Fluoroquinolones- and Collagen-Associated Severe Toxicity
Bibliographic record
Abstract
Background. Fluoroquinolones (FQs) are the most commonly used antibiotic class, so rare complications can have significant public health consequences. FQ-associated tendon ruptures have been well described, but other more severe collagen-associated adverse events may also be possible. We sought to confirm the association of FQs and tendon rupture, to clarify the potential association of FQs and retinal detachment, and to test for a previously unrecognized but potentially lethal association between FQs and aortic aneurysms. Methods. Longitudinal cohort study of all older adults turning 65 years between April 1 1997 and Mar 31 2012 in Ontario, Canada. FQ use was measured as a time-varying covariate, with patients considered to be at risk during and 30 days following treatment. Tendon ruptures, retinal detachments, and aortic aneurysm events diagnosed in province wide hospital and emergency room datasets in Ontario's universal healthcare system. Patients were observed until they experienced an outcome event, died, or reached the end of follow-up period (March 31, 2014). Results. Among 1,744,360 eligible older adults, 657,950 (38%) received at least one FQ during follow up, amounting to 22,380,515 days of FQ treatment. The patients experienced 37,338 (2.1%) tendon ruptures, 3246 (0.2%) retinal detachments, and 18,391 (1.1%) aortic aneurysms. Severe collagen-associated adverse events were more common during FQ treatment than control periods, including tendon ruptures (0.82 versus 0.26 per 100-person years [py], P < .001), retinal detachments (0.03 versus 0.02 per 100-py, P = .003) and aortic aneurysms (0.35 versus 0.13 per 100-py, P < .001). Current FQs were associated with increases in tendon rupture (HR = 3.13; 95% CI, 2.98–3.28; adjusted HR = 2.40, 95% CI, 2.24–2.57), and a similar increase in aortic aneurysms (HR = 2.72; 95% CI, 2.53–2.93; adjusted HR = 2.24; 95% CI, 2.02–2.49), which was substantially greater in magnitude than the association of these outcomes with amoxicillin. The hazard of retinal detachment was marginal (HR = 1.28; 95% CI, 0.99–1.65; adjusted HR = 1.47; 95% CI, 1.08–2.00), and not greater in magnitude than that observed with amoxicillin. Conclusion. FQ treatment is indeed associated with subsequent tendon ruptures, and may also contribute to aortic aneurysms. Disclosures. All authors: No reported disclosures.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 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) | 0.002 | 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".