Safety of valproic acid in patients with chronic obstructive pulmonary disease: a population‐based cohort study
Bibliographic record
Abstract
PURPOSE: Valproic acid is an anticonvulsant that also inhibits histone deacetylase (HDAC), a property that could worsen pulmonary function in patients with chronic obstructive pulmonary disease (COPD). The clinical significance of this property is unknown. We therefore compared the risk of COPD exacerbation in older patients with COPD commencing treatment with either valproic acid or phenytoin, an anticonvulsant that does not affect HDAC. METHODS: We conducted a population-based retrospective cohort study of Ontario residents with COPD aged 66 years or older who started treatment with valproic acid or phenytoin between 1 April 1993 and 30 November 2012. The primary outcome was a hospital admission or emergency department visit for a COPD exacerbation within 240 days of drug initiation. A secondary outcome examined initiation of oral corticosteroids in the outpatient setting. RESULTS: During the study period, we identified 4596 COPD patients who commenced valproic acid and 8478 who commenced phenytoin. Following multivariable adjustment, valproic acid did not increase the risk of the primary outcome (adjusted hazard ratio 1.00, 95% confidence interval 0.79 to 1.26). Although valproic acid was associated with a lower risk of initiating oral corticosteroids in the first thirty days following commencement of anticonvulsant therapy (adjusted hazard ratio 0.32; 95% confidence interval 0.21 to 0.49), no difference was observed during subsequent follow-up. CONCLUSION: Among older patients with COPD, treatment with valproic acid does not increase the risk of adverse pulmonary outcomes relative to phenytoin. These findings suggest that valproate-induced HDAC inhibition is of little clinical relevance in this context.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
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".