Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia.

IMPORTANCE Appropriate use of antibiotics is life-saving in neonatal early-onset sepsis (EOS), but overuse of antibiotics is associated with antimicrobial resistance and long-term adverse outcomes. Large international studies quantifying early-life antibiotic exposure along with EOS incidence are needed to provide a basis for future interventions aimed at safely reducing neonatal antibiotic exposure. OBJECTIVE To compare early postnatal exposure to antibiotics, incidence of EOS, and mortality among different networks in high-income countries. DESIGN, SETTING, AND PARTICIPANTS This is a retrospective, cross-sectional study of late-preterm and full-term neonates born between January 1, 2014, and December 31, 2018, in 13 hospital-based or population-based networks from 11 countries in Europe and North America and Australia. The study included all infants born alive at a gestational age greater than or equal to 34 weeks in the participating networks. Data were analyzed from October 2021 to March 2022. EXPOSURES Exposure to antibiotics started in the first postnatal week. MAIN OUTCOMES AND MEASURES The main outcomes were the proportion of late-preterm and full-term neonates receiving intravenous antibiotics, the duration of antibiotic treatment, the incidence of culture-proven EOS, and all-cause and EOS-associated mortality. RESULTS A total of 757 979 late-preterm and full-term neonates were born in the participating networks during the study period; 21 703 neonates (2.86%; 95% CI, 2.83%-2.90%), including 12 886 boys (59.4%) with a median (IQR) gestational age of 39 (36-40) weeks and median (IQR) birth weight of 3250 (2750-3750) g, received intravenous antibiotics during the first postnatal week. The proportion of neonates started on antibiotics ranged from 1.18% to 12.45% among networks. The median (IQR) duration of treatment was 9 (7-14) days for neonates with EOS and 4 (3-6) days for those without EOS. This led to an antibiotic exposure of 135 days per 1000 live births (range across networks, 54-491 days per 1000 live births). The incidence of EOS was 0.49 cases per 1000 live births (range, 0.18-1.45 cases per 1000 live births). EOS-associated mortality was 3.20% (12 of 375 neonates; range, 0.00%-12.00%). For each case of EOS, 58 neonates were started on antibiotics and 273 antibiotic days were administered. CONCLUSIONS AND RELEVANCE The findings of this study suggest that antibiotic exposure during the first postnatal week is disproportionate compared with the burden of EOS and that there are wide (up to 9-fold) variations internationally. This study defined a set of indicators reporting on both dimensions to facilitate benchmarking and future interventions aimed at safely reducing antibiotic exposure in early life

Less is more: Antibiotics at the beginning of life.

Antibiotic exposure at the beginning of life can lead to increased antimicrobial resistance and perturbations of the developing microbiome. Early-life microbiome disruption increases the risks of developing chronic diseases later in life. Fear of missing evolving neonatal sepsis is the key driver for antibiotic overtreatment early in life. Bias (a systemic deviation towards overtreatment) and noise (a random scatter) affect the decision-making process. In this perspective, we advocate for a factual approach quantifying the burden of treatment in relation to the burden of disease balancing antimicrobial stewardship and effective sepsis management

Metabolomic-Based Noninvasive Serum Test to Diagnose Nonalcoholic Steatohepatitis: Results From Discovery and Validation Cohorts

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease worldwide and includes a broad spectrum of histologic phenotypes, ranging from simple hepatic steatosis or nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). While liver biopsy is the reference gold standard for NAFLD diagnosis and staging, it has limitations due to its sampling variability, invasive nature, and high cost. Thus, there is a need for noninvasive biomarkers that are robust, reliable, and cost effective. In this study, we measured 540 lipids and amino acids in serum samples from biopsy-proven subjects with normal liver (NL), NAFL, and NASH. Using logistic regression analysis, we identified two panels of triglycerides that could first discriminate between NAFLD and NL and second between NASH and NAFL. These noninvasive tests were compared to blinded histology as a reference standard. We performed these tests in an original cohort of 467 patients with NAFLD (90 NL, 246 NAFL, and 131 NASH) that was subsequently validated in a separate cohort of 192 patients (7 NL, 109 NAFL, 76 NASH). The diagnostic performances of the validated tests showed an area under the receiver operating characteristic curve, sensitivity, and specificity of 0.88 +/- 0.05, 0.94, and 0.57, respectively, for the discrimination between NAFLD and NL and 0.79 +/- 0.04, 0.70, and 0.81, respectively, for the discrimination between NASH and NAFL. When the analysis was performed excluding patients with glucose levels >136 mg/dL, the area under the receiver operating characteristic curve for the discrimination between NASH and NAFL increased to 0.81 +/- 0.04 with sensitivity and specificity of 0.73 and 0.80, respectively. Conclusion: The assessed noninvasive lipidomic serum tests distinguish between NAFLD and NL and between NASH and NAFL with high accuracy.Supported by the National Institutes of Health Blueprint for Neuroscience Research (R01AT001576 to S.C.L., J.M.M.), Agencia Estatal de Investigacion of the Ministerio de Economia, Industria y Competitividad (SAF2014-52097R to J.M.M.), CIBER Hepatic and Digestive Diseases and Instituto de Salud Carlos III (PIE14/0003 to J.M.M.), Etorgai 2015-Gobierno Vasco (ER-2015/00015 to R.M., I.M.A., C.A., A.C.), Plan de Promocion de la Innovacion 2015-Diputacion Foral de Bizkaia (6/12/IN/2015/00131 to A.C., C.A.), National Institute of Diabetes and Digestive and Kidney Diseases (RO1DK81410 to A.J.S.), and Czech Ministry of Health (RVO VFN64165 to L.V.)

PPI-Delayed Diagnosis of Gastrinoma: Oncologic Victim of Pharmacologic Success

Functional neuroendocrine tumors are often low-grade malignant neoplasms that can be cured by surgery if detected early, and such detection may in turn be accelerated by the recognition of neuropeptide hypersecretion syndromes. Uniquely, however, relief of peptic symptoms induced by hypergastrinemia is now available from acid-suppressive drugs such as proton-pump inhibitors (PPIs). Here we describe a clinical case in which time to diagnosis from the onset of peptic symptoms was delayed more than 10 years, in part reflecting symptom masking by continuous prescription of the PPI omeprazole. We propose diagnostic criteria for this under-recognized new clinical syndrome, and recommend that physicians routinely measure serum gastrin levels in persistent cases of PPI-dependent dyspepsia unassociated with H. pylori

Editorial: Special Issue on ‘International policies – local affects: Regenerating the sociology of Basil Bernstein’

It is perhaps no coincidence that the lead authors of the papers in this Special Issue on ‘International policies – local affects: Regenerating the sociology of Basil Bernstein’ are mainly women scholars. What may be more surprising is that scholars working within feminist traditions with an enduring scepticism about humanistic assertions for epistemology still work with Bernstein’s oeuvre, just when it is being appropriated to buttress strong claims for epistemology, such as the calls ‘to bring knowledge back in’ to the curriculum. As a provocative introduction to the papers in the Special Issue we look at the tensions between epistemology and ontology as a way to explore Bernstein’s abiding appeal to us, and explain why, as feminist scholars, we have not simply abandoned what might seem like a grand, modernist sociological theory. We start by pointing to some of the contemporary appropriations of Bernstein’s work, and specifically those that make strong epistemological claims. Next, we introduce the renewed interest in ontology within new materialisms. We introduce concepts from the papers to read Bernstein’s work (diffractively) with and through other sources, including new material feminist onto-epistemologies, to exemplify why Bernstein leaves such a rich legacy and has ongoing relevance. In so doing, we challenge the idea that Bernstein’s theory is only about epistemology and hierarchical theory-building.No Full Tex

The role of economic evaluation in the decision-making process of family physicians: design and methods of a qualitative embedded multiple-case study

<p>Abstract</p> <p>Background</p> <p>A considerable amount of resource allocation decisions take place daily at the point of the clinical encounter; especially in primary care, where 80 percent of health problems are managed. Ignoring economic evaluation evidence in individual clinical decision-making may have a broad impact on the efficiency of health services. To date, almost all studies on the use of economic evaluation in decision-making used a quantitative approach, and few investigated decision-making at the clinical level. An important question is whether economic evaluations affect clinical practice. The project is an intervention research study designed to understand the role of economic evaluation in the decision-making process of family physicians (FPs). The contributions of the project will be from the perspective of Pierre Bourdieu's sociological theory.</p> <p>Methods/design</p> <p>A qualitative research strategy is proposed. We will conduct an embedded multiple-case study design. Ten case studies will be performed. The FPs will be the unit of analysis. The sampling strategies will be directed towards theoretical generalization. The 10 selected cases will be intended to reflect a diversity of FPs. There will be two embedded units of analysis: FPs (micro-level of analysis) and field of family medicine (macro-level of analysis). The division of the determinants of practice/behaviour into two groups, corresponding to the macro-structural level and the micro-individual level, is the basis for Bourdieu's mode of analysis. The sources of data collection for the micro-level analysis will be 10 life history interviews with FPs, documents and observational evidence. The sources of data collection for the macro-level analysis will be documents and 9 open-ended, focused interviews with key informants from medical associations and academic institutions. The analytic induction approach to data analysis will be used. A list of codes will be generated based on both the original framework and new themes introduced by the participants. We will conduct within-case and cross-case analyses of the data.</p> <p>Discussion</p> <p>The question of the role of economic evaluation in FPs' decision-making is of great interest to scientists, health care practitioners, managers and policy-makers, as well as to consultants, industry, and society. It is believed that the proposed research approach will make an original contribution to the development of knowledge, both empirical and theoretical.</p

Représentation et simulation des pratiques culturales des agriculteurs à l'échelle régionale pour estimer la demande en eau d'irrigation (application à un basin versant maïsicole du sud-ouest de la France )

Agricultural practices are a key-element to determine the irrigation water requirements. These practices depend both on soil and climate and on the general context of the farm enterprise. If one wants to simulate the evolution of the irrigation water demand at a regional scale due to some modifications of climate or farm enterprise, it is then important to provide a correct representation of the agricultural practices within the simulation model. This is the main goal of the thesis. Our approach is the result of two different questions linked to the spatial scale of the study: (a) how to represent the diversity of the agricultural practices, (b) how to simplify this diversity. Three steps have been followed: i) identification of the diversity of the agricultural practices using different sources of data (expertise, interviews, agricultural practices calendar from mail surveys, advisors proposition); ii) analyses of these data with multivariate analyses and hierarchical classifications in order to express strategies; iii) identification of keydeterminants part of regional databases that may be used to provide a spatial representation of these strategies. Some simplifications have been made: to focus only on irrigated corn (main irrigated crop in surface and in volume in the study area), to analyse only sowing and irrigation practices as the two main practices within the crop management systems that build the irrigation water demand. The choice of corn precocity is also integrated in the analysis. The study area is a watershed in the Gascogne region part of the Neste system. Agricultural practices were gathered between 2000 and 2004. From the results of the three previous steps, a model (SIMITKO) has been built that allows to estimate the sowing date, the choice of corn precocity, the sowing density and the area sown a given year. The model is stochastic and uses as input data some variables describing the production system and the climatic data of the given year. SIMITKO is linked to an existing biodecisional model (MODERATO) aimed at simulating corn irrigation strategies. This linkage provides an estimation of the regional water demand for irrigation through the aggregation of simulated demands at a plot scale. The model is evaluated on independent data obtained by a mail survey in 2005. Simulated and observed data are closed. Contrarily of pre-existing models, our model allows to estimate the variability of the irrigation water demand at a regional scale and may be used to test CAP or climate modifications. This work is part of a more general question on how to give a spatial representation of cropping systems.Les pratiques culturales sont un élément déterminant des prélèvements d'eau pour l'irrigation. Or ces pratiques sont elles-mêmes conditionnées par le contexte pédoclimatique et le contexte d'exploitation. Il est donc important pour la simulation de scénarios décrivant l'évolution du climat et des exploitations irrigantes de bien représenter ces pratiques au sein de modèles visant à estimer la demande régionale en eau d'irrigation à moyen terme. Tel est l'objectif de la thèse. La démarche suivie durant la thèse est le résultat d'une double contrainte résultant de l'étendue considérée: (a) la représentation de la diversité des pratiques culturales et (b) la simplification de cette diversité. Elle a consisté à (i) identifier la diversité des pratiques culturales par confrontation de différents types de données (expertise, entretiens, calendriers culturaux obtenus par enquêtes postales, pratiques recommandées), (ii) formaliser les pratiques sous forme de stratégies par analyses multivariées et classification ascendante hiérarchique et (iii) rechercher des indicateurs de leur distribution spatiale à travers différents types de déterminants facilement accessibles à l'échelle régionale. Il a été choisi de simplifier les processus représentés en se concentrant sur la culture ayant le plus d'influence sur la demande en eau (le maïs grain) et en étudiant deux interventions techniques (le semis, l'irrigation) et un choix technique (le choix de la précocité des variétés) au sein de l'itinéraire technique. Le terrain d'application est un bassin versant irrigué des coteaux de Gascogne au sein du système Neste. Les données sur les pratiques culturales à l'origine du modèle ont été acquises entre 2000 et 2004. A partir des résultats d'analyse des pratiques culturales, un modèle permettant d'estimer les dates de semis, les précocités semées, les densités de semis et les surfaces semées pour le maïs une année au sein de la zone a été développé. L'estimation est stochastique et se fait en fonction de variables décrivant les systèmes de production et les conditions météorologiques de l'année. Couplé à un modèle bio-décisionnel pré-existant simulant la pratique de l'irrigation et le développement des plantes à l'échelle parcellaire, il permet l'estimation de la demande régionale en eau par agrégation des résultats obtenus pour chaque parcelle. Ce modèle a été évalué grâce aux données observées obtenues par une enquête postale réalisée en 2005. Les résultats de comparaison des données observées et simulées montrent que l'estimation de la demande en eau est correcte. Par rapport aux modèles développés jusque là, ce modèle permet l'estimation de la variabilité de la demande en eau et ouvre des perspectives pour l'évaluation de scénarios prospectifs dans le cadre du changement de politique agricole commune et de l'évolution du climat. La représentation et la simulation des pratiques culturales à l'échelle régionale réalisée pendant la thèse sont une contribution aux travaux de spatialisation des systèmes de culture.TOULOUSE-ENSAT-Documentation (315552324) / SudocSudocFranceF

Cathéters pour instillation moins invasive de SURFACTANT : une étude de simulation

peer reviewedIntroduction et objectifs : l’instillation trachéale de surfactant par un cathéter fin (Less invasive surfactant therapy- LIST) chez le prématuré sous CPAP permet de diminuer la morbidité respiratoire. Plusieurs cathéters sont décrits à cette fin : une sonde oro-gastrique insérée avec (LISA-Köln, K) ou sans pince de Maggil (Take Care- Ankara, A), un cathéter veineux de 13 cm (MIST- Hobart, H), un cathéter d’angiographie de 30 cm (Stockholm, S) ou un cathéter ombilical fixé à un stylet d’intubation utilisé localement (Liège, L). L’objectif de l’étude est d’évaluer l’efficacité de ces techniques en prenant l’INSURE (Intubation-Surfactant-Extubation) comme référence. Intervention : 20 néonatologues travaillant dans 4 services ayant des stratégies d’administration du surfactant différentes ont participé. Ils ont simulé ces 6 techniques sur deux têtes d’intubation de difficulté croissante. L’efficacité de l’intervention est évaluée par le taux d’échec et la durée de procédure mesurée sur vidéo. Chaque intervenant apprécie la facilité d’utilisation sur une échelle de 1 à 9 (Difficile> facile). Résultats : Pour le premier modèle, les durées médianes de procédure pour Köln et Ankara sont allongées [K: 21s (IQR 17-24); A: 23s (15-42); H: 10s (8-16); S: 12s (10-22); L (10-20); INSURE: 14s (11-21); p<.0001]. Pour le second modèle, seul Liège permet une durée de procédure similaire à l’INSURE [K: 32s (25-44); A: 39s (27-95); H: 34s (27-46); S: 37s (29-42); L: 24s (15-35); INSURE: 24s (17-32); p<.002]. Les taux d’échec des méthodes LIST sont similaires entre eux (de 3 à 8/ 40 essais), mais supérieurs à celui de l’INSURE (0/40). Köln et Ankara sont considérés comme plus difficiles [scores de facilité : K: 5 (4-6); A: 3 (2-4); H: 6,5 (6-7); S: 7 (4-8); L: 8 (6,5-8); INSURE: 7 (6-8); p<.001]. Conclusions : les cathéters plus rigides sont plus efficaces et perçus comme plus simples d’utilisation. L’insertion d’un cathéter guidé et incurvé pourrait être plus rapide dans les cas difficiles