Les 100 médicaments essentiels. Une approche de médecine interne = 100 essential drugs. An internal medicine approach

Déclaration d'intérêts : B. Grosbois : expert pour Actélion, Celgene, Octapharma, Shire. Recherche subventionnée par LFB, Janssen, Genzyme. L. Guillevin : conseiller scientifique Actélion, expert pour (et conférences rémunérées par) GSK, CSL, Roche. L. Guillevin estime cependant n'avoir pas de conflit d'intérêt concernant le présent travail. C. Le Jeunne : expert pour Roche, Sanofi, Novartis, BSM, UCB. Essais thérapeutiques en cours pour Bayer, Pfizer, BMS. P. Morlat : expert pour Gilead, ViiV Health Care, BMS, Abbott, MSD. Ph. Morlat estime cependant n'avoir pas de conflit d'intérêt concernant le présent travail. P. Arlet, O. Aumaitre, J. Cosserat, A. Kettaneh, C. Massot et M. Thomas : aucun conflit d'intérêt.International audiencePURPOSE: Up to 4600 drugs in about 15,000 pharmaceutical forms are available in France which may be a source of misuse with increased occurrence of side effects and costs. While the World Health Organization is encouraging each developed country to work out its own list of essential drugs. The list provided in 2008 by the French Office for the safety of health products has had so far limited impact on practice, so it became obvious to a group of internists to work out a "wise list" of 100 essential medicines covering 95% of the disorders observed in France. METHODS: In June 2011, 10 internists agreed to each provide a list of 100 essential medicines, according to individual experience. In December 2011, a meeting of the participants provided a list as initial consensus and mandated five among them to make proposals for those areas neglected by too many participants or in which needless dispersion of medicines was stated. After internet-facilitated exchanges, an additional list was validated in mild-January 2012. RESULTS: Fifty-four drugs were included in the list of initial consensus (including nine selected by all 10 participants), and 46 in the additional list. So the final "wise list" included 100 drugs. In June 2012, 56 of these drugs were available as generics. This list was compared to those lists set out by five countries in the European Union. CONCLUSION: Generating such a list is feasible. Undoubtedly still non-comprehensive, this list will benefit from the expertise of 14 general practitioners who are currently working out a similar list across France. The final list will be submitted for validation by the French associations of generalist teachers and Internists

Neurotrophins are expressed in giant cell arteritis lesions and may contribute to vascular remodeling

International audienceIntroduction: Giant cell arteritis (GCA) is characterized by intimal hyperplasia leading to ischaemic manifestations that involve large vessels. Neurotrophins (NTs) and their receptors (NTRs) are protein factors for growth, differentiation and survival of neurons. They are also involved in the migration of vascular smooth muscle cells (VSMCs). Our aim was to investigate whether NTs and NTRs are involved in vascular remodelling of GCA.Methods: We included consecutive patients who underwent a temporal artery biopsy for suspected GCA. We developed an enzymatic digestion method to obtain VSMCs from smooth muscle cells in GCA patients and controls. Neurotrophin protein and gene expression and functional assays were studied from these VSMCs. Neurotrophin expression was also analysed by immunohistochemistry in GCA patients and controls.Results: Whereas temporal arteries of both GCA patients (n = 22) and controls (n = 21) expressed nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and sortilin, immunostaining was more intense in GCA patients, especially in the media and intima, while neurotrophin-3 (NT-3) and P75 receptor (P75NTR) were only detected in TA from GCA patients. Expression of TrkB, a BDNF receptor, was higher in GCA patients with ischaemic complications. Serum NGF was significantly higher in GCA patients (n = 28) vs. controls (n = 48), whereas no significant difference was found for BDNF and NT-3. NGF and BDNF enhanced GCA-derived temporal artery VSMC proliferation and BDNF facilitated migration of temporal artery VSMCs in patients with GCA compared to controls.Conclusions: Our results suggest that NTs and NTRs are involved in vascular remodelling of GCA. In GCA-derived temporal artery VSMC, NGF promoted proliferation and BDNF enhanced migration by binding to TrkB and p75NTR receptors. Further experiments are needed on a larger number of VSMC samples to confirm these results

Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in Europe: A Modified Delphi Study.

Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of a uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe. We used a modified Delphi method consisting of three questionnaire rounds and a panel meeting. A total of 129 experts from 27 European countries were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes might be acquired

2015/16 seasonal vaccine effectiveness against hospitalisation with influenza a(H1N1)pdm09 and B among elderly people in Europe: Results from the I-MOVE+ project

We conducted a multicentre test-negative caseâ\u80\u93control study in 27 hospitals of 11 European countries to measure 2015/16 influenza vaccine effectiveness (IVE) against hospitalised influenza A(H1N1)pdm09 and B among people aged â\u89¥ 65 years. Patients swabbed within 7 days after onset of symptoms compatible with severe acute respiratory infection were included. Information on demographics, vaccination and underlying conditions was collected. Using logistic regression, we measured IVE adjusted for potential confounders. We included 355 influenza A(H1N1)pdm09 cases, 110 influenza B cases, and 1,274 controls. Adjusted IVE against influenza A(H1N1)pdm09 was 42% (95% confidence interval (CI): 22 to 57). It was 59% (95% CI: 23 to 78), 48% (95% CI: 5 to 71), 43% (95% CI: 8 to 65) and 39% (95% CI: 7 to 60) in patients with diabetes mellitus, cancer, lung and heart disease, respectively. Adjusted IVE against influenza B was 52% (95% CI: 24 to 70). It was 62% (95% CI: 5 to 85), 60% (95% CI: 18 to 80) and 36% (95% CI: -23 to 67) in patients with diabetes mellitus, lung and heart disease, respectively. 2015/16 IVE estimates against hospitalised influenza in elderly people was moderate against influenza A(H1N1)pdm09 and B, including among those with diabetes mellitus, cancer, lung or heart diseases

PRISE EN CHARGE INITIALE DES HYPERCHOLESTEROLEMIES EN MEDECINE GENERALE (ENQUETE MENEE AUPRES DE 200 MEDECINS GENERALISTES DU SUD SEINE ET MARNE)

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Manifestations cliniques du parvovirus B 19 chez l'adulte immunocompétent (à propos de 2 observations d'hépatites aiguës et revue de la littérature)

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Prescriptions hors-AMM : comment en pratique les identifier, les encadrer, informer et les suivre ?

À la suite de l’affaire Médiator, et de la loi de sécurité sanitaire de décembre 2011, la prescription hors-autorisation de mise sur le marché (AMM) est une réelle préoccupation partagée par tous les acteurs de santé. Le hors-AMM au sens le plus strict est défini par toutes les prescriptions qui ne correspondent pas au résumé des caractéristiques du produit (RCP), en particulier celles qui sont en dehors des indications et des posologies définies par l’AMM, pour des raisons évidentes de sécurité. Les raisons de la prescription hors-AMM sont diverses, conscientes comme inconscientes, elles ont pour objectif de répondre d’une part aux besoins médicaux non couverts, à ceux des populations peu ou pas étudiées dans les essais mais chez lesquelles une extrapolation de l’AMM est raisonnable (prescriptions de bon sens), et d’autre part à des besoins de santé publique urgents (baclofène, femmes enceintes et médicaments du virus de l’immunodéficience humaine…). Toutes ces prescriptions mériteraient d’être étudiées en vue d’une AMM. Par contre, il existe des prescriptions hors-AMM qu’il faut limiter voire sanctionner quand il s’agit de prescriptions compassionnelles, de complaisance et/ou ne reposant sur aucun fondement scientifique. Les prescriptions hors-AMM ne sont pas faciles à dépister car si le prescripteur est tenu d’écrire la mention « hors-AMM » sur son ordonnance lorsqu’il se livre à ce type de prescription, force est de constater qu’en pratique il ne le fait qu’exceptionnellement. Les pharmaciens qui délivrent le médicament tout comme les caisses d’assurance maladie qui le remboursent, n’ont pas accès au diagnostic (ou l’indication visée) ; il faut donc, pour les identifier, avoir recours au croisement des bases de données à notre disposition (pharmacovigilance, programme de médicalisation des systèmes d’information [PMSI], livret thérapeutique hospitalier, échantillon généraliste des bénéficaires de l’Assurance maladie [EGB] ou système national d’information inter régions [SNIIRAM], données de ventes, d’études de marché…). Le dossier patient informatisé partagé par tous résoudra possiblement cette problématique. Le dispositif de recommandation temporaire d’utilisation (RTU) proposé par la loi de sécurité du médicament ne répondra à cette problématique qu’en partie pour les molécules récemment commercialisées (extension d’indication). Ce dispositif dérogatoire et transitoire autorisera une prescription hors-AMM reconnue, possiblement remboursée et surveillée pendant 3 ans. Ces RTU concerneront la faible partie du « hors-AMM » qui dispose de preuves d’une balance bénéfice-risque positive (AMM conditionnelle anciennement protocole thérapeutique temporaire [PTT]) mais ceci est loin de viser la majorité des prescriptions hors-AMM. De ce fait et afin d’améliorer le bon usage des médicaments, il apparait important de proposer un système d’encadrement de tout le « hors-AMM » à l’aide d’une commission dédiée : la commission du « hors-AMM » qui permettra de conduire à des recommandations d’utilisation (RU) ou non

Off-label Prescriptions: how to Identify Them, Frame Them, Announce Them and Monitor Them in Practice?

Following the Mediator crisis and the passage of the Health and Safety Law of December 2011, off-label prescriptions are a real concern shared by all those involved in healthcare system. Off-label, in the strictest sense of the term, is defined as all prescriptions that do not correspond to the summary of product characteristics (SPC), particularly those that fail to comply with the indications and dosage regimens defined by the marketing authorization (MA) for clear safety reasons. There are various rasons for off-label prescriptions, both conscious and unconscious. They are intended to respond to unmet medical needs, the needs of poorly studied populations or not studied at all in trials, but in relation to whom it is reasonable to extrapolate that MA would be given (common-sense prescriptions) and, additionally, to urgent public health needs (such as baclofen, pregnant women, and HIV drugs). All these prescriptions would deserve to be studied for a potential MA. However, there are off-label prescriptions that need to be restricted or even penalized in the case of compassionate prescriptions or unjustified prescriptions or prescriptions not based on any scientific grounds. Off-label prescriptions are not easy to track down because if the prescriber has to write “off-label” on his prescription, then clearly, in practice, he will only do so in exceptional cases. Neither the pharmacists who dispense the drug nor the Social Security that reimburses it, have access to the diagnosis (or targeted indication). Thus, in order to identify the off-label prescription, we must be able to cross reference the available databases (such as pharmacovigilance database, medicalized information system program [programme de médicalisation des systèmes d'information, PMSI], hospital drug formularies, general sample of beneficiaries [échantillon généraliste de bénéficiaires, EGB] or national inter-regional Health Insurance Information System [système national d'informations inter-régions d'Assurance maladie, SNIIRAM], sales data, and data from market surveys). The shared computerized patient file may resolve this problem. The temporary use recommendation (TUR) proposed by the Drug Safety Law will only partially deal with this problem for recently marketed molecules. This temporary and exceptional mechanism will authorize a recognized off-label prescription, which may be reimbursed and monitored for 3 years. These TURs will only concern a small portion of “off-label” drugs having yet a positive risk/benefit ratio (conditional MA) but this is far from matching with majority of off-label prescriptions. As such, and in order to improve the use of drugs, it is important to propose a control system for all “off-label” prescriptions with a dedicated committee: the “off-label” committee which would determine the frame of the “off-label” prescriptions

Persisting reversed clock syndrome

Abstract. Background: The reversed clock phenomenon results in the transposition of objects from one side to another. Its major manifestation consists in the reversal of clock numbers in clock-drawing test. It could be due to a stroke disrupting attentional cerebral network. This phenomenon usually regresses in a few days. Objective: To report a case of reversed clock phenomenon with disorders of space representation that did not regress spontaneously. Design: Case report. Patient: A 67 year-old woman was referred due to headaches associated with gait disorder, visual field deficit and disturbance of space representation. Results: Magnetic resonance imaging demonstrates two right cerebral infarcts mainly localized in the parieto-occipital region. A week after her stoke, clinical testing confirms a reversed clock phenomenon. The patient placed the hands of a clock in the opposite direction of what was specified. She got lost at home locating rooms in directions opposite to their real ones. Rehabilitation sessions partially improved these manifestations. Conclusion: Although it usually improves in a few days, reversed clock phenomenon can persist longer. Rehabilitation sessions based on localization exercises may be helpful in such situations