[Translated article] Genetic variants and enzyme activity in citidin deaminase: Relationship with capecitabine toxicity and recommendation for dose adjustment.

OBJECTIVE: Capecitabine, an antineoplastic drug used in the treatment of breast and colon cancer, can cause severe, even fatal toxicity in some patients. The interindividual variability of this toxicity is largely due to genetic variations in target genes and enzymes of metabolism of this drug, such as Thymidylate Synthase (TS) and Dihydropyrimidine Dehydrogenase (DPD). The enzyme Cytidine Deaminase (CDA), involved in the activation of capecitabine, also has several variants associated with an increased risk of toxicity to treatment, although its role as a biomarker is not yet clearly defined. Therefore, our main objective is to study the association between the presence of genetic variants in CDA gen, CDA enzymatic activity and the development of severe toxicity in patients treated with capecitabine whose initial dose was adjusted based on the genetic profile of the DPD gen (DPYD). METHOD: Prospective multicenter observational cohort study, focused on the analysis of the genotype-phenotype association of the CDA enzyme. After the experimental phase, an algorithm will be developed to determine the dose adjustment needed to reduce the risk of treatment toxicity according to CDA genotype, developing a Clinical Guide for capecitabine dosing according to genetic variants in DPYD and CDA. Based on this guide, a Bioinformatics Tool will be created to generate the pharmacotherapeutic report automatically, facilitating the implementation of pharmacogenetic advice in clinical practice. This tool will be a great support in making pharmacotherapeutic decisions based on the patient's genetic profile, incorporating precision medicine into clinical routine. Once the usefulness of this tool has been validated, it will be offered free of charge to facilitate the implementation of pharmacogenetics in hospital centers and equitably benefit all patients on capecitabine treatment.

Genetic variants and enzyme activity in citidin deaminase: Relationship with capecitabine toxicity and recommendation for dose adjustment. / Variantes genéticas y actividad enzimática de la citidin desaminasa: relación con la toxicidad a la capecitabina y recomendación de ajuste de las dosis.

OBJECTIVE: Capecitabine, an antineoplastic drug used in the treatment of breast and colon cancer, can cause severe, even fatal toxicity in some patients. The interindividual variability of this toxicity is largely due to genetic variations in target genes and enzymes of metabolism of this drug, such as thymidylate synthase and dihydropyrimidine dehydrogenase. The enzyme cytidine deaminase (CDA), involved in the activation of capecitabine, also has several variants associated with an increased risk of toxicity to treatment, although its role as a biomarker is not yet clearly defined. Therefore, our main objective is to study the association between the presence of genetic variants in CDA gen, CDA enzymatic activity and the development of severe toxicity in patients treated with capecitabine whose initial dose was adjusted based on the genetic profile of the dihydropyrimidine dehydrogenase gen (DPYD). METHOD: Prospective multicenter observational cohort study, focused on the analysis of the genotype-phenotype association of the CDA enzyme. After the experimental phase, an algorithm will be developed to determine the dose adjustment needed to reduce the risk of treatment toxicity according to CDA genotype, developing a clinical guide for capecitabine dosing according to genetic variants in DPYD and CDA. Based on this guide, a Bioinformatics Tool will be created to generate the pharmacotherapeutic report automatically, facilitating the implementation of pharmacogenetic advice in clinical practice. This tool will be a great support in making pharmacotherapeutic decisions based on the patient's genetic profile, incorporating precision medicine into clinical routine. Once the usefulness of this tool has been validated, it will be offered free of charge to facilitate the implementation of pharmacogenetics in hospital centers and equitably benefit all patients on capecitabine treatment.

Development, and Internal, and External Validation of a Scoring System to Predict 30-Day Mortality after Having a Traffic Accident Traveling by Private Car or Van: An Analysis of 164,790 Subjects and 79,664 Accidents.

Predictive factors for fatal traffic accidents have been determined, but not addressed collectively through a predictive model to help determine the probability of mortality and thereby ascertain key points for intervening and decreasing that probability. Data on all road traffic accidents with victims involving a private car or van occurring in Spain in 2015 (164,790 subjects and 79,664 accidents) were analyzed, evaluating 30-day mortality following the accident. As candidate predictors of mortality, variables associated with the accident (weekend, time, number of vehicles, road, brightness, and weather) associated with the vehicle (type and age of vehicle, and other types of vehicles in the accident) and associated with individuals (gender, age, seat belt, and position in the vehicle) were examined. The sample was divided into two groups. In one group, a logistic regression model adapted to a points system was constructed and internally validated, and in the other group the model was externally validated. The points system obtained good discrimination and calibration in both the internal and the external validation. Consequently, a simple tool is available to determine the risk of mortality following a traffic accident, which could be validated in other countries.