Influence of NQO1 Polymorphisms on Warfarin Maintenance Dose: A Systematic Review and Meta-Analysis (rs1800566 and rs10517)

This meta-analysis was conducted to analyze the effect of NQO1 polymorphism on the warfarin maintenance dosage. Using strict inclusion and exclusion criteria, we searched PubMed, EMBASE, and the Cochrane Library for eligible studies published prior to July 7, 2021. The required data were extracted, and experts were consulted when necessary. Review Manager Version 5.4 software was used to analyze the relationship between NQO1 polymorphisms and the warfarin maintenance dosage. Four articles involving 757 patients were included in the meta-analysis. Patients who were NQO1 rs10517 G carriers (AG carriers or GG carriers) required a 48% higher warfarin maintenance dose than those who were AA carriers. Patients with NQO1 rs1800566 CT carriers required a 13% higher warfarin dose than those who were CC carriers, with no associations observed with the other comparisons of the NQO1 rs1800566 genotypes. However, the results obtained by comparing the NQO1 rs1800566 genotypes require confirmation, as significant changes in the results were found in sensitivity analyses. Our meta-analysis suggests that the NQO1 rs10517and NQO1 rs1800566 variant statuses affect the required warfarin maintenance dose.

Possibly Appropriate Maintenance dose of Voriconazole in pediatric patients: a single center observational study

Background: Voriconazole is a triazole antifungal agent and a commonly used first-line treatment for invasive aspergillosis (IA). The study was performed to explore the factors affecting voriconazole trough concentration and maintenance dose to optimize voriconazole dosage in pediatric patients. Method: The demographic information, concentration data, CYP2C19 genotypes, and clinical outcomes of eligible pediatric patients from January 1th, 2016 to December 31th, 2018 were collected retrospective . Result: The study finally included 145 voriconazole trough concentrations from 94 pediatric patients. Steady trough concentration ranged from 0.04 to 16.11 μg/mL. Morerover, the distinction between the maximum and the minimum corrected concentration of per kilogram maintenance dosage is as high as 907 folds and children ≤2 years old showed the minimum variation compared to other individuals (P<0.001). A high inter- and intra-individual variability of voriconazole in pediatric patients were observed. Only 54.5% of the pediatric patients achieved the target range (1.0 to 5.5 μg/mL) at unadjusted initial dosage, while 35.9% of children were subtherapeutic, only 9.6% of children were supratherapeutic at unadjusted initial dosing. The younger children (≤12 years) seem to have a lower trough concentration (P=0.0096) and lower percentage of target achievements (P=0.004). And 98.97% of the maintenance dosage was below 9.0 mg/kg. For pediatric patients of different ages, it was found that most of them was underdosed. While, to achieve targeted therapeutic level for different age groups of ≤2, 2-6, 6-12, and 12-18 years, the median voriconazole maintenance doses were 5.7, 6.7, 5.0, and 3.3 mg-1kg/12h, respectively had been required in order to achieve therapeutic level (P<0.001). Conclusion: Pediatric patients especially those ≤12 years old might need a higher dosage regime to achieve therapeutic trough concentration. Importantly, early and repeat monitoring of voriconazole is essential to ensure the effectiveness and safety of voriconazole in children.

Baseline Shoulder Ultrasonography Is Not a Predictive Marker of Response to Glucocorticoids in Patients with Polymyalgia Rheumatica: A 12-month Followup Study

Objective.In this study, we evaluated whether ultrasound (US) subdeltoid bursitis (SB) and/or biceps tenosynovitis (BT) presence at baseline could represent a predictive marker of response to standard therapy after 12 months of followup, and whether a positive US examination could highlight the need of higher maintenance dosage of glucocorticoids (GC) at 6 and 12 months in patients with polymyalgia rheumatica (PMR).Methods.Sixty-six consecutive patients with PMR underwent bilateral shoulder US evaluations before starting therapy and after 12 months of followup. Absence of girdle pain and morning stiffness (clinical remission) and laboratory variables were evaluated. After diagnosis, all patients were treated with prednisone.Results.At baseline, SB and/or BT were present in 46 patients (70%), of whom 33 (72%) became negative while 13 (28%) remained positive at the 12-month US evaluation. All patients rapidly achieved a clinical remission, and at 6 months 26 (39%) also achieved a laboratory variable normalization. According to US positivity at baseline, no difference was found in remission or relapse rate after 12 months. Thirty patients (46%) at 6 months and 7 (11%) at 12 months were still taking more than 5 mg/day of prednisone. According to the US pattern at baseline, no difference was found in the mean GC dose at 6 and 12 months.Conclusion.In patients with PMR, the presence of SB and/or BT on US at diagnosis is not a predictive marker of GC response or of a higher GC dosage to maintain remission in a 12-month prospective followup study.