No abstract

Warfarin is a common anticoagulant with narrow therapeutic window and variable anticoagulation effects. Single gene polymorphisms in cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) have been shown to impact warfarin dosing in adults. Insufficient data exists on genetic and clinical factors which influence warfarin dosing in children. Pediatric patients with heart disease who received long-term warfarin therapy were tested for VKORC1 and CYP2C9 polymorphisms. Clinical and demographic data were reviewed in those children who achieved stable therapeutic international normalized ratio (INR). Multiple linear regression modeling was used to assess relationships between stable warfarin doses and genetic or clinical variables. Fifty children were tested for VKORC1 and CYP2C9 polymorphisms; 37 patients (M 26: F 11) had complete data, achieved stable therapeutic INR, and were included in dose variability analysis. There were predominance of white race 73% and male sex 70.3%. The mean age was 9.6 years (1.8-18.6 years). The mean weight was 37.8 kg (7.7-95 kg). Fontan physiology and mechanical cardiac valves were two most common indications for chronic warfarin therapy (25/37 or 67.6%). Twelve patients (32.4%) had ≥ 2 indications for warfarin therapy. Three patients had documented venous or arterial clots, and 5 patients had strokes. Congenital heart disease was present in 29 patients (78.4%), including Fontan physiology (20), complex biventricular physiology (4), and congenital mitral valve disease (5). Acquired heart disease was present in 8 patients (21.6%), including Kawasaki disease with coronary aneurysms (3), acquired mitral valve disease (3), and Marfan syndrome (2). Stable warfarin dose (mg/kg/day) was strongly associated with VKORC1 polymorphism (p < 0.0001) and goal therapeutic INR (p = 0.009). Negative correlations were observed between stable warfarin dose and age, weight, height, and BSA (p = 0.04, 0.02, 0.02, and 0.02 respectively). Factors which did not influence warfarin dose included CYP2C9 polymorphism (p = 0.17), concurrent medications (p = 0.85), sex (p = 0.4), race (p = 0.14), congenital heart disease (p = 0.09), and Fontan physiology (p = 0.76). The gene-dose effect was observed in children with homozygous wild type VKORC1 CC, who required higher warfarin dose compared to those carrying heterozygous TC or homozygous TT (p = 0.028 and 0.0004 respectively). The full multiple linear regression model revealed that VKORC1 genotypes accounted for 47% of dosing variability; CYPC29 accounted for 5%. Overall, the combination of VKORC1, CYP2C9, age, and target INR accounted for 82% of dosing variability. In children with heart disease, VKORC1 genotypes, age, and target INR are important determinants influencing warfarin dosing in children with heart disease. Future warfarin dosing algorithm in children should factor both genetic and clinical factors.

Background The Optical Surface Management System (OSMS) is a simple, fast, reproducible, and accurate solution for patient set-up and can minimize random day-to-day set-up errors. However, studies in breast cancer patients are rare. Objective To analyze 200 patient set-ups in 20 patients with breast cancer by comparing the OSMS with the conventional cone-beam computed tomography (CBCT). Method Displacements from concurrent OSMS and CBCT registrations were compared in a total of 200 setups of 20 patients to analyze the interfractional displacement and positioning displacement in three dimensions (lateral, longitudinal, and vertical directions). Results The interfractional displacement on the lateral, longitudinal, and vertical directions for OSMS versus CBCT was 0.049 ± 0.254 versus 0.041 ± 0.244 centimeters (cm); 0.018 ± 0.261 versus 0.040 ± 0.242 cm; 0.062 ± 0.254 versus 0.065 ± 0.240 cm, respectively, without any significant difference (all P > 0.05). The duration for CBCT scan was about 60 seconds (s), while that for image processing, matching, and couch displacement was at least 5 minutes (min). The average scanning time with OSMS was less than 20 s, and the total duration for positioning was less than 1 min. Conclusion OSMS is an efficient tool to improve the accuracy and increase the speed for verifying the patient positioning in radiotherapy for breast cancer.

Summary The lack of an active neighbourhood living environment can impact community health to a great extent. One such impact manifests in walkability, a measure of urban design in connecting places and facilitating physical activity. Although a low level of walkability is generally considered to be a risk factor for childhood obesity, this association has not been established in obesity research. To further examine this association, we conducted a literature search on PubMed, Web of Science and Scopus for articles published until 31 December 2018. The included literature examined the association between measures of walkability (e.g., walkability score and walkability index) and weight‐related behaviours and/or outcomes among children aged under 18 years. A total of 13 studies conducted in seven countries were identified, including 12 cross‐sectional studies and one longitudinal study. The sample size ranged from 98 to 37 460, with a mean of 4971 ± 10 618, and the age of samples ranged from 2 to 18. Eight studies reported that a higher level of walkability was associated with active lifestyles and healthy weight status, which was not supported by five studies. In addition to reviewing the state‐of‐the‐art of applications of walkability indices in childhood obesity studies, this study also provides guidance on when and how to use walkability indices in future obesity‐related research.