Life Medical Control (France)

Shiga toxin-related hemolytic uremic syndrome (STEC-HUS) is a serious condition, characterized by multiorgan thrombotic microangiopathy, mainly affecting children. Renal involvement is severe, with approximately half of patients requiring dialysis. So far, no specific treatment has been proven efficient in STEC-HUS. The use of eculizumab, a monoclonal antibody inhibiting terminal complement complex, has demonstrated remarkable success in atypical hemolytic uremic syndrome, but its use in uncontrolled studies to treat STEC-HUS has yielded inconsistent results. In this Phase 3 randomized, placebo-controlled trial in 100 pediatric patients with STEC-HUS, the findings did not show efficacy of eculizumab during the acute phase of the disease. However, the results indicated a reduction of renal sequelae in eculizumab-treated patients at 1-year follow-up. Larger prospective studies would be needed to further explore eculizumab as a potential treatment. Shiga toxin-related hemolytic uremic syndrome (STEC-HUS) in children is a severe condition, resulting in approximately 50% of patients requiring RRT. Furthermore, at least 30% of survivors experience kidney sequelae. Recently, activation of the complement alternative pathway has been postulated as a factor in STEC-HUS pathophysiology, leading to compassionate use of eculizumab, a monoclonal antibody inhibiting the terminal complement complex, in affected patients. Given the lack of therapy for STEC-HUS, a controlled study of eculizumab efficacy in treating this condition is a priority. We conducted a Phase 3 randomized trial of eculizumab in children with STEC-HUS. Patients were randomly assigned in a 1:1 ratio to receive either eculizumab or placebo during 4 weeks. Follow-up lasted for 1 year. The primary end point was RRT duration <48 hours after randomization. Secondary endpoints included hematologic and extrarenal involvement. Baseline characteristics were similar among the 100 patients who underwent randomization. The rate of RRT <48 hours did not differ significantly between the two groups (48% in the placebo versus 38% in the eculizumab group; P = 0.31) or in the course of ARF. The two groups also exhibited similar hematologic evolution and extrarenal manifestations of STEC-HUS. The proportion of patients experiencing renal sequelae at 1 year was lower in the eculizumab group than in the placebo group (43.48% and 64.44%, respectively, P = 0.04). No safety concern was reported. In pediatric patients with STEC-HUS, eculizumab treatment does not appear to be associated with improved renal outcome during acute phase of the disease but may reduce long-term kidney sequelae. EUDRACT (2014-001169-28) ClinicalTrials.gov ( NCT02205541 ).

This paper describes a currently on-going multicenter, randomized controlled trial designed to assess the efficacy of calf neuromuscular electrical stimulation (NMES) on changes in maximal walking distance in people with lower extremity peripheral artery disease (PAD), compared with a non-intervention control-group. This study (NCT03795103) encompasses five participating centers in France. PAD participants with a predominant claudication at the calf level and a maximal treadmill walking distance ≤300 m are randomized into one of the two groups: NMES group or Control group. The NMES program consists of a 12-week program of electrical stimulations at the calf-muscle level. The primary outcome of the study is the change in maximal treadmill walking distance at 12 weeks. Main secondary outcomes include changes in the pain-free treadmill walking distance; 6 min total walking distance; global positioning system (GPS)-measured outdoor walking capacity; daily physical activity level by accelerometry; self-reported walking impairment; self-reported quality of life; ankle-brachial index; and skin microvascular function, both at the forearm and calf levels. Recruitment started in September 2019 and data collection is expected to end in November 2022.

BackgroundOne limitation of the endovascular treatment of intracranial aneurysms is aneurysm recanalization. The Analysis of Recanalization after Endovascular Treatment of intracranial Aneurysm (ARETA) study is a prospective multicenter cohort study evaluating the factors associated with recanalization after endovascular treatment.MethodsThe current analysis is focused on patients treated by coiling or balloon-assisted coiling (BAC). Postoperative, mid-term vascular imaging, and evolution of aneurysm occlusion were independently evaluated by two neuroradiologists. A 3-grade scale was used for aneurysm occlusion (complete occlusion, neck remnant, and aneurysm remnant) and for occlusion evolution (improved, stable, and worsened). Recanalization was defined as any worsening of aneurysm occlusion.ResultsBetween December 2013 and May 2015, 16 French neurointerventional departments enrolled 1289 patients. A total of 945 aneurysms in 908 patients were treated with coiling or BAC. The overall rate of aneurysm recanalization at mid-term follow-up was 29.5% (95% CI 26.6% to 32.4%): 28.9% and 30.3% in the coiling and BAC groups, respectively. In multivariate analyses factors independently associated with recanalization were current smoking (36.6% in current smokers vs 24.5% in current non-smokers (OR 1.8 (95% CI 1.3 to 2.4); p=0.0001), ruptured status (31.9% in ruptured aneurysms vs 25.1% in unruptured (OR 1.5 (95% CI 1.1 to 2.1); p=0.006), aneurysm size ≥10 mm (48.8% vs 26.5% in aneurysms <10 mm (OR 2.6 (95% CI 1.8 to 3.9); p<0.0001), wide neck (32.1% vs 25.8% in narrow neck (OR 1.5 (95% CI 1.1 to 2.1); p=0.02), and MCA location (34.3% vs 28.3% in other locations (OR 1.5 (95% CI 1.0 to 2.1); p=0.04).ConclusionsSeveral factors are identified by the ARETA study as playing a role in aneurysm recanalization after coiling: current smoking, aneurysm status (ruptured), aneurysm size (≥10 mm), neck size (wide neck), and aneurysm location (middle cerebral artery). This finding has important consequences in clinical practice.Trial registration numberURL: http://www.clinicaltrials.gov; Unique Identifier: NCT01942512.

Abstract Background: During simulation training, the confederate is a member of the pedagogical team. Its role is to facilitate the interaction between participants and the environment, and is thought to increase realism and immersion. Its influence on participants' performance in full-scale simulation remains however unknown. The purpose of this study was to explore the effect of the presence of a confederate on the participants’ performance during full-scale simulation of crisis medical situations. Methods: This was a prospective, randomized study comparing 2 parallel groups. Participants were emergency medicine residents engaging in a simulation session, with or without confederates. Participants were then evaluated on their Crisis Resource Management performance (CRM). The overall performance score on the Ottawa Global Rating Scale was assessed as primary outcome and the 5 non-technical CRM skills as secondary outcomes.Results: A total of 63 simulation sessions, including 63 residents, were included for statistical analysis (n= 32 for Control group and 31 for Confederate group). The mean Overall Performance score was 3.9± 0.8 in the Control group and 4.0± 1.1 in the Confederate group, 95% confidence interval of the difference [-0.6; 0.4], p=0.60. No significant differences between the two groups were observed on each CRM items (leadership, situational awareness, communication, problem solving, resource utilization)Conclusion: In this randomized and controlled study, the presence of confederates during full-scale simulated practice of crisis medical situations does not seem to improve the CRM skills performance of Emergency medicine residents. Trial registration: this study does not need to be registered on Clintrial as it doesn’t report a health care intervention on human participants.

CDK-cyclin complexes regulate centriole duplication and microtubule nucleation at specific cell cycle stages, although their exact roles in these processes remain unclear. As the activities of CDK-cyclins are themselves positively regulated by CDC25 phosphatases, we investigated the role of centrosomal CDC25B during interphase. We report that overexpression of CDC25B, as is commonly found in human cancer, results in a significant increase in centrin 2 at the centrosomes of interphase cells. Conversely, CDC25B depletion causes a loss of centrin 2 from the centrosome, which can be rescued by treatment with the proteasome inhibitor MG132. CDC25B overexpression also promotes the formation of excess centrin 2 “foci”. These foci can accumulate other centrosome proteins, including γ-tubulin and PCM-1, and can function as microtubule organising centres, indicating that these represent functional centrosomes. Formation of centrin 2 foci can be blocked by specific inhibition of CDK2 but not CDK1. CDK2-mediated phosphorylation of Monopolar spindle 1 (Mps1) at the G1/S transition is essential for the initiation of centrosome duplication, and Mps1 is reported to phosphorylate centrin 2. Overexpression of wild-type or non-degradable Mps1 exacerbated the formation of excess centrin 2 foci induced by CDC25B overexpression, while kinase-dead Mps1 has a protective effect. Together, our data suggest that CDC25B, through activation of a centrosomal pool of CDK2, stabilises the local pool of Mps1 which in turn regulates the level of centrin 2 at the centrosome. Overexpression of CDC25B may therefore contribute to tumourigenesis by perturbing the natural turnover of centrosome proteins such as Mps1 and centrin 2, thus resulting in the de novo assembly of extra-numerary centrosomes and potentiating chromosome instability.

BackgroundOf the errors occurring in drug treatment, about 24% take place during the step of administration (Mission nationale d’expertise et d’audit hospitaliers (MeaH) 2008). Poon et al, showed in 2010 that the Bar Code Medicines Administration (BCMA) reduced drug administration errors by 41.4% and serious potential adverse drug events by 54.1%.Drug prescribing, dispensing and administration have been computerised in the 13 geriatric units at the University Hospital (CHU) of Toulouse. Since January 2012, an additional device has been deployed in 8 wards: barcode readers have been installed to read barcodes on the drug packaging to make administration safer.Purpose A quality indicator was developed in order to analyse the use of barcode readers in care units in real time, to directly reduce drug administration errors. This indicator is a management tool to ensure that the BCMA system does not deviate over time.Materials and Methods The indicator was designed with the help of a computer specialist. The request is based on an Access file that extracts administration data from the Disporao prescription software. Two parameters are determined: the number of doses administered by BCMA and the number of administered doses that could be scanned; the ratio of these two elements reflects the use of barcode readers by nurses.ResultsThe training of 89 nurses was completed in June 2012. The indicator showed that nurses scan an average of 70% of unit doses. The objective is to scan more than 95% of unit doses. Investigations are underway to understand the reasons for incompleteness (temporary nursing staff not trained, incorrect prescriptions, faulty hardware, for example) and make corrective actions.Conclusions Optimization of the deployment of BCMA in the Geriatric units of Toulouse CHU allows us to plan the development of this practise over a large number of clinical departments at a later date.No conflict of interest.

A series of five vicinal bis(alkyl-triarylphosphoniums) derived from o-bis(diphenyl-phosphino)benzene (o-dppb) is described. Each of them have been prepared by specific methods, and their formal electrostatic and possible van der Waals strain is compared through the P+...P+ distances in the crystal state. According to X-ray diffraction analyses, while the conformations of the dimethyl dication is C2 symmetric, the conformation of alka-1,n-diyl-diphosphoniums (n = 1, 2, 3) is pseudo-Cs symmetric. The solution structure of the dimethyldiphosphonium 2 was studied by NMR techniques after metathesis of the triflate counterions with enantiomerically pure X-PHAT chiral anions (X = TRIS, BIN). [(Delta)-BINPHAT] was indirectly shown to discriminate between the enantiomers of the diphosphonium, but no effective enantio-differentiation could be measured down to -70 degrees C in CD2Cl2. When associated to [(Delta)-TRISPHAT] counterions, progressive cleavage of the diphosphonium afforded the corresponding methyl-triphenyl-monophosphonium salt. In the bridged series, the diphosphoniacyclopentene dication was found to be stable in spite of the very short transannular P+...P+ distance (2.83 A). The naturally more relaxed homologous diphosphoniacyclohexene dication (P+...P+ = 3.28 A) was found to be flexible in solution, as indicated by the equivalence of the four protons of the +P-CH2CH2-P+ bridge from 20 degrees C to -80 degrees C in acetone-d6. The two diphosphoniacycloheptene dications exhibit no P+...P+ steric compression (ca 3.64 A), just as the dimethyl dication (3.70 A). In solution, the seven-membered ring of the +P-CH2CR2CH2-P+ dications (R = H, Me) remains rigidly Cs symmetric: no interconversion of the pseudo-axial and pseudo-equatorial R groups is evidenced at the NMR time scale at -95 degrees C (coalescence at -20 degrees C for R = H, at -65 degrees C for R = Me). According to DFT calculations at the B3PW91/6-31G** level in 1,2-dichloroethane (DCE: PCM, epsilon = 10.36), the lowest energy conformation is indeed Cs-symmetric. However a quasi-isoenergetic C2-symmetric conformation which is the most stable in the gas phase is also found, and is thus a likely intermediate in the observed Cs <==> Cs interconversion. This +P-CH2CMe2CH2-P+ diphosphonium was obtained by dialkylation of o-dppb with 2,2-dimethylpropan-1,3-diyl bistriflate in DCE at 80 degrees C. The use of this solvent was the key for the synthesis of this dication, which was however competitively produced along with some +P-CH2CH2-P+ dication. The latter was also obtained by a totally different route, by heating a sulfinylethyl monophosphonium salt of o-dppb in the presence of the cationic complex [Rh(cod)2][PF6]. A mechanism for this peculiar process is proposed.