PERSONALIZED MEDICINE: ALL BENEFITS FOR THE PATIENT BUT NEW CHALLENGE IN THE PHYSICIAN-PATIENT RELATIONSHIP

peer reviewedPersonalized medicine should lead to major advances for patient care since it contributes to deliver the >. In curative medicine, this approach should improve the efficacy of medications by initial selection of "good responders", and should reduce adverse events due to poor tolerance or toxicity by a better pharmacological choice and a more appropriate individualized dose adjustment. Over recent years, considerable technical advances have increasingly linked personalized medicine with predictive and preventive medicine. This progress raises hopes for major advancements in medicine, but may also cause some concern among the lay public. The patient should actively be involved in the decisions related to his/her health, in a true model of participatory medicine. Finally, personalized medicine should leave its strict technical nature and become more interested in the person as a whole, within a holistic approach also integrating psychosocial aspects that are so important in the physician-patient relationship.La médecine personnalisée devrait constituer un progrès considérable pour les malades puisqu’elle contribue à donner «le bon traitement au bon patient». En médecine curative, cette approche devrait aboutir à améliorer l’efficacité des médicaments en sélectionnant d’emblée les patients «bons répondeurs» et à réduire les problèmes de tolérance et de toxicité grâce à un meilleur choix pharmacologique et à un ajustement posologique mieux individualisé. Par ailleurs, les progrès techniques des dernières années font que la médecine personnalisée est de plus en plus intimement liée à la médecine prédictive et préventive. Ces progrès ouvrent des avancées majeures en médecine, mais peuvent soulever aussi nombre d’inquiétudes légitimes dans le grand public. Le patient se doit de collaborer activement à la démarche et aux choix concernant sa propre santé, dans le cadre d’une véritable médecine participative. Enfin, la médecine personnalisée doit sortir de sa stricte technicité pour s’intéresser à la personne dans sa globalité, dans une approche holistique et humaniste intégrant également les aspects psycho-sociaux tellement importants dans la relation médecin-malade. Mots-clés : Médecine générale - Médecine personnalisée - Médecine prédictive - Médecine préventive - Patien

2015 updated position statement of the management of hyperglycaemia in type 2 diabetes

peer reviewedThe strategy for the management ot type 2 diabetes, summarized by a group of European and American experts, has been updated early 2015. A patient-centered approach is recommended and the first drug choice is metformin combined with lifestyle improvement. After failure of metformin monotherapy, the selection of a second drug should be based on the efficacy, safety and cost of each pharmacological class. When compared to the position statement of 2012, the most important changes are the possible addition of a gliptin to a dual oral therapy or even to insulin, the commercialization of sodium-glucose cotransporters type 2 (SGLT2) inhibitors (gliflozins, to be used in dual or triple therapy, even in combination with insulin) and the possible combination of a glucagon-like peptide-I receptor agonist together with a basal insulin

Insulin Detemir in the Treatment of Type 1 and Type 2 Diabetes

Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action. Following subcutaneous injection, insulin detemir binds to albumin via fatty acid chain, thereby providing slow absorption and a prolonged metabolic effect. Insulin detemir has a less variable pharmacokinetic profile than insulin suspension isophane or insulin ultralente. The use of insulin detemir can reduce the risk of hypoglycemia (especially nocturnal hypoglycemia) in type 1 and type 2 diabetic patients. However, overall glycemic control, as assessed by glycated hemoglobin, is only marginally and not significantly improved compared with usual insulin therapy. The weight gain commonly associated with insulin therapy is rather limited when insulin detemir is used. In our experience, this new insulin analogue is preferably administrated at bedtime but can be proposed twice a day (in the morning and either before the dinner or at bedtime). Detemir is a promising option for basal insulin therapy in type 1 or type 2 diabetic patients

OBEDIS Core Variables Project : European Expert Guidelines on a Minimal Core Set of Variables to Include in Randomized, Controlled Clinical Trials of Obesity Interventions

Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing - focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity - ultimately leading to better patient care and improved obesity outcomes.Peer reviewe

Gliptins, cardiovascular safety and congestive heart failure: state of the art after TECOS

The cardiovascular safety of dipeptidyl peptidase-4 inhibitors (gliptins) has been well studied. Favourable effects of these oral antidiabetic agents have been reported in meta-analyses of phase II-III randomised controlled trials. Three large prospective trials, which were specifically designed to investigate cardiovascular safety, showed non-inferiority of saxagliptin (SAVOR-TIMI 53), alogliptin (EXA-MINE) and sitagliptin (TECOS) versus placebo as far as major cardiovascular events are concerned, including mortality. The suspected increase in the rate of hospitalisation due to congestive heart failure reported in SAVOR-TIMI 53 was neither found in EXAMINE nor recently confirmed in TECOS. Direct comparative trials, evaluating not only safety but also efficacy, with other oral antidiabetic medications would be of major interest

A new summer anthology of clinical cases

peer reviewe

PHARMACEUTICAL INDUSTRY AND PERSONALIZED MEDICINE: A PARADIGM SHIFT IN THE DEVELOPMENT OF NEW DRUGS

peer reviewedThe cost of pharmacotherapy is increasing in the health care budget. The pharmaceutical industry is facing the exhaustion of medications that are largely prescribed and have a high profitability (blockbusters). Because of patient heterogeneity, there is a great interindividual variability of the responses to drug therapy. Thus, it is essential to better detect potential > to avoid waste of resources resulting from the prescription of expensive drugs to poor responders. The development of personalized medicine, or precision medicine, certainly offers opportunities to the pharmaceutical industry, but also exposes it to new big challenges.Le coût de la pharmacothérapie devient de plus en plus important dans le budget des soins de santé. Par ailleurs, l’industrie pharmaceutique est confrontée à l’épuisement de la filière des «médicaments phare», prescrits à large échelle et dotés d’une excellente rentabilité («blockbusters»). En raison de l’hétérogénéité des patients, il existe une grande variabilité interindividuelle des réponses thérapeutiques observées. Il convient donc de mieux détecter les potentiels « bons répondeurs » de façon à ne pas gaspiller les ressources dans la prescription de médicaments coûteux à de mauvais répondeurs. L’essor de la médecine personnalisée ou de la médecine dite de précision offre certainement des opportunités à l’industrie pharmaceutique, mais l’expose aussi à de nouveaux défis importants. Mots-clés : Industrie pharmaceutique - Médicament phare - Médicine personnalisée - Recherche et développement - Thérapie ciblé

DIAGNOSTIC APPROACH OF THE PATHOPHYSIOLOGICAL TRIAD LEADING TO A DIABETIC FOOT

peer reviewedDiabetic foot is a common complication of diabetes mellitus. Its pathophysiology is most often complex with the interconnection of three different components: diabetic neuropathy, arterial disease and infection. The diagnostic approach should specify the respective role of each component, firstly thanks to a thorough medical interview and a careful clinical examination. Afterwards, well selected complementary exams will confirm the hypotheses generated by the initial clinical approach. Consequently, a specific care strategy will be implemented, ideally with the help of a multidisciplinary team. This educational clinical case is devoted to the sequential diagnostic approach of a patient with a foot ulcer in the context of a diabetic foot.Résumé : La problématique dite du «pied diabétique» est devenue une complication fréquente du diabète sucré. Sa physiopathologie est le plus souvent complexe avec une intrication habituelle de trois composantes, neuropathique, artériopathique et infectieuse. L’approche diagnostique doit permettre d’établir le rôle respectif de ces trois composantes, d’abord grâce à une anamnèse minutieuse et un examen clinique rigoureux. Ensuite, des examens complémentaires judicieusement sélectionnés permettront de conforter les hypothèses générées par la clinique et, in fine, d’établir le plan de soins le plus approprié, en favorisant une prise en charge multidisciplinaire. Cette vignette clinique est centrée sur l’approche diagnostique, clinique d’abord, paraclinique ensuite, d’un patient présentant une plaie dans un contexte de «pied diabétique »

Diabetic kidney disease: current management and potential future options

The diabetic kidney disease is the most frequent cause of end stage renal disease in Western countries. Its detection is obtained by simultaneously measuring urinary albumin excretion and estimating glomerular filtration rate through serum creatinine dosage. Many type 1 and type 2 diabetic patients can present decreased glomerular filtration rate before the occurrence of increased urinary albumin. While waiting for promising new pharmacological approaches currently evaluated in clinical trials, the best approach to stop the epidemic of diabetic nephropathy remains an early and individual multifactorial approach controlling the glucose level (without inducing hypoglycaemia), blood pressure (using a renin-angiotensin blocker), dyslipidaemia and over-weight

STRENGTHS AND WEAKNESSES OF RANDOMISED CLINICAL TRIALS: EVOLVING CHANGES ACCORDING TO PERSONALIZED MEDICINE

peer reviewedRandomised Controlled Trials (RCTs) represent the cornerstone of Evidence-Based Medicine (EBM). Based upon the rules of Good Clinical Practice (GCP), they offer many strengths but also present some weaknesses. The rigorous methodology used allows avoid bias related to confounding factors (through a control group), selection bias (through randomisation) and interpretation bias (through double blinding). However, patients recruited in clinical trials and study experimental conditions markedly differ from the situation in real life. Furthermore, clinical trials recruit a mix of good and poor responders, so that the average therapeutic response is most often mitigated. Clinical trials must evolve according to the new concepts of personalized medicine to become even more performing. In a near future, they must progress from a statistical analysis on large cohorts of patients to a more individualized analysis guided by patient phenotype and genotype characteristics.Les essais cliniques contrôlés représentent la pierre angulaire de la médecine factuelle. Construits selon les règles des bonnes pratiques cliniques, ils offrent de nombreuses forces, mais présentent également quelques faiblesses. La méthodologie rigoureuse utilisée permet, notamment, d’éviter les biais liés à des facteurs confondants (via un groupe contrôle), les biais de sélection (via la randomisation) et les biais d’interprétation (via la technique du double aveugle). Cependant, les patients recrutés dans les essais cliniques et les conditions dans lesquelles ceux-ci sont menés diffèrent fondamentalement de la situation en vie réelle. De plus, les essais cliniques recrutent un mélange de patients bons et mauvais répondeurs, ce qui conduit à une réponse thérapeutique moyenne le plus souvent mitigée. Les essais cliniques devront s’adapter au développement de la médecine personnalisée pour devenir encore plus performants. Ils devront, à l’avenir, passer d’une analyse statistique sur de grands groupes à une analyse plus individualisée en fonction des caractéristiques phénotypiques et génotypiques des patient