Voriconazole Therapeutic Drug Monitoring Among Lung Transplant Recipients Receiving Targeted Therapy for Invasive Aspergillosis
Bibliographic record
Abstract
Background. Voriconazole is the recommended treatment for invasive aspergillosis (IA) in lung transplant recipients (LTR). The use of voriconazole therapeutic drug monitoring (TDM) is increasingly recommended but its use remains controversial. We conducted a study to explore the association between voriconazole serum concentration and clinical outcome of LTR receiving targeted therapy for IA. Methods. We conducted a retrospective study of all lung transplant recipients receiving IA voriconazole targeted monotherapy who underwent serum TDM between January 2013 and December 2015 at Notre-Dame Hospital, CHUM, Montreal, Canada. Chart review was performed to collect demographic, clinical and laboratory data. Clinical outcome and mortality were assessed at 12 weeks after initiation of therapy. Classification and regression tree (CART) analysis was used to find the most predictive voriconazole level thresholds for successful outcome. Results. Among the 111 LTR during the study period, 11 received voriconazole monotherapy for targeted therapy and underwent TDM during therapy. All 11 patients had pulmonary involvement, without dissemination. At 12 weeks of therapy, 6 patients achieved successful outcome while 5 patients did not. The median TDM value among patients who achieved successful outcome versus patients who failed therapy were 0.9 (0.3–7.3) µg/mL and 0.6 (0.05–4.9) µg/mL, respectively. Two separate CART analyses were performed; 1 was based on the median voriconazole TDM concentration, the other was based on minimal voriconazole TDM concentration for each patient. Successful outcome were more likely attained among patients with median TDM concentration > 0.645 µg/mL (P = 0.06) or minimal TDM concentration > 0.415 µg/mL (P = 0.02). None of the patient died during the study period. Conclusion. Our study demonstrates that voriconazole targeted therapy among lung transplant recipients with invasive aspergillosis is associated with a better treatment response when median TDM concentration are greater than 0.645 µg/mL or when minimal TDM concentration are greater than 0.415 µg/mL. Disclosures. All authors: No reported disclosures.
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How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Observational | low |
| gpt | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Observational | low |
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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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, unvalidatedLabeled directly by 2 models reading the full record.
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".