Contribution of medico-administrative databases to health vigilance: example of post-oocyte retrieval infections.

STUDY QUESTION: Can we monitor post-oocyte retrieval infections in the French national health data system to complement the French ART vigilance system? SUMMARY ANSWER: Medico-administrative databases provide a more comprehensive view of post-oocyte retrieval infections and can be used to detect abnormal increases in frequency and outlier ART centers as a complementary tool to the ART vigilance system. WHAT IS KNOWN ALREADY: The various studies of ART complications are reassuring, showing relatively low overall complication rates. Nonetheless, the European Union has set up a vigilance system to monitor these complications. However, this system is not an exhaustive source of information and does not provide a complete overview of post-ART complications. STUDY DESIGN, SIZE, DURATION: The study population was identified from the comprehensive French national hospital discharge database. It included women under 46 years of age undergoing an oocyte retrieval in 2019, classified into three population subgroups according to the indication of oocyte retrieval: infertility (IF) , fertility preservation (FP), and oocyte donation (OD) . The study population included 52 098 women who had undergone 65 948 oocyte retrievals in 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Hospital stays and delivery of antibiotics within 31 days after oocyte retrieval were analyzed. Women and infections were characterized according to various characteristics (age, comorbidities, indication of oocyte retrieval, type of hospital stay, length of hospital stay, type of antibiotherapy, etc.). Multivariate analysis was performed to determine the relation between the occurrence of infection and women's characteristics, and results are expressed as odds ratios (ORs) and 95% CI. A funnel plot and a box plot were used to compare the infection rate per center with the national average and to detect outliers. MAIN RESULTS AND THE ROLE OF CHANCE: Infections in the month following the oocyte retrieval represented 6.9% of the procedures in 2019 (n = 4522). Of these infections, 112 were hospitalized (0.2% of oocyte retrievals), and 4410 were non-hospitalized (6.7% of oocyte retrievals). The hospitalized infections were essentially gynecological infections (40.9%) and urinary tract infections (23.5%). In 87.9% of non-hospitalized infections, a single antibiotic therapy was prescribed. Mixed-effect model analysis showed that the risk of infection was significantly higher in women under 30 years of age, in the FP population, in supplementary universal health coverage (CMU-C) beneficiaries, and women with endometriosis. Funnel plot and box plot analysis showed that three ART centers have an infection rate significantly higher than the national average. In the three centers that stand out from all the others, the objective is to return to these centers to understand the possible reasons for this observed rate and to implement corrective measures. LIMITATIONS, REASONS FOR CAUTION: Despite all its advantages, the French national health data system presents some limitations, such as the risk of inappropriate coding. Another limitation of this study is that we cannot confirm an attributable relation between the infection and the ART procedure, even if the delay of 31 days after oocyte retrieval is consistent with the occurrence of a post-retrieval complication. In addition, antibiotics may be prescribed as a 'precautionary' measure in certain situations (women with a susceptibility to infection, complicated procedures), or as antibiotic prophylaxis for embryo transfer. WIDER IMPLICATIONS OF THE FINDINGS: Despite the limits in identifying post-ART infections in medico-administrative databases, this approach is a promising way to complement the ART vigilance reporting system. This concept developed for infections will also be generalized to other complications with regular feedback to professionals. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was sought for the study. The study was supported by the Agence de la biomédecine, France. The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Gold Nanoparticle-Loaded Silica Nanospheres for Sensitive and Selective Electrochemical Detection of Bisphenol A.

In this work, silica nanospheres were used as support for gold nanoparticles and applied for bisphenol A electrochemical detection. The development of new silica-supported materials has attracted increasing attention in the scientific world. One approach of interest is using silica nanospheres as support for gold nanoparticles. These materials have a variety of applications in several areas, such as electrochemical sensors. The obtained materials were characterized by solid-state UV-vis spectroscopy, electron microscopy, X-ray diffraction, and electrochemical techniques. The electrode modified with AuSiO2700/CHI/Pt was applied as an electrochemical sensor for BPA, presenting an oxidation potential of 0.842 V and a higher peak current among the tested materials. The AuSiO2700/CHI/Pt electrode showed a logarithmic response for the detection of BPA in the range of 1-1000 nmol L-1, with a calculated detection limit of 7.75 nmol L-1 and a quantification limit of 25.8 nmol L-1. Thus, the electrode AuSiO2700/CHI/Pt was presented as a promising alternative to an electrochemical sensor in the detection of BPA.

Overview of hospitalizations in women undergoing oocyte retrieval for ART in the French national health data system.

STUDY QUESTION: What is the incidence rate of complications in women undergoing ART procedures compared to the period prior to their first oocyte retrieval? SUMMARY ANSWER: The study shows a significant increase in the post-ART incidence rate of some complications but a low overall rate of occurrence relative to the total number of oocyte retrievals. WHAT IS KNOWN ALREADY: ART, widely used in Europe, accounts for 3.3% of births in France. The various studies of ART complications are fairly reassuring, showing relatively low overall complication rates but only few studies have used exhaustive national registers. STUDY DESIGN, SIZE, DURATION: The cohort for this study was identified from the comprehensive French national hospital-discharge database and includes women under 50 years with a first oocyte retrieval (T0) in 2012-2017, classified in three population subgroups according to the indication for oocyte retrieval: infertility (IF), oocyte donation (OD), and fertility preservation (FP). This study includes 156 916 women whose first oocyte retrieval occurred in 2012-2017 and 542 775 hospitalizations in 2010-2019 (excluding first retrieval). PARTICIPANTS/MATERIALS, SETTING, METHODS: Hospitalizations for complications or others events (oocyte retrieval, delivery, pregnancy loss, and death in the hospital) during the 2 years before (control period) and after their first oocyte retrieval (post-oocyte retrieval period) were compared and expressed per 10 000 person-months (pm). MAIN RESULTS AND THE ROLE OF CHANCE: In the IF subgroup, incidence rates were significantly higher after (vs before) retrieval for hospitalized ovarian hyperstimulation syndrome (OHSS) (162 vs 6/10 000 pm), adnexal torsion (14 vs 3), venous thrombosis (8 vs 1), arterial thrombosis (3 vs 1), trauma (2 vs 1), and significantly lower for infections (61 vs 87). The higher incidences of OHSS, adnexal torsion and venous thrombosis could only partially be explained by the occurrence of pregnancy.In the FP subgroup, incidence increased significantly after (vs before) retrieval for hospitalized OHSS (55 vs 0), venous thrombosis (59 vs 4), and infections (176 vs 56). For the OD subgroup, hospitalized OHSS (116 vs 0) and bleeding (24 vs 0) were significantly higher after (vs before) retrieval. LIMITATIONS, REASONS FOR CAUTION: The French national health data system, despite all its advantages, present some limitations such as the risk of coding errors. The unavailability of some personal information and the absence of consideration of risk factors prevented us from adjusting the risk. Finally, only complications resulting in hospitalization were analyzed which probably leads to their underestimation. WIDER IMPLICATIONS OF THE FINDINGS: The use of medico-administrative bases will be a valuable tool in public health and will furnish a better overview of the complications. Further studies are needed to complete this analysis. Adding information on drugs would help to better define T0 and less severe complications. STUDY FUNDING/COMPETING INTEREST(S): N/A. TRIAL REGISTRATION NUMBER: N/A.

Antibacterial effects and ibuprofen release potential using chitosan microspheres loaded with silver nanoparticles.

The wide use of chitosan microspheres in pharmaceutical applications, mainly in the controlled release of drugs and as a bactericidal agent, has been widely reported in the literature. However, these important biomaterial applications with multifunctionality is still scarce. In this study, epichlorohydrin-crosslinked chitosan microspheres were prepared and evaluated for Ag+ adsorption and formation of silver nanoparticles. The hybrid material obtained was used to antibacterial activity and controlled drug release. The optimal pH for adsorption of Ag+ ions in aqueous medium was pH 5-7; the best fit was the Langmuir model; the optimal time for maximum adsorption was 10 h. The highest release of the drug occured at neutral pH of the intestinal fluids and remained constant for 6 h. Silver ion microspheres demonstrated activity against E. coli and S. aureus. The concentration of ibuprofen incorporated in the chitosan microspheres was 7.9 × 10-3 mol L-1 and in the microspheres with AgNPs the concentration was 1.8 × 10-2 mol L-1. The microspheres with AgNPs released more drug (77%) than the material without AgNPs.

Inactivated alpha toxin from Clostridium novyi type B in nano-emulsion protect partially protects Swiss mice from lethal alpha toxin challenge.

Nano-emulsions are promising carriers for antigen delivery. Here, we evaluated the efficacy of a water-oil nano-emulsion containing concentrated, inactivated Clostridium novyi (C. novyi) type B supernatant culture (nano-iCnB) in protecting Swiss mice against a lethal dose of alpha toxin concentrated extract. Proteins were confirmed in the nano-iCnB and their stabilities were determined according physical parameters such as Zeta Potential (ZP). Biochemical, hematological parameters and morphological appearance of liver, spleen and thigh muscle alterations were examined to determine the safety of the compound. Partial protection against lethal doses was achieved in immunized mice despite low IgG titers. These data suggest that our nano-emulsion is a simple and efficient method of promoting antigen delivery for toxin-related diseases.

[Advanced therapy: from European regulatory framework to national regulatory framework]. / Thérapie innovante: du cadre réglementaire européen au cadre réglementaire national.

The European regulation n(o) 1394/2007/CE published on the 13th of November 2007 defined and harmonized the European regulatory framework for advanced therapy medicinal products. It creates a specialized committee located at the European Medicine Agency, in charge of the assessment of these medicinal products. The consequences of this regulation are introduced in the French regulation by the law n(o) 2011-302 published on the 22nd of March 2011. It detailed notably the possibility for public establishments (except health establishments) and nonprofit organisms to create pharmaceutical establishments. This law defined also a specific category of advanced therapy medicinal products, which fall under the "hospital exemption" framework. The rules regarding the authorizations of the establishments able to prepare these types of medicinal products and the authorization of the products are defined by the n(o) 2012-1236 decree published on the 6th of November 2012.