The NACSTOP Trial: A Multicenter, Cluster‐Controlled Trial of Early Cessation of Acetylcysteine in Acetaminophen Overdose
Bibliographic record
Abstract
Historically, intravenous acetylcysteine has been delivered at a fixed dose and duration of 300 mg/kg over 20 to 21 hours to nearly every patient deemed to be at any risk for hepatotoxicity following acetaminophen overdose. We investigated a 12-hour treatment regimen for selected low-risk patients. This was a multicenter, open-label, cluster-controlled trial at six metropolitan emergency departments. We enrolled subjects following single or staggered acetaminophen overdose with normal serum alanine transaminase (ALT) and creatinine on presentation and at 12 hours, and less than 20 mg/L acetaminophen at 12 hours. Patients were allocated to intervention (250 mg/kg over 12-hour) or control (300 mg/kg over 20-hour) regimens by site. The primary outcome was incidence of "hepatic injury" 20 hours following initiation of acetylcysteine treatment, defined as ALT doubling and peak ALT greater than 100 IU/L, indicating the need for further antidotal treatment. Secondary outcomes included incidence of hepatotoxicity (ALT > 1,000 IU/L), peak international normalized ratio (INR), and adverse drug reactions. Of the 449 acetaminophen overdoses receiving acetylcysteine, 100 were recruited to the study. Time to acetylcysteine (median 7 hours [interquartile ratio 6,12] versus 7 hours [6,10]) and initial acetaminophen (124 mg/L [58,171] versus 146 mg/L [66,204]) were similar between intervention and control groups. There was no difference in ALT (18 IU/L [13,22] versus 16 IU/L [13,21]) or INR (1.2 versus 1.2) 20 hours after starting acetylcysteine between groups. No patients developed hepatic injury or hepatotoxicity in either group (odds ratio 1.0 [95% confidence interval 0.02, 50]). No patients represented with liver injury, none died, and 96 of 96 were well at 14-day telephone follow-up. Conclusion: Discontinuing acetylcysteine based on laboratory testing after 12 hours of treatment is feasible and likely safe in selected patients at very low risk of liver injury from acetaminophen overdose.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".