Pharmacokinetics (PK) of xenobiotics can differ widely between children and adults due to physiological differences and the immaturity of enzyme systems and clearance mechanisms. This makes extrapolation of adult dosimetry estimates to children uncertain, especially at early postnatal ages. While there is very little PK data for environmental toxicants in children, there is a wealth of such data for therapeutic drugs. Using published literature, a Children's PK Database has been compiled which compares PK parameters between children and adults for 45 drugs. This has enabled comparison of child and adult PK function across a number of cytochrome P450 (CYP) pathways, as well as certain Phase II conjugation reactions and renal elimination. These comparisons indicate that premature and full-term neonates tend to have 3 to 9 times longer half-life than adults for the drugs included in the database. This difference disappears by 2-6 months of age. Beyond this age, half-life can be shorter than in adults for specific drugs and pathways. The range of neonate/adult half-life ratios exceeds the 3.16-fold factor commonly ascribed to interindividual PK variability. Thus, this uncertainty factor may not be adequate for certain chemicals in the early postnatal period. The current findings present a PK developmental profile that is relevant to environmental toxicants metabolized and cleared by the pathways represented in the current database. The manner in which this PK information can be applied to the risk assessment of children includes several different approaches: qualitative (e.g., enhanced discussion of uncertainties), semiquantitative (age group-specific adjustment factors), and quantitative (estimation of internal dosimetry in children via physiologically based PK modeling).

Across diverse contexts, emerging evidence suggests that the COVID-19 pandemic is increasing levels of anxiety and stress. In calling for greater attention to people’s psychosocial and emotional well-being, global actors have paid insufficient attention to the realities of the pandemic in low- and middle-income countries, where millions of people are already exposed to intersecting vulnerabilities. Chronic poverty, protracted violence, conflict and displacement, coupled with weak health, education and protection systems, provide the backdrop of many adolescents’ lives. Drawing on qualitative in-country telephone interviews with over 500 adolescents in Ethiopia, Côte d’Ivoire and Lebanon, this article unpacks the age and gendered dimensions of COVID-19 and its response. We conclude by discussing the implications for COVID-19 recovery efforts, arguing that embedding adolescent-centred, inclusive approaches in education, community-based health and social protection responses, has the potential to mitigate the psycho-emotional toll of the pandemic on young people and promote resilience.

A significant data base has been assembled on human variability in parameters representing a series of steps in the pathway from external exposure to the production of biological responses: contact rate (e.g., breathing rates/body weight, fish consumption/body weight); uptake or absorption (mg/kg)/intake or contact rate; general systemic availability net of first pass elimination and dilution; systemic elimination or half-life; active site availability/general systemic availability; physiological parameter change/active site availability; functional reserve capacity--change in baseline physiological parameter needed to pass a criterion of abnormal function or exhibit a response. This paper discusses the current results of analyzing these data to derive estimates for distributions of human susceptibility to different routes of exposure and types of adverse effects. The degree of protection is tentatively evaluated by projecting the incidences of effects that would be expected for a tenfold lowering of exposure from a 5% incidence level if the population distribution of susceptibility were truly log-normal out to the extreme tails, and if the populations, chemicals, and responses that gave rise to the underlying data were representative of the cases to which traditional uncertainty factor is applied. The results indicate that, acting by itself, a tenfold reduction in dose from a 5% effect level is associated with effect incidences ranging from slightly less than one in ten thousand, for a median chemical/response, to a few per thousand, for chemicals and responses that have greater human interindividual variability than 19 out of 20 typical chemicals/responses. In practice, for many of the cases where the traditional tenfold factor is applied, additional protection is provided by other uncertainty factors. Nevertheless, the results generate some reason for concern that current application of traditional safety or uncertainty factor approaches may allow appreciable incidences of responses in some cases.

Performance-based funding provides powerful incentives to scale up the fight against HIV, TB, and malaria, argues a team of authors from the Global Fund.

This is the protocol for a Campbell review. The objective of this evidence and gap map is to provide an overview of the existing evidence on the effectiveness of interventions aimed at promoting mental health and reducing or preventing mental health conditions among children and adolescents in low-and middle-income countries.