ABSTRACT
AIM: In order to bridge the gap between pharmacogenomic research and its clinical application, we propose the concept of genetic electronic identity, named "GeneFace", and developed an electronic information system which integrated "drug-gene" interactions and recommendations for personalized medicine. METHODS: Based on the self-developed Precision Medicine knowledgebase, which concludes drug directions, guidelines or important literatures with high level of evidence, we developed GeneFace with Java-based open-resource application framework Spring Boot, further developed a mobile App with cross-platform framework Uni-APP. RESULTS: The App includes six modules: genetic testing appointment, genetic knowledge introduction, individualized medication advice, medication records, Geneface interpretation, and Precision Medicine knowledgebase. By detecting the genotype of more than 300 gene loci upon first use, users import the results to form a personal "drug-gene identity card". Then scan or enter the drug name in "GeneFace", the App would automatically give corresponding medication recommendations, including: risks for possible adverse drug reactions, risks for reducing the efficacy or even ineffectiveness, and possibility for dose adjustment, etc., which increase the safety of clinical drug use. People can obtain pharmacogenomics knowledge and basic drug information in the "GeneFace" app. CONCLUSION: Development as a digital therapeutic product, the expanded application of GeneFace can rapidly promote clinical applications of basic pharmacogenomics research and significantly improve drug use safety, which creating a new model for accelerating the clinical application of personalized medicine.
ABSTRACT
Purpose: Drug-induced liver injury (DILI) is a common adverse reaction in the clinic; however, there are relatively few reports of DILI in critically ill newborns and children. Making use of the Pediatric Intensive Care database (PIC), this study identifies which drugs are related to DILI in neonates and children in China. Methods: Using the PIC, we screened for patients whose liver was suspected of being injured by drugs during hospitalization. The medicine they used was then assessed by the Roussel Uclaf Causality Assessment Method (RUCAM). At the same time, we also collated drug combinations that may affect CYP (Cytochrome P) enzyme metabolism, which may cause DILI. Results: A total of 13,449 patients were assessed, of whom 77 newborns and 261 children were finally included. The main type of liver injury in neonates was mixed (83.1%), while the hepatic injury types of children were mostly distributed between hepatocellular (59.4%) and cholestatic (28.4%). In terms of the RUCAM assessment, the drugs that were most considered to cause or be associated with hepatic injury in newborns were medium and long chain fat emulsions (17%), sodium glycerophosphate (12%), and meropenem (9%); while omeprazole (11%), methylprednisolone sodium succinate (10%), and meropenem (8%) were the primary culprits of DILI in children. Drug combinations frequently seen in neonates that may affect CYP enzyme metabolism are omeprazole + budesonide (16.9%), dexamethasone + midazolam (10.4%), and midazolam + sildenafil (10.4%). In children, the commonly used drug combinations are fentanyl + midazolam (20.7%), ibuprofen + furosemide (18.4%), and diazepam + omeprazole (15.3%). Conclusions: In this study, medium and long chain fat emulsions and sodium glycerophosphate have been strongly associated with DILI in newborns, while omeprazole and methylprednisolone sodium succinate play an important role in the DILI of children. Also, attention should be paid to the effect on CYP enzymes when using multiple drugs at the same time. In future DILI cases, it is advisable to use the latest RUCAM for prospective study design so that complete case data and high RUCAM scores can be collected.
ABSTRACT
Objective:To determine the correlations of single nucleotide polymorphisms (SNPs) with atrial fibrillation (AF) in the Chinese Han population from the central plains.Methods:A total of 168 hospitalized patients,including 56 AF and 112 controls,were recruited in this case-control study.The clinical data were obtained from the medical records.All 5 SNPs,rs337711 in KCNN2,rs11264280 near KCNN3,rs17042171 near PITX2,rs6771157 and rs6795970 in SCN10A,were genotyped using amplification refractory mutation system-polymerase chain reaction or direct sequencing.The x2 test was used to compare categorical variables and preliminarily examine correlations between the genotype frequencies and AF.Subsequently,a logistic regression model was constructed to determine the associations between the SNPs and AF based on the above screened results.Odds ratios (ORs) and 95％ confidence interval (CI) were calculated to assess the strength of the correlations.Moreover,we downloaded the genotype data from the HapMap Project for linkage disequilibrium analysis ofrs17042171.Results:AF patients were likely to be of older age and longer left atrial diameter and had more coronary artery disease and higher hypertension compared with the control group (P＜0.05).Among the 5 SNPs,the frequency distribution of genotype AA for rs17042171 was significantly different between the AF and control groups (P＜0.05).After adjusting for several covariates,there was still a high risk ratio in patients with the AA genotype compared with the AC+CC genotype (OR:5.591,95％CI 2.176 to 14.365,P-B＜0.008).Similarly,stratification analysis on the AA genotype demonstrated significant differences between rs17042171 and persistent AF.However,there were not significant correlations between AF and the control groups for the other 4 SNPs (P＜0.05).Conclusion:Rs17042171,near PITX2 on chromosome 4q25,is associated with AF susceptibility in the Chinese Han population from the central plains,suggesting that this SNP can provide a new strategy for clinical diagnosis in AF patients.