Analytical Imprecision and Therapeutic Intervals for Lithium – Are There Implications for Old Age Patients with Bipolar Disorder?
Bibliographic record
Abstract
• ISBD proposed therapeutic intervals for old age are verifiable by real-world data. • Manufacuter cited therapeutic limit of 1.2 mmol/L should not be readily adopted. • Sufficient precision and method agreement exists around lithium therapeutic ranges. • At 0.4 mmol/L, overall imprecision across common lithium methods is 8.6 % CV. • The derived upper therapeutic limit of lithium is 0.91 mmol/L for younger adults. Monitoring blood levels of lithium is important for maintaining therapeutic efficacy. Age-dependent therapeutic intervals have been recommended by the International Society for Bipolar Disorder (ISBD) task force, 0.4–0.8 mmol/L and 0.4–0.7 mmol/L for adults aged 60–79 and ≥80 years old, respectively. However, the suitability of common colorimetric methods for lithium measurements in the suggested therapeutic intervals has not been characterized, nor has the proposed therapeutic interval been confirmed with real world patient data. Serum samples spiked with various concentrations of lithium ranging from 0 – 3.5 mmol/L were analyzed on six different methods for imprecision and relative comparability of lithium measurements. An indirect reference interval approach using refineR was employed to derive therapeutic limits using patient results spanning 5 years and compared with the recommended therapeutic intervals by the ISBD task force. Routinely employed colorimetric methods for lithium measurements have sufficient precision within the proposed therapeutic intervals, although select colorimetric methods are notably more imprecise at 0.4 mmol/L. The derived therapeutic intervals using patient data align with those proposed by the ISBD task force for older adults. Routine colorimetric methods used for lithium measurements have adequate precision and detection capabilities in the therapeutic windows proposed by the ISBD task force. In addition, the proposed therapeutic intervals are verifiable by real-world patient data.
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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 | 0.064 | 0.134 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| 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".