ORCID Profile
0000-0003-2515-2951
Current Organisations
Boston Children's Hospital
,
CNRS Délégation Alpes
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2022
Publisher: SAGE Publications
Date: 11-07-2017
Abstract: Extracorporeal Life Support (ECLS) risks thrombotic and hemorrhagic complications. Optimal anti-coagulation monitoring is controversial. We compared coagulation tests evaluating the heparin effect in pediatric ECLS. A retrospective study of children ( yrs) undergoing ECLS over 12 months in a tertiary pediatric intensive care unit (PICU). Variables included anti-Factor Xa activity (anti-Xa), activated partial thromboplastin time (aPTT), activated clotting time (ACT) and thromboelastogram (TEG ® 6s) parameters: ratio and delta reaction (R) times (the ratio and difference, respectively, between R times in kaolin assays with and without heparinase). Test results were correlated with unfractionated heparin infusion rate (IU/kg/hr) at the time of s ling. Mean test results of each ECLS run were evaluated according to the presence/absence of complications. Thirty-two ECLS runs (31 patients) generated 695 data-points for correlation. PICU mortality was 22% and the thrombotic complication rate was 66%. The proportion of variation in coagulation test results explained by heparin dose was 13.3% for anti-Xa, 11.9% for ratio R time, and 9.9% for delta R time, compared with % for ACT and aPTT. Incorporating in idual variation, age and antithrombin activity in a model with heparin dose explained less than 50% of the variation in test results. Correlation varied according to age, day of ECLS run and between in iduals, with parallel dose-response lines noted between patients. Significantly lower mean anti-Xa was observed in PICU non-survivors and runs with thrombosis. Lower anti-Xa was observed in ECLS runs with complications. Although absolute results from anti-Xa and TEG6 ® s showed the best correlation with heparin dose, a large proportion of variation in results was unexplained by heparin, while dose response was similar between in iduals. Population pharmacokinetic harmacodynamic modelling is required, as well as prospective trials to delineate the superior means of adjusting heparin therapy to prevent adverse clinical outcomes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2019
DOI: 10.1097/PCC.0000000000001757
Abstract: Reduction of nosocomial infections represents an increasingly recognized aspect of PICU benchmarking. We investigated the prevalence and outcomes of viral respiratory infections acquired during admission to PICU. Multicenter, statewide retrospective linkage study. Tertiary PICU. All children less than 16 years requiring PICU admission for greater than 48 hours from January 1, 2008, until December 31, 2013. Testing was performed in symptomatic patients using an extended panel polymerase chain reaction capturing nine respiratory viruses. Duration of intubation and total duration of respiratory support were primary outcomes. Of 3,607 patients admitted to PICU for greater than 48 hours, 102 (2.8%) were diagnosed with a PICU-associated viral infection out of 702 patients (19.4%) undergoing viral testing, reflecting a rate of 2.8 PICU-associated viral infections per 1,000 PICU patient days. Compared with negative/untested patients, those with PICU-associated viral infections had greater intubation duration (median 164 vs 67 p 0.001), longer respiratory support (204 vs 68 hr p 0.001), were more likely to require extracorporeal life support (odds ratio, 5.3 2.7–10.3 p 0.001), high-frequency oscillatory ventilation (odds ratio, 3.0 1.7–5.4 p 0.001), and inhaled nitric oxide (odds ratio, 2.7 1.5–5.0 p = 0.001). When comparing patients with PICU-associated viral infection with patients who tested negative for respiratory viruses, no substantial difference in these outcomes was found. The acquisition of viral infections during PICU admission is less frequent compared with previous reports on bacterial and fungal hospital-acquired infections. We did not observe worse patient-centered outcomes when comparing virus positive versus tested but negative patients. Our findings challenge the clinical value of performing viral respiratory diagnostics in PICU patients evaluated for infection.
Publisher: Springer Science and Business Media LLC
Date: 20-02-2020
Publisher: Springer Science and Business Media LLC
Date: 09-03-2019
DOI: 10.1007/S40262-019-00751-7
Abstract: Unfractionated heparin (UFH) is a commonly used anticoagulant therapy for the acute treatment and prevention of thrombosis. Its short duration of action, reversibility of effect by protamine sulfate, and extensive clinical experience are some of the advantages that support its use. However, the choice of dose and dosing regimen of UFH remains challenging for several reasons. First, UFH has a narrow therapeutic window and wide variability in the dose-response relationship. Second, its pharmacodynamic (PD) properties are difficult to characterise owing to the complex multidimensional mechanisms of interaction with the haemostatic system. Third, the complex heterogeneous chemical composition of UFH precludes precise characterisation of its pharmacokinetic (PK) properties. This review provides a comprehensive mechanistic approach to the interaction of UFH with the haemostatic system. The effect of chemical structure on its PK and PD properties is quantitatively described, and a framework for characterisation of the dose-response relationship of UFH for the purpose of dose optimisation is proposed.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2020
DOI: 10.1097/PCC.0000000000002302
Abstract: Viral infections are common in children, but there is a lack of data on severe viral infections in critically ill children. We investigated testing for viral infections in children requiring PICU admission and describe the epidemiology and outcomes. Multicenter retrospective study. Results of viral testing for nine respiratory viruses using polymerase chain reaction were collected. Children less than 16 years old nonelectively admitted to PICU over a 6-year period. Two tertiary PICUs in Queensland, Australia. None. Primary outcome was PICU length of stay. Secondary outcomes included need for and duration of intubation and mortality in PICU. Univariate and multivariate regression analyses were performed, adjusting for age, indigenous status, comorbidities, and severity of illness. Of 6,426 nonelective admissions, 2,956 (46%) were polymerase chain reaction tested for a virus of which 1,353 (46%) were virus positive. Respiratory syncytial virus was the most common pathogen identified ( n = 518, 33%), followed by rhinovirus/enterovirus and adenovirus. Across all patients who underwent polymerase chain reaction testing, identification of a respiratory virus was not significantly associated with longer overall length of stay (multivariate odds ratio, 1.08 95% CI, 0.99–1.17 p = 0.068) or longer intubation ( p = 0.181), whereas the adjusted odds for intubation and mortality were significantly lower ( p 0.01). Subgroup analyses restricted to patients with acute respiratory infections ( n = 1,241), bronchiolitis ( n = 761), pneumonia ( n = 311), confirmed bacterial infection ( n = 345), and malignancy ( n = 95) showed that patients positive for a virus on testing had significantly longer PICU length of stay (multivariate p 0.05). In children with pneumonia, identification of a respiratory virus was associated with significantly increased duration of ventilation ( p = 0.003). No association between positive test results for multiple viruses and outcomes was observed. Viral infections are common in critically ill children. Viral infections were associated with lower intubation and mortality rates compared with all children testing negative for viral infections. In several subgroups studied, identification of viral pathogens was associated with longer PICU length of stay while mortality was comparable. Prospective studies are required to determine the benefit of routine testing for respiratory viruses at the time of PICU admission.
Publisher: Wiley
Date: 25-02-2019
DOI: 10.1111/TPJ.14228
Abstract: Several plastid macromolecular protein complexes are encoded by both nuclear and plastid genes. Therefore, cytonuclear interactions are held in place to prevent genomic conflicts that may lead to incompatibilities. Allopolyploidy resulting from hybridization and genome doubling of two ergent species can disrupt these fine-tuned interactions, as newly formed allopolyploid species confront biparental nuclear chromosomes with a uniparentally inherited plastid genome. To avoid any deleterious effects of unequal genome inheritance, preferential transcription of the plastid donor over the other donor has been hypothesized to occur in allopolyploids. We used Brassica as a model to study the effects of paleopolyploidy in diploid parental species, as well as the effects of recent and ancient allopolyploidy in Brassica napus, on genes implicated in plastid protein complexes. We first identified redundant nuclear copies involved in those complexes. Compared with cytosolic protein complexes and with genome-wide retention rates, genes involved in plastid protein complexes show a higher retention of genes in duplicated and triplicated copies. Those redundant copies are functional and are undergoing strong purifying selection. We then compared transcription patterns and sequences of those redundant gene copies between resynthesized allopolyploids and their diploid parents. The neopolyploids showed no biased subgenome expression or maternal homogenization via gene conversion, despite the presence of some non-synonymous substitutions between plastid genomes of parental progenitors. Instead, subgenome dominance was observed regardless of the maternal progenitor. Our results provide new insights on the evolution of plastid protein complexes that could be tested and generalized in other allopolyploid species.
Publisher: Springer Science and Business Media LLC
Date: 03-07-2019
DOI: 10.1007/S00134-019-05675-1
Abstract: Data on childhood intensive care unit (ICU) deaths are needed to identify changing patterns of intensive care resource utilization. We sought to determine the epidemiology and mode of pediatric ICU deaths in Australia and New Zealand (ANZ). This was a retrospective, descriptive study of multicenter data from pediatric and mixed ICUs reported to the ANZ Pediatric Intensive Care Registry and binational Government census. All patients < 16 years admitted to an ICU between 1 January 2006 and 31 December 2016 were included. Primary outcome was ICU mortality. Subject characteristics and trends over time were evaluated. Of 103,367 ICU admissions, there were 2672 (2.6%) deaths, with 87.6% of deaths occurring in specialized pediatric ICUs. The proportion of ANZ childhood deaths occurring in ICU was 12%, increasing by 43% over the study period. Unadjusted (0.1% per year, 95% CI 0.096-0.104 p < 0.001) and risk-adjusted (0.1%/year, 95% CI 0.07-0.13 p < 0.001) ICU mortality rates fell. Across all admission sources and diagnostic groups, mortality declined except following pre-ICU cardiopulmonary arrest where increased mortality was observed. Half of the deaths followed withdrawal of life-sustaining therapy (51%), remaining constant throughout the study. Deaths despite maximal resuscitation declined (0.92%/year, 95% CI 0.89-0.95% p < 0.001) and brain death diagnoses increased (0.72%/year, 95% CI 0.69-0.75% p = 0.001). Unadjusted and risk-adjusted mortality for children admitted to ANZ ICUs is declining. Half of pediatric ICU deaths follow withdrawal of life-sustaining therapy. Epidemiology and mode of pediatric ICU death are changing. Further investigation at an international level will inform benchmarking, resource allocation and training requirements for pediatric critical care.
Publisher: Archives of Pathology and Laboratory Medicine
Date: 27-01-2021
DOI: 10.5858/ARPA.2020-0647-OA
Abstract: Specific reference intervals (RIs) facilitate accurate interpretation of results. Coagulation assay results may vary by demographics and also between reagents and analyzers used. Current Thromboelastograph 6s (TEG 6s) Hemostasis Analyzer RIs were generated from adult s les. To generate reagent analyzer-specific pediatric RIs for TEG 6s and coagulation parameters. A prospective, observational, single-center study of healthy children undergoing general anesthesia (January 3, 2017 to January 3, 2019). Venous blood s les were obtained for TEG 6s (Kaolin, Kaolin-Heparinase, Rapid and Functional Fibrinogen assays) and coagulation parameters (activated partial thromboplastin time, prothrombin time, thrombin clotting time, Echis time, antithrombin activity, and fibrinogen concentration using Instrumentation Laboratory ACL-TOP analyzers). Differences between activated partial thromboplastin time and prothrombin time reagents were investigated using mixed-effects regression, comparing maximum coefficients-of-variation with assay-specific allowable variation. RIs (lower/upper limits 2.5th of 97.5th percentiles) were generated using the following 2 methods: within discrete age-groups (neonates [& month], infants [1 month–1 year], young children [1–5 years], older children [6–10 years], and adolescents [11–16 years]), and modeled as functions of age and/or sex using quantile regression, including significant fractional polynomial and interaction terms. Variation between prothrombin time and activated partial thromboplastin time assays using different reagents was clinically significant. Reagent-analyzer specific pediatric RIs were generated using data from 254 children. Discrete and model-based RIs varied by age for all coagulation parameters and TEG 6s variables in all assays. We report reagent-analyzer specific pediatric RIs for TEG 6s and coagulation parameters. Observed variation reinforces recommendations for laboratory-specific RIs. These findings improve accuracy of interpretation of clinical results, provide a foundation for comparison and validation of tests in pathology, and illustrate feasibility and advantages of model-based RI approaches.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2018
No related grants have been discovered for Katie Moynihan.