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Background We investigated the association between socioclinical, inflammatory, and metabolic markers and weight gain in people with human immunodeficiency virus (HIV) on combination antiretroviral therapy (cART). Methods Individuals from the COPANA cohort of normal weight (body mass index [BMI], 18.5–24.9 [ calculated as weight in kilograms divided by height in meters squared) at cART initiation who achieved virological suppression (viral load, Results After 36 months of cART, 32 of 158 people with HIV (20%) became overweight or obese (21% female; 65% born in France and 23% born in sub-Saharan Africa; median BMI at cART initiation, 22 [interquartile range, 21–23]). After adjustment, higher BMI, originating from sub-Saharan Africa, living in a couple, and higher soluble tumor necrosis factor receptor 2 and lower adiponectin concentrations at cART initiation were associated with becoming overweight or obese. Conclusion Weight gain on cART is multifactorial. Special attention should be given to migrants from sub-Saharan Africa. Monocyte activation and adipocyte dysfunction at cART initiation affect weight regulation.

BackgroundCurrently, real-world data on rheumatoid arthritis (RA) treatment patterns in France are limited.ObjectivesThe aim of this study was therefore to describe, between 2013 and 2017, the sequence of therapies used in the treatment of patients with RA and to characterize RA treatment patterns using real-world data.MethodsA non-interventional, longitudinal study was conducted using the Echantillon Généraliste des Bénéficiaires (EGB) between 1 January 2013 and 31 December 2017. EGB is a 1/97th representative random sample from the French National Healthcare Database (SNDS) which includes claims data covering 99% of the total French population.Treatment patterns, adherence and persistence of RA treatments were described in a cohort of patients with RA, identified between 2013 and 2017.ResultsBetween 2013 and 2017, 2,553 patients with RA were identified, including 2,314 in 2017. Of the 2,314 RA patients identified in 2017 (mean age 66.2 ± 15.4 years; 73.7% female; mean Charlson comorbidity score 4.2), 1,102 (47.6%) did not receive any disease-modifying anti-rheumatic drug (DMARD). Of these, 944 (85.7%) had received at least one symptomatic treatment, including 862 (91.3%) an analgesic, 509 (53.9%) an oral corticosteroid and 384 (40.7%) non-steroidal anti-inflammatory drugs.Of the 2,553 RA patients monitored between 2013 and 2017, 1,512 (59.2%) patients received a DMARD, of which 721 (47.7%) patients received only one treatment sequence, mainly methotrexate (n=529, 35.0%), and did not discontinue or switch treatment. Switching treatment to a targeted DMARD was reported for 144 (9.5%) patients. During follow-up, 377 (25%) patients discontinued treatment. In total, 1,142 RA treatment initiations were recorded, 62.4% of which were conventional synthetic DMARDs (csDMARDs). Persistence rates (95% confidence interval) for csDMARDs, TNF inhibitors (TNFi) and other targeted DMARDs (tDMARDs) were 63.4% (59.6–67.0), 55.9% (49.2–62.0) and 59.4% (51.2–66.6) at 12 months, respectively; Medication Possession Ratio (MPR), an adherence indicator, was 80.5%, 90.8% and 71.9%, respectively.Long-term oral corticosteroids (≥6 months) were also associated with csDMARD for 42.6% of cases (n=304/713), TNFi for 39.7% (n=100/252) and another tDMARD for 53.1% (n=94/177). The average doses of long-term oral corticosteroids were 7.5 mg, 6.5 mg and 7.8 mg of prednisone equivalent per day, respectively.ConclusionUsing data obtained from the EGB, this study estimated the number of patients with RA in France to be 307,612 in 2017. Approximately half of the patients identified in the EGB cohort were not treated with a DMARD. For a substantial proportion of patients receiving DMARDs, therapeutic escalation, a switch in treatment, or long-term corticosteroid co-therapy with an average daily dose greater than 5 mg were needed. Furthermore, median persistence for most targeted DMARDs was less than 2 years, and the early discontinuation rates of up to 46.6% suggest poor DMARD tolerance in many patients.This study highlights that the medical need for RA treatment is not covered by current therapeutic strategies.Table 1.Characteristics of DMARD treatments initiated between 2013–2017 in the EGB database (N=1,142)csDMARDTNFiOther targeted DMARDTreatments initiated, n (%)713 (62.4)252 (22.1)177 (15.5)Median duration of treatment, months26.718.514.6Rate of early treatment discontinuation (≤2 dispensations within 2 months of initiation), %15.510.711.9Mean treatment adherence (MPR), %80.590.871.9AcknowledgementsThis study was funded by Galapagos NV (Mechelen, Belgium). Publications management support was provided by Aspire Scientific Ltd (Bollington, UK) and funded by Galapagos NV (Mechelen, Belgium).Disclosure of InterestsCécile Gaujoux-Viala Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Inc., Janssen, Medac, Merck-Serono, Mylan, Nordic Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Inc., Janssen, Medac, Merck-Serono, Mylan, Nordic Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB, Jean-François Bergmann Consultant of: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Galapagos, Gilead, GSK, Lilly, Novartis, Roche, Sanofi, and Takeda, Mélanie Goguillot Employee of: Stève Consultants, who carried out the study on behalf of Galapagos, Asma Melaine Employee of: Stève Consultants, who carried out the study on behalf of Galapagos, Marie Guérin Employee of: Galapagos, Alban Edouard Employee of: Galapagos, Stève Benard Employee of: Stève Consultants, who carried out the study on behalf of Galapagos, Bruno Fautrel Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celltrion, Fresenius Kabi, Galapagos, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, and UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celltrion, Fresenius Kabi, Galapagos, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, and UCB, Grant/research support from: AbbVie, Lilly, MSD, and Pfizer

Patients admitted from emergency units represent a large portion of the population in internal medicine departments. The aim of this study is to identify characteristics of patients and organization of these departments.Between June 29th and July 26th 2015, voluntary internal medicine departments from the SiFMI group prospectively filled anonymized internet forms to collect data of each patients admitted in their ward from emergency units, during seven consecutive days.Three hundred and sixty-five patients from emergency departments were admitted in 18 internal medicine inpatients departments, totalling 1100 beds and 33,530 annual stays, 56% of them for emergency units inpatients. Mean age was 68 years, 54% were women, mean Charlson score was 2.6 and 44% of the patients took at least three drugs. Main causes of hospitalization were infectious (29%) and neurological (17%) diseases. Mean length of stay was 9.2 days. The medical team was composed by a median value of 4,5 [2,75-6,25] senior full-time equivalents, 86% were internists. Each department except one received residents, two third of them were from general medicine.This study highlights a high organizational variability among internal medicine departments and patients, and sets internal medicine as a specialty with a great capacity to achieve an integrative/comprehensive management of patients and to offer a comprehensive basis for physicians in training.

Objectives HIV-infected individuals are at increased risk of incident fractures. Evaluation of trabecular bone micro-architecture is an important tool to assess bone strength, but its use has not yet been reported in middle-aged HIV-infected male individuals. The aim of the study was to compare bone micro-architecture between HIV-infected and HIV-uninfected men. Methods In this cross-sectional study, 53 HIV-infected male individuals with a mean (± standard deviation) age of 49 ± 9 years who had been receiving antiretroviral therapy including tenofovir disoproxil fumarate (DF) for at least 60 months were compared with 50 HIV-uninfected male controls, matched for age and ethnic origin. We studied the volumetric bone density and micro-architecture of the radius and tibia using high-resolution peripheral quantitative computed tomography (HR-p QCT). Results Volumetric trabecular bone density was 17% lower in the tibia (P < 10−4) and 16% lower in the radius (P < 10−3) in HIV-infected patients compared with controls. By contrast, the cortical bone density was normal at both sites. The tibial trabecular micro-architecture differed markedly between patients and controls: bone volume/total volume (BV/TV) and trabecular number were each 13% lower (P < 10−4 for both). Trabecular separation and inhomogeneity of the network were 18% and 24% higher in HIV-infected patients than in controls, respectively. The radial BV/TV and trabecular thickness were each 13% lower (P < 10−3 and 10−2, respectively). Cortical thickness was not different between the two groups. Conclusions The findings of lower volumetric trabecular bone density and disrupted trabecular micro-architectural parameters in middle-aged male HIV-infected treated patients help to explain bone frailty in these patients.

Resume Propos Le diagnostic differentiel entre la maladie tuberculose (granulomatose la plus frequente a l’echelle mondiale) et la sarcoidose (granulomatose rare) est important, car les traitements different completement. Methodes Nous avons evalue prospectivement la presence de granulomes epithelioides a la biopsie de glandes salivaires accessoires (BGSA), critere d’orientation habituel pour le diagnostic de sarcoidose, chez des patients atteints de tuberculose prouvee et vus consecutivement. Resultats Sur notre echantillon de 65 patients, 10,8 % des patients tuberculeux avaient des granulomes epithelioides sans necrose caseeuse sur leur BGSA, independamment de la localisation de la tuberculose, du statut VIH du patient ou du caractere bacillifere de l’infection. Conclusion La presence de granulomes epithelioides a la BGSA ne permet donc pas d’eliminer une maladie tuberculose lorsque le clinicien hesite entre cette affection et une sarcoidose.

Essentials In venous thromboembolism (VTE), it is uncertain if enoxaparin should be given twice or once daily. We compared the 15- and 30-day outcomes in VTE patients on enoxaparin twice vs. once daily. Patients on enoxaparin once daily had fewer major bleeds and deaths than those on twice daily. The rate of VTE recurrences was similar in both subgroups. SummaryBackground In patients with acute venous thromboembolism (VTE), it is uncertain whether enoxaparin should be administered twice or once daily. Methods We used the RIETE Registry data to compare the 15- and 30-day rates of VTE recurrence, major bleeding and death between patients receiving enoxaparin twice daily and those receiving it once daily. We used propensity score matching to adjust for confounding variables. Results The study included 4730 patients: 3786 (80%) received enoxaparin twice daily and 944 once daily. During the first 15 days, patients on enoxaparin once daily had a trend towards more VTE recurrences (odds ratio [OR], 1.79; 95% confidence interval [CI], 0.55–5.88), fewer major bleeds (OR, 0.42; 95% CI, 0.17–1.08) and fewer deaths (OR, 0.32; 95% CI, 0.13–0.78) than those on enoxaparin twice daily. At day 30, patients on enoxaparin once daily had more VTE recurrences (OR, 2.5; 95% CI, 1.03–5.88), fewer major bleeds (OR, 0.40; 95% CI, 0.17–0.94) and fewer deaths (OR, 0.58; 95% CI, 0.33–1.00). On propensity analysis, patients on enoxaparin once daily had fewer major bleeds at 15 (hazard ratio [HR], 0.30; 95% CI, 0.10–0.88) and at 30 days (HR, 0.16; 95% CI, 0.04–0.68) and also fewer deaths at 15 (HR, 0.37; 95% CI, 0.14–0.99) and at 30 days (HR, 0.19; 95% CI, 0.07–0.54) than those on enoxaparin twice daily. Conclusions Our findings confirm that enoxaparin prescribed once daily results in fewer major bleeds than enoxaparin twice daily, as suggested in a meta-analysis of controlled clinical trials.

Resume Propos Au cours d’une hospitalisation en medecine interne, les prescriptions therapeutiques des patients sont souvent modifiees. Nous avons etudie le devenir de ces modifications therapeutiques au decours de l’hospitalisation. Methodes Quatre-vingt-quatre patients ayant une prescription au long cours et un medecin traitant ont ete inclus le jour de leur sortie d’hospitalisation d’un service de medecine interne parisien. Leurs traitements d’entree et de sortie ont ete determines d’apres les comptes-rendus d’hospitalisation, et les patients ont ete contactes deux mois apres leur sortie afin d’analyser les eventuelles differences de prescriptions observees depuis la sortie de l’hopital. Resultats Les traitements a l’entree ont ete le plus souvent conserves, avec 17,7 % de traitements retires et 7 % de changement de traitement. Deux mois apres la sortie, les modifications etaient maintenues dans 85 % des cas, l’ordonnance de sortie etait renouvelee sans changement pour 77 % des patients. Les antihypertenseurs etaient la classe la plus souvent modifiee durant l’hospitalisation, avec des modifications maintenues a 65 %. Les antalgiques etaient l’autre classe la plus souvent modifiee, avec un taux de maintien global de 75 %. Les modifications therapeutiques expliquees dans les comptes-rendus d’hospitalisation avaient un taux de maintien significativement plus eleve que celles non expliquees (100 % versus 79 %, IC95 % de la difference [0,09–0,27] ; p Conclusion Les modifications de traitements decidees au cours d’une hospitalisation en medecine interne et prescrites a la sortie sont tres frequemment poursuivies en ambulatoire deux mois apres la sortie, en particulier lorsqu’elles ont ete expliquees dans le compte-rendu d’hospitalisation.

Resume Introduction L’hemorragie massive reste une cause importante de mortalite dans les pays developpes, particulierement en obstetrique, chez le polytraumatise et dans les chirurgies majeures. Le facteur VII active recombinant (rFVIIa) (Novoseven®) a ete developpe pour le traitement substitutif des hemophiles, mais etait actuellement utilise dans d’autres indications de saignement aigu. L’objectif de cette etude etait d’evaluer le respect des criteres d’utilisation hors AMM du rFVIIa selon les groupes definis par l’Afssaps, dans les hopitaux de l’assistance publique a Paris (AP–HP) en 2010. Patients et methodes Nous avons retrospectivement contacte les services d’anesthesie-reanimation des centres ayant une activite en obstetrique, d’accueil de polytraumatises, de chirurgie cardiaque, hepatique et pediatrique pour recuperer tous les dossiers d’utilisation hors AMM du rFVIIa en 2010. La qualite de l’indication et de son utilisation a ete analysee sur la base des recommandations francaises ou europeennes ou selon la litterature existante dans les domaines consideres. Trois categories de prescriptions ont ete etablies : conforme, acceptable et non conforme. Resultats Sur les 59 patients ayant recu du rFVIIa hors AMM en 2010, 49 prescriptions ont pu etre analysees. L’indication et le moment d’administration etaient conformes dans 100 % des prescriptions pour le polytraumatisme et 83 % des prescriptions pour les hemorragies du postpartum. Les criteres biologiques etaient remplis dans deux tiers des prescriptions. La prescription a ete jugee conforme ou acceptable dans 82 % des cas, toutes indications confondues. Conclusion Dans la grande majorite des cas, les prescriptions de rFVIIa, utilise hors AMM a l’AP–HP en 2010, respectaient les recommandations en vigueur.

Resume Introduction La lymphadenite histiocytaire necrosante (maladie de Kikuchi-Fujimoto) est une entite clinico-pathologique rare caracterisee par l’association d’une lymphadenopathie cervicale posterieure bien limitee et d’une fievre, touchant principalement les femmes jeunes. Observation Nous rapportons le cas d’un patient africain de 41 ans presentant une maladie de Kikuchi-Fujimoto atypique car compliquee d’un lupus cutane, d’un syndrome d’activation macrophagique et d’une meningite lymphocytaire. Une meningite tuberculeuse, initialement evoquee en raison de l’origine ethnique et de la presentation clinique, etait eliminee par l’histologie ganglionnaire caracteristique de maladie de Kikuchi-Fujimoto, la negativite des prelevements microbiologiques, l’evolution clinique et la decouverte d’une integration virale genomique d’ADN d’HHV6. Conclusion L’association d’adenopathies cervicales, d’un syndrome d’hemophagocytose, d’une meningite lymphocytaire et d’une integration genomique d’HHV-6 doit faire evoquer une maladie de Kikuchi.

We report an unusual observation of central nervous system (CNS) lymphoma in a 60-year-old woman with systemic lupus erythematosus and fatal outcome.The patient had systemic erythematosus lupus for 7 years, treated with mycophenolate mofetil and developed lymphocytic meningitis in 2015 associated to the presence of EBV in the cerebrospinal fluid and a necrotic vermis' lesion. Diagnosis of large B-cell lymphoma was histologically confirmed from stereotaxic biopsy, shortly before she died from neurological complications.Even though the current association is unusual, lymphocytic meningitis with hypoglycorrachia in patients with systemic lupus erythematosus may reveal CNS lymphoma and diagnosis confirmation requires stereotaxic biopsy in order not to delay specific therapeutic management.

To evaluate the ability of two graphologists and two practising internists not trained in graphology to differentiate letters written by subjects who have attempted to commit suicide by self-poisoning and healthy volunteers, we performed a maximal blind controlled study vs. healthy volunteers. Forty fully recovered patients who had attempted to commit suicide and 40 healthy volunteers wrote and signed a short letter or story not related to the parasuicide or their mental health status. The evaluators classified the 80 letters as 'suicide' or 'no suicide' in an intention-to-treat analysis. Letters expressing sadness were subsequently excluded for a per-protocol analysis. Correct diagnosis of suicide and of healthy controls was made in, respectively, 32 of 40 and 33 of 40 letters by the graphologists and in 27 of 40 and 34 of 40 letters by the internists. After the exclusion of 12 letters expressing sadness, the sensitivity, specificity, positive predictive value and negative predictive value were, respectively, 73, 88, 81 and 82% for the graphologists and 53, 89, 80 and 71% for the internists. Both classified the letters with significantly more effectiveness than chance (p < 0.001) with no statistically significant difference between the two groups of evaluators. We concluded that graphological analysis is able to differentiate letters written by patients who attempt suicide from those written by healthy controls. This technique shows an acceptable degree of accuracy and could therefore become an additional discharge or decision-making tool in Psychiatry or Internal Medicine.

The risk of venous thromboembolism (VTE) in medical patients is generally underestimated. However, recent studies including two large double-blind placebo-controlled trials, the Prospective Evaluation of Dalteparin Efficacy for Prevention of VTE in Immobilised Patients trial (PREVENT) and prophylaxis in MEDical patients with ENOXaparin, study show that low-molecular-weight heparins (LMWHs) provide effective thromboprophylaxis for medical patients at risk from VTE without increasing the risk of bleeding. In PREVENT the significant 45%, reduction in VTE among patients receiving dalteparin 5000 IU once daily for 14 days was attributed entirely to a reduction in clinically relevant VTE. The recently published guidelines for the prevention and treatment of VTE, issued by the American College of Chest Physicians, recommend prophylaxis with LMWHs (or low-dose unfractionated heparin) in acutely ill medical patients with risk factors for VTE (grade 1A). Current evidence should encourage the more widespread adoption of thromboprophylaxis in at-risk medical patients, and thus reduce the number of preventable deaths and complications due to VTE.

The round table elected to focus its discussion on trials that, in terms of their importance, are likely to modify medical practices and behaviour. Such trials may be pre- or postmarketing studies. For the findings of a trial to result in a change in practice, they must be credible and fulfil the basic methodological criteria. It is nonetheless appropriate to complete that binary assessment by the use of an assessment checklist appropriate to each category of users, i.e. the Regulatory Agency, prescribing physicians and patients, who are sometimes informed directly by the media. The members of the round table proposed the ‘Giens 2003 checklist’. It consists of an interpretative semi-quantitative assessment checklist based on simple messages relevant to practice. Critical assessment is a necessary prelude to the circulation of the results to the various parties involved (healthcare professionals, patients, patient associations, the media and the general public) and the process of informing those parties in readily understandable but accurate terms. The practical implementation of the results, with a change in behaviour and/or the issuing of guidelines, are subsequent stages for which a certain lag time is inevitable. The assessment of implementation programmes, together with an accurate analysis of the obstacles to changing medical practice, should, in the future, improve and accelerate the implementation of important results in order to optimise patient management.

Resume La table ronde a choisi d’orienter sa discussion sur les essais qui, par leur importance, sont susceptibles de modifier les pratiques medicales et les comportements. Ces essais peuvent etre pre- ou post-AMM (autorisation de mise sur le marche). Pour que les resultats d’un essai aboutissent a un changement de pratique, ils doivent etre credibles et repondre aux criteres fondamentaux de la methodologie. Il convient neanmoins de completer cette evaluation binaire par l’utilisation d’une grille d’evaluation adaptee a chaque categorie d’utilisateurs, qu’il s’agisse de l’Agence, des prescripteurs ou des patients parfois informes directement par la presse. Les membres de la table ronde proposent la grille de Giens 2003. Il s’agit d’une grille d’evaluation semi-quantitative interpretative faite de messages simples lies a la pratique. Ces etapes d’evaluation sont le prelude necessaire a la diffusion des resultats aux differentes personnes concernees (personnel de sante, patients, associations de patients, medias et grand public), a leur information en termes comprehensibles mais exacts. La mise en pratique des resultats avec changement de comportement et/ou l’emission de recommandations sont les etapes ulterieures, pour lesquelles un certain delai est inevitable. L’elaboration de programmes de mise en pratique, facilites par une analyse precise des freins au changement, devrait dans l’avenir ameliorer et accelerer l’application de resultats importants pour l’optimisation de la prise en charge des patients.

Orally administered medications may interact with various fruits, vegetables, herbal medicines, functional foods or dietary supplements. Drug-food interactions, which are mostly unknown from prescribers, including internists, may be responsible for changes in drug plasma concentrations, which may decrease efficacy or led to sometimes life-threatening toxicity. Aging, concomitant medications, transplant recipients, patients with cancer, malnutrition, HIV infection and those receiving enteral or parenteral feeding are at increased risk of drug-food interactions. This review focused on the most clinically relevant drug-food interactions, including those with grapefruit juice, Saint-John's Wort, enteral or parenteral nutrition, their respective consequences in the clinical setting in order to provide thoughtful information for internists in their routine clinical practice. Specific clinical settings are also detailed, such as the Ramadan or multiple medications especially in elderly patients. Drug-food interactions are also presented with respect to the main therapeutic families, including the non-steroidal anti-inflammatory drugs, analgesics, cardiovascular medications, warfarin as well as new oral anticoagulants, anticancer drugs and immunosuppressant medications. Considerable effort has been achieved to a better understanding of food-drug interactions and increase clinicians' ability to anticipate their occurrence and consequences in clinical practice. Describing the frequency of relevant food-drug interactions in internal medicine is paramount in order to optimize patient care and drug dosing on an individual basis as well as to increase patients and doctors information.

During a hospitalization in an internal medicine department, drug prescriptions are frequently modified. We studied the course of these therapeutic changes after patients' discharge.Eighty-four patients with a long-term drug prescription and a registered general practitioner were included on the day of their discharge from an internal medicine department in Paris. Their medications before and after the hospitalization were established according to the discharge letter, and patients were contacted two months after discharge in order to assess the modifications that could have occurred during these two months after discharge.Medications prescribed before the admission were often preserved, 17.7% were withdrawn, and 7% were switched to another medication. Two months after discharge, 85% of the modifications were maintained, the discharge drug prescription was renewed without a change for 77% of the patients. The drug classes that were the more frequently modified during the hospital stay were the antihypertensive therapies, with 65% of sustained modifications at two months, and analgesics, with 75% of sustained modifications. Therapeutic changes that were explained in the discharge letter were more frequently preserved at two months than those that were not explained (100% versus 79%, 95%CI of the difference [0.09-0.27]; P0.0001).Therapeutic changes decided during a hospitalization in an internal medicine unit and prescribed at discharge are mostly preserved in outpatients two months after discharge, especially when the modifications are explained in the discharge letter.

Recombinant activated factor VII (rFVIIa) (Novoseven(®)) was initially developed as a substitutive treatment in haemophiliacs but has then been used in situations of major haemorrhage in non-haemophiliacs (off-label use). The goal of the present study was to assess the practice patterns when rFVIIa is used in off-label indications in major teaching hospitals of Paris in 2010.We retrospectively identified files of patients in whom rFVIIa had been used. Physicians in charge of these patients (or the most proxy physician available) were contacted and files analysed with one of the authors. Quality of rFVIIa used in these off-label situations was determined based on either French or European guidelines or the available literature when no guidelines could be found. Three categories were defined for indication, dosage, timing, associated biological factors and overall use: adequate, acceptable (mainly adequate but lacking some characteristics of an "ideal" prescription) and inadequate (lacking most of the necessary characteristics of an "ideal" prescription).Among 59 patients who had an off-label prescription of rFVIIa, 49 prescriptions could be analysed. Indication for use and timing of administration were adequate in 100% of multiple trauma cases and 83% of obstetrical cases. Biological criteria associated with an improved efficacy were found in two thirds of prescriptions analysed. Overall, prescriptions were adequate or acceptable in 82% of cases.In the vast majority of patients who received rFVIIa for off-label indications in teaching hospitals of the Paris area in 2010, prescriptions were in line with recommendations.

Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) is a rare clinical entity characterized by the association of enlarged lymph nodes in the posterior cervical region and fever. The disease is more frequent in young women.We report a 41-year-old African patient who presented with atypical features of Kikuchi's disease including cutaneous lupus, haemophagocytosis, and lymphocytic meningitis. The ethnic origin and the clinical presentation were initially suggestive of tuberculous meningitis. However, microbiological analyses remained negative, histological findings were suggestive of Kikuchi's disease and HHV6 DNA integration was documented in our patient.Kikuchi's disease should be suspected in an African patient when lymphocytic meningitis is associated with enlarged cervical lymph nodes, hemophagocytosis and HHV6 DNA integration.

Ethanol undergoes gastric first pass metabolism by alcohol dehydrogenase (ADH). We have shown that cimetidine and famotidine both cause competitive inhibition of human gastric ADH in vitro. However, in a randomized 4-way cross-over study in 12 healthy subjects a 7-day course of treatment with cimetidine (800 mg day-1), ranitidine (300 mg day-1) or famotidine (40 mg day-1), did not modify the pharmacokinetics of ethanol given as a post-prandial 0.3 g kg-1 dose. We conclude that gastric mucosal concentrations of histamine H2-receptor blockers achieved after oral dosing are probably too low to cause significant inhibition of gastric ADH in vivo.

BK-virus is a very common polyomavirus in the global population, similar to the JC-virus responsible for Progressive Multifocal Leukoencephalopathy. BK-virus infections are an important diagnostic and therapeutic challenge in immuno-compromised patients, including: bone marrow transplant pediatric recipients in whom it may cause hemorrhagic cystitis, renal transplant recipients in whom it may cause interstitial nephropathy leading to graft loss, and in HIV infected patients in whom it may cause some types of encephalitis. Indeed, this poorly documented virus is responsible for infections with various clinical profiles, probably under-diagnosed, but could also be involved in the genesis of some cancers, especially cervix and prostate cancer. We reviewed the latest published data on this virus focusing on its possible pro-oncogenic properties. We also listed the diseases in which it is involved, with an emphasis on rare and insufficiently investigated entities. Finally, we studied the new tools available for diagnosis and treatment, and their importance in current practice.

The ANA773 is an oral prodrug of a small-molecule toll-like receptor (TLR)7 agonist. Preclinical and healthy volunteer clinical studies with ANA773 have demonstrated induction of endogenous interferon-α (IFN-α) of multiple subtypes, which supports the potential utility in the treatment of chronic hepatitis C virus (HCV) infection.To examine safety, tolerability, pharmacodynamics, pharmacokinetics and anti-viral activity of ANA773.The ANA773 was investigated in a double-blind, placebo-controlled study in 34 patients chronically infected with HCV of any genotype. Patients were treatment-naïve or had relapsed following previous interferon-based treatment. This dose escalation study was composed of four dose groups (800, 1200, 1600 and 2000mg). In each group, six to eight patients received ANA773 and two received placebo. Patients were dosed with ANA773 every-other-day for either 28 days (800, 1200 or 1600mg) or 10days (2000mg).Mild to moderate adverse events were reported, with an increase in frequency and intensity with increasing dose. No serious AEs were reported and there were no early discontinuations. There were dose-related increases in various markers of IFN-α response. The mean maximum change in serum HCV RNA level from baseline was -0.34, -0.29, -0.40, -0.97 and -1.26log(10) in the placebo, 800, 1200, 1600 and 2000mg cohorts, respectively. At the 2000mg dose, ANA773 significantly (P=0.037) reduced serum HCV RNA levels (range: 0.14 to -3.10log(10) ).The ANA773 was generally well tolerated and resulted in a dose-related IFN-dependent response leading to a significant decrease in serum HCV RNA levels in the 2000mg dose group.

We compared, in a cross-over study, the toxicity of 300 mg enteric-coated aspirin with regular aspirin used for the prevention of cardiovascular events. In terms of endoscopic haemorrhagic lesions, enteric-coated aspirin is less gastrotoxic than regular aspirin.

The clinical diagnosis of ocular toxoplasmosis is based on clinical features and biological tests: polymerase chain reaction (PCR) and the determination of intraocular specific antibody secretion (Goldmann-Witmer coefficient) on aqueous humor. Older patients may have a higher prevalence of ocular involvement and more severe ocular disease during the acute phase of recently acquired systemic infection because of altered cell-mediated immunity. Moreover, the genotype of the infecting parasite (particularly involving neotropical Type I Toxoplasma gondii strain), appears to be an important determinant of disease severity.

To move from a chemical entity to a real drug, preclinical trials have to be followed by phase I human studies to evaluate human toxicity, phase II studies to demonstrate the pharmacological activity in healthy volunteers and patients, followed by phase III studies to evaluate the real therapeutic efficacy. Then new drug authorization is granted for a product that shows good pharmaceutical quality and a positive risk-benefit ratio. However, full knowledge of a new drug is available only after several years of clinical use.

The quality of a therapeutic trial depends on several parameters. The ideal trial in prostate cancer should be a high-quality trial on a well-defined and significant population. The method used to calculate the number of subjects necessary should appear in the study. There should be a single and significant evaluation criterion and follow-up should be long given the natural history of the disease. Intention to treat is also a quality terion. Finally, the therapeutic class effect does not exist; therefore, the efficacy of inoma any new drug must be proven.

The new treatments of orphan diseases must be assessed according to the methodologic rules of therapeutic trials, in order to ensure clinically and statistically significant evaluations: randomized controled trials, single primary end-point, statistically significant and clinically relevant efficience. Although these rules may be relaxed in orphan diseases, they have to maintain the standard of therapeutic efficiency.

Atrial fibrillation (AF) is the most frequent sustained arrhythmia. After restoration of normal sinus rhythm, the recurrence rate of AF is high. Antiarrhythmic drugs have been widely used to prevent recurrence, but the effect of these drugs on mortality and other clinical outcomes is unclear.To determine, in patients who recovered sinus rhythm after AF, the effect of long-term treatment with antiarrhythmic drugs on death, stroke and embolism, adverse effects, pro-arrhythmia and recurrence of AF. If several antiarrhythmics were effective our secondary aim was to compare them.The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Libary (Issue 2, 2005), MEDLINE (1950 to May 2005) and EMBASE (1966 to May 2005) were searched. The reference lists of retrieved articles, recent reviews and meta-analyses were checked. No language restrictions were applied.Two independent reviewers selected randomised controlled trials comparing any antiarrhythmic with a control (no treatment, placebo or drugs for rate control) or with another antiarrhythmic, in adults who had AF and in whom sinus rhythm was restored. Post-operative AF was excluded.Two reviewers independently assessed quality and extracted data, on an intention-to-treat basis. Disagreements were resolved by discussion. Studies were pooled, if appropriate, using Peto odds ratio (OR).45 studies met inclusion criteria, comprising 12,559 patients. All results were calculated at 1 year of follow-up. Class IA drugs (disopyramide, quinidine) were associated with increased mortality compared with controls (OR 2.39, 95% confidence interval (CI) 1.03 to 5.59, P = 0.04, number needed to harm (NNH) 109, 95% CI 34 to 4985). Other antiarrhythmics did not modify mortality. Several class IA (disopyramide, quinidine), IC (flecainide, propafenone) and III (amiodarone, dofetilide, dronedarone, sotalol) drugs significantly reduced recurrence of AF (OR 0.19 to 0.60, number needed to treat 2 to 9), but all increased withdrawals due to adverse affects (NNH 17 to 36) and all but amiodarone and propafenone increased pro-arrhythmia (NNH 17 to 119).Several class IA, IC and III drugs are effective in maintaining sinus rhythm but increase adverse events, including pro-arrhythmia, and disopyramide and quinidine are associated with increased mortality. Any benefit on clinically relevant outcomes (embolisms, heart failure, mortality) remains to be established.

To evaluate the ability of two graphologists and two practising internists not trained in graphology to differentiate letters written by subjects who have attempted to commit suicide by self-poisoning and healthy volunteers, we performed a maximal blind controlled study vs. healthy volunteers. Forty fully recovered patients who had attempted to commit suicide and 40 healthy volunteers wrote and signed a short letter or story not related to the parasuicide or their mental health status. The evaluators classified the 80 letters as 'suicide' or 'no suicide' in an intention-to-treat analysis. Letters expressing sadness were subsequently excluded for a per-protocol analysis. Correct diagnosis of suicide and of healthy controls was made in, respectively, 32 of 40 and 33 of 40 letters by the graphologists and in 27 of 40 and 34 of 40 letters by the internists. After the exclusion of 12 letters expressing sadness, the sensitivity, specificity, positive predictive value and negative predictive value were, respectively, 73, 88, 81 and 82% for the graphologists and 53, 89, 80 and 71% for the internists. Both classified the letters with significantly more effectiveness than chance (p0.001) with no statistically significant difference between the two groups of evaluators. We concluded that graphological analysis is able to differentiate letters written by patients who attempt suicide from those written by healthy controls. This technique shows an acceptable degree of accuracy and could therefore become an additional discharge or decision-making tool in Psychiatry or Internal Medicine.

Troponin is now the gold standard for the diagnosis of myocardial infarction. Aiming at improving the management of a patient suspect of an acute coronary syndrome, this article will point the interpretation of troponin dosages according to the clinical presentation and concomitant diseases.First, the interest of troponin dosage as compared with other markers of myocardial ischemia will be underlined. Then, the literature available about troponin in cardiovascular diseases but also in extracardiac diseases will be analysed. Finally, the difficulties of assay will be discussed.The availability of a sensitive and specific marker such as troponin is definitively a progress in the management of patients with an acute coronary syndromes. But it remains a biological contribution to the global management of the patient. It is important to know the causes susceptible to increase the levels of troponin to avoid a wrong interpretation of the dosage, leading to diagnostic but also therapeutic mistakes.

Compliance is the appropriateness of patient behaviour to therapeutic prescriptions. Good compliance increases treatment efficacy although its constraints may harm quality of life. Factors affecting compliance are related to the patient, the disease, health-care workers, family and treatment itself. Psycho-sociologic theories have attempted to explain patient behaviour. In clinical trials, compliance has to be optimized, i.e. in the protocol, during the study and the statistical analysis. In real life, compliance concerns all those involved in health-care, particularly for education, training and motivation of the patients and their immediate environment. Observational surveys relating to compliance are needed to determine prioriites and to develop a "compliance approach" based on improving information and the use of tools for better therapeutic adherence. Evaluation of the quality of life and patient satisfaction aspects is necessary to validate this approach.

The prevention of preventable adverse therapeutic events (iatrogenic), especially drug related, is a major medical goal for patients, economics and the community. Its incidence is 5 to 15 per cent of hospitalization days. Preventable iatrogenic is a main problem in terms of public health owing to its human and economic consequences. Prevention of iatrogenic is based on better knowledge of its reality, on well-adapted initial and long-term intensive training of physicians, other healthcare workers and also patients and citizens. A better healthcare system is also needed.

Quality in healthcare has to evaluate the efficacy, the cost effectiveness and patient satisfaction. Quality of treatment could be evaluated with randomized clinical trials and with satisfaction measurement, leading to professional recommendations. Quality of therapeutic strategy is based on the evaluation of patient monitoring. The quality of the healthcare worker is based on initial training, accreditation and various audits. The final quality in healthcare depends on the competence of the prescriber but also on the medical information, the logistics and the control of prescriptions. Improvements in quality will be obtained by better medical training, patient information and application of professional recommendations. These recommendations have to change gradually to be adapted to medical progress and evidence-based medicine.

The purpose of the French Transparency Commission is to provide scientific advice concerning the usefulness, interest and good use of drugs.The work of the Transparency Commission lies at the interface between the French or European marketing approval procedures and the health and economic prerequisites of the French community.The opinion of the French Transparency Commission is used to assess the medical service provided by a new drug and the improvement of this medical service subsequent to its use. This opinion is taken into consideration for establishing the reimbursement rate applied by the social security organizations and the selling price set by the administration. The expert opinions and recommendations established by the Transparency Commission participate in implementing good use of drugs.

Despite a lack of data, the antiviral agent ganciclovir is not indicated in AIDS patients with diarrhoea because of its presumed poor oral bioavailability. To assess the effect of diarrhoea on ganciclovir intestinal absorption, we conducted a pharmacokinetic study in 42 HIV-infected patients categorized into three groups: A, HIV stage A and B (n = 15); B, AIDS stage C (n = 13); C, AIDS with chronic diarrhoea and wasting syndrome (n = 14).Each patient was evaluated for nutritional (body mass index, albumin, transferrin serum levels), inflammatory (haptoglobin, orosomucoid), immunological (CD4 count, plasma viral load) and intestinal (D-xylose test, faecal fat and nitrogen output, intestinal permeability) status. Ganciclovir (1 g) was administered orally to fasted patients. Six blood samples were collected over 24 h. Serum was analysed for ganciclovir by h.p.l.c. Population pharmacokinetic analysis was performed using a nonlinear mixed effects modelling program, MP2.Mean intestinal permeability (lactulose/mannitol urinary ratio) was increased in group C (0.2) compared with group A (0.05) and B (0.1) patients. Drug concentration-time profiles were best described by a two-compartment model. Apparent oral clearance (CL/F) and central volume of distribution (V1/F) were influenced by clinical status (group). For groups A and B combined, final parameter estimates of CL/F and V1/F were 256 +/- 98 l h(-1) and 1320 +/- 470 l, respectively. Final parameter estimates for group C were 118 +/- 108 l h(-1) and 652 +/- 573 l for CL/F and V1/F, respectively. The 95% confidence intervals on differences between A and B combined and C were statistically significant ([ + 70, + 206] for CL/F, and [+ 314, + 1022] for V1/F). Compared with groups A and B, ganciclovir CL/F was significantly decreased in group C patients.AIDS patients with diarrhoea and severe disease may benefit from ganciclovir therapy, but a dose adjustment may be required according to their digestive and immunological status.

The pharmacokinetic characteristics of reboxetine, a unique selective noradrenaline reuptake inhibitor (selective NRI) for the treatment of depression, were studied in 12 healthy, elderly volunteers (mean age 81 years +/- 9 years). All subjects received a single 4-mg dose of reboxetine, and plasma reboxetine concentrations were measured by HPLC. Reboxetine was well tolerated by all subjects. Exposure to reboxetine was higher in this group of very elderly subjects, compared with data obtained in a similar study of young, healthy volunteers. Cmax in the elderly was 271 +/- 86 ng/ml, compared with 111 +/- 28 ng/ml in the young subjects after a single 4-mg dose, although in both groups Cmax was observed after 2 h. The AUC infinity was nearly four times that in the younger subjects (8345 +/- 3107 ng.h/ml vs. 2106 +/- 881 ng.h/ml) and the t1/2 was twice as long (24 +/- 6 h vs. 12 +/- 3 h). Renal clearance was also reduced. Reboxetine 8-10 mg/day has been effective and well tolerated in clinical trials in non-elderly depressed patients. The increased exposure to reboxetine observed in our very elderly subjects supports a reduction of the starting dose to 4 mg/day (in two divided doses) in the elderly.