Prediction of Thiopurine Metabolite Levels Based on Haematological and Biochemical Parameters

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F19%3A00512143" target="_blank" >RIV/61389030:_____/19:00512143 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/19:10400195 RIV/00098892:_____/19:N0000093 RIV/00064203:_____/19:10400195 RIV/61989592:15110/19:73599084 RIV/61989592:15310/19:73599084

Výsledek na webu

<a href="http://dx.doi.org/10.1097/MPG.0000000000002436" target="_blank" >http://dx.doi.org/10.1097/MPG.0000000000002436</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1097/MPG.0000000000002436" target="_blank" >10.1097/MPG.0000000000002436</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Prediction of Thiopurine Metabolite Levels Based on Haematological and Biochemical Parameters

Popis výsledku v původním jazyce

Objectives: Therapeutic drug monitoring of thiopurine erythrocyte levels is not available in all centers and it usually requires quite a long time to obtain the results. The aims of this study were to build a model predicting low levels of 6-thioguanine and 6-methylmercaptopurine in pediatric inflammatory bowel disease (IBD) patients and to build a model to predict nonadherence in patients treated with azathioprine (AZA). Methods: The study consisted of 332 observations in 88 pediatric IBD patients. Low AZA dosing was defined as 6-thioguanine levels <125 pmol/8 × 108 erythrocytes and 6-methylmercaptopurine levels <5700 pmol/8 × 108 erythrocytes. Nonadherence was defined as undetectable levels of 6-thioguanine and 6-methylmercaptopurine <240 pmol/8 × 108 erythrocytes. Data were divided into training and testing part. To construct the model predicting low 6-thioguanine levels, nonadherence, and the level of 6-thioguanine, the modification of random forest method with cross-validation and resampling was used. Results: The final models predicting low 6-thioguanine levels and nonadherence had area under the curve, 0.87 and 0.94, sensitivity, 0.81 and 0.82, specificity, 0.80 and 86, and distance, 0.31 and 0.21, respectively, when applied on the testing part of the dataset. When the final model for prediction of 6-thioguanine values was applied on testing dataset, a root-mean-square error of 110 was obtained. Conclusions: Using easily obtained laboratory parameters, we constructed a model with sufficient accuracy to predict patients with low 6-thioguanine levels and a model for prediction of AZA treatment nonadherence (web applications: https://hradskyo.shinyapps.io/6TG-prediction/ and https://hradskyo.shinyapps.io/Non-adherence/).

Název v anglickém jazyce

Prediction of Thiopurine Metabolite Levels Based on Haematological and Biochemical Parameters

Popis výsledku anglicky

Objectives: Therapeutic drug monitoring of thiopurine erythrocyte levels is not available in all centers and it usually requires quite a long time to obtain the results. The aims of this study were to build a model predicting low levels of 6-thioguanine and 6-methylmercaptopurine in pediatric inflammatory bowel disease (IBD) patients and to build a model to predict nonadherence in patients treated with azathioprine (AZA). Methods: The study consisted of 332 observations in 88 pediatric IBD patients. Low AZA dosing was defined as 6-thioguanine levels <125 pmol/8 × 108 erythrocytes and 6-methylmercaptopurine levels <5700 pmol/8 × 108 erythrocytes. Nonadherence was defined as undetectable levels of 6-thioguanine and 6-methylmercaptopurine <240 pmol/8 × 108 erythrocytes. Data were divided into training and testing part. To construct the model predicting low 6-thioguanine levels, nonadherence, and the level of 6-thioguanine, the modification of random forest method with cross-validation and resampling was used. Results: The final models predicting low 6-thioguanine levels and nonadherence had area under the curve, 0.87 and 0.94, sensitivity, 0.81 and 0.82, specificity, 0.80 and 86, and distance, 0.31 and 0.21, respectively, when applied on the testing part of the dataset. When the final model for prediction of 6-thioguanine values was applied on testing dataset, a root-mean-square error of 110 was obtained. Conclusions: Using easily obtained laboratory parameters, we constructed a model with sufficient accuracy to predict patients with low 6-thioguanine levels and a model for prediction of AZA treatment nonadherence (web applications: https://hradskyo.shinyapps.io/6TG-prediction/ and https://hradskyo.shinyapps.io/Non-adherence/).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30402 - Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction)

Projekt

<a href="/cs/project/EF16_019%2F0000868" target="_blank" >EF16_019/0000868: Molekulární, buněčný a klinický přístup ke zdravému stárnutí</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Pediatric Gastroenterology and Nutrition

ISSN

0277-2116

e-ISSN

—

Svazek periodika

69

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

6

Strana od-do

"e105"-"e110"

Kód UT WoS článku

000506845100003

EID výsledku v databázi Scopus

2-s2.0-85072193210