Das GRADE-System: ein internationaler Ansatz zur Vereinheitlichung der Graduierung von Evidenz und Empfehlungen in Leitlinien. [The GRADE System: an international approach to standardize the graduation of evidence and recommendations in guidelines]

Clinical practice guidelines have become an important source of information to support clinicians in the management of individual patients. However, current guideline methods have limitations that include the lack of separating the quality of evidence from the strength of recommendations. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) working group, an international collaboration of guideline developers, methodologists, and clinicians have developed a system that addresses these shortcomings. Core elements include transparent methodology for grading the quality of evidence, the distinction between quality of the evidence and strength of a recommendation, an explicit balancing of benefits and harms of health care interventions, an explicit recognition of the values and preferences that underlie recommendations. The GRADE system has been piloted in various practice settings to ensure that it captures the complexity involved in evidence assessment and grading recommendations while maintaining simplicity and practicality. Many guideline organizations and medical societies have endorsed the system and adopted it for their guideline processes.

How to identify and recruit nurses to a survey 14 and 24 years after graduation in a context of scarce data : lessons learnt from the 2012 nurses at work pilot study on nurses' career paths

Nursing workforce data are scarce in Switzerland, with no active national registry of nurses. The worldwide nursing shortage is also affecting Switzerland, so that evidence-based results of the nurses at work project on career paths and retention are needed as part of the health care system stewardship; nurses at work is a retrospective cohort study of nurses who graduated in Swiss nursing schools in the last 30 years. Results of the pilot study are presented here (process and feasibility). The objectives are (1) to determine the size and structure of the potential target population by approaching two test-cohorts of nursing graduates (1988 and 1998); (2) to test methods of identifying and reaching them 14 and 24 years after graduation; (3) to compute participation rates, and identify recruitment and participation biases.

Learning collaboration in General Internal Medicine: a pilot project for undergraduate students in nursing, physiotherapy and medicine

Background: A form of education called Interprofessional Education (IPE) occurs when two or more professions learn with, from and about each other. The purpose of IPE is to improve collaboration and the quality of care. Today, IPE is considered as a key educational approach for students in the health professions. IPE is highly effective when delivered in active patient care, such as in clinical placements. General internal medicine (GIM) is a core discipline where hospital-based clinical placements are mandatory for students in many health professions. However, few interprofessional (IP) clinical placements in GIM have been implemented. We designed such a placement. Placement design: The placement took place in the Department of Internal Medicine at the CHUV. It involved students from nursing, physiotherapy and medicine. The students were in their last year before graduation. Students formed teams consisting of one student from each profession. Each team worked in the same unit and had to take care of the same patient. The placement lasted three weeks. It included formal IP sessions, the most important being facilitated discussions or "briefings" (3x/w) during which the students discussed patient care and management. Four teams of students eventually took part in this project. Method: We performed a type of evaluation research called formative evaluation. This aimed at (1) understanding the educational experience and (2) assessing the impact of the placement on student learning. We collected quantitative data with pre-post clerkship questionnaires. We also collected qualitative data with two Focus Groups (FG) discussions at the end of the placement. The FG were audiotaped and transcribed. A thematic analysis was then performed. Results: We focused on the qualitative data, since the quantitative data lacked of statistical power due to the small numbers of students (N = 11). Five themes emerged from the FG analysis: (1) Learning of others' roles, (2) Learning collaborative competences, (3) Striking a balance between acquiring one's own professional competences and interprofessional competences, (4) Barriers to apply learnt IP competences in the future and (5) Advantages and disadvantages of IP briefings. Conclusions: Our IP clinical placement in GIM appeared to help students learn other professionals' roles and collaborative skills. Some challenges (e.g. finding the same patient for each team) were identified and will require adjustments.

Evaluation à l'aide d'un livre de bord des compétences cliniques acquises par des stagiaires en médecine. [Evaluation using a logbook of mastering of clinical skills by medical students]

La maîtrise des compétences cliniques est extrêmement importante pour le médecin. Leur enseignement est aujourd'hui facilité grâce à la disponibilité du «Swiss Catalogue of Learning Objectives for Undergraduate Medical Training» où sont décrits les niveaux de compétence à atteindre au terme des études de médecine. Un carnet de bord a été préparé à la Faculté de biologie et de médecine de Lausanne à partir de ce document. Il a permis de mettre en évidence chez les étudiants une très nette amélioration de la maîtrise des compétences cliniques entre le début et la fin des stages en médecine interne, chirurgie/orthopédie, pédiatrie, gynécologie/obstétrique et psychiatrie. Un tel outil devrait permettre dans l'avenir de mieux guider l'apprentissage des étudiants et de suivre leurs progrès à chaque étape du curriculum. [Abstract] The mastering of the clinical skills is of utmost importance for the physician. The teaching of the skills is nowadays made easier with the <<Swiss Catalogue of Learning Objectives for Undergraduate Medical Training>> which lists all the skills and their respective level of expected mastering at graduation. In order to do a survey on how good the students are at those skills, a logbook based on this document has been setup at the Faculty of biology and medicine of the University of Lausanne. This has shown that students went through a clear progression of the mastering of the skills during their elective year in internal medicine, surgery/orthopaedics, paediatric, obstetric and gynaecology as well as psychiatry. Such an instrument should in the future help to better guide the learning process of the clinical skills and to do a better follow-up of their progress.

Wolves in sheep's clothing: SDO asymmetrically predicts perceived ethnic victimization among White and Latino students across three years

Dominant groups have claimed to be the targets of discrimination on several historical occasions during violent intergroup conflict and genocide.The authors argue that perceptions of ethnic victimization among members of dominant groups express social dominance motives and thus may be recruited for the enforcement of group hierarchy. They examine the antecedents of perceived ethnic victimization among dominants, following 561 college students over 3 years from freshman year to graduation year. Using longitudinal, cross-lagged structural equation modeling, the authors show that social dominance orientation (SDO) positively predicts perceived ethnic victimization among Whites but not among Latinos, whereas victimization does not predict SDO over time. In contrast, ethnic identity and victimization reciprocally predicted each other longitudinally with equal strength among White and Latino students. SDO is not merely a reflection of contextualized social identity concerns but a psychological, relational motivation that undergirds intergroup attitudes across extended periods of time and interacts with the context of group dominance.

Adoption of the Healthy Heart Kit by Alberta family physicians

OBJECTIVE: The Healthy Heart Kit (HHK) is a risk management and patient education kit for the prevention of cardiovascular disease (CVD) and the promotion of CV health. There are currently no published data examining predictors of HHK use by physicians. The main objective of this study was to examine the association between physicians' characteristics (socio-demographic, cognitive, and behavioural) and the use of the HHK. METHODS: All registered family physicians in Alberta (n=3068) were invited to participate in the "Healthy Heart Kit" Study. Consenting physicians (n=153) received the Kit and were requested to use it for two months. At the end of this period, a questionnaire collected data on the frequency of Kit use by physicians, as well as socio-demographic, cognitive, and behavioural variables pertaining to the physicians. RESULTS: The questionnaire was returned by 115 physicians (follow-up rate = 75%). On a scale ranging from 0 to 100, the mean score of Kit use was 61 [SD=26]. A multiple linear regression showed that "agreement with the Kit" and the degree of "confidence in using the Kit" was strongly associated with Kit use, explaining 46% of the variability for Kit use. Time since graduation was inversely associated with Kit use, and a trend was observed for smaller practices to be associated with lower use. CONCLUSION: Given these findings, future research and practice should explore innovative strategies to gain initial agreement among physicians to employ such clinical tools. Participation of older physicians and solo-practitioners in this process should be emphasized.

Post-transcriptional regulation of circadian gene expression by miRNAs

La grande majorité des organismes vivants ont développé un système d'horloges biologiques internes, appelées aussi horloges circadiennes, contrôlant l'expression de gênes impliqués dans de nombreux processus moléculaires et comportementaux. Au cours de la dernière décennie, des analyses « microarray » et séquençages à haut débit sur divers tissus de mammifères, indiquent que jusqu'à 20% du transcriptome serait sous contrôle circadien. Il était jusqu'à présent admis que la majorité des ARNm ayant une accumulation rythmique était générée par une transcription qui était elle-même rythmique. Toutefois, de récentes études ont suggéré qu'une proportion considérable des ARNm cycliques serait en fait générée par des mécanismes post-transcriptionnelles, incluant une régulation par micro-ARN (miARN). Lorsque j'ai débuté mon travail de thèse, l'influence des miARN sur l'expression des gènes circadiens, au niveau pangénomique, était encore méconnue. Par l'utilisation d'un modèle murin, dont la biogenèse des miARN a été spécifiquement désactivée au niveau des cellules hépatiques (knockout conditionnel pour Dicer), je me suis donc intéressée au rôle que jouaient ces molécules régulatrices sur la rythmicité de l'expression génique dans le foie. Des séquençages sur l'ensemble du transcriptome révèlent que l'horloge interne du foie est étonnement résistante à la perte totale des miARN. Nous avons cependant trouvé que les miARN agissent de façon importante sur la régulation de l'expression des gènes contrôlés par l'horloge moléculaire. La corégulation par les miARN, affectant jusqu'à 30% des gènes transcrits de façon rythmiques, conduit ainsi à une modulation de phase et d'amplitude du rythme de l'abondance des ARNm. En revanche, seuls peu de transcrits dépendent uniquement des miARN pour la rythmicité de leur accumulation. Enfin, mon travail met en évidence plusieurs miARN spécifiques, qui semblent préférentiellement moduler l'expression des gènes cycliques et permet l'identification de voies hépatiques particulièrement sujettes à une double régulation par les miARN et l'horloge biologique interne. La première masse d'analyses a essentiellement porté sur le rôle que jouent les miARN au niveau de l'expression des gènes contrôlés par l'horloge interne. Dans deux études de suivi, je me suis penchée sur deux aspects supplémentaires et complémentaires de la manière dont les miARN et l'oscillation de l'expression des gènes interagissent. Dans les hépatocytes murins, spécifiquement privés de Dicer, je me suis demandée si un phénotype horloge avait pu être masqué, dû à un entraînement stable de l'horloge du foie par l'horloge maîtresse du cerveau. J'ai donc commencé une série d'expériences ambitieuses (impliquant la mesure de la rythmicité du foie in vivo, chez l'animal vivant) afin de déséquilibrer l'entrainement de l'horloge hépatique via l'utilisation d'un protocole nutritionnel spécifique. Les premiers résultats suggèrent que dans des conditions où l'animal subit une restriction alimentaire pendant la journée, les miARN sont importants dans la cinétique d'adaptation des organes périphériques à un nouvel horaire de sustentation. Dans une deuxième ligne de recherche, j'ai plus profondément étudié quels seraient les miARN responsables des rythmes post-transcriptionnels des ARNm, en utilisant le séquençage de « small » ARN sur 24h. L'analyse est en cours et se poursuivra après l'obtention de mon diplôme. De façon générale, mon travail révèle d'importants et nouveaux rôles des miARN dans la modulation de l'expression circadienne des gènes hépatiques. De plus, le set de données générées dans l'étude déjà publiée, peut dorénavant servir de ressource valable pour de prochaines investigations sur le rôle physiologique que les miARN jouent au niveau du foie. -- Most living organisms have developed internal timing systems, called circadian clocks, to drive the rhythmic expression of genes involved in many molecular and behavioral processes. Over the last decade, microarray analyses and high- throughput sequencing from various mammalian tissues have indicated that up to 20% of the transcriptome are under circadian control. It was generally assumed that the majority of rhythmic mRNA accumulation is generated by rhythmic transcription. However, recent studies have suggested that a considerable proportion of mRNA cycling may actually be generated by post-transcriptional mechanisms, including by microRNAs. When I started my thesis work, it was still unknown how miRNAs influence circadian gene expression in a genome-wide fashion. Using a mouse model in which miRNA biogenesis can be inactivated in hepatocytes (conditional Dicer knockout mouse), I have thus addressed the role that these regulatory molecules play in rhythmic gene expression in the liver. Whole transcriptome sequencing revealed that the hepatic core clock was surprisingly resilient to total miRNA loss. However, we found that miRNAs acted as important regulators of clock-controlled gene expression. Co- regulation by miRNAs, which affected up to 30% of rhythmically transcribed genes, thus led to the modulation of phases and amplitudes of mRNA abundance rhythms. By contrast, only very few transcripts were strictly dependent on miRNAs for their rhythmic accumulation. Finally, my work highlights several specific miRNAs that appear to preferentially modulate cyclic gene expression, and identifies pathways in the liver that are particularly prone to dual regulation through miRNAs and the clock. The first bulk of analyses mainly dealt with the role that miRNAs play at the level of rhythmic clock output gene expression. In two follow-up studies I further delved into two additional, complementary aspects of how miRNAs and gene expression oscillations interact. First, I addressed whether a core clock phenotype in the hepatocyte-specific Dicer knockout could have been masked due to the stable entrainment of the liver clock by the animals' master clock in the brain. I thus started a series of ambitious experiments (involving the in vivo recording of liver rhythms in live animals) to bring the stable entrainment of the liver clock out of equilibrium using specific feeding protocols. My first results suggest that under conditions when animals are challenged by food restriction to daytime, miRNAs are important for the kinetics of adapting to unusual mealtime in peripheral tissue. In a second line of research, I have more carefully investigated which miRNAs are responsible for post- transcriptional mRNA rhythms using small RNA sequencing around-the-clock. The analyses are ongoing and will be continued after my graduation. Overall, my work uncovered important and novel roles of miRNA activity in shaping hepatic circadian gene expression; moreover, the datasets collect in the published studies can serve as a valuable resource for further investigations into the physiological roles that miRNAs play in liver. -- L'alternance du jour et de la nuit dirige depuis longtemps la vie quotidienne des êtres humains et de la plupart des organismes sur terre. Ce cycle de 24 heures façonne beaucoup de changements comportementaux et physiologiques tels que la vigilance, la température corporelle et le sommeil. Les rythmes journaliers, appelés rythmes circadiens, sont dirigés par des horloges biologiques tournant dans presque chaque cellule du corps. Une structure dans le cerveau agit en tant qu'horloge maitresse pour synchroniser les horloges internes entre elles et en fonction des signaux de jour/nuit extérieurs. Dans les cellules "les gènes de l'horloge" sont activés et désactivés une fois par jour ce qui déclenche des cycles dans lesquels des protéines sont produites de manière circadienne. Ces rythmes protéiques sont spécialisés pour chaque tissu ou organe et peuvent les aider à réaliser leurs tâches quotidiennes. Les rythmes circadiens peuvent être générés d'autres manières n'impliquant pas directement les composants des gènes de l'horloge. Les ARN messagers (ARNm) sont des molécules intermédiaires dans la production de protéines à partir d'ADN. Dans le foie des souris jusqu'à 20% des molécules d'ARNm sont produites suivant des rythmes circadiens. Le foie réalise des tâches essentielles dans le contrôle du métabolisme incluant celui des hydrates de carbone, des graisses et du cholestérol. Un timing précis est important afin de traiter les substances nutritives correctement lors des repas il en résulte une variation des quantités de certains ARNm et protéines coïncidant avec les repas. Les microARNs constituent une autre classe de molécules ARN de très petite taille qui régulent l'efficacité de traduction des ARNm en protéines et la stabilité des ARNm. Lors de mon travail de thèse, j'ai exploré de manière approfondie l'influence de ces petits régulateurs sur les rythmes circadiens du foie de souris. Ces expériences qui impliquaient le "Knock-out" d'un gène essentiel à la production de microARNs montrent qu'au lieu de générer les rythmes des ARNm, les microARNs les ajustent pour répondre aux besoins spécifiques du foie comme assurer leur pic au bon moment de la journée. Le ciblage de microARNs spécifiques peut révéler de nouvelles stratégies pour rectifier ces rythmes lorsque par exemple les fonctions métaboliques ne fonctionnent plus normalement. -- The rising and setting of the sun have long driven the daily schedules of humans and most organisms on the earth. This 24-hr cycle shapes many behavioural and physiological changes, such as alertness, body temperature, and sleep. These daily rhythms, which are called circadian rhythms, are dictated by biological clocks that are ticking in almost every single cell of the body. A region in the brain acts as a master clock to synchronize the internal clocks with each other and with the outside light/dark cycles. In cells, "core clock genes" are turned on and off once per day, which triggers cycles that cause some proteins to be produced in a circadian manner. The protein rhythms are specialized to a particular tissue or organ, and may help them to carry out their designated daily tasks. However, circadian rhythms might also be produced by other ways that do not involve these core clock components. Messenger RNAs (mRNAs) are intermediate molecules in the production of proteins from DNA. In the mouse liver, up to 20% of mRNA molecules are produced in circadian cycles. The liver performs essential tasks that control metabolism-including that of carbohydrates, fats, and cholesterol. Precisely timing when certain mRNAs and proteins reach peaks and troughs in their activities to coincide with mealtimes is important for nutrients to be properly processed. Other RNA molecules called microRNAs, i.e. RNAs of very small size, regulate at which rate mRNA molecules are translated into proteins. In my thesis work, I have explored at the influence of these small regulators on circadian rhythms in the mouse liver in greater detail. These experiments, which involved "knocking out" a gene that is essential for the production of microRNAs, show that rather than generating the mRNA rhythms, the microRNAs appear to adjust them to meet the specific needs of the liver, such as ensuring that they peak at the right time-of-day. Targeting specific microRNA molecules may reveal new strategies to tweak these rhythms, which could help to improve conditions when metabolic functions go wrong.