Developing regional weight-for-age growth references for malaria-endemic countries to optimize age-based dosing of antimalarials.

OBJECTIVE: To derive regional weight-for-age growth references to help optimize age-based dosing of antimalarials in Africa, the Americas, South-East Asia and the Western Pacific. METHODS: A weight-for-age database was constructed from pre-existing population-based anthropometric data obtained from household surveys and research groups. It contained data collected between 1995 and 2012 on 1,263,119 individuals (909,368 female, 353,751 male) older than 14 days and younger than 50 years in 64 malaria-endemic countries. Regional growth references were generated using a generalized additive model for location, scale and shape by combining data with varying distributions from a range of sources. Countries were weighted by their population at risk of malaria to enable references to be used in optimizing the dosing of antimalarials. FINDINGS: Large differences in weight-for-age distributions existed between the regions and between the regions and global growth standards. For example, the average adult male from the Americas weighed 68.1 kg ­ 6.0 kg more than males in South-East Asia and the Western Pacific (average: 62.1 kg). For adult women, the difference was over 10.4 kg: the average was 60.4 kg in the Americas and 50.0 kg in South-East Asia and the Western Pacific. CONCLUSION: There were substantial variations in weight-for-age growth curves between malaria-endemic areas. The growth reference charts derived here can be used to guide the evidence-based optimization of aged-based dosing regimens for antimalarials and other drugs often prescribed by age.

Oral choline supplementation in children with intestinal failure.

Choline deficiency leads to steatohepatitis, elevated transaminases, susceptibility to septic shock, and an increased risk of central catheter thrombosis. Children with intestinal failure (IF) are at risk for choline deficiency. In an unblinded, open-label study, we studied 7 children with IF on parenteral nutrition, measured their plasma free choline level, and, if low, supplemented enterally with adequate intake (AI) doses of choline. Four to 6 weeks later we remeasured their plasma free choline. Unlike adults, infants did not respond to oral choline supplementation at AI doses. Additionally, we have calculated plasma free choline percentiles versus age for normal children.

Estimating regional centile curves from mixed data sources and countries.

Regional or national growth distributions can provide vital information on the health status of populations. In most resource poor countries, however, the required anthropometric data from purpose-designed growth surveys are not readily available. We propose a practical method for estimating regional (multi-country) age-conditional weight distributions based on existing survey data from different countries. We developed a two-step method by which one is able to model data with widely different age ranges and sample sizes. The method produces references both at the country level and at the regional (multi-country) level. The first step models country-specific centile curves by Box-Cox t and Box-Cox power exponential distributions implemented in generalized additive model for location, scale and shape through a common model. Individual countries may vary in location and spread. The second step defines the regional reference from a finite mixture of the country distributions, weighted by population size. To demonstrate the method we fitted the weight-for-age distribution of 12 countries in South East Asia and the Western Pacific, based on 273 270 observations. We modeled both the raw body weight and the corresponding Z score, and obtained a good fit between the final models and the original data for both solutions. We briefly discuss an application of the generated regional references to obtain appropriate, region specific, age-based dosing regimens of drugs used in the tropics. The method is an affordable and efficient strategy to estimate regional growth distributions where the standard costly alternatives are not an option.

Smooth centile curves for skew and kurtotic data modelled using the Box-Cox power exponential distribution.

The Box-Cox power exponential (BCPE) distribution, developed in this paper, provides a model for a dependent variable Y exhibiting both skewness and kurtosis (leptokurtosis or platykurtosis). The distribution is defined by a power transformation Y(nu) having a shifted and scaled (truncated) standard power exponential distribution with parameter tau. The distribution has four parameters and is denoted BCPE (mu,sigma,nu,tau). The parameters, mu, sigma, nu and tau, may be interpreted as relating to location (median), scale (approximate coefficient of variation), skewness (transformation to symmetry) and kurtosis (power exponential parameter), respectively. Smooth centile curves are obtained by modelling each of the four parameters of the distribution as a smooth non-parametric function of an explanatory variable. A Fisher scoring algorithm is used to fit the non-parametric model by maximizing a penalized likelihood. The first and expected second and cross derivatives of the likelihood, with respect to mu, sigma, nu and tau, required for the algorithm, are provided. The centiles of the BCPE distribution are easy to calculate, so it is highly suited to centile estimation. This application of the BCPE distribution to smooth centile estimation provides a generalization of the LMS method of the centile estimation to data exhibiting kurtosis (as well as skewness) different from that of a normal distribution and is named here the LMSP method of centile estimation. The LMSP method of centile estimation is applied to modelling the body mass index of Dutch males against age.