Neutralising Antibodies against Ricin Toxin

The Centers for Disease Control and Prevention have listed the potential bioweapon ricin as a Category B Agent. Ricin is a so-called A/B toxin produced by plants and is one of the deadliest molecules known. It is easy to prepare and no curative treatment is available. An immunotherapeutic approach could be of interest to attenuate or neutralise the effects of the toxin. We sought to characterise neutralising monoclonal antibodies against ricin and to develop an effective therapy. For this purpose, mouse monoclonal antibodies (mAbs) were produced against the two chains of ricin toxin (RTA and RTB). Seven mAbs were selected for their capacity to neutralise the cytotoxic effects of ricin in vitro. Three of these, two anti-RTB (RB34 and RB37) and one anti-RTA (RA36), when used in combination improved neutralising capacity in vitro with an IC50 of 31 ng/ml. Passive administration of association of these three mixed mAbs (4.7 µg) protected mice from intranasal challenges with ricin (5 LD50). Among those three antibodies, anti-RTB antibodies protected mice more efficiently than the anti-RTA antibody. The combination of the three antibodies protected mice up to 7.5 hours after ricin challenge. The strong in vivo neutralising capacity of this three mAbs combination makes it potentially useful for immunotherapeutic purposes in the case of ricin poisoning or possibly for prevention

Instruments and factors associated with quality of life in systemic lupus erythematosus

Le lupus érythémateux disséminé (LES) est une maladie systémique auto-immune chronique dont le retentissement sur la vie des patients est très lourd. Au cours de la décennie écoulée, des échelles de qualité de vie spécifique du lupus systémique ont été développées pour compléter les données obtenues avec les questionnaires génériques. Dans une première partie de ce travail, nous exposons la définition du concept de qualité de vie et les différentes manières de la mesurer. Nous présentons ensuite l’état des connaissances sur les facteurs influençant la qualité de vie au cours du LES. Dans une seconde partie, nous exposons les résultats obtenus sur une cohorte de 182 patients atteints de LES (étude FRESHQOLA) ayant pour but de valider la version française du questionnaire spécifique LupusQoL. La validité et la fiabilité du questionnaire étaient satisfaisantes. Dans une seconde partie, nous présentons les résultats de la sensibilité au changement du même questionnaire, et nous montrons que le LupusQoL permet de capter un changement dans l’état de santé des patients, et qu’il serait plus sensible au changement que le questionnaire générique SF-36 pour mesurer une amélioration de leur état de santé. Dans une troisième partie, nous présentons les résultats de l’étude EQUAL sur 330 patients ayant pour objectif la validation du questionnaire SLEQOL. Outre la fiabilité et la validité du questionnaire, nous avons réalisé une analyse de fonctionnement différentiel d’item entre les patients de notre cohorte et un échantillon de patients issus de la cohorte de développement de l’échantillon à Singapour. Le SLEQOL était fiable et valide malgré 4 items montrant un fonctionnement différentiel modéré. Dans une quatrième partie, nous présentons l’analyse des facteurs associés à la qualité de vie mesurée par les questionnaires spécifiques LupusQoL, SLEQOL et les questionnaires génériques SF-36 et WHOQOL dans cette même cohorte de 330 patients. La qualité de vie dans les domaines physique, mental et social était fortement associée aux facteurs socio-économiques et en particulier la précarité sociale, telle que mesurée par le score EPICES. Les femmes avaient une altération de la qualité de vie spécifique, tandis que le surpoids et le tabagisme influençaient les questionnaires génériques mais pas les questionnaires spécifiques, suggérant que dans ces situations, les patients n’attribuent pas la gêne à leur lupus. Enfin, l’atteinte articulaire était la manifestation clinique de la maladie la plus fortement associée à une diminution de la qualité de vie. Ces résultats ouvrent donc des perspectives dans la compréhension du retentissement du lupus systémique sur le quotidien des patients et nous permettront de mieux comprendre les résultats des essais cliniques et études épidémiologiques à venir.Systemic Lupus Erythematosus (SLE) is a chronic systemic auto-immune disease that considerably impairs patients’ daily living. During the past 10 years, disease-specific health related quality of life questionnaires have been developed in order to complete the information obtained using generic questionnaires in SLE patients. In the first part of our work, we present the definition of the concept of quality of life and the different way to measure it. In the second part, we present the results of a cohort study of 182 SLE patients that aimed to validate the French version of the SLE-specific questionnaire LupusQoL. Validity and reliability of the questionnaire were found to be satisfactory. In the second part, we present the results concerning responsiveness of the same questionnaire. We showed that LupusQol was able to capture a change in patients’ health state, and that it could be more responsive than the generic SF-36 questionnaire in patients with improving symptoms. In the third part, we present the results of a study involving 330 patients that aimed to validate the SLEQOL questionnaire. Besides determining the validity and reliability of the questionnaire, we conducted a differential item functioning analysis between patients of our cohort and patients from the development cohort of the SLEQOL in Singapore. The SLEQOL was found to be reliable and valid despite 4 items showing a moderate differential item functioning. In the fourth part, we present the results of the analysis of factors associated with quality of life in SLE patients, as measured by SLEQOL and LupusQoL specific questionnaires, and WHOQOL and SF-36 generic questionnaires in the same cohort of 330 patients. Quality of life in physical, mental and social domains was strongly associated with socio-economic factors, especially the social precariousness, as measured by the EPICES score. Women had a lower generic quality of life, whereas overweight and smoking influenced the generic questionnaires but not the specific ones, suggesting that in those situation, patients did not attribute their problem to lupus. Finally, articular involvement of the disease was the clinical symptom with the strongest association with quality of life impairment. This study opens up new areas of research that will lead to better understanding of SLE burden and improve the interpretation of results from future clinical trials and epidemiological studies

Facteurs influençant l'immunogénicité d'un vaccin contre la grippe pandémique A (H1N1) 2009 chez les patients atteints de lupus érythémateux systémique

DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF

Le Talc (de son extraction à ses utilisations)

Le talc, minéral utilisé depuis des millénaires par l'homme n'a jamais été aussi présent dans notre vie de tous les jours qu'aujourd'hui via une utilisation dans différentes industries, mais également dans le domaine de la santé. En effet, le minéral le plus tendre de la planète possède des propriétés très intéressantes comme par exemple un fort pouvoir lubrifiant et anti-collant ainsi qu'une bonne inertie chimique. Grâce à ses caractéristiques particulières, le talc est utilisé dans de nombreux secteurs allant de l'industrie papetière à l'industrie cosmétique en passant par l'industrie agro-alimentaire. Il est utilisé de façon notable dans l'industrie pharmaceutique lors de la fabrication des comprimés. Cet usage nécessite un talc de grande qualité, qui dès son extraction fera l'objet d'un tri méticuleux. La carrière la plus grande d'Europe se situe à Luzenac, en Ariège. Son exploitation témoigne de la rigueur nécessaire à l'obtention de talc et suit une politique de développement durable bien définie. Le talc, qui a autrefois été impliqué malgré lui dans des drames comme l'affaire du talc Morhange est devenu un thème d'études concernant une toxicité éventuelle lors de son inhalation ou d'un usage périnéal. De plus, de par son origine, il peut se retrouver contaminé par de l'amiante, compliquant ainsi parfois ces investigations.TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Survival Analysis is Preferable to a Count of Events When Assessing the Effects of Tobacco Exposure in Systemic Lupus Erythematosus: Comment on the Article by Montes et al

SCOPUS: le.jFLWINinfo:eu-repo/semantics/publishe

Clinical trial outcomes for SLE: what we have and what we need

The paradigm of drug approval in SLE currently relies on successful large phase III randomised controlled trials and a set of primary, secondary and additional end points. Taken together, these outcomes offer a nuanced understanding of the efficacy and safety of the investigational agent. In this review, we thoroughly examine the main outcomes used in SLE trials and highlight unmet requirements as well as potential venues for future trial design in SLE. Disease activity indices can be broadly categorised into global-specific and organ-specific indices, in particular for skin, joints and kidneys, but there is no universal consensus about their use in clinical trials. Because each of these instruments has its own intrinsic strengths and weaknesses, the assessment of treatment response has progressed from relying solely on one individual disease activity index to using composite responder definitions. Those are typically measured from the trial baseline to the end point assessment date and may be combined with the need to taper and maintain glucocorticoids (GCs) within prespecified ranges. Remission and low disease activity are two critical states in the perspective of ‘Treat-to-Target’ trials, but are not fully recognised by regulators. While significant progress has been made in clinical trial outcomes for SLE, there is a clear need for continued innovation. Addressing these challenges will require collaboration between researchers, clinicians, patients as well as with regulatory agencies to refine existing outcome measures, incorporate meaningful and ethnically diverse patient perspectives, foster relevant digital opportunities and explore new therapeutic avenues, including early use of investigational agents. By doing so, we can advance our ability to manage SLE effectively and safely and improve the lives of those living with this complex and impactful autoimmune disease

Giant cell arteritis (Horton's disease) in very elderly patients aged 80 years and older: A study of 25 cases

International audienceAimAnalysis of the characteristics of very elderly patients with giant cell arteritis (GCA).MethodsPatients aged 80 years and older diagnosed with GCA in our department between 1 January 2002 and 31 July 2008 were retrospectively included. For each patient, we recorded general characteristics, reason(s) for hospitalization, specialty of the physician or department that referred the patient to us, medical history, treatment at admission, GCA clinical features, time to diagnosis of GCA, biological screening and GCA treatment.ResultsWe analyzed 25 clinical records, 18 women and seven men with a mean age of 83.9 years. General weakness, visual loss and inflammatory syndrome were the principal reasons for hospitalization. Patients were mainly referred by general practitioners or ophthalmological departments. At diagnosis, headache and musculoskeletal disorders were the most frequent signs (52% each), before general weakness and visual disorders. Time to diagnosis was 2.2 months. Inflammatory syndrome was very frequent (92%). Biopsy of the temporal artery confirmed GCA in 16 cases. Corticosteroid therapy (CST) mean dose was 0.9 mg/kg/day. Because of the positive evolution, CST was stopped in nine patients after 22.7 ± 15 months. A total of 22 patients received a preventive osteoporosis treatment. After 3 months of CST, clinical signs and IS vanished in 22 patients. CST complications, mainly infection, appeared in 17 patients.ConclusionClinical and biological features of GCA in the very elderly patients of the present study were comparable with those described in the literature in younger patients. However, it must be pointed out that our patients were not compared with a younger population in this study

Development and validation of a lateral flow immunoassay for rapid detection of NDM-producing <em>Enterobacteriaceae</em>

International audienceThe global spread of carbapenemase-producing Enterobacteriaceae (CPE) that are often resistant to most, if not all, classes of antibiotics is a major public health concern. The NDM-1 carbapenemase is among the most worrisome carbapenemases given its rapid worldwide spread. We have developed and evaluated a lateral flow immunoassay (LFIA) (called the NDM LFIA) for the rapid and reliable detection of NDM-like carbapenemase-producing Enterobacteriaceae from culture colonies. We evaluated the NDM LFIA using 175 reference enterobacterial isolates with characterized β-lactamase gene content and 74 nonduplicate consecutive carbapenem-resistant clinical isolates referred for expertise to the French National Reference Center (NRC) for Antibiotic Resistance during a 1-week period (in June 2016). The reference collection included 55 non-carbapenemase producers and 120 carbapenemase producers, including 27 NDM producers. All 27 NDM-like carbapenemase producers of the reference collection were correctly detected in less than 15 min by the NDM LFIA, including 22 strains producing NDM-1, 2 producing NDM-4, 1 producing NDM-5, 1 producing NDM-7, and 1 producing NDM-9. All non-NDM-1 producers gave a negative result with the NDM LFIA. No cross-reaction was observed with carbapenemases (VIM, IMP, NDM, KPC, and OXA-48-like), extended-spectrum β-lactamases (ESBLs) (TEM, SHV, and CTX-M), AmpCs (CMY-2, DHA-2, and ACC-1), and oxacillinases (OXA-1, -2, -9, and -10). Similarly, among the 74 referred nonduplicate consecutive clinical isolates, all 7 NDM-like producers were identified. Overall, the sensitivity and specificity of the assay were 100% for NDM-like carbapenemase detection with strains cultured on agar. The NDM LFIA was efficient, rapid, and easy to implement in the routine workflow of a clinical microbiology laboratory for the confirmation of NDM-like carbapenemase-producing Enterobacteriaceae

Assessment of Prescriptions in Elderly Patients Hospitalized in Medicine Departments

Drug-related iatrogenesis is an important issue in the elderly population, and preventing iatrogenic accidents helps to reduce hospitalizations. Our study’s objective was to evaluate prescriptions in the geriatric population of our establishment. The study conducted is a targeted clinical audit. Ten criteria were tested on the hospital prescriptions of people over 75 years old in 11 medical departments, before and after improvement actions. The non-compliance threshold was set at 10% of prescriptions for each criterion. In each phase, 165 patients were included. Four criteria were non-compliant (NC) in the first phase: the presence of Potentially Inappropriate Medications for the Elderly (PIMs) (NC = 57.6%), the adaptation of the medication to renal clearance (NC = 24.9%), the presence of illogical combination (NC = 9.7%), and the total anti-cholinergic score of the prescription (NC = 12.1%). After the implementation of improvement actions, the number of non-compliant criteria decreased between the two phases, from four to two. We obtained a significant improvement for three of the four criteria found to be non-compliant in the first phase. The criterion adaptation to renal function is close to compliance (NC = 10.1%) and the PIMs criterion remained non-compliant after reassessment (NC = 32.1%). Vigilance must be ongoing in order to limit drug iatrogeny, particularly in frail elderly patients