Desmopressin and the risk of hyponatremia: A population-based cohort study
Bibliographic record
Abstract
BACKGROUND: Desmopressin was approved by the Food and Drug Administration (FDA) in 1978 for use in diabetes insipidus and bleeding disorders, but it is also prescribed off-label for patients with nocturia. Quantifying the potential risks facing adult patients taking desmopressin has taken on added importance because a new intranasal formulation of desmopressin was approved by the FDA in 2017. Like the old formulation, the main active ingredient is desmopressin acetate, but the new formulation also contains an excipient designed to enhance absorption. Our objective was to quantify the rate of hyponatremia in routine clinical care for patients prescribed the older formulation of desmopressin. METHODS AND FINDINGS: We conducted a population-based new-user cohort study from 1 February 2006 to 1 February 2017 using a nationwide commercial health plan database. Patients newly prescribed the older formulation of desmopressin were propensity-score (PS)-matched to patients newly prescribed oxybutynin. As a sensitivity analysis, tamsulosin was used as the comparator rather than oxybutynin. The primary outcome was a primary position diagnosis of hyponatremia. Proportional hazard models after 1:1 PS matching were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). We identified 3,137 adults who were newly prescribed desmopressin and matched them to 3,137 adults who were newly prescribed oxybutynin. Mean age was 70, 55% were male, 13% filled a prescription for a diuretic during the baseline time period, and the mean baseline sodium prior to receiving either study drug was 140 mmol/L (normal: 135-145). The rate of hyponatremia was 146 per 1,000 person-years for adults prescribed desmopressin compared to 11 per 1,000 person-years for adults prescribed oxybutynin, corresponding to a 13-fold higher rate (HR 13.19; 95% CI 6.69, 26.01; p < 0.01). When follow-up was truncated at 30 days, a similar increased rate was observed (HR 19.41; 95% CI 7.11, 52.99; p < 0.01). A higher rate of hyponatremia was also observed with desmopressin when tamsulosin was the comparator (HR 12.10; 95% CI 6.54, 22.37; p < 0.01). Important limitations of our study include unmeasured confounding (for example, over-the-counter medication use, dietary intake), missing data (i.e., only 20% of patients had a baseline serum sodium), and a lack of data on the newer formulation of desmopressin. CONCLUSIONS: Use of an older formulation of desmopressin was associated with a marked increased rate of subsequent hyponatremia compared to use of other medications indicated for lower urinary tract symptoms. Such risks should be clearly communicated to patients prescribed this formulation of desmopressin.
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How this classification was reachedexpand
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 | 0.001 | 0.001 |
| 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) | 0.001 | 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 teacher head, 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".