Assessment of pain during labor with pupillometry: a prospective observational study.: Pupillometry and labor pain

International audienceBACKGROUND: Pain intensity is usually self-rated by patients with a numeric rating scale (NRS) but this scale cannot be used for noncommunicating patients. In anesthetized patients, experimental noxious stimulus increases pupillary diameter (PD) and pupillary light reflex amplitude (PLRA), the difference between PD before and after light stimulation. Labor pain is an intense acute nonexperimental stimulus, effectively relieved by epidural analgesia. In this prospective observational study, we therefore describe the effects of labor pain and pain relief with epidural analgesia on PD and PLRA, determine their association with pain intensity and determine the ability of a single measurement of PD or PLRA to assess pain. METHODS: In the first stage, pain (11-point NRS), PD, and PLRA were measured in 4 conditions in 26 laboring women: before and after epidural analgesia and in the presence and absence of a uterine contraction. Pupillometry values among the 4 conditions were compared, and the strength of the association between absolute values of pain and PD or PLRA and between pain and changes in PD or PLRA brought about by uterine contraction was assessed with r(2). In the second stage, 1 measurement was performed in 104 laboring women. The strength of the association between pain and PD or PLRA was assessed with r(2). The ability of PD or PLRA to discriminate pain (NRS > 4) was also assessed. RESULTS: In the first stage, a statistically significant increase in pain, PD, and PLRA was observed during a contraction, and this change was abolished after epidural analgesia. The r(2) for the association between pain and changes in PD (r(2) = 0.25 [95% confidence interval, 0.07-0.46] or PLRA (r(2) = 0.34 [0.14-0.56]) brought about by a uterine contraction was higher than the r(2) for the association between pain and absolute values of PD (r(2) = 0.14 [0.04-0.28]) or PLRA (r(2) = 0.22 [0.10-0.37]) suggesting a stronger association for changes than for absolute values. In the second stage, r(2) was 0.23 [0.10-0.38] for PD and 0.26 [0.11-0.40] for PLRA and the area under the receiver operating characteristics curve was 0.82 [0.73-0.91] and 0.80 [0.71-0.89], respectively. CONCLUSIONS: Changes in PD and PLRA brought about by a uterine contraction may be used as a tool to assess analgesia in noncommunicating patients

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Impact of diet and effect of strain on the adaptation of Escherichia coli in its natural environment : the digestive tract

Escherichia coli est une bactérie commensale du tube digestif qui, dans certainesconditions dépendantes de la souche et de l’hôte, peut devenir un redoutable pathogèneintestinal ou extra-intestinal responsable d’une morbi-mortalité significative. L’espèce E. colipossède une structure clonale au sein de laquelle on peut différencier des groupesphylogénétiques. De façon intéressante cette structure est partiellement prédictive de lavirulence. En particulier, le groupe phylogénétique B2, est composé de souches souvent isoléesde pathologies extra-intestinales mais qui sont aussi de bonnes commensales. En effet, de façoninquiétante, la prévalence de ce groupe augmente dans le tube digestif des individus des paysindustrialisés. Cela suggère un potentiel couplage entre des facteurs œuvrant à l’échelle despopulations humaines comme l’alimentation et le fond génétique de la souche bactérienne.Plusieurs expériences d’évolution in vivo d’E. coli dans le tube digestif de souris ont déjà étémenées et ont permis de montrer une forte adaptation notamment liée aux ressourcesénergétiques et au métabolisme de sucres. Ces études souffraient cependant de plusieurslimitations comme l’utilisation d’une souche de laboratoire, d’un milieu non naturel ou encored’un seul régime alimentaire. L’objectif de ma thèse a donc été d’étudier les modes d’adaptationd’isolats naturels de E. coli dans le tube digestif. Cette étude a été effectuée à plusieurs niveaux:à la fois in natura, mais aussi in vivo en fonction du fond génétique des souches et del’alimentation de l’hôte.Dans un premier temps, nous avons eu l’opportunité de suivre l’adaptation in naturad’un isolat de E. coli ED1a dominant dans le tube digestif d’un individu vivant en régionparisienne et sans problème de santé. Nous avons pu observer que E. coli ED1a, appartenant augroupe phylogénétique B2, évoluait de façon neutre dans le tube digestif. Le recours auxexpérimentations in vivo sur modèle murin au long court (plus d’un an) s’est avéré nécessairepour étudier l’impact de l’alimentation et du fond génétique de la souche dans l’adaptation deE. coli dans le tube digestif. Le propos de la première expérimentation était d’étudierl’adaptation d’un isolat naturel de E. coli 536 (appartenant au groupe phylogénétique B2 etinitialement issu d’infection urinaire), dans un tube digestif de souris se rapprochant le pluspossible des conditions naturelles (en utilisant le principe de transmission du microbiote digestifde la mère à la progéniture) et soumises à deux régimes alimentaires : standard ou riche en graset en sucre. Nous avons pu mettre en évidence une activation constitutive de l’opéron lactosesurvenant lors de la période d’allaitement des progénitures pour ensuite évoluer de manièreneutre quelque soit le régime alimentaire. Le propos de la deuxième expérimentation étaitd’étudier l’impact du fond génétique de la souche combinée à l’alimentation en étudiantl’évolution de deux isolats naturels de E. coli 536 et HS (appartenant au groupe phylogénétiqueA et issu d’une situation commensale chez un humain) dans le tube digestif de souris traitées àla streptomycine. Nous avons pu distinguer deux profils d’adaptation en fonction de la soucheet de l’alimentation. Il semblerait que l’intensité de l’adaptation dépende préférentiellement dela souche et probablement de son fond génétique, et que les cibles de l’adaptation dépendentplutôt du régime alimentaire. Plus précisément, ces cibles semblent principalement êtreassociées au métabolisme de sucres. Ces études constituent un progrès important dans lacompréhension des pressions sélectives agissant sur E. coli in vivo.Escherichia coli is a commensal bacteria of the digestive tract. Under certain strain andhost conditions, it may become a serious intestinal or extra-intestinal pathogen responsible fora significant morbidity and mortality. The E. coli species has a clonal structure within whichphylogenetic groups can be distinguished. Interestingly this structure is partially predictive ofvirulence. In particular, phylogenetic group B2, is composed of strains often isolated in extradigestive disease but are also good commensals. Indeed, disturbingly, the prevalence of thisgroup is increasing in the digestive tract of individuals of industrialized countries. This suggestsa potential coupling between factors working at the level of human populations such as foodand the genetic background of the bacterial strain. Several in vivo evolution experiments of E.coli in the digestive tract of mice have already been conducted and allowed to show a strongadaptation particularly related to energy resources and sugar metabolism. These studies,however, suffered from several limitations such as the use of a laboratory strain, in a non-naturalenvironment and subject to a single diet. The objective of my thesis was to study the adaptationof natural isolates of E. coli in digestive tract. This study was carried out at several levels: bothin natura, but also in vivo depending on the genetic background of the strains and host diet.First, we had the opportunity to follow the adaptation in natura of a dominant ED1a E.coli isolate in the digestive tract of an individual living in the Paris region and without anyhealth problem. We observed that E. coli ED1a, belonging to phylogenetic group B2, evolvedneutrally in the digestive tract. Subsequently, in vivo long-term experiment (over a year) mousemodel was used to study the impact of diet and genetic background of strain in the adaptationof E. coli to the digestive tract. The purpose of the first experiment was to study the adaptationof a natural isolate of E. coli, strain 536 (belonging to the phylogenetic group B2 and initiallyisolated in urinary tract infection), in a mouse digestive tract as close as possible to the naturalconditions (using the principle of transmission of digestive microbiota from mother tooffspring) and two diets: standard or high in fat and sugar. We were able to demonstrate aconstitutive activation of the lactose operon occurring during the lactation period of offspringand then a neutral evolution regardless of the diet. The purpose of the second mice experimentwas to study the impact of the host diet on the evolution of two natural isolates of E. coli, strain536 and strain HS, the latter belonging to the phylogenetic group A, a group known to be mostlycommensal in human. We used this time mice treated with streptomycin. We were able todistinguish two adaptation profiles according to the strain and diet. The intensity of adaptationdepended on the strain and probably its genetic background, and the target of adaptationdepended on the diet. More precisely, the targets of adaptation were mainly associated with thesugar metabolism.These studies represent an important advance in the understanding of the selectivepressures acting on E. coli in vivo

Impact de l'alimentation et de l'effet souche sur l'adaptation de Escherichia coli dans son environnement naturel : le tube digestif

Escherichia coli is a commensal bacteria of the digestive tract. Under certain strain andhost conditions, it may become a serious intestinal or extra-intestinal pathogen responsible fora significant morbidity and mortality. The E. coli species has a clonal structure within whichphylogenetic groups can be distinguished. Interestingly this structure is partially predictive ofvirulence. In particular, phylogenetic group B2, is composed of strains often isolated in extradigestive disease but are also good commensals. Indeed, disturbingly, the prevalence of thisgroup is increasing in the digestive tract of individuals of industrialized countries. This suggestsa potential coupling between factors working at the level of human populations such as foodand the genetic background of the bacterial strain. Several in vivo evolution experiments of E.coli in the digestive tract of mice have already been conducted and allowed to show a strongadaptation particularly related to energy resources and sugar metabolism. These studies,however, suffered from several limitations such as the use of a laboratory strain, in a non-naturalenvironment and subject to a single diet. The objective of my thesis was to study the adaptationof natural isolates of E. coli in digestive tract. This study was carried out at several levels: bothin natura, but also in vivo depending on the genetic background of the strains and host diet.First, we had the opportunity to follow the adaptation in natura of a dominant ED1a E.coli isolate in the digestive tract of an individual living in the Paris region and without anyhealth problem. We observed that E. coli ED1a, belonging to phylogenetic group B2, evolvedneutrally in the digestive tract. Subsequently, in vivo long-term experiment (over a year) mousemodel was used to study the impact of diet and genetic background of strain in the adaptationof E. coli to the digestive tract. The purpose of the first experiment was to study the adaptationof a natural isolate of E. coli, strain 536 (belonging to the phylogenetic group B2 and initiallyisolated in urinary tract infection), in a mouse digestive tract as close as possible to the naturalconditions (using the principle of transmission of digestive microbiota from mother tooffspring) and two diets: standard or high in fat and sugar. We were able to demonstrate aconstitutive activation of the lactose operon occurring during the lactation period of offspringand then a neutral evolution regardless of the diet. The purpose of the second mice experimentwas to study the impact of the host diet on the evolution of two natural isolates of E. coli, strain536 and strain HS, the latter belonging to the phylogenetic group A, a group known to be mostlycommensal in human. We used this time mice treated with streptomycin. We were able todistinguish two adaptation profiles according to the strain and diet. The intensity of adaptationdepended on the strain and probably its genetic background, and the target of adaptationdepended on the diet. More precisely, the targets of adaptation were mainly associated with thesugar metabolism.These studies represent an important advance in the understanding of the selectivepressures acting on E. coli in vivo.Escherichia coli est une bactérie commensale du tube digestif qui, dans certainesconditions dépendantes de la souche et de l’hôte, peut devenir un redoutable pathogèneintestinal ou extra-intestinal responsable d’une morbi-mortalité significative. L’espèce E. colipossède une structure clonale au sein de laquelle on peut différencier des groupesphylogénétiques. De façon intéressante cette structure est partiellement prédictive de lavirulence. En particulier, le groupe phylogénétique B2, est composé de souches souvent isoléesde pathologies extra-intestinales mais qui sont aussi de bonnes commensales. En effet, de façoninquiétante, la prévalence de ce groupe augmente dans le tube digestif des individus des paysindustrialisés. Cela suggère un potentiel couplage entre des facteurs œuvrant à l’échelle despopulations humaines comme l’alimentation et le fond génétique de la souche bactérienne.Plusieurs expériences d’évolution in vivo d’E. coli dans le tube digestif de souris ont déjà étémenées et ont permis de montrer une forte adaptation notamment liée aux ressourcesénergétiques et au métabolisme de sucres. Ces études souffraient cependant de plusieurslimitations comme l’utilisation d’une souche de laboratoire, d’un milieu non naturel ou encored’un seul régime alimentaire. L’objectif de ma thèse a donc été d’étudier les modes d’adaptationd’isolats naturels de E. coli dans le tube digestif. Cette étude a été effectuée à plusieurs niveaux:à la fois in natura, mais aussi in vivo en fonction du fond génétique des souches et del’alimentation de l’hôte.Dans un premier temps, nous avons eu l’opportunité de suivre l’adaptation in naturad’un isolat de E. coli ED1a dominant dans le tube digestif d’un individu vivant en régionparisienne et sans problème de santé. Nous avons pu observer que E. coli ED1a, appartenant augroupe phylogénétique B2, évoluait de façon neutre dans le tube digestif. Le recours auxexpérimentations in vivo sur modèle murin au long court (plus d’un an) s’est avéré nécessairepour étudier l’impact de l’alimentation et du fond génétique de la souche dans l’adaptation deE. coli dans le tube digestif. Le propos de la première expérimentation était d’étudierl’adaptation d’un isolat naturel de E. coli 536 (appartenant au groupe phylogénétique B2 etinitialement issu d’infection urinaire), dans un tube digestif de souris se rapprochant le pluspossible des conditions naturelles (en utilisant le principe de transmission du microbiote digestifde la mère à la progéniture) et soumises à deux régimes alimentaires : standard ou riche en graset en sucre. Nous avons pu mettre en évidence une activation constitutive de l’opéron lactosesurvenant lors de la période d’allaitement des progénitures pour ensuite évoluer de manièreneutre quelque soit le régime alimentaire. Le propos de la deuxième expérimentation étaitd’étudier l’impact du fond génétique de la souche combinée à l’alimentation en étudiantl’évolution de deux isolats naturels de E. coli 536 et HS (appartenant au groupe phylogénétiqueA et issu d’une situation commensale chez un humain) dans le tube digestif de souris traitées àla streptomycine. Nous avons pu distinguer deux profils d’adaptation en fonction de la soucheet de l’alimentation. Il semblerait que l’intensité de l’adaptation dépende préférentiellement dela souche et probablement de son fond génétique, et que les cibles de l’adaptation dépendentplutôt du régime alimentaire. Plus précisément, ces cibles semblent principalement êtreassociées au métabolisme de sucres. Ces études constituent un progrès important dans lacompréhension des pressions sélectives agissant sur E. coli in vivo

NG-6445_ED6110902_lib23176_1587_5

Sequence corresponding to 6D31

NG-6445_ED5110902_lib23175_1587_5

Sequence corresponding to 5D31

NG-6445_ED8300502_lib23170_1587_5

Sequence corresponding to 8D21

NG-6445_ED5300502_lib23167_1587_5

Sequence corresponding to 5D21

NG-6445_ED7300502_lib23169_1587_5

Sequence corresponding to 7D21

NG-6445_1h311001_lib23162_1553_6

Sequence corresponding to 8D