Dataset Information

A Critical Evaluation of Enoxaparin Dose Adjustment Guidelines in Children.

ABSTRACT:

Objectives

The purposes of this study are to perform a large-scale evaluation of the standardized dosage adjustment nomogram recommended by the American College of Chest Physicians (CHEST) for the management of enoxaparin in hospitalized pediatric patients and to determine the necessity of routine and repeated anti-factor Xa (anti-Xa) levels.

Methods

A retrospective cohort study was designed, and charts were reviewed in a single tertiary care institution for all patients who received enoxaparin between October 1, 2010, through September 30, 2016. Patients were included if they were receiving treatment doses of enoxaparin according to the pediatric CHEST guidelines, had a subtherapeutic or supratherapeutic anti-Xa level drawn at 3.5 to 6 hours after a dose, had a dose changed in an attempt to attain a therapeutic anti-Xa level, and had a second anti-Xa level drawn 3.5 to 6 hours after the dose change. Descriptive statistical methods were used to characterize the ability of dose adjustment via a nomogram to attain an anti-Xa of 0.5 to 1 unit/mL.

Results

A total of 467 patients were identified who received the appropriate initial dose and dosage adjustment and whose levels were drawn according to the CHEST guidelines. In patients who had an initial anti-Xa level of <0.35 units/mL and received the nomogram recommended dose increase of 25% ± 5%, 28 out of 96 patients (29.2%) reached therapeutic levels. Of 197 patients who had an initial anti-Xa level between 0.35 and 0.49 units/mL and who received the nomogram recommended dose increase of 10% ± 5%, 116 (58.9%) reached therapeutic levels. Of 50 patients with an initial anti-Xa level between 1.1 and 1.5 units/mL and who received the nomogram dose decrease of 20% ± 5%, 31 (62%) reached therapeutic levels.

Conclusions

The current dosage adjustment nomogram recommended by the CHEST guidelines does not reliably lead to therapeutic anti-Xa levels when used to adjust enoxaparin doses in pediatric patients.

SUBMITTER: Dinh CN

PROVIDER: S-EPMC6478360 | biostudies-literature | 2019 Mar-Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Critical Evaluation of Enoxaparin Dose Adjustment Guidelines in Children.

Dinh Christine Nguyen CN Moffett Brady S BS Galati Marianne M Lee-Kim YoungNa Y Yee Donald L DL Mahoney Donald D

The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG 20190301 2

<h4>Objectives</h4>The purposes of this study are to perform a large-scale evaluation of the standardized dosage adjustment nomogram recommended by the American College of Chest Physicians (CHEST) for the management of enoxaparin in hospitalized pediatric patients and to determine the necessity of routine and repeated anti-factor Xa (anti-Xa) levels.<h4>Methods</h4>A retrospective cohort study was designed, and charts were reviewed in a single tertiary care institution for all patients who recei ...[more]

PMID: 31019405

Similar Datasets

Project description:AimCurrent enoxaparin dosing guidelines in children are based on total body weight. This is potentially inappropriate in obese children as it may overestimate the drug clearance. Current evidence suggests that obese children may require lower initial doses of enoxaparin, therefore the aim of this work was to characterise the pharmacokinetics of enoxaparin in obese children and to propose a more appropriate dosing regimen.MethodsData from 196 unique encounters of 160 children who received enoxaparin treatment doses were analysed. Enoxaparin concentration was quantified using the chromogenic anti factor Xa (anti-Xa) assay. Patients provided a total of 552 anti-Xa samples. Existing published pharmacokinetic (PK) models were fitted and evaluated against our dataset using prediction-corrected visual predictive check plots (pcVPCs). A PK model was fitted using a nonlinear mixed-effects modelling approach. The fitted model was used to evaluate the current standard dosing and identify an optimal dosing regimen for obese children.ResultsPublished models of enoxaparin pharmacokinetics in children did not capture the pharmacokinetics of enoxaparin in obese children as shown by pcVPCs. A one-compartment model with linear elimination best described the pharmacokinetics of enoxaparin. Allometrically scaled fat-free mass with an estimated exponent of 0.712 (CI 0.66-0.76) was the most influential covariate on clearance while linear fat-free mass was selected as the covariate on volume. Simulations from the model showed that fat-free mass-based dosing could achieve the target anti-Xa activity at steady state in 77.5% and 78.2% of obese and normal-weight children, respectively, compared to 65.2% and 75.5% for standard total body weight-based dosing.ConclusionsA population PK model that describes the time course of anti-Xa activity of enoxaparin was developed in a paediatric population. Based on this model, a unified dosing regimen was proposed that will potentially improve the success rate of target attainment in overweight/obese patients without the need for patient body size categorisation. Therefore, prospective validation of the proposed approach is warranted.

Project description:Objective: To report the quality and clinical heterogeneity of the published clinical practice guidelines (CPGs) on nutrition in pregnancy. Methods: MEDLINE, Embase, Scopus, and ISI Web of Science databases were searched. The following aspects related to nutrition in pregnancy were addressed: specific requirements during pregnancy, description of a balanced diet, weight gain, prevention of food-borne, nutrition in peculiar sub-groups of women, and maternal or perinatal outcomes. The assessment of the risk of bias and quality assessment of the included CPGs were performed using “The Appraisal of Guidelines for REsearch and Evaluation (AGREE II)” tool divided in six quality domains: scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, editorial independence. Mean ± standard deviation (SD) was used to summarize the scores across all the guidelines per domain. The quality of each guideline was computed using the scoring system proposed by Amer et al. A cut-off of >60% was sued to define a CGP as recommended. Results: Eighteen CPGs were included. There was a substantial heterogeneity in the recommended dose for vitamins, folic acid, and micronutrient intake during pregnancy among the different published CPGs. 27.8% (5/18) of the CPGs recommended a daily intake of folic acid of 200 mcg, 38.8% (7/18) 400 mcg, 16.7% (3/18) 600 mcg while the remaining CPGs suggested dose between 400 and 600–800 mc per day. Adequate maternal hydration was advocated in the large majority of included CPGs, but a specific amount of water intake was not reported in 83.3% (15/18) cases. There was also significant heterogeneity in various other aspects of nutrition recommendation among the different CPGs, including gestational weight gain (55.5%), prevention of food-borne diseases in pregnancy (72.2%), nutrition in particular groups of pregnant women (83.3%), maternal and perinatal outcomes (72.2%). The AGREE II standardized domain scores for the first overall assessment (OA1) had a mean of 65% but only half scored more than 60%. Conclusion: The published CPGs on nutrition in pregnancy show an overall good methodology, but also a substantial heterogeneity as regard as different major aspects on nutrition in pregnancy.

Project description:The landscape of local and systemic therapy of renal cell carcinoma (RCC) is rapidly changing. The increase in the incidental finding of small renal tumors has increased the application of nephron-sparing procedures, while ten novel agents targeting the vascular endothelial growth factor (VEGF) or the mammalian target of rapamycin pathways, or inhibiting the interaction of the programmed death 1 receptor with its ligand, have been approved since 2006 and have dramatically improved the prognosis of metastatic RCC (mRCC). These rapid developments have resulted in continuous changes in the respective Clinical Practice Guidelines/Expert Recommendations. We conducted a systematic review of the existing guidelines in MEDLINE according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement, aiming to identify areas of agreement and discrepancy among them and to evaluate the underlying reasons for such discrepancies. Data synthesis identified selection criteria for nonsurgical approaches in renal masses; the role of modern laparoscopic techniques in the context of partial nephrectomy; selection criteria for cytoreductive nephrectomy and metastasectomy in mRCC; systemic therapy of metastatic non-clear-cell renal cancers; and optimal sequence of available agents in mRCC relapsed after anti-VEGF therapy as the major areas of uncertainty. Agreement or uncertainty was not always correlated with the availability of data from phase III randomized controlled trials. Our review suggests that the combination of systematic review and critical evaluation can define practices of wide applicability and areas for future research by identifying areas of agreement and uncertainty among existing guidelines.Implications for practiceCurrently, there is uncertainity on the role of surgery in MRCC and on the choice of available guidelines in relapsed RCC. The best practice is individualization of targeted therapies. Systematic review of guidelines can help to identify unmet medical needs and areas of future research.

Dataset Information

A Critical Evaluation of Enoxaparin Dose Adjustment Guidelines in Children.

Objectives

Methods

Results

Conclusions

Publications

A Critical Evaluation of Enoxaparin Dose Adjustment Guidelines in Children.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets