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.

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.

Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial.

OBJECTIVE: To assess the effectiveness and safety of melatonin in treating severe sleep problems in children with neurodevelopmental disorders. DESIGN: 12 week double masked randomised placebo controlled phase III trial. SETTING: 19 hospitals across England and Wales. PARTICIPANTS: 146 children aged 3 years to 15 years 8 months were randomised. They had a range of neurological and developmental disorders and a severe sleep problem that had not responded to a standardised sleep behaviour advice booklet provided to parents four to six weeks before randomisation. A sleep problem was defined as the child not falling asleep within one hour of lights out or having less than six hours' continuous sleep. INTERVENTIONS: Immediate release melatonin or matching placebo capsules administered 45 minutes before the child's bedtime for a period of 12 weeks. All children started with a 0.5 mg capsule, which was increased through 2 mg, 6 mg, and 12 mg depending on their response to treatment. MAIN OUTCOME MEASURES: Total sleep time at night after 12 weeks adjusted for baseline recorded in sleep diaries completed by the parent. Secondary outcomes included sleep onset latency, assessments of child behaviour, family functioning, and adverse events. Sleep was measured with diaries and actigraphy. RESULTS: Melatonin increased total sleep time by 22.4 minutes (95% confidence interval 0.5 to 44.3 minutes) measured by sleep diaries (n=110) and 13.3 (-15.5 to 42.2) measured by actigraphy (n=59). Melatonin reduced sleep onset latency measured by sleep diaries (-37.5 minutes, -55.3 to -19.7 minutes) and actigraphy (-45.3 minutes, -68.8 to -21.9 minutes) and was most effective for children with the longest sleep latency (P=0.009). Melatonin was associated with earlier waking times than placebo (29.9 minutes, 13.6 to 46.3 minutes). Child behaviour and family functioning outcomes showed some improvement and favoured use of melatonin. Adverse events were mild and similar between the two groups. CONCLUSIONS: Children gained little additional sleep on melatonin; though they fell asleep significantly faster, waking times became earlier. Child behaviour and family functioning outcomes did not significantly improve. Melatonin was tolerable over this three month period. Comparisons with slow release melatonin preparations or melatonin analogues are required. TRIAL REGISTRATION: ISRCT No 05534585.

Pharmacovigilance in children in Camagüey Province, Cuba.

PURPOSE: Our aim was to describe the adverse drug reactions (ADRs) detected following increased education about pharmacovigilance and drug toxicity in children in Camagüey Province, Cuba. METHODS: Over a period of 24 months (January 2009 to December 2010), all reports of suspected ADRs in children to the Provincial Pharmacovigilance Centre in Camagüey Province were analysed. ADRs were classified in relation to causality and severity. RESULTS: There were 533 reports involving suspected ADRs in children in the period. Almost one third of the reports received were classified as moderate (155, 29%) or severe (10, 2%). There was one fatality in association with the use of ceftriaxone. Vaccines and antibiotics were responsible for most of the ADR reports (392, 74%) and for all ten severe ADRs. After an intensive educational package, both within the community and the Children's Hospital, the number of reports increased from 124 in 2008 to 161 in 2009 and 372 in 2010. This was equivalent to a reporting rate of 879 and 2,031 reports per million children per year for 2009 and 2010, respectively. CONCLUSIONS: The incidence of ADRs in children Camagüey Province, Cuba, is greater than previously reported. An educational intervention about pharmacovigilance and drug toxicity in children can improve the reporting of ADRs.

Adverse drug reactions in children in Camagüey Province, Cuba.

OBJECTIVE: To determine the incidence of adverse drug reactions (ADRs) in children in Camagüey Province, Cuba. METHODS: A national pharmacovigilance programme has been established in Cuba and involves suspected ADRs being reported to provinces. All suspected ADRs reported to Camagüey Province during 2008 were analysed and classified in relation to causality and severity. RESULTS: Over a 12-month period, there were 124 reports of 152 suspected ADRs in children. Most ADRs were mild (98, 79%), but two were fatal and five others were severe. Antibiotics were the group of medicines most likely to be associated with ADRs. The overall report rate of suspected ADRs was 634 per million children per year, which is considerably higher than previously reported rates. CONCLUSIONS: ADRs in children are more frequent than previously reported. A successful pharmacovigilance programme can be established in lower middle income countries.

Clinical trials: the viewpoint of children with a chronic illness compared with healthy children.

The views of over 200 children (11-16 years old, who were either healthy or attending paediatric medical clinics with a chronic illness) on issues relating to paediatric clinical trials were determined by a questionnaire. Children with a chronic illness had a better understanding of the concept of dosing of medicines (40% vs 23%) and placebo (34% vs 20%). They were more likely to support children's involvement in clinical trials (51% vs 37%). The altruistic nature of children in both groups was similar. It was of concern, however, that 57-63% children would participate as healthy volunteers in a cancer drug trial. Both groups were able to differentiate between the different types of illnesses where it is appropriate to study medicines in children (86-89% for illness where there is no treatment; 34-40% for 'me-too' drugs). Young people should be given more opportunities to be involved in decision-making regarding clinical trials of medicines.

Adverse drug reactions in children in Camagüey Province, Cuba

Objective To determine the incidence of adverse drug reactions (ADRs) in children in Camagüey Province, Cuba. Methods A national pharmacovigilance programme has been established in Cuba and involves suspected ADRs being reported to provinces. All suspected ADRs reported to Camagüey Province during 2008 were analysed and classified in relation to causality and severity. Results Over a 12-month period, there were 124 reports of 152 suspected ADRs in children. Most ADRs were mild (98, 79 por ciento), but two were fatal and five others were severe. Antibiotics were the group of medicines most likely to be associated with ADRs. The overall report rate of suspected ADRs was 634 per million children per year, which is considerably higher than previously reported rates. Conclusions ADRs in children are more frequent than previously reported. A successful pharmacovigilance programme can be established in lower middle income countries(AU)

Objetivo: Determinar la incidencia de reacciones adversas a medicamentos (RAM) en los niños en la provincia de Camagüey, Cuba. Métodos Se realizó un programa de farmacovigilancia nacionales se ha establecido en Cuba y consiste en sospecha de reacciones adversas que se informa a las provincias. Todos los ADR sospechosos notificados a la provincia de Camagüey durante el año 2008 fueron analizados y clasificados en relación a la causalidad y la gravedad. Resultados Durante un período de 12 meses, había 124 informes de reacciones adversas de 152 sospechosos en los niños. La mayoría de las RAM fueron leves (98, 79 percent), pero dos de ellos mortales y otros cinco fueron graves. Los antibióticos fueron el grupo de medicamentos más probable que esté asociado a la ADR. El tipo de informe general de las ADR se sospecha fue 634 por cada millón de niños al año, que es considerablemente más alta que la publicada tarifas. Conclusiones ADR en los niños son más frecuentes que lo reportado anteriormente. Un programa de farmacovigilancia éxito se puede establecer en los países de ingreso medio(AU)

Child health in Colombia.

Colombia is a country with major problems, mainly a high degree of inequality and an unacceptably high level of violence (both armed military conflict and crime related). There are unacceptably high variations in health and health provision. Despite these difficulties, there are important steps being taken by both the government and independent organisations to try and improve child health and to achieve the Millennium Development Goals in relation to poverty, hunger and health issues. The participation of different sectors and stakeholders (including government, non-governmental organisations and other organisations of civil society) is essential to overcome Colombian history and to promote a better place for children.

Clinical pharmacokinetics of penicillins in the neonate: a review of the literature.

BACKGROUND: Sepsis is common in neonates and a major cause of morbidity and mortality. Sixty percent of preterm neonates receive at least one antibiotic during the first week of life, with penicillins being the most frequently administered antibiotics. The clearance (Cl), serum half-life (t((1/2))) and volume of distribution (Vd) of penicillins are different in the neonate than in the adult. As such, the pharmacokinetics of penicillins need be studied in neonates in order to optimise therapy in this age class with these drugs. OBJECTIVES: The aim of this study was to review the published data on the pharmacokinetics of penicillins in the neonate in order to provide a critical analysis of the literature and, consequently, a useful tool in the hands of the physician. METHODS: The bibliographic search was performed electronically using the PubMed and EMBASE databases as search engines. An initial search was performed with the keywords "pharmacokinetics", "penicillins" and "neonates". Secondly, other searches were performed using the keywords "pharmacokinetics" and "neonates", followed by the name of a single antibiotic. The search included articles up to 2007. RESULTS: There have been few pharmacokinetic studies on the use of penicillins in neonates. The results from those few studies that have been carried out suggest that the Cl is reduced and t((1/2)) prolonged in the neonate as compared with the more mature infant. There is little variation in Vd during the first week of life. In the premature neonate, Cl is reduced compared to the full-term infant. As postnatal age proceeds, the Cl of penicillins increases. CONCLUSIONS: More pharmacokinetic studies are required to provide a sound scientific basis for planning a dosage regimen with penicillins in the neonate.

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.

Case-control study of acute renal failure in patients with cystic fibrosis in the UK.

BACKGROUND: There has been a recent increase in the number of reported cases of acute renal failure (ARF) in cystic fibrosis (CF). A case-control study was conducted to determine the factors which are associated with an increased risk of ARF. METHODS: 24 cases of confirmed ARF were identified in patients with CF from 20 UK CF centres presenting between 1997 and 2004. Using the UK CF database, sex- and age-matched controls were identified. Risk factors were analysed by conditional logistic regression and Mantel-Haenszel analysis. RESULTS: 21 of the 24 patients with ARF had received an aminoglycoside at the time of their episode of ARF or in the preceding week compared with only 3 of 42 controls during the same time period (OR 81.8, 95% CI 4.7 to 1427, p<0.001). In the year before the episode of ARF, significantly more cases than controls had received gentamicin (19/24 cases vs 1/42 controls, p<0.001). The numbers receiving tobramycin were similar (9/24 cases vs 16/42 controls, p = 0.9). A known risk factor for renal impairment (prior renal disease, acute dehydration or long-term treatment with a nephrotoxic drug) was present in 18/24 cases and 7/42 controls (OR 24.0, 95% CI 3.1 to 186.6, p = 0.002). CONCLUSIONS: In patients with CF the use of an intravenous aminoglycoside is a risk factor for ARF; gentamicin is more nephrotoxic than tobramycin. Most patients who develop ARF have a risk factor which necessitates withholding aminoglycosides or more closely monitoring their use.

Clinical trials: the viewpoint of children.

The views of 30 children (8-16 years old) attending paediatric medical clinics on paediatric clinical trials were determined by semi-structured interviews. Nineteen children recognised that there were risks involved with taking part in clinical trials. Risks concerned with being paid were recognised by all children.

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

No disponible