Association of proton pump inhibitor and histamine H2-receptor antagonists with restless legs syndrome
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
Restless legs syndrome (RLS) is a common sensorimotor disorder, which can disrupt sleep and is thought to be caused in part by low cellular iron stores. Proton pump inhibitors (PPI) and histamine H2-receptor antagonists (H2A) are among the most commonly used drugs worldwide and show evidence of causing iron deficiency. We conducted a case/non-case observational study of blood donors in the United States (N = 13,403; REDS-III) and Denmark (N = 50,323; Danish Blood Donor Study, DBDS), both of which had complete blood count measures and a completed RLS assessment via the Cambridge-Hopkins RLS questionnaire. After adjusting for age, sex, race, BMI, blood donation frequency, smoking, hormone use, and iron supplement use, PPI/H2A use was associated with RLS (odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.13-1.76; p = 0.002) in REDS-III for both PPI (OR = 1.43; CI, 1.03-1.95; p = 0.03) and H2A (OR = 1.56; CI, 1.10-2.16; p = 0.01). DBDS exhibited a similar association with PPIs/H2As (OR = 1.29; CI, 1.20-1.40; p < 0.001), and for PPIs alone (OR = 1.27; CI, 1.17-1.38; p < 0.001), but not H2As alone (OR = 1.18; CI, 0.92-1.53; p = 0.2). We found no evidence of blood iron stores mediating this association. The association of PPI, and possibly H2A, consumption with RLS independent of blood iron status and other factors which contribute to RLS risk suggest the need to re-evaluate use of PPI/H2A in populations at particular risk for RLS.
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 | 0.000 |
| 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