The effect of heparin type & symptom duration on noncritically ill patients hospitalized for COVID-19: secondary analyses of an international multiplatform RCT
Bibliographic record
Abstract
In patients with COVID-19, hospitalization is associated with progression to the need for ICU-level organ support and mortality. It is important to have effective treatments to slow or halt progression and to identify patients at high risk of progressing. Therapeutic-dose heparin reduces progression to organ support and mortality in noncritically ill patients hospitalized for COVID-19, however, the differential treatment effects for various heparin types are unknown. Symptom duration prior to hospitalization may impact disease progression and treatment effects of therapeutic-dose heparin. This thesis evaluated 3 objectives: 1) differential treatment effects of therapeutic-dose heparin by heparin type, 2) effects of symptom duration on disease progression, and 3) effects of symptom duration on heparin treatment. We analyzed heparin type in noncritically ill patients hospitalized for COVID-19 by performing a secondary analysis of patients enrolled in the ATTACC and ACTIV-4a randomized controlled trials. Analyses of symptom duration only included patients from ATTACC. Patients were enrolled between May 2020 and January 2021 in Brazil, Canada, Mexico, Spain, and the US. Patients were randomized to either usual care venous thromboprophylaxis or therapeutic-dose heparin. Treatment effects were modeled using proportional odds logistic regression within a Bayesian framework. The primary ordinal outcome consisted of 1) survival without organ support, 2) survival with organ support, and 3) death. Analysis of heparin type comprised 832 patients assigned to usual care venous thromboprophylaxis and 987 to therapeutic-dose heparin (total n=1819), of whom 90% were administered enoxaparin (n=887). Therapeutic-dose enoxaparin likely reduced progression to organ support and mortality compared to usual care venous thromboprophylaxis (adjusted odds ratio [OR] 1.19 95% credible interval [CrI] 0.94-1.52, posterior probability [Pr] 92.5%). Analysis of non-enoxaparin heparins was limited by small sample sizes. Analyses of symptom duration consisted of 499 patients assigned to usual-care venous thromboprophylaxis and 638 assigned therapeutic-dose heparin (total n=1137). Shorter symptom duration prior to admission was associated with increased progression to organ support and mortality (adjusted OR for 1 day less of symptoms 1.08, 95% CrI 1.04-1.13, Pr >99.9%) but likely did not modify treatment effects of therapeutic-dose heparin (Pr 27.2%).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.017 | 0.031 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.015 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".