Defeating the Hydra of Excess Cardiovascular Disease Risk in Rheumatoid Arthritis — How Close Are We to Completing the Task?
Bibliographic record
Abstract
For his Second Labor, Heracles was tasked with slaying the Hydra, a serpentine monster from ancient Greek mythology who possessed many heads. When Heracles attempted to decapitate the monster, two new heads grew in place of each severed head, an expression of hopelessness of such struggle for anyone but the hero. The invulnerability of the Hydra was because of its one immortal head. Once the immortal head was cut off, the monster was defeated, and Heracles’ second task was completed. Much like slaying the monstrous Hydra, conquering the disproportionally increased risk of nearly all forms of fatal and nonfatal cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) compared to the general population has been an unsolved lingering problem, long awaiting the arrival of its hero. Fueled by systemic autoimmune inflammation, this 1.5- to 2-fold excess CVD risk has been invulnerable to traditional CVD management strategies. Growing attention to tight control of RA disease activity and widespread use of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and biologic DMARD (bDMARD) have dramatically changed the landscape of RA outcomes in the new millennium, providing hopes for defeating the increased CVD risk. A metaanalysis of observational studies highlighted the potential for up to 30% CVD risk reduction in RA with the use of methotrexate (MTX) and tumor necrosis factor-α inhibitors (TNFi)1. A large retrospective study from Sweden demonstrated even greater benefits, including the reduction of CVD risk in RA patients who responded to TNFi to that of the general population level2. Remission of RA disease activity, especially if achieved early in the disease course, has been associated with reduction of the CVD risk to a level comparable to the general population level3,4, identifying systemic inflammation as the “immortal head” of the excess CVD risk in … Address correspondence to Dr. E. Myasoedova, Mayo Clinic College of Medicine and Science, Division of Rheumatology, 200 1st St. SW, Rochester, MN 55905, USA. Email: myasoedova.elena{at}mayo.edu.
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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 | 0.015 | 0.079 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.004 |
| Scholarly communication | 0.006 | 0.007 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.005 | 0.012 |
| Insufficient payload (model declined to judge) | 0.007 | 0.003 |
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".