Search

Background: Precision Medicine offers tailored prevention, diagnosis, treatment and management to patients that considers genomic, lifestyle and environmental factors. If implementation of PM is to advance, effective, focused upskilling of frontline healthcare workers through quality continuing professional development (CPD) is needed. This study reports on an evidence-based approach to needs assessment to investigate the acceptability of pharmacists, advanced practice nurses and general practitioners towards a national blended training programme in PM. Needs assessment avoids a top-down approach and supports a design that is fit for purpose, acceptable to the target professions and fills a perceived gap in current practice. Methods: This study reports on 2 focus groups (n=12) delivered in French and German with equal professional participation of the targeted professions. The focus groups were audio recorded, transcribed by intelligent verbatim and translated to English. NVivo was used for data analysis and interpretation following a hybrid approach using the Framework Method and thematic analysis.Results: Precision Medicine as a new topic is largely unfamiliar to frontline healthcare professionals. Insight was gathered on acceptable learning objectives and results will be validated with a follow up survey to a wider audience. All participants shared their concerns on their readiness to implement a precision approach within their professions. Additional raised points include insufficient system infrastructure and supporting network of experts, a lack of time to attend training, and a lack of clarity for use in practice.Conclusions: Our results conclude that an adaptable and flexible training programme in PM is timely, contextually relevant and conducive to the needs of targeted health professions for successful implementation. A training programme in PM will require support across sectors and stakeholders, supporting insurance models, educated patients and integrated care supported by innovative technology. Precision Medicine is on our horizon and it is not a question of if but when and to what extent Precision Medicine will become a new normal for frontline healthcare professionals.

Anhand zweier Patienten, die wegen Muskelschmerzen und Farbveranderungen des Urins nach korperlicher Belastung vorstellig wurden, werden Diagnose und Management der belastungsinduzierten Rhabdomyolyse aufgezeichnet.

Une patiente de 43 ans consulte les urgences en raison de pejoration de lombalgies avec irradiations douloureuses dans la region sus-pubienne et vers les cuisses. Elle rapporte egalement la presence d’urines rouges.

Eine 43-jahrige Patientin kommt aufgrund sich verschlimmernder Lumbalgien mit Schmerzausstrahlung in den suprapubischen Bereich und die Oberschenkel in die Notaufnahme. Sie berichtet ferner von rotem Urin.

2017 has continued to bring important progress in all areas of internal medicine, impacting our daily practice. From bedside screening for beta-lactam allergies, to statins as primary prevention in the elderly, SGLT2 inhibitors in heart failure, azithromycin in severe asthmatics and tofacitinib in ulcero-haemorrhagic recto-colitis, internal medicine journals are full of novelties. Every year, the chief residents of the CHUV internal medicine ward meet up to share their readings: here is their selection of eleven articles, chosen, summarized and commented for you.L’année 2017 a vu d’importants progrès dans tous les domaines de la médecine interne, avec un impact important sur notre pratique quotidienne. Du dépistage au lit du patient des allergies aux bêta-lactames, aux statines en prévention primaire chez les personnes âgées, en passant par l’utilisation des inhibiteurs SGLT2 dans l’insuffisance cardiaque, de l’azithromycine chez les asthmatiques sévères et du tofacitinib en cas de rectocolite ulcéro-hémorragique (RCUH), les nouveautés abondent dans la littérature. Chaque année, les chefs de clinique du Service de médecine interne du Centre hospitalier universitaire vaudois (CHUV) se réunissent pour partager leurs lectures : voici une sélection de onze articles choisis, revus et commentés pour vous.

The year 2016 was rich in significant advances in all areas of internal medicine. Many of them have an impact on our daily practice in general internal medicine. From the treatment of NSTEMI in population older than 80, to new sepsis and septic shock criteria to antidotes of new oral anticoagulants, this selection offers to the readers a brief overview of the major advances. The chief residents in the Service of internal medicine of the Lausanne University hospital are pleased to share their readings.L’année 2016 a été riche en avancées importantes dans tous les domaines de la médecine. L’impact de ces avancées sera palpable dans notre pratique en médecine interne générale. De la prise en charge du NSTEMI (infarctus myocardique sans élévation ST) dans la population des plus de 80 ans, aux nouveaux critères du sepsis et du choc septique, aux antidotes des nouveaux anticoagulants oraux en passant par la déprescription médicamenteuse, les nouveautés dans la littérature ont été abondantes. Chaque année, les chefs de clinique du Service de médecine interne du Centre hospitalier universitaire vaudois (CHUV) se réunissent pour partager leurs lectures. Onze de leurs choix sont ici revus et commentés.

The year 2015 gave us many scientific publications, among whom some will have an impact on our daily practice and some will influence our way of considering some well known diseases. Chief residents in the Service of internal medicine of the Lausanne University hospital, gathered like every year, to share their readings together in order to presentyou a small part of the many publications of 2015, which have been considered to have an impact on our future daily practice.

OBJECTIVE Our laboratory has previously established in vitro that a caspase-generated RasGAP NH2-terminal moiety, called fragment N, potently protects cells, including insulinomas, from apoptotic stress. We aimed to determine whether fragment N can increase the resistance of pancreatic β-cells in a physiological setting. RESEARCH DESIGN AND METHODS A mouse line, called rat insulin promoter (RIP)-N, was generated that bears a transgene containing the rat insulin promoter followed by the cDNA-encoding fragment N. The histology, functionality, and resistance to stress of RIP-N islets were then assessed. RESULTS Pancreatic β-cells of RIP-N mice express fragment N, activate Akt, and block nuclear factor κB activity without affecting islet cell proliferation or the morphology and cellular composition of islets. Intraperitoneal glucose tolerance tests revealed that RIP-N mice control their glycemia similarly as wild-type mice throughout their lifespan. Moreover, islets isolated from RIP-N mice showed normal glucose-induced insulin secretory capacities. They, however, displayed increased resistance to apoptosis induced by a series of stresses including inflammatory cytokines, fatty acids, and hyperglycemia. RIP-N mice were also protected from multiple low-dose streptozotocin-induced diabetes, and this was associated with reduced in vivo β-cell apoptosis. CONCLUSIONS Fragment N efficiently increases the overall resistance of β-cells to noxious stimuli without interfering with the physiological functions of the cells. Fragment N and the pathway it regulates represent, therefore, a potential target for the development of antidiabetes tools.

OBJECTIVE The gluco-incretin hormones glucagon-like peptide (GLP)-1 and gastric inhibitory peptide (GIP) protect β-cells against cytokine-induced apoptosis. Their action is initiated by binding to specific receptors that activate the cAMP signaling pathway, but the downstream events are not fully elucidated. Here we searched for mechanisms that may underlie this protective effect. RESEARCH DESIGN AND METHODS We performed comparative transcriptomic analysis of islets from control and GipR−/−;Glp-1-R−/− mice, which have increased sensitivity to cytokine-induced apoptosis. We found that IGF-1 receptor expression was markedly reduced in the mutant islets. Because the IGF-1 receptor signaling pathway is known for its antiapoptotic effect, we explored the relationship between gluco-incretin action, IGF-1 receptor expression and signaling, and apoptosis. RESULTS We found that GLP-1 robustly stimulated IGF-1 receptor expression and Akt phosphorylation and that increased Akt phosphorylation was dependent on IGF-1 but not insulin receptor expression. We demonstrated that GLP-1–induced Akt phosphorylation required active secretion, indicating the presence of an autocrine activation mechanism; we showed that activation of IGF-1 receptor signaling was dependent on the secretion of IGF-2. We demonstrated, both in MIN6 cell line and primary β-cells, that reducing IGF-1 receptor or IGF-2 expression or neutralizing secreted IGF-2 suppressed GLP-1–induced protection against apoptosis. CONCLUSIONS An IGF-2/IGF-1 receptor autocrine loop operates in β-cells. GLP-1 increases its activity by augmenting IGF-1 receptor expression and by stimulating secretion; this mechanism is required for GLP-1–induced protection against apoptosis. These findings may lead to novel ways of preventing β-cell loss in the pathogenesis of diabetes.

The caspase-3-generated RasGAP N-terminal fragment (fragment N) inhibits apoptosis in a Ras-PI3K-Akt-dependent manner. Fragment N protects various cell types, including insulin-secreting cells, against different types of stresses. Whether fragment N exerts a protective role during the development of type 1 diabetes is however not known. Non-obese diabetic (NOD) mice represent a well-known model for spontaneous development of type 1 diabetes that shares similarities with the diseases encountered in humans. To assess the role of fragment N in type 1 diabetes development, a transgene encoding fragment N under the control of the rat insulin promoter (RIP) was back-crossed into the NOD background creating the NOD-RIPN strain. Despite a mosaic expression of fragment N in the beta cell population of NOD-RIPN mice, islets isolated from these mice were more resistant to apoptosis than control NOD islets. Islet lymphocytic infiltration and occurrence of a mild increase in glycemia developed with the same kinetics in both strains. However, the period of time separating the mild increase in glycemia and overt diabetes was significantly longer in NOD-RIPN mice compared to the control NOD mice. There was also a significant decrease in the number of apoptotic beta cells in situ at 16 weeks of age in the NOD-RIPN mice. Fragment N exerts therefore a protective effect on beta cells within the pro-diabetogenic NOD background and this prevents a fast progression from mild to overt diabetes.