Validation of the school age self-administered pediatric bleeding questionnaire (Self-PBQ) in children aged 8-12 years.

BACKGROUND: In the pediatric population, pathologic bleeding is often challenging to identify. The pediatric bleeding questionnaire (PBQ) was developed as a screening tool for von Willebrand disease (VWD) but was designed to be self-completed by children above 12 years of age. The study objective was to determine whether a modified Self-PBQ could be completed by 8- to 12-year-old children with adult assistance. PROCEDURE: The initial phase involved seven children who underwent cognitive debriefing to identify problems in the questionnaire, resulting in modifications to wording and response options. In phase 2, children completed the modified Self-PBQ independently or with assistance from their parent at five Canadian treatment centers. Parents filled out the Self-PBQ separately to serve as a comparison. Bleeding scores derived from the child self-report were compared to those of the parent proxy. RESULTS: Twenty-nine out of 31 patient/parent pairs successfully completed the Self-PBQ. Child and parent scores demonstrated a high level of agreement with an intraclass correlation (ICC) of 0.825. In the age subgroup analysis, the ICC was 0.834 and 0.824 for the 8- to 9-year-old and 10- to 12-year-old groups, respectively. The ICC was also determined in children with type 1 VWD (ICC = 0.829) versus those with more severe bleeding disorders (ICC = 0.802). Thus, age and disease severity had no significant effect on degree of agreement. CONCLUSIONS: Our study shows that agreement was maintained even in younger children aged 8-9 years and in children with varying bleeding phenotypes. This supports the administration of the modified Self-PBQ to 8- to 12-year-old children.

Nutrient Insufficiencies/Deficiencies in Children With Sickle Cell Disease and Its Association With Increased Disease Severity.

BACKGROUND: Sickle cell disease (SCD) is characteristically described as a disease of hemolytic anemia and vaso-occlusive crises (VOCs). However, patients suffer from a multitude of other problems including impaired development, chronic pain, and increased susceptibility to infection. Nutritional deficiency has been implicated as a contributor to these issues. PROCEDURE: We reported the nutrition status with respect to vitamin D, zinc, B6, B12, folate, and homocysteine serum levels in Canadian children with SCD (n = 91). We also tested for associations between nutrients and markers of disease severity and growth. RESULTS: Almost half the sample (42%) had multiple nutrient insufficiencies/deficiencies, and a further 27% had a single insufficiency/deficiency. The most common insufficiency/deficiency was zinc in 57% followed by calcidiol (25 dihydroxyvitamin D (25(OH)D)) (52%). Sixteen percent of patients had low vitamin B6 levels, while folate, calcitriol (1,25(OH)D), and homocysteine levels were normal. Increased number of vitamin insufficiencies/deficiencies was associated with increasing disease severity (P = 0.018). Zinc insufficiency/deficiency was significantly associated with an increased number of home pain crises (P = 0.001) and an increased incidence of hospitalizations for VOCs (P = 0.01). CONCLUSIONS: Our findings show that patients with SCD commonly have multiple nutrient insufficiencies/deficiencies and support the growing evidence for the link between low zinc and increased VOC. It also indicates that increased nutrient insufficiencies/deficiencies are associated with increased disease severity in SCD. Prospective studies with larger samples are needed to further elucidate the relationship between nutrient deficiencies and SCD, and to determine whether nutrient supplementation can improve the disease course.

The metabolic consequences of hepatic AMP-kinase phosphorylation in rainbow trout.

AMP-activated protein kinase (AMPK), a phylogenetically conserved serine/threonine protein kinase, is proposed to function as a "fuel gauge" to monitor cellular energy status in response to nutritional environmental variations. However, in fish, few studies have addressed the metabolic consequences related to the activation of this kinase. This study demonstrates that the rainbow trout (Oncorhynchus mykiss) possesses paralogs of the three known AMPK subunits that co-diversified, that the AMPK protein is present in the liver and in isolated hepatocytes, and it does change in response to physiological (fasting-re-feeding cycle) and pharmacological (AICAR and metformin administration and incubations) manipulations. Moreover, the phosphorylation of AMPK results in the phosphorylation of acetyl-CoA carboxylase, a main downstream target of AMPK in mammals. Other findings include changes in hepatic glycogen levels and several molecular actors involved in hepatic glucose and lipid metabolism, including mRNA transcript levels for glucokinase, glucose-6-phosphatase and fatty acid synthase both in vivo and in vitro. The fact that most results presented in this study are consistent with the recognized role of AMPK as a master regulator of energy homeostasis in living organisms supports the idea that these functions are conserved in this piscine model.