Paracetamol poisoning is a common presentation in paediatrics. Toxicity may cause hepatocellular injury, in certain cases progressing to fulminant liver failure. Young children appear less at risk of hepatotoxicity due to an increased metabolic capacity for paracetamol. A single dose of 150 mg/kg can cause hepatocellular damage. Children who ingest multiple supratherapeutic doses can accumulate significant concentrations and may suffer worse outcomes. Older children who intentionally overdose may also suffer worse outcomes, especially those who present late. The risk of hepatotoxicity after a single overdose can be predicted using a widely used nomogram, although it was derived from adult data. The cornerstone of management is administering the antidote N-acetylcysteine when hepatotoxicity is likely to occur. The National Poisons Information Service is available to be consulted at all hours. When severe poisoning is suspected, the child may require referral to a liver unit in view of possible liver transplantation.

Background: The greatest burden of disease in children lies in the developing world; however, previous reviews have suggested that few randomized controlled trials (RCTs) involving children take place in developing countries. Children in developing countries deserve the same standard of medicines as those in developed countries, i.e. appropriate medications for the specific diseases that occur. Objective: To elucidate published pediatric therapeutic RCTs that have taken place in the developing world and to determine whether they are appropriate for the major diseases occurring there, and to explore their approach to safety monitoring. Methods: A previously assembled database of pediatric RCTs published between 1996 and 2002, from journals indexed in MEDLINE, was analyzed. The main country of setting of the RCTs was categorized as having low, medium or high development status according to the Human Development Index (HDI). Articles were read to add the WHO International Classification of Diseases 10th Revision (ICD-10) category of the disease studied, the WHO Collaborating Centre for Drug Statistics Methodology Anatomical Therapeutic Chemical (ATC) classification system category of the main drug therapy studied, the source of funding, and ethical approval to the variables already recorded in the database. Results: One hundred and fifty-eight (22%) of the 733 RCTs analyzed took place in medium and low HDI (developing) countries. The disease areas studied seemed appropriate, with 89 (56%) of the 158 RCTs studying infectious and parasitic diseases. Ninety-nine (63%) RCTs from developing countries were trials of antiparasitic and anti-infective drugs. Compared with studies from high HDI countries, a significantly lower proportion of articles from medium and low HDI countries mentioned ethical committee or institutional review board approval, and safety monitoring. Only one paper from low and medium HDI countries mentioned the presence of a safety monitoring committee/data safety monitoring board. Conclusions: Published pediatric drug RCTs conducted in developing countries appear to study appropriate diseases but the results show that fewer RCTs are undertaken compared with the developed world. The standard of reporting for RCTs from developing countries needs attention to ensure that adequate information can be obtained, especially with regard to safety monitoring.

Objective: To elucidate the current situation of randomised drug trials involving the paediatric population. Methods: Systematic review of paediatric randomised controlled trials of medicinal products published in 2007. Three major databases were searched with validated search strategies; Medline, Embase and Cochrane Central Register of Controlled Clinical Trials. Data was collected on the location, participants, class of drug and methodological quality of the trials. Results: Six hundred and four trials were found involving more than 100,000 paediatric participants. Only about a quarter (146, 24%) were conducted in low and lower-middle income countries. Few studies (42, 7%) were performed in neonates. Many trials recruiting both adult and paediatric patients inadequately describe the characteristics of the paediatric participants. The most studied areas were nervous system (155, 26%), anti-infective (101, 17%) respiratory (74, 12%) or antiparasitic (45, 8%) drugs. A high proportion of the studies (36%) used an inactive placebo as the comparator. Paediatric randomised drug trials performed in low and low-middle income countries were of lower methodological quality (mean Jadad score 2.90 vs 3.27, p<0.01), studied more antiparasitic and anti-infectives (47% vs 16%, p<0.01) but fewer reported that ethical approval was obtained (83% vs 93%, p<0.01), compared to those conducted in high or upper-middle income countries. Conclusions: There are a significant number of randomised controlled drug trials involving children taking place throughout the world. To develop the evidence base for safe and effective medicines for the benefit of the whole paediatric population, high quality and ethical clinical trials should involve a wide range of children