Meta-analiza podataka o razlikama u izloženosti psihijatrijskim lekovima između sporih i normalnih CYP2C19/CYP2D6 metabolizera
Bibliographic record
Abstract
Postoji mogućnost da genetski predodređene razlike između osoba u kapacitetu CYP450\nenzima mogu uticati na farmakoterapiju u psihijatriji. Cilj ovog istraživanja bio je precizna\nkvantifikacije uticaja CYP2C19/CYP2D6 fenotipa na izloženost antidepresivima i\nantipsihoticima metodom meta-analize odnosa srednjih vrednosti. Drugi cilj bio je\nispitivanje uticaja CYP2C19 fenotipa na efikasnost i podnošljivost antidepresiva pomoću\nkliničke studije u kojoj su hospitalizovani pacijenti praćeni četiri nedelje.\nSerija meta-analiza podataka iz 94 jedinstvene studije na ukupno 8379 precizno je\nkvantifikovala povećanu izloženost escitalopramu (+163%; 95%CI: +140%, 189%;\nn=1262, p<0,0001) i sertralinu (+38%; 95%CI: +27%, +51%; n=917, p<0,0001) kod osoba\nsa genetski predviđenim smanjenim kapacitetom CYP2C19 enzima, kao i povećanu\nizloženost risperidonu (+36%; 95%CI: +28%, +44%; n=1492, p<0,0001), aripiprazolu\n(+48%; 95%CI: +41%, +57%; n=1038, p<0,0001) i haloperidolu (+68%; CI95%: 40%,\n102%; n=423, p<0.0001) kod osoba sa genetski predviđenim smanjenim kapacitetom\nCYP2D6 enzima. Klinička studija demonstrirala je da su, u toku četiri nedelje, osobe sa\nsporijim CYP2C19 metabolizmom imale 36% (95%CI: 20-52%, p<0,0001) manje izraženo\npoboljšanje simptoma depresije (praćeno Hamilton skalom za depresiju) i značajno veći\nintenzitet neželjenih efekata vezanih za gastrointestinalni (q=0,002) i centralni nervni\nsistem (q=0,045) što je mereno Toronto skalom, u odnosu na kontrolne osobe.\nZbog visoke preciznosti kvantifikacije, rezultati meta-analiza mogu poslužiti kao osnova za\nkliničke smernice za precizno doziranje ispitivanih lekova na osnovu CYP2C19/CYP2D6\ngenotipa. Takođe, rezultati kliničke studije naglašavaju da CYP2C19 genotip može biti\nklinički važna informacija u psihijatrijskoj praksi.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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 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".