Systematic Review and Meta-analysis of the Diagnostic Accuracy of Lactose Breath Hydrogen or Lactose Tolerance Testing for Predicting the North European Lactase Polymorphism C/T-13910
Bibliographic record
Abstract
Purpose: Accuracy of two indirect tests of lactose maldigestion, lactose breath hydrogen (LBH) and lactose tolerance tests (LTT) have not been systematically reviewed in predicting any genotype. We perform a meta-analysis comparing the north-European genetic polymorphism C/T-13910 with either LBH or LTT. Using LBH, we examine the effect on diagnostic accuracy of loading dose, inclusion of children in studies and the latitude of study center to determine whether mixed contribution of other polymorphisms interfere. Proof of accuracy for this polymorphism would allow general assumptions to be made from indirect tests for other polymorphisms. Methods: An electronic data base of the literature as well as individual references in articles were searched with the theme of genetics of lactase and comparisons with LBH or LTT were carried out and assessed by 2 authors. Due to heterogeneity, random effects model was used to report summary accuracy measures with 95% confidence intervals (CI). Results: The search revealed 18 studies of which 16 evaluated LBH, 2 of 18 as well as 2 of the remaining 16 studies evaluated LTT (4 total). Overall, sensitivity and specificity were 0.88 (CI, 0.85-0.90) and 0.85 (CI, 0.82-0.87). Change in lactose load to 50 g increased sensitivity to 0.92 (CI, 0.89-0.94) while using ≤ 25 g increased specificity to 0.95 (CI, 0.90-0.98). Removing 4 studies with children (< 18yr) increased sensitivity and specificity to 0.90 (CI, 0.87-0.93) and 0.91 (CI, 0.88-0.93) respectively. Diagnostic Odds Ratio (DOR) for LBH was 118(CI, 59.8-234) (Heterogeneity Index, 42%). Alteration to low dose lactose load reduced DOR to 77.4 (CI, 18.2-328.9) while elimination of studies with children increased DOR to 196.7 (CI, 99.4-387.15). There was no significant effect of latitude. The LTT showed sensitivity, specificity and DOR of 0.95 (CI 0.90-0.98), 0.95 (CI, 0.89-0.98) and 251.01 (CI, 70.98-887.69) respectively. Removal of 1 study reduced DOR to 130.19 (CI, 28.0-603.7) and heterogeneity to 0 %. Publication bias was noted. Conclusion: Diagnostic accuracy of both tests is good and individually reflects intended genetic status for C/T-13910. These results apply to normal populations within defined age groups. The 50 g load in LBH is the most sensitive while a 25 g is more specific for lactose digestion status. These small differences could be useful clinically and suggest loads to be used in epidemiological or clinical situations. This meta-analysis indirectly suggests, that the two most frequently used clinical tests for lactase phenotype, would both individually, accurately predict true genetic lactase status, independent of predominant population genetic polymorphisms.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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 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".