New treatment options for lupus – a focus on belimumab

Belimumab is the first biologic approved for patients with systemic lupus erythematosus (SLE). Belimumab is the first of a new class of drug targeting B cell-stimulating factors or their receptors to reach the market. Its target, BLyS, also known as BAFF (B cell-activating factor from the tumor necrosis factor family), is a type II transmembrane protein that exists in both membrane-bound and soluble forms. Additionally to a robust rational from murine experiments conducted in lupus prone mice, BLyS circulating levels are increased in SLE patients. After the negative results of a Phase II trial, two Phase III trials met their primary endpoints. Some SLE patients are still refractory to the standard options of care or necessitate prolonged high-dose corticotherapy and/or long-term immunosuppressive regimens. However, some experts still feel that the effect of this biologic might not be clinically relevant and blame the use of the new systemic lupus response index as well as the discrepancies between both trials and the noninclusion of the severe form of the disease as nephritis. In this review, we aim to discuss the characteristics of belimumab, critically evaluate the different steps of its development, and consider its future place in the arsenal against SLE, taking into account the patients’ perspectives

Management of adult Clostridium difficile digestive contaminations: a literature review

WOS:000457394800002Clostridium difficile infections (CDI) dramatically increased during the last decade and cause a major public health problem. Current treatments are limited by the high disease recurrence rate, severity of clinical forms, disruption of the gut microbiota, and colonization by vancomycin-resistant enterococci (VRE). In this review, we resumed current treatment options from official recommendation to promising alternatives available in the management of adult CDI, with regard to severity and recurring or non-recurring character of the infection. Vancomycin remains the first-line antibiotic in the management of mild to severe CDI. The use of metronidazole is discussed following the latest US recommendations that replaced it by fidaxomicin as first-line treatment of an initial episode of non-severe CDI. Fidaxomicin, the most recent antibiotic approved for CDI in adults, has several advantages compared to vancomycin and metronidazole, but its efficacy seems limited in cases of multiple recurrences. Innovative therapies such as fecal microbiota transplantation (FMT) and antitoxin antibodies were developed to limit the occurrence of recurrence of CDI. Research is therefore very active, and new antibiotics are being studied as surotomycin, cadazolid, and rinidazole

Pathophysiology and treatment of typical and atypical haemolytic uremic syndrome.

International audienceHemolytic uremic syndrome is a rare disease, frequently responsible for renal insufficiency in children. Recent findings have led to renewed interest in this pathology. The discovery of new gene mutations in the atypical form of HUS and the experimental data suggesting the involvement of the complement pathway in the typical form, open new perspectives for treatment. This review summarizes the current state of knowledge on both typical and atypical hemolytic uremic syndrome pathophysiology and examines new perspectives for treatment.Le syndrome hémolytique urémique est une maladie rare, souvent responsables de l'apparition d une insuffisance rénale chez les enfants. Des découvertes récentes ont conduit à un regain d'intérêt dans cette pathologie. La découverte de nouvelles mutations génétiques dans la forme atypique et les données expérimentales suggérant l'implication de la voie du complément dans la forme typique ouvrent de nouvelles perspectives pour le traitement. Cette revue résume l'état actuel des connaissances sur la physiopathologie du syndrome hémolytique urémique typique et atypique et présente les nouvelles perspectives de traitement

Chickenpox: An update

WOS:000458597200001Despite its benign characteristics, chickenpox is a childhood disease responsible for complications and deaths, particularly in the high-risk population. VariZIG (R), not commercialized in France, is a good alternative for seronegative individuals exposed to the virus and not eligible for vaccination. The efficacy of routine vaccination has been demonstrated with a decrease in chickenpox incidence and with the development of herd immunity. Over time, the protective antibody titer of vaccinated people decreases and can be maintained by two doses of the vaccine. A tetravalent measles-mumps-rubella-chickenpox vaccine, used in the United States, has a good tolerability in spite of the occurrence of fever and febrile seizures. Routine vaccination would contribute to make savings in France, by reducing direct and indirect costs of chickenpox. (C) 2018 Elsevier Masson SAS. All rights reserved

Pathophysiology and treatment of typical and atypical haemolytic uremic syndrome.

International audienceHemolytic uremic syndrome is a rare disease, frequently responsible for renal insufficiency in children. Recent findings have led to renewed interest in this pathology. The discovery of new gene mutations in the atypical form of HUS and the experimental data suggesting the involvement of the complement pathway in the typical form, open new perspectives for treatment. This review summarizes the current state of knowledge on both typical and atypical hemolytic uremic syndrome pathophysiology and examines new perspectives for treatment.Le syndrome hémolytique urémique est une maladie rare, souvent responsables de l'apparition d une insuffisance rénale chez les enfants. Des découvertes récentes ont conduit à un regain d'intérêt dans cette pathologie. La découverte de nouvelles mutations génétiques dans la forme atypique et les données expérimentales suggérant l'implication de la voie du complément dans la forme typique ouvrent de nouvelles perspectives pour le traitement. Cette revue résume l'état actuel des connaissances sur la physiopathologie du syndrome hémolytique urémique typique et atypique et présente les nouvelles perspectives de traitement

Misuse of antibiotics reserved for hospital settings in outpatients: a ă prospective clinical audit in a university hospital in Southern France

26th European Congress of Clinical Microbiology and Infectious Diseases ă (ECCMID), Amsterdam, NETHERLANDS, APR 09-12, 2016International audienceSome antibiotics are reserved essentially for hospital settings owing to ă cost effectiveness and in order to fight the emerging antibiotic ă resistance crisis. In some cases, antibiotics reserved exclusively for ă use in hospitals may be prescribed in outpatients for serious infections ă or in the absence of a therapeutic alternative. A 30-day prospective ă audit of outpatient prescriptions of antibiotics reserved exclusively ă for use in hospitals was performed. The objective of this study was to ă evaluate the relevance of outpatient antibiotic prescriptions by ă measuring appropriateness according to guidelines. During the study ă period, 53 prescriptions were included, only 40% of which were ă appropriate. Among the 32 inappropriate prescriptions, 4 cases lacked ă microbial arguments, 1 case was not adequate for the infection type, 1 ă case involved an incorrect antibiotic dosage, 1 case involved an ă incorrect interval of dose administration, 3 cases had a therapeutic ă alternative and 22 cases were not recommended. Of the 53 prescriptions, ă 66% were started in hospital and 34% in outpatients. Only 25% of ă cases were prescribed with infectious diseases specialist (IDS) advice, ă 64% were based on microbiological documentation and 13% had a negative ă bacterial culture. Inappropriate prescriptions were usually observed in ă antibiotic lock therapy, skin infections, Clostridium difficile colitis, ă intra-abdominal infections and intravascular catheter-related ă infections. Outpatient prescriptions of antimicrobial drugs reserved ă exclusively for use in hospitals are frequently inappropriate. We ă recommend a real-time analysis algorithm with the involvement of an IDS ă for monitoring prescriptions to improve the quality of these ă prescriptions and possibly to prevent antibiotic resistance. (C) 2016 ă Elsevier B. V. and International Society of Chemotherapy. All rights ă reserved

Environmental monitoring by surface sampling for cytotoxics: a review

International audienceObject: Environmental monitoring is usually conducted by surface sampling to detect and quantify the presence of cytotoxic drugs after their reconstitution and administration. This technique reveals the origins of residual contamination and is an important component in order to protect healthcare workers from the potential risk of occupational exposure. The aim of this work is to compare various techniques and results of surface sampling for cytotoxics.Materials and methods: For each technique, sample processing methods and their analysis were compared from literature data. Sampling is often performed by the wiping technique. After treatment, various single or multi-compound technical analyses are used, in particular liquid or gas chromatography involving different detection methods: ultraviolet, mass spectrometry, plasma torch, voltammetry. Some methods are validated to ensure reliability.Results: Despite published guidelines and the use of isolator technology for the preparation of cytotoxic drugs, workplace contamination persists, leading to chemotherapeutic agents’ exposure of healthcare workers. Efforts need to be maintained with particular emphasis on harmonization and on determining alert level for cytotoxic contamination

Stability Study of Parenteral N-Acetylcysteine, and Chemical Inhibition of Its Dimerization

Parenteral N-acetylcysteine has a wide variety of clinical applications, but its use can be limited by a poor chemical stability. We managed to control parenteral N-acetylcysteine stability, and to study the influence of additives on the decrease of N-acetylcysteine degradation. First, an HPLC-UV dosing method of N-acetylcysteine and its main degradation product, a dimer, was validated and the stability without additive was studied. Then, the influence of several additives (ascorbic acid, sodium edetate, tocopherol and zinc) and of temperature on N-acetylcysteine dimerization was evaluated. Finally, the influence of zinc gluconate at different concentrations (administrable to patients) was investigated. Zinc gluconate at 62.5 µg·mL−1 allows the stabilization of 25 mg·mL−1 N-acetylcysteine solution for at least 8 days when stored at 5 ± 3 °C