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Background High levels of outpatient antibiotic use remain observed in many European countries. Several studies have shown a strong relationship between antibiotic use and bacterial resistance. Aim To assess the long-term effect of a standardised educational seminar on antibiotic prescriptions by GPs. Design and setting Randomised controlled trial of 171 GPs (of 203 initially randomised) in France. Method GPs in the control group (n = 99) received no antibiotic prescription recommendation. Intervention group GPs (n = 72) attended an interactive seminar presenting evidence-based guidelines on antibiotic prescription for respiratory infections. The proportion of prescriptions containing an antibiotic in each group and related costs were compared to the baseline up to 30 months following the intervention. Data were obtained from the National Health Insurance System database. Results In the intervention group, 4-6 months after the intervention, there was a significant decrease in the proportion of prescriptions containing an antibiotic from 15.2 ± 5.4% to 12.3 ± 5.8% (-2.8% [95% CI = -3.8 to -1.9], P<0.001). By contrast, an increase was observed in controls from 15.3 ± 6.0 to 16.4 ± 6.7% (+1.1% [95% CI = +0.4 to +1.8], P<0.01), resulting in a between-group difference of 3.93% ([95% CI = 2.75 to 5.11], P<0.001). The between-group difference was maintained 30 months after intervention (1.99% [95% CI = 0.56 to 3.42], P<0.01). Persistence of the intervention effect over the entire study period was confirmed in a hierarchical multivariate analysis. Conclusion This randomised trial shows that a standardised and interactive educational seminar results in a long-term reduction in antibiotic prescribing and could justify a large-scale implementation of this intervention. [ABSTRACT FROM AUTHOR]

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2D materials, such as transition metal dichalcogenides, are ideal platforms for spin-to-charge conversion (SCC) as they possess strong spin-orbit coupling (SOC), reduced dimensionality and crystal symmetries as well as tuneable band structure, compared to metallic structures. Moreover, SCC can be tuned with the number of layers, electric field, or strain. Here, SCC in epitaxially grown 2D PtSe 2 by THz spintronic emission is studied since its 1T crystal symmetry and strong SOC favor SCC. High quality of as-grown PtSe 2 layers is demonstrated, followed by in situ ferromagnet deposition by sputtering that leaves the PtSe 2 unaffected, resulting in well-defined clean interfaces as evidenced with extensive characterization. Through this atomic growth control and using THz spintronic emission, the unique thickness-dependent electronic structure of PtSe 2 allows the control of SCC. Indeed, the transition from the inverse Rashba-Edelstein effect (IREE) in 1-3 monolayers (ML) to the inverse spin Hall effect (ISHE) in multilayers (>3 ML) of PtSe 2 enabling the extraction of the perpendicular spin diffusion length and relative strength of IREE and ISHE is demonstrated. This band structure flexibility makes PtSe 2 an ideal candidate to explore the underlying mechanisms and engineering of the SCC as well as for the development of tuneable THz spintronic emitters., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Aim: To evaluate the pCR rate and toxicity of the addition of weekly carboplatin (Cp) to paclitaxel (wP) and dose-dense (dd) epirubicin/cyclophosphamide (EC) in an open-label phase II study in TNBC patients., Methods: Patients were included if they had stage II and III TNBC and received wP (80 mg/m 2 /week) concurrent with weekly Cp (AUC = 2) for 12 weeks, followed by bi-weekly epirubicin (90 mg/m 2 ) and cyclophosphamide (600 mg/m 2 ) plus granulocyte colony-stimulating factor (G-CSF) for four cycles, followed by surgery. The primary endpoint was the rate of pCR [(ypT0/isypN0)]. Secondary endpoints included safety and drug delivery., Results: Sixty-three eligible patients were included. Median age was 51 years (range 29-74); 88.9% had stage II disease, 46% were clinically node positive, and 77.8% had grade 3 tumors. Fifty-four percent achieved a pCR. Twelve percent missed two or more doses of wP, whereas at least two cycles of EC were missed in 9.5%. The rate of tolerance without delays or dose reductions is very low (16%). Sixty-two percent had G3/4 neutropenia. Febrile neutropenia occurred in 18 patients of which more than eighty percent occurred during EC despite primary prophylaxis with G-CSF. Thrombocytopenia grade 3/4 was noticed in 11 pts. Three patients developed grade 3 peripheral neuropathy., Conclusion: The addition of weekly carboplatin to neoadjuvant paclitaxel and dd EC leads to a pCR rate comparable to prior studies (54%). However, hematological toxicity and febrile neutropenia rate was unexpectedly high. Future investigations could focus on reversing the sequence, which may lead to better hematological tolerability.

Van der Waals heterojunctions composed of graphene and transition metal dichalcogenides have gain much attention because of the possibility to control and tailor band structure, promising applications in two-dimensional optoelectronics and electronics. In this report, we characterized the van der Waals heterojunction MoSe 2 /few-layer graphene with a high-quality interface using cutting-edge surface techniques scaling from atomic to microscopic range. These surface analyses gave us a complete picture of the atomic structure and electronic properties of the heterojunction. In particular, we found two important results: the commensurability between the MoSe 2 and few-layer graphene lattices and a band-gap opening in the few-layer graphene. The band gap is as large as 250 meV, and we ascribed it to an interface charge transfer that results in an electronic depletion in the few-layer graphene. This conclusion is well supported by electron spectroscopy data and density functional theory calculations. The commensurability between the MoSe 2 and graphene lattices as well as the band-gap opening clearly show that the interlayer interaction goes beyond the simple van der Waals interaction. Hence, stacking two-dimensional materials in van der Waals heterojunctions enables us to tailor the atomic and electronic properties of individual layers. It also permits the introduction of a band gap in few-layer graphene by interface charge transfer.

Aims: Trebananib, a peptide-Fc fusion protein, inhibits angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. This randomised, double-blind, placebo-controlled phase 3 study evaluated whether trebananib plus pegylated liposomal doxorubicin (PLD) improved progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer., Methods: Women with recurrent ovarian cancer (platinum-free interval ≤12 months) were randomised to intravenous PLD 50 mg/m 2 once every 4 weeks plus weekly intravenous trebananib 15 mg/kg or placebo. PFS was the primary end-point; key secondary end-points were objective response rate (ORR) and duration of response (DOR). Owing to PLD shortages, enrolment was paused for 13 months; the study was subsequently truncated., Results: Two hundred twenty-three patients were enrolled. Median PFS was 7.6 months (95% CI, 7.2-9.0) in the trebananib arm and 7.2 months (95% CI, 4.8-8.2) in the placebo arm, with a hazard ratio of 0.92 (95% CI, 0.68-1.24). However, because the proportional hazards assumption was not fulfilled, the standard Cox model did not provide a reliable estimate of the hazard ratio. ORR in the trebananib arm was 46% versus 21% in the placebo arm (odds ratio, 3.43; 95% CI, 1.78-6.64). Median DOR was improved (trebananib, 7.4 months [95% CI, 5.7-7.6]; placebo, 3.9 months [95% CI, 2.3-6.5]). Adverse events with a greater incidence in the trebananib arm included localised oedema (61% versus 32%), ascites (29% versus 9%) and vomiting (45% versus 33%)., Conclusions: Trebananib demonstrated anticancer activity in this phase 3 study, indicated by improved ORR and DOR. Median PFS was not improved. No new safety signals were identified., Trial Registration: ClinicalTrials.gov, NCT01281254., (Copyright © 2016. Published by Elsevier Ltd.)

Reminders have been used in various settings, but failed to produce convincing evidence of benefits on patient adherence to colorectal cancer (CRC) screening. The aim of this study was to assess the effectiveness of sending general practitioners (GPs) printed reminders about CRC screening. We conducted a cluster-randomized controlled trial involving 144 GPs in the Val-de-Marne district (France), who provided care for any reason to 20 778 patients eligible for CRC screening between June 2010 and November 2011. Data were collected from the main statutory health-insurance programme and local cancer screening agency. GPs were randomly assigned in a 1 : 1 proportion to the intervention or the control group. Every 4 months, intervention-group GPs received a computer-generated printed list of patients who had not performed scheduled faecal occult blood test (FOBT) screening. The primary outcome was patient adherence to FOBT screening or exclusion from CRC screening for medical reasons. The screening adherence rate was 31.2% [95% confidence interval (CI) 30.3-32.1] in the control group and 32.9% (95% CI 32.0-33.8) in the intervention group [crude relative risk, 1.05 (95% CI 1.01-1.09), P<0.01]. This rate was not significantly different between groups by multilevel modelling accounting for clustering and confounding variables [adjusted relative risk, 1.07 (95% CI 0.95-1.20), P=0.27]. Computer-generated printed reminders sent to GPs did not significantly improve patient adherence to organized CRC screening by the FOBT.

Background: The participation rate in organized breast cancer screening in France is lower than recommended. Non-participants either use opportunistic screening or do not use either screening modality., Objective: To assess any differences in perceptions, attitudes and knowledge related to breast cancer screening between users of opportunistic screening and non-users of any screening mammograms and to identify potential barriers to participation in organized screening., Methods: Six focus groups were conducted in May 2010 with 34 French non-participants in organized screening, 15 who used opportunistic screening (OpS group) and 19 who used no screening (NoS group). The guide used for both groups explored perceptions and attitudes related to health, cancer and screening; perceptions of femininity; and knowledge about breast cancer screening. Thematic content analysis was performed., Results: Perceptions, attitudes and knowledge differed between the two groups. Women in the OpS group perceived a high susceptibility to breast cancer, visited their gynaecologist regularly, were unfamiliar with organized screening modalities and had doubts about its quality. NoS women had very high- or low-perceived susceptibility to breast cancer, knew about screening modalities, had doubts about its usefulness and expressed negative opinions of mammograms., Conclusions: Differences in perceptions and attitudes related to breast cancer screening partially explain why some women choose opportunistic screening or no screening. General practitioners and gynaecologists are in a unique position to provide individually tailored preventative messages to improve participation in organized screening.

Objective: To determine the impact of physiologic changes of pregnancy on pharmacokinetics of chemotherapeutic agents., Design: A preclinical and a clinical case-control trial., Setting: Institute of Primate Research Nairobi and collaborating hospitals in Belgium, the Netherlands and Czech Republic., Population: Pregnant and nonpregnant women and baboons receiving chemotherapy., Methods: Chemotherapy pharmacokinetics was compared between the pregnant and nonpregnant state. Standard-dosed chemotherapy regimens were administered in pregnant and nonpregnant baboons/women, followed by serial blood samplings. Drug plasma levels were determined using high performance liquid chromatography and atomic absorption spectrometry., Main Outcome Measures: Area under the curve (AUC), maximal plasma concentration, terminal elimination half-life, clearance and distribution volume of each drug in pregnant and nonpregnant state., Results: Intraindividual comparative pharmacokinetic data were obtained for doxorubicin and paclitaxel/platinum in three and two baboons, respectively. In the clinical trial, two patients were exposed to doxorubicin and one patient was exposed to paclitaxel/platinum during and after pregnancy. Furthermore, a pooled analysis was performed based on 16 cycles of pregnant and 11 cycles of nonpregnant women. Numbers of pregnant/nonpregnant patients were 5/2, 7/5, 4/4 and 2/2 for paclitaxel, doxorubicin, epirubicin and platinum, respectively. For all drugs tested in the preclinical and clinical study, a decreased AUC and maximal plasma concentration and an increased distribution volume and clearance were observed in pregnancy., Conclusions: Although numbers were too small for statistical significance, pregnancy-associated physiologic alterations appear to lead to a decrease in plasma exposure of chemotherapeutic drugs. The importance of long-term follow-up of women treated with chemotherapy during pregnancy is underscored.

A quantitative method for the simultaneous determination of docetaxel (Taxotere), paclitaxel (Taxol), 6alpha-hydroxypaclitaxel, and p-3'-hydroxypaclitaxel in human plasma and oral fluid is developed and validated. Oral fluid (this term is now preferred to saliva) was sampled with a Salivette collection device. The procedure used a simple liquid/liquid extraction with methyl tert-butyl ether followed by LC-ESI-MS/MS. Gradient elution was applied and provided increased robustness to ion suppression by the drug formulation vehicle (polysorbate 80 and Cremophor EL). Adduct ion formation with sodium and potassium was noticed and controlled by mobile-phase optimization. The protonated analytes generated in the positive ion mode were monitored through multiple reaction monitoring. Calibration was performed by internal standardization with cephalomannine, and regression curves were constructed ranging between 2 and 1000 ng/mL in plasma and 0.125 and 62.5 ng/mL in oral fluid, using a weighing factor of 1/x2. The regression curves were quadratic for paclitaxel and docetaxel and linear for the paclitaxel metabolites. Accuracy varied from 91.3 to 103.6%, and imprecision did not exceed 12.7% for all analytes in plasma and oral fluid. In conclusion, a sensitive and robust method was obtained, which fulfilled all validation criteria.