Les médecines complémentaires sont nombreuses et variées, leur recours est largement répandu et en hausse. Selon les pratiques, les données d’évaluation sont plus ou moins riches, mais il y a peu de conclusions consensuelles quant à leur efficacité, même en cas de littérature abondante. Nous commencerons par un état des lieux de l’adéquation des méthodes conventionnelles utilisées pour l’évaluation du médicament, à savoir de l’essai contrôlé randomisé (ECR) et des méta-analyses, pour l’évaluation des médecines complémentaires.A travers trois applications pratiques, nous réfléchirons ensuite à l’apport d’autres méthodes, moins reconnues à ce jour dans le champ de l’evidence based medecine mais pouvant apporter d’autres éclairages. En particulier, nous discuterons de l’intérêt des méthodes mixtes, des études qualitatives et de l’exploitation des grandes bases de données médico-administratives. Nous réaliserons une revue mixte sur l’évaluation de l’hypnose pour le travail et l’accouchement, une étude qualitative sur l’expérience du qi gong par des patientes hospitalisées pour anorexie mentale sévère, et nous étudierons le potentiel d’exploitation du Système National d'Information Inter Régimes de l'Assurance Maladie (SNIIRAM) pour évaluer les médecines complémentaires. Les deux premiers axes nous amèneront à questionner le choix des critères de jugement et des instruments de mesure utilisés dans les ECR et nous inciteront à accorder davantage de place et de légitimité à la perspective du patient. Plus largement, cela nous invitera à remettre en cause la suprématie traditionnellement accordée aux études quantitatives pour la remplacer par une vision non hiérarchique mais synergique des approches qualitatives et quantitatives. Le troisième axe nous permettra d’identifier les limites actuelles à l’exploitation du SNIIRAM pour l’évaluation des médecines complémentaires, à la fois sur le plan technique et sur le plan de la représentativité. Nous proposerons des mesures concrètes pour rendre possible et pertinente son exploitation dans le champ de l'évaluation des médecines complémentaires.Enfin, dans la discussion générale, nous tiendrons compte du fait que l’évaluation des médecines complémentaires n’a pas pour but d’autoriser ou non une mise sur le marché. Ainsi, contrairement à l'évaluation des médicaments, l'évaluation des médecines complémentaires ne s'inscrit pas toujours dans une visée de prise de décision. Nous soulignerons l’importance de tenir compte de la visée (visée de connaissance ou visée de décision) dans l’élaboration d’une stratégie de recherche et nous proposerons deux stratégies différentes en nous appuyant sur la littérature et les résultats issus de nos trois exemples d'application. Concernant la stratégie de recherche à visée de prise de décision, nous montrerons l’importance des étapes de définition de l’intervention, d’identification des critères de jugement pertinents, et d’optimisation de l’intervention, avant la réalisation d’essais pragmatiques visant à évaluer l’efficacité en vie réelle. Nous verrons comment la volonté d’évaluer ces pratiques nous renvoie à des défis en terme de réglementation et nous soulignerons par ailleurs la nécessité d’évaluer la sécurité de ces pratiques en développant des systèmes de surveillance adaptés. / Complementary medicines are numerous and varied, their use is widespread and increasing.Quality and quantity of evaluation data depend on the type of complementary medicines, but there are few consensual conclusions about their effectiveness, even in the case of abundant literature. We will start with an inventory of the adequacy of the conventional methods used for drug evaluation, namely randomized controlled trials (RCT) and meta-analyzes, for the evaluation of complementary medicines. Through three practical applications, we will then consider the contribution of other methods, less recognized to date in the field of evidence-based medicine but potentially contributive to shed light on other perspectives. In particular, we will discuss the advantages of mixed methods, qualitative studies and the exploitation of large health administrative databases. We will conduct a mixed-method review of the assessment of hypnosis for labor and childbirth, a qualitative study on the experience of qi gong by patients hospitalized for severe anorexia nervosa and we will study the potential of the French national health insurance database (SNIIRAM) to evaluate complementary medicines. The first two axis will lead us to question the choice of outcomes and measurement tools used in RCTs and to value and legitimate the patient's perspective. More broadly, it will invite us to question the hierarchical vision of qualitative and quantitative research that traditionally attributes supremacy to quantitative studies. It will encourage us to replace it with a synergistic vision of qualitative and quantitative approaches. The third axis will enable us to identify the current limits to the use of SNIIRAM for the evaluation of complementary medicines, both technically and in terms of representativeness. We will propose concrete measures to make its exploitation possible and relevant in the field of evaluation of complementary medicines.Finally, in the general discussion, we shall take account of the fact that the evaluation of complementary medicines is not part of a marketing authorization process. Thus, contrary to drug evaluation, complementary medicines evaluation does not always imply decision making. We will emphasize the importance of considering the aim (aim of knowledge or aim of decision) in the development of a research strategy. We will propose two different strategies based on the literature and the results from our three examples. Concerning the research strategy aimed at decision-making, we will show the importance of defining the intervention, identifying the relevant outcomes, and optimizing the intervention first, before carrying out pragmatic clinical trials to evaluate its effectiveness. We will discuss the regulatory challenges complementary medicine evaluation confronts us to, and stress the need to assess the safety of these practices by developing appropriate monitoring systems.

This paper examines the correspondence, manuscripts, and speeches of ex-mental patient activists. I chronicle the activities of the emergent psychiatric survivors movement from its beginnings in the early 1970’s focusing on the work of the Boston based activist, Judi Chamberlin (1944-2010). This paper examines how mental patients in post-war America began to organize in order to have their voices included in the process of their own recovery. I present Chamberlin’s experience as a mental patient as being representative of the “rootlessness” that many post-war women experienced. Chamberlin’s work as an ex-patient activist presented one aspect of the overall struggle on the part of mental patients to claim their place in a wider society. I also pay attention to interdisciplinary scholarly analyses of madness to investigate how discussion of the subject influenced ex-patient activists, as well as whether or not the ex-patients’ narrative reciprocally influenced the scholarly discussion about madness. In the final chapters, I also look at how the successes of this social movement ironically led to the prevalence of today’s diagnostic models of treatment that rely heavily on pharmacological methods and highly regimented evidence-based psychotherapies while still excluding patients’ voices. The voices of mental patients both in the asylum era and today have been excluded from the treatment process.

Cholangiocarcinoma (CCA) has a high mortality rate and its occurrence is rising. This increase prompts the need for improved CCA treatments. Studies have suggested that CCA is highly reliant on the sphingosine-1-phosphate-receptor-2 (S1PR2) and sphingosine kinase 2 (SphK2). Recently, a competitive SphK2 inhibitor, ABC294640, has been approved for clinical trial. ABC294640 has the potential to treat CCA, which is support by a phase I clinical study that was able to temporarily treat a patient suffering from metastasized CCA with ABC294640. To determine the viability of ABC294640 as a treatment for CCA, this study focused on determining the effects of ABC294640 on rat CCA cell lines. We found that ABC294640 inhibited the growth and migration of CCA and CAFs cells. The growth and count of 3-D organotypic co-culture of CCA and CAFs, which forms the “duct-like” structures, were reduced by ABC294640. The potential of inhibiting SphK2 as a treatment for CCA is supported by our finding of increased expression of S1PR2 and SphK2 in CCA patient liver samples. In conclusion, ABC294640 represents a potential therapeutic agent for CCA.

Winged scapula is a condition characterized by lateral or medial protrusion of the scapula caused by nerve damage leading to muscular paralysis. The purpose of this systematic review of literature is to evaluate the current research literature related to the effectiveness of therapy options for winged scapula. Eleven peer reviewed English language research articles published from 1998 to present were included for evaluation. Study results revealed positive therapeutic outcomes for physical therapy and scapular bracing. Results also showed positive outcomes for the use of transcutaneous electrical nerve stimulation and acupuncture for the treatment of nerve related conditions similar to winged scapula. Additional research is needed to evaluate the effectiveness of transcutaneous electrical nerve stimulation and acupuncture for winged scapula patients specifically.

Associated with health care reform, there has been a growing interest among healthcare professionals regarding use of energy-based therapies as a complementary therapeutic intervention. The purpose of this integrative literature review was to examine the impact of energy-based therapies (i.e. healing touch, reiki, therapeutic touch) on patients’ postoperative recovery. The methodology included identifying appropriate peer-reviewed, English-language research articles on the topic area that were published between 2006 to 2018. Following a search in select data bases, articles focusing on the topic were critiqued, analyzed and synthesized by the researcher. Consistent and inconsistent findings along with gaps in the literature are noted. In general, the research supported positive postoperative recovery outcomes when energy-based therapies were included along with standard postoperative nursing care. This theses highlights implication for nursing practice, education, and policy and identifies study limitations. Given that research is limited on this topic area, additional studies are needed to establish supporting evidence to ascertain the effects of energy-based therapies when used as a complementary postoperative intervention.

ABSTRACT Purpose: The purpose of this study was to examine the relationship between self-reported sedentary time (ST) and the cumulative risk of preserved ejection fraction heart failure (HFpEF) and reduced ejection fraction heart failure (HFrEF) using a diverse cohort of U.S. adults 45-84 years of age. Methods: Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), we identified 6,814 subjects (52.9% female). All were free of baseline cardiovascular disease. Cox regression was used to calculate the hazard ratios (HR) associated with baseline ST and risk of overall heart failure (HF), HFpEF, and HFrEF. Weekly self-reported ST was dichotomized based on the 75th percentile (1,890 min/wk). Results: During an average of 11.2 years of follow-up there were 178 first incident HF diagnoses; 74 HFpEF, 69 HFrEF and 35 with unknown EF. Baseline ST >1,890 min/wk was significantly associated with an increased risk of HFpEF (HR [95% CI]; 1.87 [1.13 – 3.09], p= 0.01), but not HFrEF (HR [95% CI]; 1.30 [0.78 – 2.15], p= 0.32). The relationship with HFpEF remained significant in separate fully adjusted models including either waist circumference (HR [95% CI]; 2.16 [1.23 – 3.78], p < 0.01) or body mass index (HR [95% CI]; 2.17 [1.24 – 3.80], p < 0.01). Additionally, every 60 minute increase in weekly ST was associated with a significant 3% increased risk of HFpEF (HR [95% CI]; 1.03 [1.01 – 1.05], p < 0.01). Conclusions: Sedentary time > 1,890 min/wk (~4.5 h/d) is a significant independent predictor of HFpEF, but not HFrEF.

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity at this therapeutic target, i.e. the human DAT. This was achieved by expressing the human DAT protein in transgenic plant cells and selecting gain-of-function mutants for survival on medium containing a neurotoxin that is accumulated by the human DAT. This created a sub-population of mutants with increased DAT inhibitory activity. Some of the active metabolites in these mutants are novel (i.e. not detectable in wild-type cells). Others are cytoprotective, and also protect DAergic neurons against the neurotoxin. This provides proof-of-concept for a novel plant drug discovery platform, which is applicable to many different therapeutic target proteins and plant species.

Contexte : Les enfants atteints de maladies chroniques utilisent souvent des médecines complémentaires. Plusieurs études traitent de l’utilisation de ces traitements et des facteurs qui y sont associés chez les enfants atteints d’arthrite juvénile mais aucune étude n’est longitudinale. De plus, aucune n’a documenté l’utilisation de ces traitements chez les enfants ayant des incapacités physiques en attente de services publics de réadaptation. Objectifs : Les objectifs de cette étude étaient de déterminer la fréquence d’utilisation des médecines complémentaires chez les enfants atteints d’arthrite juvénile et d’incapacités physiques, d’évaluer leur efficacité telle que perçue par les parents et d’explorer les facteurs associés à leur utilisation. Méthodes : Une cohorte d’enfants atteints d’arthrite juvénile idiopathique (n=182, âge moyen : 10,2 ans) qui fréquentent des cliniques d’arthrite et une cohorte d’enfants ayant des incapacités physiques en attente de services de réadaptation publics (n=224, âge moyen : 2,6 ans) ont été suivis durant une période d’un an. L’utilisation des médecines complémentaires et la perception de leur efficacité d’après les parents ont été évaluées à l’aide de statistiques descriptives à chaque trois mois pour la cohorte d’enfants atteints d’arthrite et au début de l’étude pour la cohorte d’enfants ayant des incapacités physiques. Les facteurs associés à l’utilisation de ces traitements ont été explorés par des analyses de type GEE (« Generalized estimating equations ») et des régressions polytomique et logistique. Résultats : L’utilisation antérieure de ces médecines était de 51,1% pour les enfants atteints d’arthrite et de 15% pour les enfants ayant des incapacités physiques. Les médecines complémentaires étaient considérées comme étant efficaces dans 72% des cas par les parents d’enfants atteints d’arthrite et dans 83% des cas par les parents d’enfants ayant des incapacités physiques. Les facteurs associés à l’utilisation des médecines complémentaires chez les enfants atteints d’arthrite étaient l’utilisation antérieure des médecines complémentaires par les parents et la perception des parents que les médicaments prescrits ne sont pas utiles pour leur enfant. Chez les enfants ayant des incapacités physiques, les facteurs associés à l’utilisation des médecines complémentaires étaient l’origine culturelle canadienne, un niveau de scolarité plus élevé que le diplôme d’études secondaires et une moins bonne qualité de vie reliée à la santé. Finalement, l’utilisation des médecines complémentaires semblait associée à de moins bons résultats chez les enfants atteints d’arthrite. Conclusion: Une proportion non-négligeable des enfants participant à la présente étude ont utilisé des médecines complémentaires. Leur utilisation était plus fréquente chez les enfants atteints d’arthrite juvénile idiopathique, surtout chez ceux dont les parents avaient déjà utilisé les médecines complémentaires par le passé et chez ceux qui trouvaient la médication peu efficace. Chez les enfants ayant des incapacités physiques, l’utilisation des médecines complémentaires était associée à des facteurs socio-démographiques et à des besoins plus élevés en matière de santé. Les médecines complémentaires étaient considérées comme étant efficaces dans les deux cohortes mais leur utilisation était associée à de faibles résultats chez les enfants atteints d’arthrite. Ces résultats démontrent l’importance d’évaluer l’utilisation des médecines complémentaires afin de mieux renseigner les parents et de les aider à prendre les meilleures décisions possibles concernant le traitement de leur enfant. / Background: Children with chronic diseases often use complementary and alternative health care (CAHC). Several studies described the use of these treatments and the factors associated with it. However, no longitudinal studies were conducted to determine the use of these treatments over time. Furthermore, no study has evaluated CAHC use in children who were waiting for public rehabilitation services. Objective: The aim was to determine the frequency of CAHC use in children with juvenile idiopathic arthritis (JIA) and children with various physical disabilities (PD), to evaluate its effectiveness from the parents’ points of view and to explore the factors associated with their utilization. Methods: A cohort of children with JIA (n=182, mean age: 10.2 years) who attended arthritis clinics and a cohort of children with physical disabilities (n=224, mean age: 2.6 years) waiting for public rehabilitation services were followed for one year. We evaluated the use of CAHC and its effectiveness from the parents’ points of view at three month intervals for children with JIA and at the beginning of the study for children with PD, using descriptive statistics. We explored factors associated with their utilization, using GEE (“Generalized estimating equations »), polytomous and logistic regression. Results : Previous use of CAHC was 51.1% for children with JIA and 15% for children with PD. CAHC was considered beneficial in 72% of the cases by parents of children with JIA and in 83% of the cases by parents of children with PD. Factors associated with higher use of CAHC in children with JIA were previous use of CAHC by parents and lower perceived helpfulness of prescribed medications (p<0.05). In children with PD, factors associated with higher use of CAHC were Canadian cultural background, mother’s level of education higher than high school and lower health-related quality of life. Finally, in children with JIA, CAHC use was associated with worse outcomes. Conclusions: Many children in our study used CAHC. Its use was more common in children with JIA, particularly among those whose parents used it previously and found medications to be less helpful. For children with PD, use of CAHC was associated with socio-demographic factors as well as higher children’s health needs. CAHC were perceived to be beneficial in both cohorts but its use was associated with worse outcomes for children with JIA. This underlines the importance for health professionals to evaluate CAHC use in order to better inform parents, which may help them make the best decisions regarding their child’s treatment.

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