Potential of pharmacogenetics in minimizing drug therapy problems in cystic fibrosis.

BACKGROUND: With advancements in CF drug development, people with cystic fibrosis (PwCF) now take a median of seven medications daily, increasing treatment complexity, risk of drug therapy problems (DTPs), and interference with treatment goals. Given that some of these DTPs can be prevented with preemptive pharmacogenetic testing, the overall goal of this study was to test the clinical utility of a multi-gene pharmacogenetics (PGx) panel in potentially reducing DTPs in PwCF. METHODS: A population based retrospective study of patients with CF was conducted at the University of Utah Health Care System. The patients were genotyped for CYP450 enzymes using a pharmacogenomic assay, and their drug utilization information was obtained retrospectively. This pharmacogenomic information was combined with clinical guidelines to predict the number of actionable PGx interventions in this patient cohort. RESULTS: A total of 52 patients were included in this study. In the patient sample, a minimum of one order of actionable PGx medication was observed in 75 % of the cases. Results revealed that 4.2 treatment modifications per 10 patients can be enabled with the help of a PGx intervention in this patient population. Additionally, our findings suggest that polymorphisms in CYP2D6 and CYP2C19 are most likely to be the primary contributors to DTP's within PwCF. CONCLUSION: This study provides evidence that the PGx panel has the potential to help alleviate the clinical burden of DTPs in PwCF and can assist in informing pharmacotherapy recommendations. Future research should validate these findings and evaluate which subgroups of PwCF would most benefit from pharmacogenetic testing.

Catheter ablation versus medical therapy in atrial fibrillation: an umbrella review of meta-analyses of randomized clinical trials.

This umbrella review synthesizes data from 17 meta-analyses investigating the comparative outcomes of catheter ablation (CA) and medical treatment (MT) for atrial fibrillation (AF). Outcomes assessed were mortality, risk of hospitalization, AF recurrence, cardiovascular events, pulmonary vein stenosis, major bleeding, and changes in left ventricular ejection fraction (LVEF) and MLHFQ score. The findings indicate that CA significantly reduces overall mortality and cardiovascular hospitalization with high strength of evidence. The risk of AF recurrence was notably lower with CA, with moderate strength of evidence. Two associations reported an increased risk of pulmonary vein stenosis and major bleeding with CA, supported by high strength of evidence. Improved LVEF and a positive change in MLHFQ were also associated with CA. Among patients with AF and heart failure, CA appears superior to MT for reducing mortality, improving LVEF, and reducing cardiovascular rehospitalizations. In nonspecific populations, CA reduced mortality and improved LVEF but had higher complication rates. Our findings suggest that CA might offer significant benefits in managing AF, particularly in patients with heart failure. However, the risk of complications, including pulmonary vein stenosis and major bleeding, is notable. Further research in understudied populations may help refine these conclusions.

Comparative Efficacy and Safety of Interventions for the Treatment of Oral Lichen Planus: A Systematic Review and Network Meta-Analysis.

BACKGROUND: This systematic review and network meta-analysis aimed to assess comparative efficacy and safety of interventions to treat symptomatic, biopsy-proven oral lichen planus (OLP). METHODS: Search was conducted for trials published in Medline, Embase and Cochrane Central Register of Controlled Trials. Network meta-analysis was performed on data from randomized controlled trials that assessed efficacy and safety of interventions used in the treatment of OLP. Agents were ranked according to their effectiveness in treatment of OLP based on outcomes using surface under the cumulative ranking [SUCRA]. RESULTS: In total, 37 articles were included in the quantitative analysis. Purslane was clinically significant and ranked first in improving clinical symptoms [RR = 4.53; 95% CI: 1.45, 14.11], followed by aloe vera [RR = 1.53; 95% CI: 1.05, 2.24], topical calcineurin [RR = 1.38; 95% CI: 1.06, 1.81] and topical corticosteroid [RR = 1.35 95% CI: 1.05, 1.73]. Topical calcineurin demonstrated the highest incidence of adverse effects [RR, 3.25 [95% CI: 1.19, 8.86. Topical corticosteroids were significant in achieving clinical improvement of OLP with RR1.37 [95% CI: 1.03, 1.81]. PDT [MD = -5.91 [95% CI: -8.15, -3.68] and showed statistically significant improvement in the clinical score for OLP. CONCLUSIONS: Purslane, aloe vera and photodynamic therapy appear promising in treatment of OLP. More high-quality trials are recommended for strengthening the evidence. Although topical calcineurin is significantly efficacious in the treatment of OLP, significant adverse effects are a concern for clinical use. Based on the current evidence, topical corticosteroids are recommended for treatment of OLP owing to their predictable safety and efficacy.