Population pharmacokinetics and pharmacodynamics of lumefantrine in young Ugandan children treated with artemether-lumefantrine for uncomplicated malaria

Background. The pharmacokinetics and pharmacodynamics of lumefantrine, a component of the most widely used treatment for malaria, artemether-lumefantrine, has not been adequately characterized in young children. Methods. Capillary whole-blood lumefantrine concentration and treatment outcomes were determined in 105 Ugandan children, ages 6 months to 2 years, who were treated for 249 episodes of Plasmodium falciparum malaria with artemether-lumefantrine. Results. Population pharmacokinetics for lumefantrine used a 2-compartment open model with first-order absorption. Age had a significant positive correlation with bioavailability in a model that included allometric scaling. Children not receiving trimethoprim-sulfamethoxazole with capillary whole blood concentrations <200 ng/mL had a 3-fold higher hazard of 28-day recurrent parasitemia, compared with those with concentrations >200 ng/mL (P =. 0007). However, for children receiving trimethoprim-sulfamethoxazole, the risk of recurrent parasitemia did not differ significantly on the basis of this threshold. Day 3 concentrations were a stronger predictor of 28-day recurrence than day 7 concentrations. Conclusions. We demonstrate that age, in addition to weight, is a determinant of lumefantrine exposure, and in the absence of trimethoprim-sulfamethoxazole, lumefantrine exposure is a determinant of recurrent parasitemia. Exposure levels in children aged 6 months to 2 years was generally lower than levels published for older children and adults. Further refinement of artemether-lumefantrine dosing to improve exposure in infants and very young children may be warranted. © 2016 The Author.

Perceptions of European medical staff on the facilitators and barriers to physical closeness between parents and infants in neonatal units

AIM: Studies have provided insights into factors that may facilitate or inhibit parent-infant closeness in neonatal units, but none have specifically focused on the perspectives of senior neonatal staff. The aim of this study was to explore perceptions and experiences of consultant neonatologists and senior nurses in five European countries with regard to these issues. METHODS: Six small group discussions and three one-to-one interviews were conducted with 16 consultant neonatologists and senior nurses representing nine neonatal units from Estonia, Finland, Norway, Spain and Sweden. The interviews explored facilitators and barriers to parent-infant closeness and implications for policy and practice and thematic analysis was undertaken. RESULTS: Participants highlighted how a humanising care agenda that enabled parent-infant closeness was an aspiration, but pointed out that neonatal units were at different stages in achieving this. The facilitators and barriers to physical closeness included socio-economic factors, cultural norms, the designs of neonatal units, resource issues, leadership, staff attitudes and practices and relationships between staff and parents. CONCLUSION: Various factors affected parent-infant closeness in neonatal units in European countries. There needs to be the political motivation, appropriate policy planning, legislation and resource allocation to increase measures that support closeness agendas in neonatal units. This article is protected by copyright. All rights reserved.