Lack of a significant change in caffeine metabolism in underweight children as determined by the caffeine breath test.

OBJECTIVE: Limited data from pharmacokinetic studies in underweight and severely malnourished children have indicated an impaired activity of their hepatic enzymes. We used the caffeine breath test to assess the metabolising activity of cytochrome P450 1A2 (CYP1A2) enzyme in underweight children. METHODS: Underweight children from the paediatric outpatient clinic, Lagos State University Teaching Hospital, Ikeja in Nigeria, were studied. After an overnight fast, 15 underweight children took 3 mg/kg labelled caffeine orally. Breath samples were collected in duplicate at -20, -10 and -1 min and at 15 min intervals for 2 h. The mean cumulative per cent dose recovered (CPDR) of labelled caffeine in the expired carbon dioxide was determined over the study period. This was repeated after 2-6 weeks of nutritional rehabilitation. RESULTS: The mean areas under the enrichment-time curve before and after nutritional rehabilitation were 0.539±0.320 and 0.620±0.322 atom per cent excess minute, respectively. The difference between the two values was not statistically significant (p=0.528). The mean CPDR in the exhaled carbon dioxide of the underweight children over a period of 2 h was 7.56±4.01% and 7.95±3.68% before and after nutritional rehabilitation, respectively, and there was no significant difference in the mean values (p=0.603). CONCLUSIONS: The metabolism of caffeine was not significantly affected in underweight children compared with after 2-6 weeks of nutritional rehabilitation. This suggests that hepatic CYP1A2-metabolising activity was not significantly impaired in underweight children.

Practical pharmacokinetics: what do you really need to know?

Having some understanding of pharmacokinetics is important for all clinicians when prescribing medications. Key elements to effective and safe prescribing include making sure that we don't underdose a medication making it ineffective, but also do not overprescribe a treatment known to cause toxic effects. In paediatrics, there are significant physiological and developmental differences that add to the challenges of safe prescribing. This article aims to provide the clinician with some basic paediatric pharmacokinetic principles with clinical examples to aid their prescribing skills.

Access to medicines by child refugees in the East Midlands region of England: a cross-sectional study.

OBJECTIVES: To explore access to primary healthcare and drug therapy by refugee children in the East Midlands region of England. DESIGN: Interviews with refugees with children and a control group of British parents with children. SETTING: East Midlands region of England. PARTICIPANTS: 50 refugees with children and a control group of 50 parents with children. MAIN OUTCOME MEASURES: Number of medicines used by children in the last month and the past 6 months. Health of parents and children. Registration with a general practitioner (GP). RESULTS: All families in both groups were registered with a GP. There was no difference in the number of children in the two groups experiencing illnesses .In the last month, 30 refugee children received 60 medicines and 31 control children 63 medicines. In the past 6 months, 48 refugee children received 108 medicines and 43 control children 96 medicines. There was no difference between the two groups of children in relation to the likelihood of receiving any medicines in either the last month (P=0.839) or the past 6 months (p=0.81). Children in the refugee group were more likely to receive prescribed medicines for the last month (p=0.008) and the past 6 months (p<0.001). They were also less likely to receive over the counter (OTC) medicines in the past 6 months (p=0.009). CONCLUSIONS: The refugee children in this study in the East Midlands had access to primary healthcare, medicines and a family doctor. They were more likely to receive prescribed medicines and less likely to receive OTC medicines, especially paracetamol.

Intravenous salbutamol for childhood asthma: evidence-based medicine?

Intravenous salbutamol is commonly used to treat children with severe asthma unresponsive to inhaled ß2-agonist therapy. However, in this setting, there is little clinical trial data demonstrating its effectiveness. Additionally, there are significant concerns that intravenous salbutamol-dosing recommendations for children with acute asthma are excessive, and unnecessarily raise the potential for adverse reactions, such as lactic acidosis and tachycardia which, by increasing respiratory workload, exacerbate respiratory failure. Here, we review salbutamol clinical pharmacology and toxicology, evidence relating to its use in acute asthma and highlight gaps in the evidence base.

Ethical issues of clinical trials in children: a European perspective.

Children should not be harmed by their participation in clinical trials, therefore should no clinical trials be performed? This is a view that needs to be balanced as clinical trials provide the evidence we need to allow children safe and effective prescribing of medicines. Therefore, is it unethical not to involve this population in research? This review looks at new ethical guidance released to support the recently introduced European legislation for the licensing of medicines.

Safety in paediatric clinical trials--a 7-year review.

AIM: The safety of clinical trials in children has not been previously studied. We aimed to identify how safety is monitored and the extent of adverse drug reactions (ADRs). METHODS: A literature review of the Medline Database for therapeutic clinical trials involving oral and intravenous medicines in children from 1996 to 2002. Papers were read to determine the safety monitoring and the presence of adverse events (AEs) or ADRs. RESULTS: Seven hundred thirty-nine trials were identified. Thirteen (2%) had safety monitoring committees (SMCs). Five hundred twenty-three (71%) trials reported AEs and 151 (20%) of these trials reported a serious AE. ADRs were present in 270 (36.5%) trials, with 80 (11%) of trials having a moderate or severe ADR. Six clinical trials were terminated early because of significant drug toxicity. All of these had SMCs. There were deaths in 83 (11%) trials. In the majority of trials, mortality was thought to be unrelated to the investigational drug; however, in two trials mortality was higher in the treatment group. CONCLUSIONS: About 11% of trials have a moderate or severe ADR. All paediatric clinical trials should have a SMC.

Educational interventions to reduce prescribing errors.

OBJECTIVE: Little is known about teaching paediatricians to prescribe or about assessing their competency. This study aimed to identify educational interventions to reduce dose calculation errors. DESIGN: Literature review, a questionnaire survey of paediatric healthcare professionals, observation and interviews were performed. RESULTS: Literature review identified one paper describing an in-service test for medical trainees. 319/559 questionnaires were returned (57%). 34 mentioned educational interventions, 15 centres provided further information on teaching and assessment methods and 13 provided presentations, usually at doctors' induction. Many interventions had a similar format, including describing differences from adult prescribing, common errors and how to calculate doses. Paediatric clinical pharmacists play a significant role in delivering training and competency assessment. CONCLUSION: Teaching of paediatric prescribing takes place mostly in the format of lectures during doctors' induction. Few centres assess competency and no validated tool exists. There has been little evaluation of the impact of teaching on competency to prescribe.

British and Canadian views on the ethics of paediatric clinical trials.

BACKGROUND: Ethical problems are quoted as a reason not to perform clinical trials in children. Little is known about the views of researchers regarding ethics. OBJECTIVES: A pilot study was conducted to assess the applicability of a questionnaire design containing trial scenarios to examine views regarding the use of children in drug trials and to elicit possible international differences. SETTING: Paediatricians and researchers in the United Kingdom and Canada. METHODS: Responders were presented with a questionnaire containing direct questions and six trial scenarios, each containing an ethical dilemma. Responders were asked regarding their own approval and their perceived opinion of whether an ethical review board (ERB) would approve. RESULTS: One hundred questionnaires (50 each country) were received. Few responders had research ethics training (14% United Kingdom and 8% Canada). Most (80 and 88%) felt children could be harmed by participation in trials and half (47 and 59%) felt children should only participate if they receive direct benefit. Many (58 and 61%) disagreed with payments beyond travel expenses. In the trial scenarios, 34% of responders were willing to enter healthy children in a pharmacokinetics study of an antibiotic for cystic fibrosis and 22% considered their ERBs would approve. Only a third (33%) would enter children in an analgesia trial that was placebo-controlled. CONCLUSION: Using healthy children and placebos in trials caused concern. Similar views were found between the two countries. The majority had no training in research ethics. The study highlights the usefulness of a questionnaire with clinical trial scenarios to try to elicit views on the ethics of conducting research in children.

Un registro europeo de ensayos clínicos en niños / A European registry of clinical trials in children

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Serum total bile acid levels in patients receiving rifampicin and isoniazid.

Serum bile acid levels in 61 patients receiving daily doses of rifampicin and isoniazid for the treatment of tuberculosis have been investigated. Bile acids were measured using 3 alpha-hydroxysteroid dehydrogenase in a continuous-flow system. Abnormally elevated levels were found in 44 patients (72%) during the period of study up to 80 days after onset of treatment. The results showed a mean of 24.9 mumol/l and a positively skewed distribution. Whilst marginally raised levels of bilirubin were seen in some samples (mean 8.2 mumol/l), these did not reflect the marked changes observed in bile acids. Patients receiving rifampicin and isoniazid may therefore have markedly elevated levels of total serum bile acids, while other tests used to assess liver function can remain normal.