High-Throughput Assessment of Real-World Medication Effects on QT Interval Prolongation: Observational Study
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
BACKGROUND: Drug-induced prolongation of the corrected QT interval (QTc) increases the risk for Torsades de Pointes (TdP) and sudden cardiac death. Medication effects on the QTc have been studied in controlled settings but may not be well evaluated in real-world settings where medication effects may be modulated by patient demographics and comorbidities as well as the usage of other concomitant medications. OBJECTIVE: We demonstrate a new, high-throughput method leveraging electronic health records (EHRs) and the Surescripts pharmacy database to monitor real-world QTc-prolonging medication and potential interacting effects from demographics and comorbidities. METHODS: We included all outpatient electrocardiograms (ECGs) from September 2008 to December 2019 at a large academic medical system, which were in sinus rhythm with a heart rate of 40-100 beats per minute, QRS duration of <120 milliseconds, and QTc of 300-700 milliseconds, determined using the Bazett formula. We used prescription information from the Surescripts pharmacy database and EHR medication lists to classify whether a patient was on a medication during an ECG. Negative control ECGs were obtained from patients not currently on the medication but who had been or would be on that medication within 1 year. We calculated the difference in mean QTc between ECGs of patients who are on and those who are off a medication and made comparisons to known medication TdP risks per the CredibleMeds.org database. Using linear regression analysis, we studied the interaction of patient-level demographics or comorbidities on medication-related QTc prolongation. RESULTS: We analyzed the effects of 272 medications on 310,335 ECGs from 159,397 individuals. Medications associated with the greatest QTc prolongation were dofetilide (mean QTc difference 21.52, 95% CI 10.58-32.70 milliseconds), mexiletine (mean QTc difference 18.56, 95% CI 7.70-29.27 milliseconds), amiodarone (mean QTc difference 14.96, 95% CI 13.52-16.33 milliseconds), rifaximin (mean QTc difference 14.50, 95% CI 12.12-17.13 milliseconds), and sotalol (mean QTc difference 10.73, 95% CI 7.09-14.37 milliseconds). Several top QT prolonging medications such as rifaximin, lactulose, cinacalcet, and lenalidomide were not previously known but have plausible mechanistic explanations. Significant interactions were observed between demographics or comorbidities and QTc prolongation with many medications, such as coronary disease and amiodarone. CONCLUSIONS: We demonstrate a new, high-throughput technique for monitoring real-world effects of QTc-prolonging medications from readily accessible clinical data. Using this approach, we confirmed known medications for QTc prolongation and identified potential new associations and demographic or comorbidity interactions that could supplement findings in curated databases. Our single-center results would benefit from additional verification in future multisite studies that incorporate larger numbers of patients and ECGs along with more precise medication adherence and comorbidity data.
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.
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 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 it