Compliance with antibiotic therapy guidelines in french paediatric intensive care units: a multicentre observational study.

BACKGROUND: Bacterial infections (BIs) are widespread in ICUs. The aims of this study were to assess compliance with antibiotic recommendations and factors associated with non-compliance. METHODS: We conducted an observational study in eight French Paediatric and Neonatal ICUs with an antimicrobial stewardship programme (ASP) organised once a week for the most part. All children receiving antibiotics for a suspected or proven BI were evaluated. Newborns < 72 h old, neonates < 37 weeks, age ≥ 18 years and children under surgical antimicrobial prophylaxis were excluded. RESULTS: 139 suspected (or proven) BI episodes in 134 children were prospectively included during six separate time-periods over one year. The final diagnosis was 26.6% with no BI, 40.3% presumed (i.e., not documented) BI and 35.3% documented BI. Non-compliance with antibiotic recommendations occurred in 51.1%. The main reasons for non-compliance were inappropriate choice of antimicrobials (27.3%), duration of one or more antimicrobials (26.3%) and length of antibiotic therapy (18.0%). In multivariate analyses, the main independent risk factors for non-compliance were prescribing ≥ 2 antibiotics (OR 4.06, 95%CI 1.69-9.74, p = 0.0017), duration of broad-spectrum antibiotic therapy ≥ 4 days (OR 2.59, 95%CI 1.16-5.78, p = 0.0199), neurologic compromise at ICU admission (OR 3.41, 95%CI 1.04-11.20, p = 0.0431), suspected catheter-related bacteraemia (ORs 3.70 and 5.42, 95%CIs 1.32 to 15.07, p < 0.02), a BI site classified as "other" (ORs 3.29 and 15.88, 95%CIs 1.16 to 104.76, p < 0.03), sepsis with ≥ 2 organ dysfunctions (OR 4.21, 95%CI 1.42-12.55, p = 0.0098), late-onset ventilator-associated pneumonia (OR 6.30, 95%CI 1.15-34.44, p = 0.0338) and ≥ 1 risk factor for extended-spectrum ß-lactamase-producing Enterobacteriaceae (OR 2.56, 95%CI 1.07-6.14, p = 0.0353). Main independent factors for compliance were using antibiotic therapy protocols (OR 0.42, 95%CI 0.19-0.92, p = 0.0313), respiratory failure at ICU admission (OR 0.36, 95%CI 0.14-0.90, p = 0.0281) and aspiration pneumonia (OR 0.37, 95%CI 0.14-0.99, p = 0.0486). CONCLUSIONS: Half of antibiotic prescriptions remain non-compliant with guidelines. Intensivists should reassess on a day-to-day basis the benefit of using several antimicrobials or any broad-spectrum antibiotics and stop antibiotics that are no longer indicated. Developing consensus about treating specific illnesses and using department protocols seem necessary to reduce non-compliance. A daily ASP could also improve compliance in these situations. TRIAL REGISTRATION: ClinicalTrials.gov: number NCT04642560. The date of first trial registration was 24/11/2020.

Quality of reporting of adverse events in clinical trials of covid-19 drugs: systematic review.

Objective: To assess the quality of reporting of adverse events in clinical trials of covid-19 drugs based on the CONSORT (Consolidated Standards of Reporting Trials) harms extension and according to clinical trial design, and to examine reporting of serious adverse events in drug trials published on PubMed versus clinical trial summaries on ClinicalTrials.gov. Design: Systematic review. Data sources: PubMed and ClinicalTrials.gov registries were searched from 1 December 2019 to 17 February 2022. Eligibility criteria for selecting studies: Randomised clinical trials evaluating the efficacy and safety of drugs used to treat covid-19 disease in participants of all ages with suspected, probable, or confirmed SARS-CoV-2 infection were included. Clinical trials were screened on title, abstract, and text by two authors independently. Only articles published in French and English were selected. The Cochrane risk of bias tool for randomised trials (RoB 2) was used to assess risk of bias. Results: The search strategy identified 1962 randomised clinical trials assessing the efficacy and safety of drugs used to treat covid-19, published in the PubMed database; 1906 articles were excluded after screening and 56 clinical trials were included in the review. Among the 56 clinical trials, no study had a high score for quality of reporting of adverse events, 60.7% had a moderate score, 33.9% had a low score, and 5.4% had a very low score. All clinical trials with a very low score for quality of reporting of adverse events were randomised open label trials. For reporting of serious adverse events, journal articles published on PubMed under-reported 51% of serious adverse events compared with clinical trial summaries published on ClinicalTrials.gov. Conclusions: In one in three published clinical trials on covid-19 drugs, the quality of reporting of adverse events was low or very low. Differences were found in the number of serious adverse events reported in journal articles versus clinical trial summaries. During the covid-19 pandemic, risk assessment of drugs in clinical trials of covid-19 drugs did not comply with good practice recommendations for publication of results. Systematic review registration: European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) EUPAS45959.

Analysis of Growth After Transphyseal Anterior Cruciate Ligament Reconstruction in Children.

BACKGROUND: Pediatric transphyseal anterior cruciate ligament reconstruction (ACLR) bears several advantages and is widely used. The main concern is the risk of growth disturbance. Our purpose was to investigate the incidence and risk factors of growth disturbance in skeletally immature patients who underwent transphyseal ACLR. We hypothesized that this procedure would generate neither clinically relevant limb length discrepancy (LLD) nor axis deviation. METHODS: This prospective, consecutive, single-center series included skeletally immature patients who underwent primary transphyseal ACLR using semitendinosus tendon autograft, with a 2-year follow-up bone length standing radiograph of both lower limbs from pelvis to ankle in anterior posterior view. Lower limb length, mechanical axis deviation (MAD), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) were measured. The definition of postoperative growth disturbance was defined as ≥10 mm for LLD or ≥3 degrees for axis deviation in comparison to the contralateral lower limb. Predictive variables included age at surgery, gender, side, and diameter of bone tunnels. Student or Mann-Whitney test was used for numerical variables, and Chi-square test or Fisher exact test was used for categorical variables. P values <0.05 were considered statistically significant. RESULTS: Fifty consecutively treated patients were included. Forty-seven patients (31 boys, 16 girls) with a mean age of 13.2 years (range, 9 to 16) at the time of surgery were available for analysis. Six patients had an LLD of at least 10 mm. Twenty-five patients had a difference in MPTA of a least 3 degrees (range, 5 to 8). Sixteen patients had a difference in LDFA of a least 3 degrees (range, 4 to 9). No patients presented with a clinical deformity or related symptoms. Regarding coronal alignment, there was no statistical difference in mechanical axis deviation, LDFA, or MPTA. Gender, side, age, and bone tunnel diameter did not influence growth disturbance. CONCLUSIONS: Transphyseal pediatric ACLR generated a high rate of growth disturbances (leg length discrepancy and axis deviation) although none clinically relevant. Mild proximal tibial axis deviation in patients operated on near skeletal maturity should be further investigated. LEVEL OF EVIDENCE: Level III. STUDY DESIGN: Case-control study.

Increased reporting of venous and arterial thromboembolic events reported with tixagevimab-cilgavimab for coronavirus disease 2019.

OBJECTIVES: As two phase three clinical trials indicated a disproportion in the number of thromboembolic events in the tixagevimab/cilgavimab group than in the placebo group, there has been a cardiovascular safety concern with the use of anti-SARS-CoV-2 monoclonal antibody (mAb). Whether tixagevimab/cilgavimab use in real life increases the risk of thromboembolic events is unclear. METHODS: We used VigiBase, WHO's individual case safety reports database, to assess the risk of reporting arterial or venous thromboembolic events in patients with COVID-19 (aged ≥12 years) exposed to tixagevimab/cilgavimab compared with patients with COVID-19 exposed to other anti-SARS-CoV-2 mAbs, including casirivimab/imdevimab, bamlanivimab/etesevimab and sotrovimab. RESULTS: Among the 8952 reports of patients with an anti-SARS-CoV-2 mAb, 31 reports of thromboembolic events were associated with tixagevimab/cilgavimab, mainly deep vein thrombosis (10), pulmonary embolism (8) and myocardial infarction (7). Compared with other anti-SARS-CoV-2 mAbs, the use of tixagevimab/cilgavimab was associated with an increased risk of reporting arterial thromboembolic events (reporting OR 3.25; 95% CI 1.73, 6.10). Concerning venous thromboembolic events, a significant increase in the risk of reporting was observed with the use of tixagevimab/cilgavimab (reporting OR 3.59; 95% CI 2.16, 5.96). DISCUSSION: This observational study corroborates in a real-world setting in which the cardiovascular safety signal has already been found for tixagevimab/cilgavimab in two clinical trials. Owing to these thromboembolic safety concerns and considering the lack of clinical trials supporting protection against the omicron variant, there is an urgent need to improve knowledge on the effectiveness of tixagevimab/cilgavimab with new COVID-19 variants.

Myocarditis and pericarditis in adolescents after first and second doses of mRNA COVID-19 vaccines.

AIMS: While some concerns about vaccination-related pericarditis and/or myocarditis have been raised, no published data are available on pericarditis and/or myocarditis with mRNA COVID-19 vaccines in the age group of adolescents, particularly 12-15 years. The objective of this study was to determine whether the risk of reporting pericarditis and/or myocarditis with mRNA COVID-19 vaccines varied according to dose of vaccination, age, sex, and type of pericarditis and/or myocarditis in adolescents between 12 and 17 years. METHODS AND RESULTS: We performed an observational study reviewing all reports of adolescents vaccinated with mRNA COVID-19 vaccines and recorded in VigiBase®, the World Health Organization global database of individual case safety reports. We included all reports registered between 1 January 2021 and 14 September 2021. Reporting odds ratios (RORs) with their 95% confidence interval (CI) were calculated to estimate the risk of reporting pericarditis and/or myocarditis. Among 4942 reports with mRNA COVID-19 vaccines in adolescents, we identified 242 pericarditis and/or myocarditis. Compared with the first dose of mRNA COVID-19 vaccines, the second dose was associated with an increased risk of reporting pericarditis and/or myocarditis (ROR 4.95; 95% CI 3.14, 7.89). The risk of reporting pericarditis and/or myocarditis was 10 times higher in boys than in girls and no difference between the two types of vaccines could be demonstrated. CONCLUSION: This investigation including only adolescent data suggests for the first time that the second dose of mRNA COVID-19 vaccines increases the risk of reporting myocarditis/pericarditis compared with the first dose particularly in boys without significant difference between tozinameran and elasomeran.

Transfer of Visual Learning Between a Virtual and a Real Environment in Honey Bees: The Role of Active Vision.

To study visual learning in honey bees, we developed a virtual reality (VR) system in which the movements of a tethered bee walking stationary on a spherical treadmill update the visual panorama presented in front of it (closed-loop conditions), thus creating an experience of immersion within a virtual environment. In parallel, we developed a small Y-maze with interchangeable end-boxes, which allowed replacing repeatedly a freely walking bee into the starting point of the maze for repeated decision recording. Using conditioning and transfer experiments between the VR setup and the Y-maze, we studied the extent to which movement freedom and active vision are crucial for learning a simple color discrimination. Approximately 57% of the bees learned the visual discrimination in both conditions. Transfer from VR to the maze improved significantly the bees' performances: 75% of bees having chosen the CS+ continued doing so and 100% of bees having chosen the CS- reverted their choice in favor of the CS+. In contrast, no improvement was seen for these two groups of bees during the reciprocal transfer from the Y-maze to VR. In this case, bees exhibited inconsistent choices in the VR setup. The asymmetric transfer between contexts indicates that the information learned in each environment may be different despite the similar learning success. Moreover, it shows that reducing the possibility of active vision and movement freedom in the passage from the maze to the VR impairs the expression of visual learning while increasing them in the reciprocal transfer improves it. Our results underline the active nature of visual processing in bees and allow discussing the developments required for immersive VR experiences in insects.