervention provided on-site contraceptive counseling and free access to birth control. Financial incentives also seemed to effectively increase women’s contraception intake. Case management interventions including pregnant and postpartum women with heavy levels of substance use showed promising results in terms of initiation of contraception, but rates of unintended pregnancy over long-term follow-up were nevertheless elevated. Finally, some interventions integrated family planning services into specialized centers taking care of pregnant and postpartum women with substance abuse. However, most studies aimed at postpartum and post-abortion contraception used a non-comparative design and had a number of methodological flaws. The risk of bias in most studies is high. All interventions with a primary or secondary focus on the prevention of unintended pregnancy in women using psychoactive substances short-term improvements in contraception intake, but it is unclear if these effects last or have any impact on unintended pregnancy rates in the long-term

Alcohol withdrawal is an oxidative stress challenge for the brain: does it pave the way toward severe alcohol-related cognitive impairment?

Alcohol use is a leading cause of mortality, brain morbidity, neurological complications and minor to major neurocognitive disorders. Alcohol-related neurocognitive disorders are consecutive to the direct effect of chronic and excessive alcohol use, but not only. Indeed, patients with severe alcohol use disorders (AUD) associated with pharmacological dependence suffer from repetitive events of alcohol withdrawal (AW). If those AW are not managed by adequate medical and pharmacological treatment, they may evolve into severe AW, or be complicated by epileptic seizure or (DT). In addition, we suggest that AW favors the occurrence of Wernicke's encephalopathy (WE) in patients with known or unknown thiamine depletion. We reviewed the literature on oxidative stress as a core mechanism in brain suffering linked with those conditions: AW, epileptic seizure, DT and WE. Thus, we propose perspectives to further develop research projects aiming at better identifying oxidative stress brain damage related to AW, assessing the effect of repetitive episodes of AW, and their long-term cognitive consequences. This research field should develop neuroprotective strategies during AW itself or during the periwithdrawal period. This could contribute to the prevention of severe alcohol-related brain damage and cognitive impairments

Alcohol Withdrawal Is an Oxidative Stress Challenge for the Brain: Does It Pave the Way toward Severe Alcohol-Related Cognitive Impairment?

International audienceAlcohol use is a leading cause of mortality, brain morbidity, neurological complications and minor to major neurocognitive disorders. Alcohol-related neurocognitive disorders are consecutive to the direct effect of chronic and excessive alcohol use, but not only. Indeed, patients with severe alcohol use disorders (AUD) associated with pharmacological dependence suffer from repetitive events of alcohol withdrawal (AW). If those AW are not managed by adequate medical and pharmacological treatment, they may evolve into severe AW, or be complicated by epileptic seizure or delirium tremens (DT). In addition, we suggest that AW favors the occurrence of Wernicke's encephalopathy (WE) in patients with known or unknown thiamine depletion. We reviewed the literature on oxidative stress as a core mechanism in brain suffering linked with those conditions: AW, epileptic seizure, DT and WE. Thus, we propose perspectives to further develop research projects aiming at better identifying oxidative stress brain damage related to AW, assessing the effect of repetitive episodes of AW, and their long-term cognitive consequences. This research field should develop neuroprotective strategies during AW itself or during the periwithdrawal period. This could contribute to the prevention of severe alcohol-related brain damage and cognitive impairments