Lack of Effect of Rivipansel on QTc Interval in Healthy Adult African American Male Subjects.

Rivipansel is a pan-selectin inhibitor in phase 3 development for the treatment of vaso-occlusive crises in patients with sickle cell disease. This single-dose, randomized, 3-period, 3-treatment (400 mg moxifloxacin open-label, 4 g rivipansel-blinded, and placebo-blinded) crossover study evaluated the effect of rivipansel on the QT/QTc interval in 48 healthy male African American subjects (age, 21-53 years; weight, 60-115 kg). Time-matched, placebo-adjusted change from baseline QT interval using Fridericia's correction method (QTcF) was determined using a repeated-measures mixed-effects model. The highest upper bound of the 2-sided 90% confidence interval (CI) for QTcF change was 3.22 milliseconds 3 hours postdose. Moxifloxacin showed the anticipated QTcF effect, indicating that the study had adequate sensitivity to detect changes in the QTcF interval. The study concluded that no QTcF effect was demonstrated with rivipansel compared with placebo, as the upper bound of the 2-sided 90%CI was less than 10 milliseconds at all times. Exposure-response modeling for rivipansel concentrations and change from baseline in QTcF data corroborated a lack of effect with rivipansel compared with placebo. Single doses of rivipansel 4 g by intravenous infusion over 20 minutes were well tolerated in this study.

Nocturnal enuresis in normal Jamaican children: implications for therapy

The prevalence of nocturnal enuresis has been investigated in 477 children (243 boys, 234 girls) attending government Basic Schools in Kingston, Jamaica. Enuresis, defined as wet at least 2 nights a week, occurred in 62 percent, 48 percent, 42 percent and 40 percent at 2, 3, 4 and 5 years of age, respectively. Enuresis, defined as wet at least one night a month, occurred in 68 percent, 58 percent, 53 percent and 52 percent, respectively. There was no significant difference between the sexes. Children with a family history of enuresis (first degree relatives wet beyound 8 years of age) were more likely to be enuretic than those with no family history, the difference reaching statistical significance for girls (<0.001) and for the sexes combined (p <0.001) but not for boys alone (p=0.06). The prevalence of nocturnal enuresis in Jamaican children is higher than reported for Black children elsewhere, which in turn is higher than in their White counterparts. Cultural attitudes to bed-wetting contribute to this variation and have implications for choice of therapy, both in Jamaica and elsewhere. (AU)

Nocturnal enuresis in sickle cell haemoglobinopathies

The prevalence of nocturnal enuresis (wet at least two nights a week) was investigated in children, aged 8, who were being followed up as part of a prospective cohort study. There were 175 children with homozygous sickle cell disease, 106 with sickle cell haemoglobin C disease, and 150 controls with a normal haemoglobin genotype. In homozygous sickle cell disease, 48 boys (52 percent) and 31 girls (38 percent) were enuretic, a significantly higher prevalence than in those with sickle cell haemoglobin C disease - five boys (10 percent) and 11 girls (20 percent) - or in normal children - 16 boys (22 percent) and 13 girls (17 percent). There was no significant difference between children with sickle cell haemoglobin C disease and the normal genotype. Boys with homozygous sickle cell disease were significantly more likely to be enuretic if they came from large families; there was a similar trend for girls with homozygous sickle cell disease, although it did not reach significance. Enuresis was more common in boys with homozygous sickle cell disease who had low concentrations of fetal haemoglobin and in girls with sickle cell haemoglobin C disease who had high mean corpuscular haemoglobin concentrations. Similar associations were not shown for girls with homozygous sickle cell disease or boys with sickle cell haemoglobin C disease. (AU)