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We aimed to assess the risk factors of venous thrombosis (VT) and arterial thrombosis (AT) in adults with primary immune thrombocytopenia (ITP), particularly in relation to treatments. The population comprised all incident primary ITP adults in France between 2009 and 2017 (FAITH cohort; NCT03429660) built in the national health database. Outcomes were the first hospitalisation for VT and AT. Multivariable Cox regression models included baseline risk factors, time-varying exposure to ITP drugs, splenectomy and to cardiovascular drugs. The cohort included 10 039 patients. A higher risk of hospitalisation for VT was observed with older age, history of VT, history of cancer, splenectomy [hazard ratio (HR) 3·23, 95% confidence interval (CI) 2·26-4·61], exposure to corticosteroids (HR 3·55, 95% CI 2·74-4·58), thrombopoietin-receptor agonists (TPO-RAs; HR 2·28, 95% CI 1·59-3·26) and intravenous immunoglobulin (IVIg; HR 2·10, 95% CI 1·43-3·06). A higher risk of hospitalisation for AT was observed with older age, male sex, a history of cardiovascular disease, splenectomy (HR 1·50, 95% CI 1·12-2·03), exposure to IVIg (HR 1·85, 95% CI 1·36-2·52) and TPO-RAs (HR 1·64, 95% CI 1·26-2·13). Rituximab was not associated with an increased risk. These findings help to estimate the risk of thrombosis in adult patients with ITP and to select treatment.

Background In 2020 the coronavirus disease 19 (COVID-19) pandemic imposed a total and sudden lockdown. We aimed to investigate the consequences of the first COVID-19 lockdown (mid-March – mid-April 2020) on motor and non-motor symptoms (NMS) in a cohort of French people with Parkinson's disease (PwP). Methods PwP were enrolled either by an on-line survey sent from the national France Parkinson association (FP) to reach the French community of PwP or as part of outpatients' telemedicine visits followed by an hospital-based Parkinson Expert Center (PEC). All patients were evaluated using the same standardized questionnaire assessing motor and NMS (including a list of most disabling, new or worsened symptoms and Patient's Global Impression-Improvement scales [PGI-I]) psycho-social queries and quality of life. Results 2653 PwP were included: 441 (16.6%) in the PEC group and 2122 (83.4%) in the community-based group. Physiotherapy was interrupted among 88.6% of the patients. 40.9% referred a clinical modification of their symptoms. Based on the questionnaire, pain (9.3%), rigidity (9.1%) and tremor (8.5%) were the three most frequently new or worsened reported symptoms. Based on the PGI-I, the motor symptoms were the most affected domain, followed by pain and psychic state. PwP in community-based group tended to have more frequent worsening for motor symptoms, motor complications, pain and confusion than those of the PEC group. Conclusions The first COVID-19 lockdown had a negative impact on motor and NMS of PwP. Efforts should be allocated to avoid interruption of care, including physiotherapy and physical activities and implement telemedicine. .

Aim: To compare different β-adrenoceptor antagonists for the risk of reporting nightmare. Methods: The study involved two approaches: first, we investigated in VigiBase®, the World Health Organization Individual Case Safety Report (ICSR) database, the disproportionality between exposure to each β-adrenoceptor antagonists and reports of nightmares between 1967 and 2019. Second, in a pharmacoepidemiological–pharmacodynamic analysis, we assessed whether use of β-adrenoceptor antagonists with moderate and high lipid solubility or strong 5-HT1A affinity were associated with an increased risk of reporting nightmares. We conducted multivariate logistic regression to estimate reporting odds ratios (RORs) of nightmares compared to all other adverse drug reactions. Results: Of the 126,964 reports recorded with β-adrenoceptor antagonists, 1138 (0.9%) were nightmares. The highest risk of reporting a nightmare was found with exposure of pindolol (adjusted ROR 2.82, 95%CI, 2.19–3.61), metoprolol (1.89, 1.66–2.16), and alprenolol (1.77, 1.06–2.97). Compared to use of low lipid solubility β-adrenoceptor antagonists, use of moderate or high lipid solubility β-adrenoceptor antagonists were significantly more associated with nightmare reports (aROR moderate vs. low 1.72, 95%CI 1.47–2.00 and aROR high vs. low 1.84, 95%CI 1.53–2.22). Use of moderate or high 5-HT1A affinity of β-adrenoceptor antagonists was associated with an increased ROR of nightmares compared with low 5-HT1A affinity of β-adrenoceptor antagonists (aROR moderate vs. low 1.22, 95%CI 1.04–1.43 and aROR high vs. low 2.46, 95%CI 1.93–3.13). Conclusion: In our large pharmacovigilance study, nightmares are more frequently reported for pindolol and metoprolol, and among β-adrenoceptor antagonists with high lipid solubility and high 5-HT1A receptor affinity.

Aims Adverse drug reactions (ADRs) are important causes of death. However, the main involved drugs are relatively unknown. The present study was performed to characterise death-related drugs recorded in a large pharmacovigilance database during the last 10 years. Methods A retrospective analysis of VigiBase, the World Health Organization pharmacovigilance database, was performed investigating fatal ADRs registered between 1 January 2010 and 31 December 2019 in male and female patients aged ≥18 years and reported by physicians. Analyses were descriptive investigating age, sex and suspected drugs. Differences in reporting according to sex, age and continents were investigated using disproportionality analysis with calculation of reporting odds ratio and its 95% confidence interval. Results Among the 23 millions ADRs recorded in VigiBase, 3 250 967 were included with 43 685 fatal. They were reported mainly in patients older than 75 years. The 3 most frequently involved drug classes were antineoplastic/immunomodulating drugs followed by nervous system and cardiac drugs. The top 3 individual drugs were denosumab, lenalidomide and thalidomide with marked differences according to age, sex, continents and countries. The risk of reporting fatal ADRs was higher in males, in the Americas and in patients ≥65 years. Conclusion Fatal ADRs registered in a large pharmacovigilance database during the last 10 years correspond to just over 1% of the total number of ADRs. They occurred more in males, after 65 years and with antineoplastic/immunomodulating drugs in general. Our study also highlighted, for the first time, important differences in fatal ADRs between continents and countries.

Several papers have reported that tramadol can induce hypoglycemia. However, in some reports, confounding factors can be found, like coadministration of hypoglycemic drugs. We used the WHO pharmacovigilance database (VigiBase® ) to investigate whether tramadol alone could be associated with hyponatremia. All 2010-2019 ICSRs (Individual Case Safety Reports) with the PT term "hyponatremia" and tramadol were included. Two disproportionality analyses were performed: 1/after inclusion of all reports, 2/after exclusion of concomitant hypoglycemic drugs. Results are expressed as Reporting Odds Ratios (ROR; 95% CI). Among 10 038 436 ICSRs, 97 639 were included. In comparison with codeine, a significant association was found between tramadol use and reports of hypoglycemia before [ROR = 1.54 (1.43-1.66)] or after [ROR = 1.43 (1.31-1.56)] exclusion of hypoglycemic drugs. Tramadol use is associated with a higher risk of hypoglycemia reports than codeine, the other step 2 analgesic, in the presence as well as in the absence of other hypoglycemic drugs. We concluded that hypoglycemia is an adverse drug reaction of tramadol, which can be observed in diabetic as well as in non-diabetic patients.

Background Patients with Hailey-Hailey and Darier diseases present with disabling inflammatory lesions located in large skin folds, which are often exacerbated or induced by sweating. Quality of life is highly impaired because of pain and recurrent skin infections. An improvement in skin lesions after botulinum toxin A injections has previously been reported in some patients but no prospective interventional studies are available. The aim of this open-label, 6-month, interventional pilot study (NCT02782702) was to evaluate the effectiveness and safety of botulinum toxin A for patients with moderate to very severe skin lesions located in folds. Results Thirty patients (26 Hailey-Hailey/4 Darier) were included. Botulinum toxin A proved effective within the first month in two-thirds of patients, taking all study parameters (itchiness, cutaneous pain, sweating and odour, infections, psychosocial impairment and quality of life) into account and persisted during the 6-month follow-up period. No patient was classed as a BtxA non-responder, but 11 (37%) Hailey-Hailey patients (the most severe ones), experienced a relapse during the study. No serious side effects were reported. Mild transient clear fluid discharge at the site of the injections was reported for 27% of patients. Conclusions Botulinic toxin seems to be an effective and safe treatment for Hailey-Hailey and Darier diseases. Nevertheless, it may prove insufficient for the severest of Hailey-Hailey cases and could be considered as supplementary to other conventional treatments. Further studies are required to confirm our results on larger Darier cohorts.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide from epicenter of Wuhan, China since December 2019. The aim of our study was to describe the clinical characteristics and outcome of hospitalized patients with SARS-CoV-2 pneumonia at the Toulouse university hospital, France. Patients and methods We selected the patients included from March 7, 2020 to April 20, 2020 in the retrolective Covid-clinic-Toul cohort that follows all hospitalized patients with SARS-CoV-2 infection at the Toulouse Hospital. Cases were confirmed by real-time reverse transcriptase polymerase chain reaction. We report demographics, clinical, biological and radiological features, as well as unfavorable outcome at Day 14 after admission (admission in an intensive care unit, mechanical ventilation, death). Results Among 263 hospitalized patients, the median age was 65 years and 155 (58.9%) were males. Two hundred and twenty-seven patients (86.3%) had at least one comorbidity. The median time from first symptom to hospital admission was 7.0 days (interquartile range: 4–10). On day 14 after admission, 111 patients (42.2%) had been transferred to intensive care unit (ICU), including 50 (19.0%) on Day 1; 61 (23.1%) needed mechanical ventilation and 19 patients (7.2%) had died. Patients admitted to ICU at Day 1 of admission (n = 50) were more frequently men (66.0% vs 57.3%), smokers (25.0% vs 7.1%), with obesity (42.0% vs 24.7%) and had a higher mean level of C-reactive protein (median: 110.9 mg/L vs 46.2 mg/L). Conclusion This cohort provides epidemiological data on SARS-CoV-2 in hospitalized patients in a University hospital in the South of France.

International audience; Patients with COVID-19 are sometimes already being treated for one or more other chronic conditions, especially if they are elderly. Introducing a treatment against COVID-19, either on an outpatient basis or during hospitalization for more severe cases, raises the question of potential drug-drug interactions. Here, we analyzed the potential or proven risk of the co-administration of drugs used for the most common chronic diseases and those currently offered as treatment or undergoing therapeutic trials for COVID-19. Practical recommendations are offered, where possible.

Prior studies have demonstrated an increased prevalence of autoimmune markers in patients with immune thrombocytopenia (ITP). Clinical experience has suggested that there may be an association between autoimmune markers and poor outcomes in ITP, but current guidelines do not encourage routine testing in these patients. We retrospectively assessed the prevalence of autoimmune markers in adult patients with ITP from our institutional database and used multiple logistic regression analyses to test for an association between autoimmune marker positivity and thrombotic events or clinical remission. We also assessed whether positivity for common autoimmune markers was associated with positivity for platelet autoantibodies. There was a high rate of autoimmune marker positivity in this population, with antinuclear antibody (65%), antithyroid peroxidase antibody (31%), and direct antiglobulin (29%) the most commonly found. Antithyroid peroxidase antibody positivity was associated with a lower probability of remission (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.09-0.79; P = .017). Lupus anticoagulant positivity was associated with a higher rate of thrombosis (OR, 8.92; 95% CI, 1.94-40.95; P = .005), and antinuclear antibody was strongly associated with thrombosis (P = .001). There was no relation between platelet autoantibody positivity and the presence of autoimmune markers. These results suggest that many patients with ITP have a state of immune dysregulation that extends beyond platelet autoantibodies and that certain autoimmune markers may be prognostically useful in this disorder.

Fluoroquinolones are widely used to treat bacterial infections. Many in vitro and in vivo studies have established a chemical relationship between fluoroquinolones’ particular chemical structure and photosensitivity. The aim of this study was to establish a relationship between the chemical structure of fluoroquinolones and the risk of photosensitivity adverse effects from real-world data. All the Individual Case Safety Reports (ICSRs) related to fluoroquinolones and registered in the World Health Organization global database (VigiBase®) up to December 31, 2017 were collected. A disproportionality analysis was performed in order to quantify the photosensitivity risk for each fluoroquinolone by calculating their reporting odds ratio (ROR). Up to December 31, 2017, 282,805 ICSRs related to fluoroquinolones were selected, of which 1647 were photosensitivity adverse event cases. Sparfloxacin had the highest adjusted ROR of 161.10 (95% confidence interval [CI] 133.66–194.02) followed by grepafloxacin (40.30 [26.30–59.60]) closely followed by lomefloxacin (32.61 [28.61–37.07]), then enoxacin (11.04 [8.33–14.32]) and fleroxacin (8.22 [5.06–12.56]). This study confirms the high reporting rate of photosensitivity adverse effects for sparfloxacin from real-world data. Moreover, our data suggest more photosensitivity adverse effects reporting for fluoroquinolones with a halogen at their 8th position.

In 2018, 1.07 million pregnant women received antiretroviral drugs, raising whether this affects pregnancy outcomes. We assessed the adverse pregnancy outcomes associated with prenatal antiretroviral drug exposure, notified to the French ANRS pharmacovigilance system.An exhaustive case report series has been performed using the ANRS pharmacovigilance database. All ANRS-sponsored HIV clinical research studies using antiretroviral drugs either in pregnant women or women of childbearing age were eligible from 2004 to 2019. We analysed the following pregnancy outcomes: abortion, ectopic pregnancy, stillbirth, prematurity (37 weeks of gestational age), low birth weight (2500 g) and congenital abnormalities. A logistic regression was performed to assess the odds ratio (OR) for each outcome separately (if occurrence50) compared to the outcome observed when exposed to non-nucleoside-reverse-transcriptase-inhibitor (NNRTI)-based regimen as the reference.Among the 34 studies selected, 918 deliveries occurred, of whom 88% had pregnancy outcomes documented. Pregnant women were mainly exposed to PI (n = 387, 48.6%), NNRTI (n = 331, 41.5%) and INI-based combinations (n = 40, 5.0%, 18 on dolutegravir). Compared to NNRTI-based combinations, there was no significant association observed with exposure to other antiretroviral combination for spontaneous abortion, prematurity or low birth weight, except an increased risk of low birth weight in new-born exposed to exclusive nucleoside-reverse-transcriptase-inhibitor (NRTI) combinations (n = 4; OR 7.50 [1.49-37.83]).Our study, mainly based on protease inhibitor (PI) and NNRTI-based regimens, is overall reassuring on the risk of adverse pregnancy outcomes, except for NRTI which should be interpreted cautiously (small number, indication bias). In this study, the number of integrase inhibitor (INI)-based combinations was too low to draw any conclusions.

International audience; We conducted a retrospective Covid-clinic-Toul cohort study at Toulouse university hospital, in southern France (2800 beds, tertiary hospital covering an area of about 3 million inhabitants) and selected hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia from September 1st, 2020 to October 31st, 2020. We compared their demographics, clinical, biological and radiological features, as well as unfavorable outcome (admission in an intensive care unit, mechanical ventilation, death) at Day 14 after admission to those of hospitalized patients during the 1st wave (March 11, 2020 to April 20, 2020).

International audience; Objective: Mechanical thrombectomy (MT) is not recommended for acute stroke with large vessel occlusion (LVO) and a large volume of irreversibly injured tissue (“core”). Perfusion imaging may identify a subset of patients with large core who benefit from MT.Methods: We compared two cohorts of LVO-related patients with large core (>50 ml on diffusion-weighted-imaging or CT-perfusion using RAPID), available perfusion imaging, and treated within 6 hrs from onset by either MT + Best Medical Management (BMM) in one prospective study, or BMM alone in the pre-MT era from a prospective registry. Primary outcome was 90-day modified Rankin Scale≤2. We searched for an interaction between treatment group and amount of penumbra as estimated by the mismatch ratio (MMRatio = critical hypoperfusion/core volume).Results: Overall, 107 patients were included (56 MT + BMM + 51 BMM): Mean age was 68 ± 15 yrs, median core volume 99 ml (IQR: 72-131) and MMRatio 1.4 (IQR: 1.0-1.9). Baseline clinical and radiological variables were similar between the 2 groups, except for a higher intravenous thrombolysis rate in the BMM group. The MMRatio strongly modified the clinical outcome following MT (Pinteraction < 0.001 for continuous MMRatio); MT was associated with a higher rate of good outcome in patients with, but not in those without, MMRatio>1.2 (adjusted OR [95%CI] = 6.8 [1.7-27.0] vs. 0.7 [0.1-6.2], respectively). Similar findings were present for MMRatio≥1.8 in the subgroup with core≥70 ml. Parenchymal hemorrhage on follow-up imaging was more frequent in the MT + BMM group regardless of the MMRatio.Interpretation: Perfusion imaging may help select which patients with large core should be considered for MT. Randomized studies are warranted. This article is protected by copyright. All rights reserved.

Several vaccines are being developed as part of the COVID‐19 pandemic. The results of clinical trials for these vaccines were published with efficacy values of more than 90%, using mainly relative risk (RR). In this paper, we decided to reanalyse the data using the different validated methods of risk expression. Using main publications, absolute risks (AR), AR reduction (ARR), number needed to treat (NNT) were calculated for five COVID‐19 vaccines (tozinameran Comirnaty®, Moderna, Vaxzevria®, Janssen, and Sputnik V vaccines). AR, ARR, NNT, and RR values varied according to COVID‐19 vaccines. The order of the different vaccines was not the same according to the chosen efficacy parameters. This is a further example of the need to express results of clinical trials, using not only RR, but also AR, ARR, and NNT in order to clearly present the clinical interest of drugs.

International audience; BACKGROUND: The efficacy of rifaximin in the secondary prevention of overt hepatic encephalopathy (HE) is well documented, but its effectiveness in preventing a first episode in patients after transjugular intrahepatic portosystemic shunt (TIPS) has not been established. OBJECTIVE: To determine whether rifaximin prevents overt HE after TIPS compared with placebo. DESIGN: Randomized, double-blind, multicenter, placebo-controlled trial. (ClinicalTrials.gov: NCT02016196). PARTICIPANTS: 197 patients with cirrhosis undergoing TIPS for intractable ascites or prevention of variceal rebleeding. INTERVENTION: Patients were randomly assigned to receive rifaximin (600 mg twice daily) or placebo, beginning 14 days before TIPS and continuing for 168 days after the procedure. MEASUREMENTS: The primary efficacy end point was incidence of overt HE within 168 days after the TIPS procedure. RESULTS: An episode of overt HE occurred in 34% (95% CI, 25% to 44%) of patients in the rifaximin group (n = 93) and 53% (CI, 43% to 63%) in the placebo group (n = 93) during the postprocedure period (odds ratio, 0.48 [CI, 0.27 to 0.87]). Neither the incidence of adverse events nor transplant-free survival was significantly different between the 2 groups. LIMITATIONS: The study’s conclusion applies mainly to patients with alcoholic cirrhosis, who made up the study population. The potential benefit of rifaximin 6 months after TIPS and beyond remains to be investigated. CONCLUSION: In patients with cirrhosis treated with TIPS, rifaximin was well tolerated and reduced the risk for overt HE. Rifaximin should therefore be considered for prophylaxis of post-TIPS HE. PRIMARY FUNDING SOURCE: French Public Health Ministry.

Central venous catheter (CVC) insertion is a common practice for anesthetists, but this invasive procedure generates anxiety and pain in patients that are often underestimated. We compared target-controlled infusion of remifentanil and local lidocaine infiltration with placebo and local lidocaine infiltration to decrease pain scores during CVC placement.We included conscious, adult patients without contraindication to remifentanil or lidocaine. We excluded pregnant women, emergency situations, and opioid abuse. Patients requiring CVC were randomly assigned, using computer-generated allocation numbers stored in sealed envelopes, to receive target-controlled infusion of remifentanil or placebo-all patients received local anesthesia with lidocaine. All patients were hospitalized in a recovery room or intensive care unit, monitored, and received 4 L/min of oxygen.The primary outcome was global pain (Verbal Numeric Rating Pain Scale) during the procedure. Secondary outcomes were pain perceived at every stage of the procedure, anxiety, patient satisfaction, operational ease, and side effects.In this double-blind study, we included 90 patients (split into 2 groups of 45 patients). Global pain was significantly reduced in the remifentanil group: 20 of 100 (95% confidence interval, 16-40) versus 50 of 100 (95% confidence interval, 40-60) in the placebo group; P=0.0009. No major adverse events were observed during this study, and there were no significant differences between both groups regarding side effects.Target-controlled infusion of remifentanil is an effective drug to reduce pain during CVC insertion in association with lidocaine-based local anesthesia, in conscious patients.

International audience; Pharmacoepidemiology is the study of interactions between drugs and human populations, investigating, in real conditions of life, benefits, risks and use of drugs. Pharmacoepidemiology applies to drugs and their pharmacological evaluations, the different methods also used in epidemiology to assess in real conditions of life, benefits, risks and use of drugs. Pharmacoepidemiologic studies are ad-hoc studies or studies on databases. Specific methods exist to measure drug exposure, as well as indicators of compliance and misuse of drugs. Various designs for descriptive and explanatory studies exist, in a context in which a growing proportion of studies are carried out using medico-administrative data. The limits traditionally affecting the study designs are modified in this context, almost any design selected for the conduct of a study from these databases then deriving from a cohort in whom the information has been recorded prospectively and exhaustively.

Antibiotics (ABs) exposure of population is known as the main driving force for the emergence and spread of bacterial resistance in the community. Pharmacoepidemiology is the study of interactions between drugs and human populations, investigating, in real conditions of life, benefits, risks and use of drugs. Thus, pharmacoepidemiology is particularly of interest to monitor ABs use in both hospital and community settings. This can help to better understanding determinants of ABs use and to evaluate their impact. ABs use can also be a marker of an infection, which can be an ADR of other drugs. The development of pharmacoepidemiology should improve the "rational use" of ABs.

Delivering of 80% planned relative dose intensity (RDI) of fludarabine-cyclophosphamide-rituximab (FCR) is key to benefit from longer progression free survival (PFS) and survivals in CLL. In this randomized trial, we sought to investigate whether a telephone intervention strategy (called AMA) delivered by an oncology nurse could reduce the risk of RDI 80% by alleviating adverse events and supporting patients' adherence. Sixty FCR patients were randomized 1:1 for AMA (stratified on Binet stage C). As per guidelines, patients received pegfilgrastim as primary prophylaxis of febrile neutropenia. At the end of therapy, RDI 80% was reported in 31% of patients, shortening PFS (median 26 months versus not reached, P = 0.021) and OS at 3 years (100 vs 70%, P = 0.0089). Oncology nurse interventions tended to significantly reduce this event (RDI 80%: 41.4% in non-AMA versus 20.7% in AMA patients (p = 0.09)). By adjusting our logistic regression model on published parameters exposing to RDI 80%, we found that AMA protected significantly against the risk of reduced RDI (OR = 0.22, IC95% 0.05-0.84, p = 0.04), independently of grade 3/4 neutropenia ( 15% per cycle) and febrile neutropenia ( 5% per cycle) events. As a conclusion, we confirmed that 20% reduction of FCR dose-intensity was detrimental for PFS/OS, but that oncology nurse interventions reduced the risk of dose concessions.

Domperidone is widely used during pregnancy, although the risks associated with pregnant women have not been adequately evaluated. The objective of this study was to compare the rate of pregnancy outcomes and congenital anomalies between pregnant women exposed and unexposed to domperidone during pregnancy. We conducted a retrospective cohort study comparing pregnant women exposed and unexposed to domperidone during pregnancy. We used the EFEMERIS database containing the prescriptions and dispensing of drugs to pregnant women in Haute-Garonne, who had a pregnancy outcome between July 2004 and December 2017. We compared pregnant women who were exposed to domperidone at least once during pregnancy to unexposed pregnant women. Logistic regression and Cox proportional risk models were applied. Overall, 13,964 pregnancies (10.3% of pregnancies) were given domperidone. A reduction in the number of pregnant women exposed to domperidone (2004: 17.1% to 2017: 1.2%) was noted. More than 75% of pregnancies were exposed to domperidone in the first trimester of pregnancy. The rate of natural pregnancy termination in pregnant women exposed to domperidone was lower than that in unexposed pregnant women (adjusted hazard ratio = 0.78 [0.71–0.87]). The malformation rate in fetuses/newborns exposed in utero (first trimester) to domperidone is comparable to that of unexposed fetuses/newborns (adjusted odd ratio = 0.89 [0.77–1.03]). This is the first comparative study to enrol a large number of pregnant women exposed to domperidone. Data regarding the malformation rate following exposure to domperidone during the first trimester of pregnancy are reassuring. Women exposed to domperidone during pregnancy have a decreased risk for natural pregnancy termination, probably owing to an indication bias.

Fil: Rascol, Olivier. Universidad de Toulouse. Hospital Universitario de Toulouse; Francia Fil: Rascol, Olivier. Centro NeuroToul COEN; Francia Fil: Rascol, Olivier. Clínica de Toulouse. Centro de Investigación. Departamentos de Neurociencias y Farmacología Clínica; Francia Fil: Cochen De Cock, Valérie. Clínica Beau Soleil. Departamento de Neurología; Francia Fil: Cochen De Cock, Valérie. Universidad de Montpellier. EuroMov Digital Health in Motion; Francia Fil: Pavy-Le Traon, Anne. Centro de referencia de atrofia multisistémica; Francia Fil: Pavy-Le Traon, Anne. Universidad de Toulouse. Hospital Universitario de Toulouse. Instituto de Enfermedades Cardiovasculares y Metabólicas. Centro de Investigación Clínica de Toulouse. Departamento de Neurociencias; Francia Fil: Foubert-Samier, Alexandra. Universidad de Toulouse. Hospital Universitario de Toulouse. Instituto de Enfermedades Cardiovasculares y Metabólicas. Departamento de Neurociencias, Centro de investigación Clínica de Toulouse; Francia Fil: Thalamas, Claire. Universidad de Toulouse. Hospital Universitario de Toulouse. Centro de Investigación Clínica de Toulouse; Francia Fil: Thalamas, Claire. Hospital Universitario de Burdeos; Francia Fil: Sommet, Agnès. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Pérez Lloret, Santiago. Universidad Abierta Interamericana. Centro de Investigaciones Biomédicas; Argentina Fil: Pérez Lloret, Santiago. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas; Argentina Fil: Fabbri, Margherita. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Azulay, Jean Philippe. Universidad de Aix-Marsella. Sistema de Hospitales Universitarios Públicos de Marsella; Francia Fil: Corvol, Jean-Christophe. Universidad de la Sorbona; Francia Fil: Corvol, Jean-Christophe. Hospital de la Pitié-Salpêtrière; Francia Fil: Corvol, Jean-Christophe. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Couratier, Philippe. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Damier, Philippe. Hospital Nord Laennec. Centro de Investigación Clínica; Francia Fil: Defebvre, Luc. Universidad en Lille; Francia Fil: Defebvre, Luc. Hospital Universitario de Marsella. Departamento de Neurología y Patología del Movimiento; Francia Fil: Durif, Franck. Centro Hospitalario Universitario, Clermont-Ferrand. Departamento de Neurología; Francia Fil: Durif, Franck. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Geny, Christian. Universidad de Montpellier. Departamento de Neurología; Francia Fil: Houeto, Jean-Luc. Centro Hospitalario Universitario de Limoges; Francia Fil: Houeto, Jean-Luc. Centro de referencia de atrofia multisistémica. Departamento de Neurología. Centro de Expertos en Parkinson; Francia Fil: Rascol, Olivier. Centro de referencia de atrofia multisistémica; Francia Fil: Remy, Philippe. Red Francesa de Infraestructura de Investigación Clínica. Centros Expertos en Parkinson; Francia Fil: Remy, Philippe. Instituto de Investigaciones Biomédicas Mondor; Francia Fil: Tranchant, Christine. Hospital Universitario de Estrasburgo. Red Francesa de Infraestructura de Investigación Clínica. Departamento de Neurología; Francia Fil: Verin, Marc. Universidad de Rennes. Hospital Universitario de Rennes. Red Francesa de Infraestructura de Investigación Clínica. Centro de expertos en Parkinson; Francia Fil: Tison, François. Centro de referencia de atrofia multisistémica. Departamento de Neurología de Enfermedades Neurodegenerativas; Francia Fil: Meissner, Wassilios G. Instituto de Investigación del Cerebro; Nueva Zelanda Fil: Meissner, Wassilios G. Universidad de Otago. Departamento de Medicina; Nueva Zelanda Abstract: Background: There are no effective treatments for multiple system atrophy (MSA). Objective: The objective of this study was to assess the efficacy and safety of the serotonin reuptake inhibitor fluoxetine (40 mg/d) for the symptomatic treatment of MSA. Methods: This was a double-blind, parallel-group, placebo-controlled, randomized trial in patients with "probable" MSA. The primary outcome was the change from baseline to week 12 in the mean total score of the Unified MSA Rating Scale (UMSARS Parts I + II). Secondary outcomes included change from baseline to week 6 in total UMSARS, and change from baseline to week 12 in the Scales for Outcomes in Parkinson Disease-Autonomic Dysfunction, Beck Depression Inventory, and different domains of the MSA-Quality of Life Questionnaire. Exploratory outcomes included change from baseline to week 12 in the UMSARS Parts I and II separately and change from baseline to week 24 in the total UMSARS score. Results: A total of 81 patients were randomly assigned, with no significant difference in the primary outcome (-2.13 units [95% confidence interval, CI, -4.55 to 0.29]; P = 0.08). There was a greater reduction on fluoxetine in the change from baseline to 12-week in UMSARS Part II (exploratory outcome: -1.41 units [95% CI, -2.84; 0.03]; p = 0.05) and in MSA-QoL emotional/social dimension (secondary outcome: -6.99 units [95% CI, -13.40; -0.56]; p < 0.03). A total of 5 deaths occurred (3 on fluoxetine and 2 on placebo). Conclusion: The MSA-FLUO failed to demonstrate fluoxetine superiority over placebo on the total UMSARS score, whereas trends in motor and emotional secondary/exploratory outcomes deserve further investigation.

Background The impact of prior exposure to systemic corticosteroids on COVID-19 severity in patients hospitalized for a SARS-CoV-2 pneumonia is not known. The present study was designed to answer to this question. Methods The population study was the Covid-Clinic-Toul cohort which records data about all hospitalized patients with a positive reverse transcriptase polymerase chain reaction for a SARS-CoV-2 infection at Toulouse University hospital, France. Exposure to systemic corticosteroids was assessed at hospital admission. A propensity score (PS) according to corticosteroid exposure was calculated including comorbidities, clinical, radiological and biological variables that impact COVID-19 severity. The primary outcome was composite, including admission to intensive care unit, need of mechanical ventilation and death occurring during the 14 days after hospital admission. Logistic regression models adjusted for the PS (overlap weighting) provided odds ratios (ORs) and their 95% confidence intervals (95% CIs). Results Overall, 253 patients were included in the study. Median age was 64 years, 140 patients (59.6%) were men and 218 (86.2%) had at least one comorbidity. Seventeen patients (6.7%) were exposed to corticosteroids before hospital admission. Chronic inflammatory disease (n = 8) was the most frequent indication. One hundred and twenty patients (47.4%) met the composite outcome. In the crude model, the OR of previous exposure to systemic corticosteroids was 1.64; 95% CI: 0.60–4.44. In the adjusted model, it was 1.09 (95% CI: 0.65–1.83). Conclusion Overall, this study provide some evidences for an absence of an increased risk of unfavorable outcome with previous exposure to corticosteroids in the general setting of patients hospitalized for COVID-19.

International audience; Data are lacking on the impact of ACEI/ARB exposure on unfavorable outcome in the population of patients hospitalized for COVID‐19 with hypertension/cardiovascular disease, particularly in Europe. The ACE‐CoV study was designed to assess this question. The study was conducted in the Covid‐Clinic‐Toul cohort, which contains data about all patients hospitalized at Toulouse University hospital, France with a SARS‐CoV‐2 infection since March, 2020. We selected the patients with a history of cardiovascular disease (heart failure or coronary disease) and/or arterial hypertension. We conducted a subgroup analysis in patients with arterial hypertension. ACEI/ARB exposures at admission were assessed. The outcome was composite: admission to intensive care unit, need of mechanical ventilation or death during the 14 days after admission to hospital. We used logistic regression models with propensity scores (PS) weighted by overlap weighting (OW) and inverse probability of treatment weighting (IPTW). Between March 2020 and April 20, 2020, the Covid‐Clinic‐Toul included 263 patients. Among them, 111 were included in the ACE‐CoV study population. In OW‐PS‐adjusted analyses, the association of exposure to ACEIs or ARBs with outcome occurrence was OR: 1.56 (95% CI: 0.73–3.33). It was 0.99 (95% CI: 0.68–1.45) for ACEIs and 1.64 (95% CI: 0.77–3.50) for ARBs. Analyses with weighting by the IPTW‐PS method gave similar results. Results were similar when considering the subgroup of patients with arterial hypertension. The ACE‐CoV study found no association between exposure to ACEIs or ARBs and unfavorable outcome in hospitalized patients for COVID‐19 with a history of cardiovascular disease/arterial hypertension.

International audience; Objectives: Pyrazinamide (PZA) has a controversial safety profile in older patients. We aimed to assess the frequency and risk factors for adverse drug reactions (ADRs) in patients over 75 years of age treated for tuberculosis with or without PZA.Methods: We conducted a retrospective monocentric study including patients aged over 75 years treated for active tuberculosis between 2008 and 2018. The frequency, type, seriousness, and causality assessment of ADRs to anti-tuberculosis treatment were compared between patients receiving PZA or not. Risk factors for ADRs were investigated using univariable and multivariable analyses by logistic regression.Results: Among the 110 patients included, 54 (49.1%) received PZA (group 1) and 56 (50.9%) did not (group 2). ADRs to anti-tuberculosis drugs occurred in 31 patients (57.4%) in groups 1 and 15 (26.8%) in group 2 (p = 0.003). PZA-related ADRs occurred in 40.7% of exposed patients. Frequency of renal ADRs was higher in group 1 (9.3% vs 0%; p = 0.026). Rates of hepatic (18.5% vs 12.5%; p = 0.38), digestive (22.2% vs 8.9%; p = 0.054), and allergic (14.8% vs 5.4%; p = 0.12) ADRs were numerically higher in group 1 although the differences were not statistically significant. Serious ADRs occurred more frequently in group 1 (24.1% vs 8.9%; p = 0.03). The use of PZA was the only independent risk factor for ADRs to anti-tuberculosis drugs (odds ratio 3.75, 95% CI 1.5-9.6; p = 0.0056). No risk factors for PZA-related ADRs were identified.Conclusion: In older French patients, the use of PZA was associated with more frequent ADRs to anti-tuberculosis drugs.

Background Despite known limitations, the decision to operate on abdominal aortic aneurysm (AAA) is primarily on the basis of measurement of maximal aneurysm diameter. Purpose To identify volumetric and computational fluid dynamics parameters to predict AAAs that are likely to progress in size. Materials and Methods This study, part of a multicenter prospective registry (NCT01599533), included 126 patients with AAA. Patients were sorted into stable (≤10-mL increase in aneurysm volume) and progression (>10-mL increase in aneurysm volume) groups. Initial AAA characteristics of the derivation cohort were analyzed (maximal diameter and surface, thrombus and lumen volumes, maximal wall pressure, and wall shear stress [WSS]) to identify relevant parameters for a logistic regression model. Model and maximal diameter diagnostic performances were assessed in both cohorts and for AAAs smaller than 50 mm by using area under the receiver operating characteristic curve (AUC). Results Eighty-one patients were included (mean age, 73 years ± 7 years [standard deviation]; 78 men). The derivation and validation cohorts included, respectively, 50 and 31 participants. In the derivation cohort, there was higher mean lumen volume and lower mean WSS in the progression group compared with the stable group (60 mL ± 14 vs 46 mL ± 18 [P = .005] and 66% ± 6 vs 53% ± 9 [P = .02], respectively). Mean lumen volume and mean WSS at baseline were correlated to total volume growth (r = 0.47 [P = .002] and -0.42 [P = .006], respectively). In the derivation cohort, a regression model including lumen volume and WSS to predict aneurysm enlargement was superior to maximal diameter alone (AUC, 0.78 vs 0.52, respectively; P = .003); although no difference was found in the validation cohort (AUC, 0.79 vs 0.71, respectively; P = .51). For AAAs smaller than 50 mm, a regression model that included both baseline WSS and lumen volume performed better than maximal diameter (AUC, 0.79 vs 0.53, respectively; P = .01). Conclusion Combined analysis of lumen volume and wall shear stress was associated with enlargement of abdominal aortic aneurysms at 1 year, particularly in aneurysms smaller than 50 mm in diameter. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Mitsouras and Leach in this issue.

Summary Purpose To describe drug prescriptions in pregnant women in France and to identify teratogenic and fetotoxic drug prescriptions. Methods This study was carried out using data from Echantillon Generaliste des Beneficiaires (EGB), a French national health database which includes 1/97th of the French population. Our study population included all pregnant women, aged 10 to 60, who were registered in the EGB and had a pregnancy outcome between 2015 and 2016. Drugs prescribed and dispensed to women during pregnancy and the 3 months before, were collected and described for each year and according to pregnancy trimesters. Prescriptions of major teratogen or fetotoxic drugs were described. Results We identified 18,279 pregnancies. Among them, 93% received drug prescriptions and dispensations during pregnancy with an average of 7.4 ± 5.5 different drugs. “Alimentary tract and metabolism (75.4%)”, “nervous system (64.0%)” and “blood and blood forming organs (58.7%)” classes were the most frequently prescribed to pregnant women. The 5 most frequently prescribed drugs were paracetamol (60.6%), iron (49.2%), folic acid (45.6%), phloroglucinol (44.0%) and colecalciferol (41.4%). The most commonly prescribed drugs included some that have not yet been well evaluated in pregnancy. Prescriptions and dispensations of teratogenic or fetotoxic drugs, as Non-Steroidal Anti-Inflammatory Drugs and retinoids were observed. Valproic acid prescriptions to pregnant women have become extremely rare. Conclusion This descriptive study demonstrates that numerous drugs are prescribed and dispensed to pregnant women in France. These include drugs with a proven teratogenic or fetotoxic effect and many drugs that have not yet been well evaluated in pregnancy.

Introduction: Target mismatch (TMM) identifies salvageable penumbra independent of time from stroke onset. Current guidelines do not recommend advanced imaging to select patients for mechanical thrombectomy (MT) within 6 hours after onset but indicate that more research is needed. To address this question, we designed a prospective multicenter cohort study to compare the rate of functional neurological recovery (mRS ≤2 @ 3 months) in patients treated by MT for ICA/M1/M2 occlusions within 6 hours after onset according to the presence of a TMM on baseline imaging. Hypothesis: 60% of patients with TMM vs. 35% of no TMM, would achieve an mRS≤2 at 3 months. Sample size calculation: 200 patients. Methods: Consecutive patients eligible for MT within 6 hrs after onset, who underwent CTP or DWI/PWI imaging before treatment were enrolled. No NIHSS or ASPECTS restrictions were applied. Treating teams were blinded of CTP/DWI/PWI maps. mRS at 3 months was rated by an investigator blinded to clinical/imaging/treatment information. Automatically processed maps by RAPID software were reviewed after the end of follow-up. TMM definition followed EXTEND-IA criteria: MM volume >10mL, MM ratio>1.2, Core volume 1.2 and MM volume>10 mL. Imaging-based subgroups (TMM vs. No TMM) were defined after the end of follow-up. Results: 218 patients were enrolled. Baseline imaging profile distribution was 71% TMM, 29% no TMM, (in the no TMM group, 76% had a core volume > 70 mL); 82% MM and 18% no MM. Reperfusion(TICI 2B-3) was achieved in 86% of the patients after a median delay of 4.4 hrs (95%CI 3.6-5.9). 61% of the patients in the TMM group vs. 35% in the no TMM group had an mRS ≤2 @ 3 months, p Conclusion: Patients with salvageable penumbra on advanced imaging experienced a larger benefit from MT than those without. Patients with no penumbra did not appear to benefit from reperfusion.

Three studies have suggested a potential positive association between the use of tamoxifen in breast cancer and Parkinsonism, mainly after long-term exposure. To explore this potential signal, we performed a case/non-case study using the World Health Organization Global Individual Case Safety Reports (ICSRs) database, VigiBase® between 1979 and 2018. Among women ≥ 55 years, we measured the risk of reporting “Parkinsonism” compared with all other adverse drug reactions [as a reporting odds ratio (ROR 95% CI)] for tamoxifen compared to all other drugs or aromatase inhibitors. During the study period, 356 ICSRs of Parkinsonism reported with tamoxifen were identified. We failed to find a positive association between tamoxifen exposure and Parkinsonism in comparison with exposure to other drugs (ROR = 0.79; 95% CI 0.71–0.88) or aromatase inhibitors (ROR = 0.39; 95% CI 0.33–0.46). This study did not find evidence for Parkinsonism associated with tamoxifen.

Background and objectives Noncirrhotic nontumoral extrahepatic portal vein obstruction (EHPVO) is the second leading cause of portal hypertension (PHT) and is mainly related to prothrombotic disorders. Patients with EHPVO often require prolonged oral anticoagulation therapy (OAT) together with variceal band ligation (VBL) to prevent thrombosis recurrence and PHT-related bleeding, respectively. The benefit-risk balance of VBL in this context remains unknown. We aimed to assess upper gastrointestinal bleeding (UGB) risk and variceal eradication efficacy in EHPVO patients undergoing a VBL program without stopping OAT. Patients and methods All patients with EHPVO treated (group A) or not (group B) with OAT and undergoing the VBL program were included between 2001 and 2010 in two tertiary French liver centers. We compared the incidence, source, and severity of UGB and variceal eradication efficacy. All EHPVO patients were then matched 1 : 1 with compensated cirrhotic patients with PHT not receiving OAT (group C) to compare UGB incidence and VBL efficacy. Results Forty-three EHPVO patients (30 with and 13 without OAT) and 43 cirrhotic patients were included for a total of 471 VBL sessions. The incidence of UGB was similar between group A (nine episodes/121 sessions) and group B (6/130), and tended to be higher in EHPVO patients (group A and B) than in cirrhotic patients (2/220). There was no difference between groups when considering bleeding source or severity and variceal eradication efficacy (84%). Conclusion VBL can be performed safely and efficiently without stopping anticoagulation therapy in EHPVO patients.

The aim of this study was to compare the infectious risk between a group of psoriasis patients treated by biological drugs (BD) and a group treated by traditional systemic treatments (TST). We built a retrospective observational cohort study from the French health insurance database in the Midi-Pyrénées area (2.9 million inhabitants, southwest of France) using data from 01/01/2010 to 12/31/2013. We compared the infectious risk between 'exposed' patients treated with BD (adalimumab, etanercept, infliximab, or ustekinumab) and 'unexposed' patients treated by TST (phototherapy, acitretin, methotrexate, or cyclosporine). We realized a survival analysis on the first infectious event, defined as an anti-infective drug delivery or a hospital diagnosis of infection. We selected 101 'exposed' and 788 'unexposed' patients. In our multivariate Cox model, 'exposure' did not seem to decrease the time frame of the first infectious event compared with 'nonexposure' (HR = 0.94, P = 0.62). Among all treatment, the safest seemed to be ustekinumab while the least safe was etanercept. We found factors statistically associated with the risk of infection: gender (female vs. male), economic deprivation, chronic hepatitis B or C, history of cancer, at least one infectious event, and the number of different drugs during the 6-month period before the study. We did not find any difference of infective risk between the BD and the TST. This result enhances the recent PSONET registries conclusions.

Introduction Simulation studies showed that generic antiretroviral (ARV) drug utilization could lead to significant cost reduction of HIV treatment in developed world. This study aimed to quantify ARV utilization and costs in European countries between 2006 and 2015. We also assessed the impact of generic ARV drug utilization on cost reduction in real-life. Methods ARV drug utilization in 14 European countries (France, Italy, Germany, Denmark, Netherlands, Norway, Sweden, Finland, Iceland, Croatia, Czech Republic, Estonia, Latvia, and Lithuania) were analysed using defined daily dose (DDD)/1000 inhabitants/year. ARV drug cost was estimated in million euro/year and euro/1000 inhabitants/year. The impact of generics on cost reduction was assessed in three countries: France, Denmark, and Czech Republic, using four parameters: expected savings, observed savings, brand price-reduction savings and overall savings. Results Between 2006 and 2015, median ARV drug utilization increased from 234 DDDs per 1000 inhabitants per year (IQR 124–388) to 385 (229–670). The median cost increased from €3751/1000 inhabitants/year (1109–4681) to €9158 (3269–10,646). Between 2013 and 2015, overall savings of €0.9, €1.6, and €33.7 million were respectively observed in Denmark, Czech Republic, and France. Conclusion Overall savings observed in real-life from generic ARV drugs in Denmark were related to high rate of low-price generic utilization, contrarily to France and Czech Republic where these were more related to brand price-reduction than generic utilization itself.

Background Acute convexity subarachnoid hemorrhage (cSAH) and cortical superficial siderosis (cSS) are neuroimaging markers of cerebral amyloid angiopathy (CAA) that may arise through similar mechanisms. We sought to compare the prevalence of cSS between patients with CAA presenting with acute cSAH versus lobar intracerebral hemorrhage (ICH), and to explore the physiopathology of cSS by examining neuroimaging associations. Methods We retrospectively analyzed data from 116 consecutive patients with probable CAA (mean age, 77.4 ± 7.3 years) presenting with acute cSAH (n = 45) or acute lobar ICH (n = 71). MRI scans were analyzed for cSS and other imaging markers. We compared the two groups’ clinical and imaging data and explored the associations between cSAH and cSS. Results Patients with cSAH presented mostly with transient focal neurological episodes. Prevalence of cSS was higher among cSAH patients than among ICH patients (88.9% vs. 57.7%; p < 0.001). In multivariable logistic regression analysis, focal (OR: 6.73; 95% CI: 1.75–25.81; p = 0.005) and disseminated (OR: 11.68; 95% CI: 3.55–38.35; p < 0.001) cSS were independently associated with acute cSAH, whereas older age (OR: 0.93; 95% CI: 0.87–0.99; p = 0.025) and chronic lobar ICH count (OR: 0.45; 95% CI: 0.25–0.80; p = 0.007) were associated with acute lobar ICH. Conclusions Among patients with CAA, cSS is independently associated with acute cSAH. These findings suggest that cSAH may be involved in the pathogenesis of the cSS observed in CAA. Longitudinal studies are warranted to assess this potential causal relationship. This article is protected by copyright. All rights reserved.

Objectives In recent clinical trials some cardiac arrhythmias were reported with use of remdesivir for COVID-19. To address this safety concern, we investigated whether use of remdesivir for COVID-19 is associated with an increased risk of bradycardia. Methods Using VigiBase®, the World Health Organization Global Individual Case Safety Reports database, we compared the cases of bradycardia reported in COVID-19 patients exposed to remdesivir with those reported in COVID-19 patients exposed to hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. All reports of patients with COVID-19 registered up to the 23th of September 2020 were included. We conducted disproportionality analyses allowing the estimation of reporting odds ratios (RORs) with 95% Confident Intervals (95% CI). Results We found 302 cardiac effects including 94 bradycardia (31%) among the 2,603 reports with remdesivir prescribed in COVID-19 patients. Most of reports were serious (75, 80%) and in 16 reports (17%) evolution was fatal. Compared with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids, the use of remdesivir was associated with an increased risk of reporting bradycardia (ROR 1.65; 95% CI 1.23, 2.22). Consistent results were observed in other sensitivity analyses. Conclusions This post-marketing study in a real-world setting suggests that the use of remdesivir is significantly associated with an increased risk of reporting bradycardia and serious bradycardia when compared with the use of with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. This result is in line with pharmacodynamic properties of the remdesivir.

Resume Objectif Cet article propose une description de la consommation regionale francaise d’antibiotiques fortement pourvoyeurs de resistances bacteriennes (amoxicilline + acide clavulanique, cephalosporines de 3e generation et fluoroquinolones). Methodes Les donnees de remboursements des antibiotiques ont ete obtenues via Open Medic. Le profil de consommation a ete etabli par certains indicateurs de l’European Surveillance of Antimicrobial Consumption (ESAC) exprimes en daily defined dose per 1000 inhabitants per day (DID) et/ou en pourcentages. Resultats Provence-Alpes-Cote d’Azur-Corse (34,4 DID) et Midi-Pyrenees-Languedoc-Roussillon (33,5 DID) consomment le plus d’antibiotiques systemiques et d’antibiotiques pourvoyeurs de resistances. Les regions Pays-de-la-Loire (26,7 DID), Bretagne (29,1 DID), Centre-Val-de-Loire (29,7 DID) et Auvergne-Rhone-Alpes (29,7 DID) consomment le moins d’antibiotiques systemiques et d’antibiotiques pourvoyeurs de resistances. Conclusion Meme si de nombreux facteurs environnementaux et socioeconomiques pouvaient expliquer cette variabilite de consommation entre les regions francaises, une correlation entre volume de consommation et mesusage n’est pas a exclure.

Study objectives Morphine is the reference treatment for severe acute pain in an emergency department. The purpose of this study was to describe and analyse opioid-related ADRs (adverse drug reactions) in a large cohort of emergency department patients, and to identify predictive factors for those ADRs. Methods In this prospective, observational, pharmaco-epidemiological international cohort study, all patients aged 18 years or older who were treated with morphine were enrolled. The study was done in 23 emergency departments in the US and France. Baseline numerical rating scale score and initial and total doses of morphine titration were recorded. Logistic regression analysis was used to study the effects of demographic, clinical and medical history covariates on the occurrence of opioid-induced ADRs within 6 h after treatment. Results A total of 1128 patients were included over 10 months. Median baseline initial pain scores were 8/10 (7–10) versus 3/10 (1–4) after morphine administration. Median titration duration was 10 min (IQR, 1–30). The occurrence of opioid-induced ADRs was 25% and 2% were serious. Patients experienced mainly nausea and drowsiness. Medical history of travel sickness (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.01–2.86) and history of nausea or vomiting post morphine (OR, 3.86; 95% CI, 2.29–6.51) were independent predictors of morphine related ADRs. Conclusion Serious morphine related ADRs are rare and unpredictable. Prophylactic antiemetic therapy could be proposed to patients with history of travel sickness and history of nausea or vomiting in a postoperative setting or after morphine administration.

The potential favorizing role of drugs in sleep apnea syndrome (SAS) is unknown. This study investigates drugs associated with SAS in a pharmacovigilance database. SAS recorded as adverse drug reactions (ADRs) in VigiBase® , the WHO pharmacovigilance database (more than 11 million reports), from 1978 to 2015 was selected. The risk of SAS reports was estimated using the case-noncase method, with cases being SAS and noncases all other recorded ADRs. During this 37-year period, 3325 ADRs including the word SAS were registered (0.05% of the database). Mean age was 51.2 ± 16.9 years with 52% men. ADRs were 'serious' in around 82% of cases. The case-noncase study found an association between SAS and exposition with sodium oxybate, rofecoxib, quetiapine, and clozapine for individual drugs and coxibs, antipsychotics, benzodiazepines, and opium alkaloids for drug classes. The potential role of other drugs is discussed. This study suggests that SAS can be associated with some drugs (mainly psychotropics) that are able to reveal or aggravate such a disease. Physicians should take into account the role of drugs in the etiological appraisal and management of SAS.

The purpose of this study was to measure the rate of substitution failure to generic antiepileptic drugs (AEDs) compared to two other pharmacotherapeutic classes (neuroleptics, beta-blockers). We conducted a cohort study involving beneficiaries of the French health insurance system from January 2009 to November 2012. Substitution failure to generic drugs was estimated by the rate of switchback (i.e. from generic drug back to its branded drug). We selected the patients who had a dispensation of a branded AED for 60 days or more during the 90 days preceding the generic substitution. Cox proportional hazard regression was used to model time to switchback for antiepileptics vs. other therapeutic classes in the 90 days after generic substitution, adjusting for age, gender and polytherapy. The cohort included 6727 patients of whom 1947 were exposed to AEDs, 2398 to neuroleptics and 2382 to beta-blockers. The switchback rate was 62% for AEDs. AED users were more likely to switch back as compared to beta-blocker (crude hazard ratio 1.87; 95% CI 1.68–2.07 for patients under 75) or neuroleptic users. The same observation was made in patients above 75 years (crude hazard ratio 1.36; 95% CI 1.16–1.60). Compared to beta-blocker users, AED users were more likely to switch back to the branded drug, whereas this difference was not observed with neuroleptics. These results could reflect a poor acceptance of switching AEDs to generic compounds in France.

Hypotension frequently occurs during spinal anesthesia (SA), especially in the elderly. Phenylephrine is effective to prevent SA-induced hypotension during cesarean delivery. The objective of this study was to evaluate the efficacy and safety of prophylactic infusion of phenylephrine after SA for orthopedic surgery in the elderly.This prospective, randomized, double-blind, and placebo-controlled study included 54 patients older than 60 years undergoing elective lower limb surgery under SA (injection of 10 mg of isobaric bupivacaine with 5 μg of sufentanyl).Patients were randomized to group P (100-μg/mL solution of phenylephrine solution at 1 mL/min after placement of SA) or the control group C (0.9% isotonic sodium chloride solution). The flow of the infusion was stopped if the mean arterial blood pressure (MAP) was higher than the baseline MAP and maintained or restarted at 1 mL/min if MAP was equal to or lower than the baseline MAP. Heart rate and MAP were collected throughout the case.Hypotension was defined by a 20% decrease and hypertension as a 20% increase from baseline MAP. Bradycardia was defined as a heart rate lower than 50 beats per minute.Twenty-eight patients were randomized to group P and 26 patients to group C. MAP was higher in group P than in group C (92 ± 2 vs 82 ± 2 mm Hg, mean ± SD, P.001). The number of hypotensive episodes per patient was higher in group C compared with group P (9 [0-39] vs 1 [0-10], median [extremes], P.01), but the number of hypotensive patients was similar between groups (19 [73%] vs 20 [71%], P= 1). The time to onset of the first hypotension was shorter in group C (3 [1-13] vs 15 [1-95] minutes, P= .004). The proportion of patients without hypotension (cumulative survival) was better in group P (P= .04). The number of hypertensive episodes per patient and the number of bradycardic episodes per patient were similar between groups (P= not significant).Prophylactic phenylephrine infusion is an effective method of reducing SA-induced hypotension in the elderly. Compared with a control group, it delays the time to onset of hypotension and decreases the number of hypotensive episodes per patient. More data are needed to evaluate clinical outcomes of such a strategy.

Pain after tumorectomy and sentinel lymph node dissection is poorly reported in the literature. We carried out a prospective survey aimed at assessing pain three months after such minor surgery for breast cancer. The study was approved by the local ethics committee. Most surgeries followed a standard protocol involving general anesthesia with no regional analgesia technique, laryngeal mask, sufentanil and propofol for induction, and multimodal analgesia during the postoperative period. Three months after the surgery, a questionnaire was sent to the patients with a pre-stamped envelope for return. The questions probed responses required to calculate a Brief Pain Inventory score and modified neuropathic pain score (DN3). Over a 5-month period, 150 patients (aged 60 (11) years, body mass index of 25 (6) kg/m2) were included in the final analysis. In the recovery room, 43% of patients required morphine at a mean dose of 5.2 (1.8) mg. Three months post surgery, 60 patients (40%) reported persistent pain for which 62% took analgesic drugs. We found no risk factor associated with this persistent pain among our studied population. Neuropathic pain was noted in 61% of patients who reported persistent pain primarily associated with periareolar incision. Pain persisted up to three months after minor surgery for breast cancer in 40% of patients with mostly a neuropathic component (61%).