ABSTRACT
Aim: Few genome-wide association studies (GWASs) have been conducted to identify predictors of drug concentrations. The authors therefore sought to discover the pharmacogenomic markers involved in metoprolol pharmacokinetics. Patients & methods: The authors performed a GWAS of a cross-sectional study of 993 patients from the Montreal Heart Institute Biobank taking metoprolol. Results: A total of 391 and 444 SNPs reached the significance threshold of 5 × 10-8 for metoprolol and α-OH-metoprolol concentrations, respectively. All were located on chromosome 22 at or near the CYP2D6 gene, encoding CYP450 2D6, metoprolol's main metabolizing enzyme. Conclusion: The results reinforce previous findings of the importance of the CYP2D6 locus for metoprolol concentrations and confirm that large biobanks can be used to identify genetic determinants of drug pharmacokinetics at a GWAS significance level.
Subject(s)
Genome-Wide Association Study , Metoprolol , Humans , Metoprolol/therapeutic use , Metoprolol/pharmacokinetics , Cytochrome P-450 CYP2D6/genetics , Pharmacogenetics , Cross-Sectional StudiesABSTRACT
Objective. Despite a rise in the use of digital education in health professional education (HPE), little is known about the comparative effectiveness of paper-based reading and its digital alternative on reading comprehension. The objectives of this study were to identify, appraise, and synthesize the evidence regarding the effect of how media is read on reading comprehension in the context of HPE.Methods. Observational, quasi-experimental, and experimental studies published before April 16, 2021, were included if they compared the effectiveness of paper-based vs digital-based reading on reading comprehension among HPE students, trainees, and residents. Random-effects meta-analyses were performed using standardized mean differences.Results. From a pool of 2,208 references, we identified and included 10 controlled studies that had collectively enrolled 817 participants. Meta-analyses revealed a slight but nonsignificant advantage to students reading paper-based HPE texts rather than digital text (standardized mean difference, -0.08; 95% CI -0.28 to 0.12). Subgroup analyses revealed that students reading HPE-related texts had better reading comprehension when reading text on paper rather than digitally (SMD = -0.36; 95% CI -0.69 to -0.03). Heterogeneity was low in all analyses. The quality of evidence was low because of risks of bias across studies.Summary. Current evidence suggests little to no difference in students' comprehension when reading HPE texts on paper vs digitally. However, we observed effects favoring reading paper-based texts when texts relevant to the students' professional discipline were considered. Rigorous studies are needed to confirm this finding and to evaluate new means of boosting reading comprehension among students in HPE programs.
