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A paradigm shift seems to emerge, not only in industrial engineering ("Industry 4.0") but also in medicine: we are on the threshold to "Medicine 4.0". For many years, molecular biology had a leading position in life sciences, but today scientists start realizing that microelectronic systems, due to an increasing miniaturization, are reaching the scale of human cells and consequently can be used for therapeutic approaches. This article shows how microelectronics can play a major role in modern medicine, through the example of customized chemotherapy. This consists in determining, before the beginning of the treatment, what kind of chemotherapy or drug combination will be most effective for a given patient, and at which dose. This of course allows the lessening of a patient burden during treatment, but also to be more efficient and, in the long run, to save money. In order to do this, we have developed the Intelligent Microplate Reader (IMR), which allows us to accurately test different drugs on living cells by mimicking part of their usual environment., (© 2018 médecine/sciences – Inserm.)

The tip of a long term central venous access should be located at the junction of the superior vena cava with the right atrium in order to reduce the incidence of dysfunction and venous thromboses. Picc-lines have their place for treatments of less than 6 months with obvious advantages in terms of discretion and comfort. Long-term sequential chemotherapy is an indisputable indication of an implantable port, while long-term parenteral nutrition is an indication of a tunneled cuffed catheter. In case of mediastinal compression, the risk-benefit ratio favors femoral access. Catheter related venous thrombosis or infection do not necessarily require the withdrawal of the device. A device that is no longer used should be removed when the likelihood of recurrence of the disease is low or too far., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objectives: To assess the outpatient medication management in care units two years after the release of an institutional procedure. To assess the patients' satisfaction with their treatment and with the information transmitted by healthcare professionals., Methods: An audit of clinical practices was conducted in 23 units of our universitary hospital - general, surgery, emergency departments. Questionnaires were developed and validated by an institutional working group and were composed of three themes: management of the outpatient medication at the admission, awareness of tools and information transmission. Two physicians (a senior and a resident), a registered nurse, a head nurse and a patient were interviewed., Results: Eighty-one medical and paramedical team members and 21 patients were interviewed for the study. According to statements collected, the procedure was unknown by 100% of the interviewed surgeons and 69% of the interviewed physicians. The practices being used by the medical units were more in line with recommendations than the surgery units. Among the patients interviewed, 19 (86%) were satisfied with the information they received during their hospitalization and 4 (19%) managed their own medication treatment with the help of a nurse in only 36% of the cases according to their statements., Conclusions: The management of outpatient medications during hospitalization is representative of the difficulties to master the continuity of pharmaceutical care at the various transition points. Coordination and cooperation between the different healthcare professionals and patients are the major key success to ensure an optimized healthcare procedure., (Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Some patients are exposed to complex clinical situations, which impose a careful analysis of both the indications and contraindications of ongoing pharmacological treatments as well as of the dosing or drug adjustments to be proposed. This article illustrates some problems encountered when a new drug therapy is initiated, when medications with narrow therapeutic window should be supervised and when some drugs should be stopped mainly for safety reasons. The clinical case relates the story of a patient with type 2 diabetes, arterial hypertension and coronary heart disease, who presents a congestive heart failure associated with an episode of atrial fibrillation and a severe renal insufficiency.

Any pharmacological treatment should ideally be effective and safe. The supervision of an ongoing therapy should control that individualized goals are reached while tolerance and safety are present. In case of not reaching the predefined objectives, the causes of failure should first be screened (for instance, exclusion of poor patient compliance), and the treatment should be then optimized: dose adjustment, add-on of another drug (if possible synergistic combination) and/or shift to a more effective pharmacological therapy. In some cases, therapeutic monitoring may be useful or even mandatory in order to better adjust drug dosing and thus guarantee both efficacy and safety.

Initiating a new pharmacological therapy is an important step in the global medical approach. Such a decision is the final step of a careful reasoning and should respect some rules in order to guarantee the best efficacy, but also safety for the patient. Clinical inertia should be avoided, but the essential principles of the evidence based medicine should also be taken into account. This concise article summarizes the main fundamental rules and cautions that should be respected by any clinician when initiating a new pharmacological therapy.

Purpose: The objective of this study was to reduce the risk of errors when administering oral medications to infants aged 28 days to 2 years., Material and Methods: The method of the preliminary risk analysis (PRA) was implemented by a multidisciplinary group in a hospital service of pediatrics. The study focused on the phase of preparation of drugs by nurses before administration., Results: This analysis revealed 41 scenari, 16 were criticality unacceptable. In particular, their analysis highlighted the impact of the drug dosage form, the lack of scientific information and the human factor on this preparation. Eleven action sheets have been written., Discussion: The risk management requires significant human investment, material resources and organizational solutions: formations, information, i.e. computerized prescribing, dispensing and administering system, centralized drug preparations, automated drugs cabinets or unit drug daily dispensing system., Conclusion: Control these risks means to get specific actions at pediatric wards, enhance dispensing system by the hospital pharmacist and the support of the pharmaceutical industry to get commercially available pediatric drugs., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Market Access Agreements (MAA) for drugs have emerged in response to the need to control health expenditures, as well as to the uncertainty about the true benefit of a drug. It is possible to group MAA in two types of agreements: financial agreements and outcome-based agreements. MAA is a growing trend and is shifting towards conditional access. However, the willingness to use these contracts and their implementation differ across countries, and some are still resistant to put them in place. The MAA challenges to overcome encompass the complexity of the schemes, the administrative burden and the difficulty of evaluating MAA. It is likely that these agreements might experience further evolution in the future to become a faster pathway for therapeutic innovations, at a fair price., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Introduction: Perspectives for innovative pharmaceutical molecules and intravesical administration of pharmacological agents are presented in the present review carried out from a recent literature., Materials and Methods: This review of the literature was built by using the PubMed and ScienceDirect databases running 20keywords revealing 34publications between 1983 and 2012. The number of referenced articles on ScienceDirect has increased in recent years, highlighting the interest of scientists for intravesical drug administration and the relevance of innovating drug delivery systems., Results: Different modalities of intravesical administration using physical (e.g., iontophoresis, electroporation) or chemical techniques (e.g., enzyme, solvent, nanoparticles, liposomes, hydrogels) based on novel formulation methods are reported. Finally, the development of biopharmaceuticals (e.g., bacillus Calmette-Guérin, interferon α) and gene therapies is also presented and analyzed in this review., Conclusion: The present review exhibits new development in the pipeline for emerging intravesical drug administration strategies. Knowledge of all these therapies allows practitioners to propose a specific and tailored treatment to each patient with limiting systemic side effects., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

The global treatment of cancer patients has become a public health issue. To meet growing nursing needs, home hospitalisation teams provide an important contribution. Experts in administering chemotherapy at home, the nurses of the Santé Service association support patients in their wish to remain at home.

Medication management in home care is an error prone process. In a small pilot project in Flanders, community pharmacists collaborated with physicians and home care nurses through a shared electronic care plan, to optimize the medication management of their home care patients. The pilot project shows that GPs and nurses are positive about the possible contribution of the pharmacist in medication management of home care patients. A larger follow up study is necessary to further identify possible roles of pharmacists in home care and to show related health benefits.

Patient compliance is a dynamic behaviour, which varies in time and in shape. The impact of poor adherence is medical (loss of immediate benefits and/or long-term) and economic (direct and indirect costs). Adhering and remaining engaged in the daily drug treatment appear to be a challenge for the chronic patient. In this context, we propose as a first step, to describe the evolution of the wording around adherence. This evolution is underlying the paradigm shifts behind this concept and opens new areas for action. Based on this new angle of view that represents the patient's adherence with its drug therapy, we detail the various factors influencing medication adherence categorized into five dimensions: illness, medication, demographic and socio-economic, patient and/or patient support and care system. The impact of these factors is described and explanatory models underlying explicited. Understanding of the issues underlying adherence to drug treatment will help consider further personalized interventions, multi-faceted response to the multiplicity of influencing factors., (Copyright © 2011. Published by Elsevier Masson SAS.)

The MDRD (Modification of diet in renal disease) equation enables glomerular filtration rate (GFR) estimation from serum creatinine only. Thus, the laboratory can report an estimated GFR (eGFR) with each serum creatinine assessment, increasing therefore the recognition of renal failure. Predictive performance of MDRD equation is better for GFR < 60 ml/min/1,73 m2. A normal or near-normal renal function is often underestimated by this equation. Overall, MDRD provides more reliable estimations of renal function than the Cockcroft-Gault (C-G) formula, but both lack precision. MDRD is not superior to C-G for drug dosing. Being adjusted to 1,73 m2, MDRD eGFR has to be back adjusted to the patient's body surface area for drug dosing. Besides, C-G has the advantage of a greater simplicity and a longer use.

Objective: Available commercial drugs in France are often unsuitable for children. The aim of this study was, for every medicinal form orally or parenterally administered, to identify and to quantify difficulties met by the nurses administering drugs to paediatric inpatients and to propose solutions to main identified problems., Material and Method: The study was realized in 14 hospitals by direct observation. The observer, provided with a questionnaire, followed during a time slot of at least 2 h for one or several nurses and raised all the oral or injectable administrations., Results: One thousand and nine hundred forty-six observations were performed. The children were 12.6 +/- 17 months old, and weighed 8.5 +/- 9.4 kg. Injectable drugs: half of the observations showed a posology and a mode of dilution not corresponding to the summary of product characteristics. Eight percent of orally administered drugs were injectable drugs. In 35.5% of cases, administered amount was lower than the quarter of the present quantity in the therapeutic unity. The rest of the therapeutic unity was thrown (77.2% of cases). Liquid oral forms: liquid oral forms were ready for use regarding 83.8% of cases. The medicine was readministered to the same patient (23.5%), and/or administered to other patients (80.0%). Capsules: 66.9% of the administered capsules were prepared by the hospital pharmacies. The pharmacies organized with an unit dose drug dispensing system produced significantly more preparations than those working by global distribution (P < 0.0001). In 58.4% of cases, the administered capsule was an off-label drug. Tablets: 46% of drug administration concerned a tablet without pediatric indication. 46.7% of tablets were cut, 74% were crushed. Bags: in 35.2% of observations, the bag was not administered in its entirety., Conclusion: Our study confirms the unsuitability of drugs to paediatric inpatients, the necessity of recommendations of good practices in the administration of drugs to paediatric inpatients, and proposes corrective actions.

The simulation of therapeutic models and clinical trial simulation have recently attracted attention as emerging techniques for developing new active molecules and the exploration of possible clinical trial results. Such approaches have benefited from fundamental progress in the development of 'in silico' models, as well as progress in nonlinear mixed-effect pharmacokinetic-pharmacodynamic models. Mixing the two approaches allows simulation of 'virtual' patients, who receive virtual treatments or placebo. These have various uses, such as proof of concept, decision analysis or experimental design optimisation. Also, the effect of departures from protocol on clinical trial results can easily be evaluated by the use of simulation. This technique is now implemented by the pharmaceutical industry for optimising phase II and III experimental designs when a good biomarker or a clinical outcome model is available, but the use of an in silico therapeutic model as a proof of concept is only just beginning. In order to see such methodologies used more widely in drug development, multidisciplinary efforts need to be initiated, new modelling and simulation tools developed, and sound modelling and simulation practice documents need to be adopted. A reduction in the number of failed clinical development projects, the number of negative phase II and III clinical trials, or in just their cost and duration, are among the expected benefits of modelling and simulation in clinical drug development.

Introduction: This retrospective study analyses causes as well as clinical, immunological and virological consequences of antiretroviral treatment interruptions (Ti) of more than 30 days in HIV-1 infected adults., Methods: This causes were classified as related to drug toxicity, therapeutic or adherence failure. We studied therapeutic regimens before Ti and after treatment reinitiation (TR), clinical events related to Ti, CD4 cells and viral loads before Ti and at months 3, 6, 9, and 12 after TR., Results: Out of 188 Ti analysed, 42.6% were related to therapeutic failure, 33.5% to drug toxicity, and 23.9% to adherence failure. Eight Aids defining clinical events were reported during Ti, in patients with low CD4 cells and high viral load (P < 0.05). Viral loads evolution after TR was better if Ti was related to treatment failure (P < 0.05), was prolonged (P < 0.05), and if CD4 cells were high before Ti and at TR (P < 0.05). Median CD4 cells was of 296/mm(3) at month 12 after TR vs 382 before Ti., Conclusions: Ti consequences are strongly related to CD4 cells, which decrease sharply during Ti, increasing Aids defining events probability. Prospective randomised clinical studies are needed to define usefulness of Ti.

Recent therapeutic strategies are presenting concerning the use of morphine, benzodiazepines, hypoglycemic agents, glucocorticoids and several specific treatments are indicated. Three new molecules deserve special attention: tiotropium, fondaparinux and omalizumab.

A reassessment of the interest of therapeutic drug monitoring (TDM) is needed for a better definition of its applications. It rests on the hypothesis of the existence of an interindividual variability of the dose-effect relationship, this variability being influenced by pharmacokinetic variability. Different types of endpoints were used in validation studies (pharmacokinetic, indirect, economic) and few studies have used clinical endpoints. The question should be: does TDM allow for a better dose adjustment than one based only on criteria other than drug concentration? Retrospective studies have a 'diagnostic test' approach and only prospective clinical trials will provide a real validation. Factors which limit the setting up of such studies are: the number of subjects to include, the often imprecise measurement of drug exposure and poor knowledge of the pharmacokinetic-pharmacodynamic relationship and its variability.

Two independent expert groups assess new medicines in France: that of the journal Prescrire (P), and the official Transparency Commission (CT). Each uses its own 5-level scale to assess its contribution to therapeutics (P: (1) bravoi, (2) interesting, (3) adds something, (4) possibly useful, (5) nothing new; CT: (1) major, (2) important, (3) moderate, (4) modest, (5) none). We have compared the gradings for new drugs in P from 1993 to 1998 (except vaccines, generics and items for exclusive hospital use) to those of CT. Of 414 P gradings, 14 were without opinion, 54 were not found in CT (old or unexamined products), and 82 had been examined but not graded. The 264 graded pairs were 99 new substances (NS), 17 new combinations (NA), 50 new indications (NI), 56 new formulations (NF), 27 new dosages (ND), 10 new forms of packaging (NC), and 5 late gradings or reregardings (CR). For NS and NA, there were 21 discordances (2 degrees difference or more) between P and CT. When P is shifted one point to the left (better gradings), the number of discordances decreases to 2. NI, NF, ND, NC were less often graded by CT (respectively 63 per cent, 67 per cent, 54 per cent, 31 per cent of gradings). For NI, high CT grading results in 15 discordances (30 per cent). For NF, ND, NC the concordance is good (respectively 3, 1, 0 discordances). For CR, 13 of 18 products (72 per cent) are downgraded for P, and are discordant with the 5 initial CT grades. In 3 per cent of cases, P emits no opinion, CT gives a high grading in 2/3, never null (these are for severe diseases). In conclusion, the two groups of experts come to similar conclusions considering different objectives (use or not a new drug vs. give indications for reimbursement) and the time distortion. Discrepancies can also be explained thus, but some can result from differences in appreciation of the data.

A therapeutic strategy is a hierarchical set of appropriate measures to provide an answer to a pathological state. A drug is a part of this set (together with the diagnosis, the environment and the other medicinal interventions or not). A new drug's place in a therapeutic strategy can be evaluated according to one or several referential(s) when it (or they) exist, referentials which express the state of knowledge before launch of the new drug. The drug's profile (indication or contraindication, etc.), at the point when the marketing authorization is given, is purely theoretical. One must evaluate the real place of the drug under its real conditions of use (pragmatic trials, observable surveys). A new drugs' place in a therapeutic strategy can only be evaluated in the course of time unless a therapeutic revolution occurs.