Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

African Linguistics in Central and Eastern Europe, and in the Nordic Countries

Non peer reviewe

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Notes pour servir à un essai de grammaire touarègue : (dialecte de l'Ahaggar)

Charles de Foucauld. Publ. par René Basse

Impact de l’administration continue des antibiotiques sur la charge en soins infirmiers

Background: Sepsis has an estimated incidence rate of 48 cases per 100,000 person-years in children, and a mortality rate of 5.6% (17% in cases of septic shock). In these situations, rapidly effective antibiotic therapy must be administered. However, for these patients with sepsis, the PK/PD parameters are particularly difficult to monitor, and this is why time-dependent antibiotics are widely prescribed in continuous infusion for adult patients in critical condition. In Pediatric Critical Care units, the practice is developing, based on an increasingly extensive literature on children. If excessive, the workload of nurses in such hospital departments can have a negative impact on the quality and safety of care, and on the working life of caregivers. Aim: To assess the impact of continuous antibiotic administration on nursing workload. Methods: The time spent by nurses on antibiotic therapy management was compared according to the different methods of administration. Measurements were taken before and after the implementation of a protocol for continuous antibiotic therapy in the pediatric critical care unit of the Grenoble-Alpes University Hospital. The measurements were taken over a period of 8 months between August 2024 and March 2025. Results: A total of 126 time measurements were taken over the study period. The time spent daily on managing Cefotaxime antibiotic therapy was significantly shorter when administration was continuous. This is true whether the intermittent administration is divided into 3 or 4 doses per day (19'45” vs. 12'32”, p=0.002, and 26'20” vs. 12'32”, p<0.001, respectively), representing a reduction of 36.5% and 52.4% in nursing time. For Piperacillin/Tazobactam administered every 8 hours, the difference in time is not significant (p=0.08), but compared to discontinuous administration every 6 hours, continuous administration significantly reduces the time by 46.5% (28'25” vs. 15'12”, p=0.01). However, a secondary study on the workload felt by nurses does not show a significant difference when the administration of antibiotics changes to continuous. Conclusion: The continuous administration of antibiotics does not increase the workload of nurses in a pediatric critical care unit. In some cases, this practice even reduces nursing time, time that can be spent on improving the safety and quality of care provided to children in these units.Introduction : Chez les enfants, le sepsis a un taux d’incidence estimé à 48 cas pour 100.000 personnes-années et sa mortalité est de 5,6% (17% en cas de choc septique). Face à ces situations, une antibiothérapie rapidement efficace doit être mise en place. Mais pour ces patients en sepsis, les paramètres PK/PD sont particulièrement difficiles à suivre, c’est pourquoi les antibiotiques temps-dépendant sont largement prescrits en administration continue chez les patients adultes en situation critique. Dans les services de Soins Critiques Pédiatriques, la pratique tend à se développer, basée sur une littérature de plus en plus fournie chez l’enfant. La charge de travail des infirmiers dans de tels services hospitaliers peut avoir, si elle est excessive, un effet néfaste sur la qualité et la sécurité des soins, et la qualité de vie professionnelle des soignants. Objectif : Évaluer l’impact de l’administration continue des antibiotiques sur la charge de travail des infirmiers. Méthodes : Le temps consacré par les infirmiers à la gestion de l’antibiothérapie a été comparé selon les différentes modalités d’administration. Des mesures avant et après l’implémentation d’un protocole d’antibiothérapie en administration continue ont été faites dans le service de soins critiques pédiatriques du CHU Grenoble-Alpes. Les mesures ont été réalisées sur une période de 8 mois entre août 2024 et mars 2025. Résultats : Au total, 126 mesures de temps ont été réalisées sur la période de l’étude. Le temps quotidien consacré à la gestion d’une antibiothérapie par Céfotaxime était significativement plus court lorsque l’administration était continue. Ceci se vérifie que l’administration discontinue soit répartie en 3 fois ou en 4 fois par jour (respectivement 19’45” vs 12’32”, p=0,002 ; et 26’20” vs 12’32”, p<0,001), soit une réduction de 36,5% et 52,4% du temps infirmier. Pour la Pipéracilline/Tazobactam administrée toutes les 8 heures, la différence de temps n’est pas significative (p=0,08), mais par rapport à une administration discontinue toutes les 6 heures, l’administration continue permet une réduction significative du temps de 46,5% (28’25” vs 15’12”, p=0,01). Cependant, une étude secondaire portant sur la charge de travail ressentie par les infirmiers ne montre pas de différence significative lorsque l’administration des antibiotiques devient continue. Conclusion : L’administration continue des antibiotiques n’augmente pas la charge de travail des infirmiers dans un service de soins critiques pédiatriques. Dans certains cas, cette pratique diminue même le temps de travail infirmier, temps qui pourra être consacré à améliorer par ailleurs la sécurité et la qualité des soins prodigués aux enfants de ces unités