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Record W4403038820 · doi:10.1111/cts.70040

Pharmacokinetic model‐guided enoxaparin dosing in the Neonatal ICU: Retrospective cohort study to plan for prospective feasibility trial

2024· article· en· W4403038820 on OpenAlexaff
Haden T. Bunn, Catherine T. Schentag, Leonardo R. Brandão, Vijay Ivaturi, Tamorah Lewis

Bibliographic record

VenueClinical and Translational Science · 2024
Typearticle
Languageen
FieldMedicine
TopicPneumonia and Respiratory Infections
Canadian institutionsPublic Health OntarioUniversity of TorontoHospital for Sick Children
Fundersnot available
KeywordsDosingMedicinePharmacokineticsDoseRetrospective cohort studyPharmacodynamicsAnesthesiaTherapeutic indexPharmacologySurgeryDrug

Abstract

fetched live from OpenAlex

Traditional milligram per kilogram (mg/kg) dosing of enoxaparin in neonates frequently fails to achieve target anti-Xa levels promptly, necessitating repeated laboratory monitoring and dose adjustments. This study investigated whether a personalized dosing strategy based on predicted individual clearance and volume of distribution could improve outcomes, comparing standard-of-care (SOC) mg/kg dosing to pharmacokinetic (PK) model-informed precision dosing (MIPD). A retrospective analysis was conducted on hospitalized neonates treated with enoxaparin at less than 44 weeks postmenstrual age from 2019 to 2022. Data on demographics, drug dosing, PK model covariates, and clinical outcomes were extracted from electronic health records and analyzed using the Pumas-AI Lyv dosing tool. The primary focus was on comparing the initial SOC dose to the MIPD-recommended dose. The secondary outcome measured was the time required to achieve therapeutic anti-Xa levels. The study included 168 neonates with a median postnatal age of 15 days (range 1-149) and a median dosing weight of 3.1 kg (range: 0.82-5.2). MIPD-recommended initial doses were 20%-60% higher than SOC doses in 32% of the cases and over 60% higher in 11% of cases. Neonates who received SOC doses that were much lower than the MIPD recommendation showed the longest delays in reaching therapeutic anti-Xa levels. The results indicate that PK model-informed of enoxaparin dosing leads to higher initial dosages than SOC in neonates, potentially reducing the time to therapeutic anti-Xa levels. These findings are being utilized to define dosing limits for a prospective trial of MIPD in neonatal intensive care settings.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.028
Threshold uncertainty score0.240

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.132
GPT teacher head0.463
Teacher spread0.331 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2024
Admission routes1
Has abstractyes

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