Pediatric antibiotic stewardship programs in Europe: a pilot survey among delegates of The European Academy of Pediatrics

BackgroundAntimicrobial resistance (AMR) is one of the leading causes of morbidity and mortality worldwide. Efforts to promote the judicious use of antibiotics and contain AMR are a priority of several medical organizations, including the WHO. One effective way to achieve this goal is the deployment of antibiotic stewardship programs (ASPs). This study aimed to survey the current situation of pediatric ASPs in European countries and establish a baseline for future attempts to harmonize pediatric ASPs and antibiotic use in Europe.MethodsA web-based survey was conducted among national delegates of the European Academy of Paediatrics (EAP). The survey assessed the presence of pediatric ASPs in the representatives’ countries in the inpatient and outpatient settings, the staff included in the programs, and their detailed activities regarding antibiotic use.ResultsOf the 41 EAP delegates surveyed, 27 (66%) responded. Inpatient pediatric ASPs were reported in 74% (20/27) countries, and outpatient programs in 48% (13/27), with considerable variability in their composition and activities. Guidelines for managing pediatric infectious diseases were available in nearly all countries (96%), with those for neonatal infections (96%), pneumonia (93%), urinary tract (89%), peri-operative (82%), and soft tissue (70%) infections being the most common. Pediatric ASPs were reported at the national (63%), institutional (41%), and regional/local (<15%) levels. Pediatricians with infectious disease training (62%) and microbiologists (58%) were the most common members of the program personnel, followed by physician leaders (46%), infectious disease/infection control physicians (39%), pharmacists (31%), and medical director representatives (15%). Activities of the pediatric ASPs included educational programs (85%), monitoring and reporting of antibiotic use (70%) and resistance (67%), periodic audits with feedback (44%), prior approval (44%), and post-prescription review of selected antibiotic agents (33%).ConclusionAlthough pediatric ASPs exist in most European countries, their composition and activities vary considerably across countries. Initiatives to harmonize comprehensive pediatric ASPs across Europe are needed

Inflammatory Bowel Disease in Patients with Congenital Chloride Diarrhoea

Publisher Copyright: © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn's and Colitis Organisation. All rights reserved. For permissions, please email: [email protected]: Congenital chloride diarrhoea [CLD] is a rare autosomal recessive disease caused by mutations in the solute family carrier 26 member 3 [SLC26A3] gene. Patients suffer from life-long watery diarrhoea and chloride loss. Inflammatory bowel disease [IBD] has been reported in individual patients with CLD and in scl26a3-deficient mice. Methods: We performed an international multicentre analysis to build a CLD cohort and to identify cases with IBD. We assessed clinical and genetic characteristics of subjects and studied the cumulative incidence of CLD-associated IBD. Results: In a cohort of 72 patients with CLD caused by 17 different SLC26A3 mutations, we identified 12 patients [17%] diagnosed with IBD. Nine patients had Crohn's disease, two ulcerative colitis and one IBD-unclassified [IBD-U]. The prevalence of IBD in our cohort of CLD was higher than the highest prevalence of IBD in Europe [p < 0.0001]. The age of onset was variable [13.5 years, interquartile range: 8.5-23.5 years]. Patients with CLD and IBD had lower z-score for height than those without IBD. Four of 12 patients had required surgery [ileostomy formation n = 2, ileocaecal resection due to ileocaecal valve stenosis n = 1 and colectomy due to stage II transverse colon cancer n = 1]. At last follow-up, 5/12 were on biologics [adalimumab, infliximab or vedolizumab], 5/12 on immunosuppressants [azathioprine or mercaptopurine], one on 5-ASA and one off-treatment. Conclusions: A substantial proportion of patients with CLD develop IBD. This suggests the potential involvement of SL26A3-mediated anion transport in IBD pathogenesis. Patients with CLD-associated IBD may require surgery for treatment failure or colon cancer.Peer reviewe

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

Pediatric antibiotic stewardship programs in Europe: a pilot survey among delegates of The European Academy of Pediatrics

Background: Antimicrobial resistance (AMR) is one of the leading causes of morbidity and mortality worldwide. Efforts to promote the judicious use of antibiotics and contain AMR are a priority of several medical organizations, including the WHO. One effective way to achieve this goal is the deployment of antibiotic stewardship programs (ASPs). This study aimed to survey the current situation of pediatric ASPs in European countries and establish a baseline for future attempts to harmonize pediatric ASPs and antibiotic use in Europe. Methods: A web-based survey was conducted among national delegates of the European Academy of Paediatrics (EAP). The survey assessed the presence of pediatric ASPs in the representatives’ countries in the inpatient and outpatient settings, the staff included in the programs, and their detailed activities regarding antibiotic use. Results: Of the 41 EAP delegates surveyed, 27 (66%) responded. Inpatient pediatric ASPs were reported in 74% (20/27) countries, and outpatient programs in 48% (13/27), with considerable variability in their composition and activities. Guidelines for managing pediatric infectious diseases were available in nearly all countries (96%), with those for neonatal infections (96%), pneumonia (93%), urinary tract (89%), peri-operative (82%), and soft tissue (70%) infections being the most common. Pediatric ASPs were reported at the national (63%), institutional (41%), and regional/local (<15%) levels. Pediatricians with infectious disease training (62%) and microbiologists (58%) were the most common members of the program personnel, followed by physician leaders (46%), infectious disease/infection control physicians (39%), pharmacists (31%), and medical director representatives (15%). Activities of the pediatric ASPs included educational programs (85%), monitoring and reporting of antibiotic use (70%) and resistance (67%), periodic audits with feedback (44%), prior approval (44%), and post-prescription review of selected antibiotic agents (33%). Conclusion: Although pediatric ASPs exist in most European countries, their composition and activities vary considerably across countries. Initiatives to harmonize comprehensive pediatric ASPs across Europe are needed

Searching for VHE gamma-ray emission associated with IceCube neutrino alerts using FACT, H.E.S.S., MAGIC, and VERITAS

The realtime follow-up of neutrino events is a promising approach to search for astrophysical neutrino sources. It has so far provided compelling evidence for a neutrino point source: the flaring gamma-ray blazar TXS 0506+056 observed in coincidence with the high-energy neutrino IceCube-170922A detected by IceCube. The detection of very-high-energy gamma rays (VHE, E&gt;100GeV E &gt; 100 G e V ) from this source helped establish the coincidence and constrained the modeling of the blazar emission at the time of the IceCube event. The four major imaging atmospheric Cherenkov telescope arrays (IACTs) - FACT, H.E.S.S., MAGIC, and VERITAS - operate an active follow-up program of target-of-opportunity observations of neutrino alerts sent by IceCube. This program has two main components. One are the observations of known gamma-ray sources around which a cluster of candidate neutrino events has been identified by IceCube (Gamma-ray Follow-Up, GFU). Second one is the follow-up of single high-energy neutrino candidate events of potential astrophysical origin such as IceCube-170922A. GFU has been recently upgraded by IceCube in collaboration with the IACT groups. We present here recent results from the IACT follow-up programs of IceCube neutrino alerts and a description of the upgraded IceCube GFU system

Measurement of prompt D+D^+ and Ds+D^+_{s} production in pPbp\mathrm{Pb} collisions at sNN=5.02 \sqrt {s_{\mathrm{NN}}}=5.02\,TeV

International audienceThe production of prompt $D^+$ and $D^+_{s}$ mesons is studied in proton-lead collisions at a centre-of-mass energy of $\sqrt {s_{\mathrm{NN}}}=5.02\,$TeV. The data sample corresponding to an integrated luminosity of $(1.58\pm0.02)\mathrm{nb}^{-1}$ is collected by the LHCb experiment at the LHC. The differential production cross-sections are measured using $D^+$ and $D^+_{s}$ candidates with transverse momentum in the range of $0<p_{\mathrm{T}} <14\,\mathrm{GeV}/c$ and rapidities in the ranges of $1.5<y^*<4.0$ and $-5.0<y^*<-2.5$ in the nucleon-nucleon centre-of-mass system. For both particles, the nuclear modification factor and the forward-backward production ratio are determined. These results are compared with theoretical models that include initial-state nuclear effects. In addition, measurements of the cross-section ratios between $D^+$, $D^+_{s}$ and $D^0$ mesons are presented, providing a baseline for studying the charm hadronization in lead-lead collisions at LHC energies

Measurement of prompt D+D^+ and Ds+D^+_{s} production in pPbp\mathrm{Pb} collisions at sNN=5.02 \sqrt {s_{\mathrm{NN}}}=5.02\,TeV

International audienceThe production of prompt $D^+$ and $D^+_{s}$ mesons is studied in proton-lead collisions at a centre-of-mass energy of $\sqrt {s_{\mathrm{NN}}}=5.02\,$TeV. The data sample corresponding to an integrated luminosity of $(1.58\pm0.02)\mathrm{nb}^{-1}$ is collected by the LHCb experiment at the LHC. The differential production cross-sections are measured using $D^+$ and $D^+_{s}$ candidates with transverse momentum in the range of $0<p_{\mathrm{T}} <14\,\mathrm{GeV}/c$ and rapidities in the ranges of $1.5<y^*<4.0$ and $-5.0<y^*<-2.5$ in the nucleon-nucleon centre-of-mass system. For both particles, the nuclear modification factor and the forward-backward production ratio are determined. These results are compared with theoretical models that include initial-state nuclear effects. In addition, measurements of the cross-section ratios between $D^+$, $D^+_{s}$ and $D^0$ mesons are presented, providing a baseline for studying the charm hadronization in lead-lead collisions at LHC energies

Search for Bc+→π+μ+μ−B_c^+\to\pi^+\mu^+\mu^- decays and measurement of the branching fraction ratio B(Bc+→ψ(2S)π+)/B(Bc+→J/ψπ+){\cal B}(B_c^+\to\psi(2S)\pi^+)/{\cal B}(B_c^+\to J/\psi \pi^+)

International audienceThe first search for nonresonant $B_c^+\to\pi^+\mu^+\mu^-$ decays is reported. The analysis uses proton-proton collision data collected with the LHCb detector between 2011 and 2018, corresponding to an integrated luminosity of 9 fb$^{-1}$. No evidence for an excess of signal events over background is observed and an upper limit is set on the branching fraction ratio ${\cal B}(B_c^+\to\pi^+\mu^+\mu^-)/{\cal B}(B_c^+\to J/\psi \pi^+) < 2.1\times 10^{-4}$ at $90\%$ confidence level. Additionally, an updated measurement of the ratio of the $B_c^+\to\psi(2S)\pi^+$ and $B_c^+\to J/\psi \pi^+$ branching fractions is reported. The ratio ${\cal B}(B_c^+\to\psi(2S)\pi^+)/{\cal B}(B_c^+\to J/\psi \pi^+)$ is measured to be $0.254\pm 0.018 \pm 0.003 \pm 0.005$, where the first uncertainty is statistical, the second systematic, and the third is due to the uncertainties on the branching fractions of the leptonic $J/\psi$ and $\psi(2S)$ decays. This measurement is the most precise to date and is consistent with previous LHCb results