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1.
Seizure ; 56: 20-25, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29427834

RESUMO

PURPOSE: This study aims to describe the incidence of adverse drug reactions (ADRs) in children receiving antiepileptic drugs (AEDs) and compare ADRs to the individual drugs when given as monotherapy. METHOD: Paediatric patients (≤18 years old) were enrolled for this prospective observational study over a 6-month period, between September 2015 and March 2016. Adverse reactions to antiepileptic drugs (AEDs) were elicited at the time of enrolment and after 3 months using the Paediatric Epilepsy Side Effects Questionnaire. RESULTS: A total of 1139 suspected ADRs were reported in 124 participants. Eighteen different AEDs were prescribed. Sixty-six children (53%) were receiving AED monotherapy at the time of recruitment; 34/66 (52%) of whom received new generation AEDs. Levetiracetam was the most frequently prescribed AED (62/124, 50%). When only children receiving AED monotherapy were considered, fatigue, drowsiness, weight gain, dizziness were less likely with levetiracetam (p < .01). Slow thinking and decreased concentration were less likely with levetiracetam or carbamazepine than valproic acid (p < .05). Five patients (four on polytherapy) discontinued AED treatment due to ADRs and 2 had a dose reduction. CONCLUSIONS: Levetiracetam and carbamazepine were better tolerated than sodium valproate.


Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Adolescente , Carbamazepina , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Levetiracetam , Masculino , Piracetam/análogos & derivados , Inquéritos e Questionários , Ácido Valproico
3.
BMJ Paediatr Open ; 1(1): e000039, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29637101

RESUMO

Objectives: This study aims to characterise paediatric reports with lamotrigine (LTG) and Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN), and to explore whether potential risk factors can be identified. Design: This is a retrospective review of suspected adverse drug reaction (ADR) reports. Reported time from LTG start to SJS/TEN onset, indication for use and dose was explored. To identify potential risk groups, report features (eg, ages, patient sex, co-reported drugs) for LTG and SJS/TEN were contrasted with two reference groups in the same database, using shrinkage logOR. Setting: Reports were retrieved from VigiBase, the WHO global database of individual case safety reports, in January 2015. Patients: Data for patients aged ≤17 years old were extracted. Results: There were 486 reports of SJS/TEN in LTG-treated paediatric patients. Ninety-seven per cent of the cases with complete information on time to onset of SJS/TEN occurred within 8 weeks of initiation of LTG therapy. The median time to onset was 15 days (IQR: 10-22 days). The proportion of SJS/TEN with LTG and valproic acid (VPA) co-reporting was significantly more than non-cutaneous ADRs (43% vs 19%, (logOR: 1.60 (99% CI: 1.33 to 1.84)). Conclusions: The results suggest that VPA co-medication with LTG therapy is a risk factor for SJS/TEN in the paediatric population. Although this relationship has been identified from individual case reports, this is the first supportive study from a large compilation of cases. SJS/TEN risk is highest in first 8 weeks of treatment with LTG in children and clinicians should be aware of this risk during this period.

4.
BMJ Paediatr Open ; 1(1): e000088, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29637124

RESUMO

Objectives: This study aims to determine global anti-epileptic drug (AED) utilisation prevalence and describe utilisation trends in different countries. Methods: Databases Embase (1980-May 2017), Medline (1946-May 2017) and PubMed were searched for original research on AED utilisation. All paediatric national or regional database studies and surveys were included. Results: Twenty-one studies were identified. Five were excluded from the analysis as the data were collected before 2005, leaving 16 studies. Monotherapy regimen varied between 58% and 94% in different countries. In several of the studies, sodium valproate was the most frequently prescribed AED. However, there is a trend towards increasing utilisation of new-generation AEDs, particularly levetiracetam, in some countries. Conclusion: Monotherapy was used in 58%-94%of patients. There is increasing utilisation of the new-generation AEDs, in particular lamotrigine, levetiracetam and topiramate. Old-generation AEDs are still used in the majority of patients. There is a need for up-to-date studies to determine the prevalence of AEDs in children.

5.
BMJ Paediatr Open ; 1(1): e000116, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29637140

RESUMO

Background: Epilepsy is a common chronic disease of children that can be treated with anti-epileptic drugs (AEDs). AEDs, however, have significant side effects. Newer AEDs are thought to have fewer side effects. There have, however, been few comparative studies of AED toxicity. The aim is to compare the safety profile of the most frequently used AEDs by performing a multicentre prospective cohort study. This protocol describes the planned study. Design: A multicentre prospective cohort study of children on AED treatment in hospitals across the UK. Ethical approval will be obtained. Sample size: Three thousand children on treatment for epilepsy will be recruited from paediatric clinics. It is expected that this sample size will have the potential to compare toxicity between the most frequently used AEDs. Duration of study: 24 months. Outcome measure: Adverse drug reactions (ADRs) to AEDs. These will be identified by the use of a validated questionnaire, the Paediatric Epilepsy Side Effect Questionnaire. They will be evaluated using the Naranjo algorithm. Preventability will be assessed using the Schumock and Thornton scale. Discussion: Toxicity of individual AEDs when given as monotherapy and polytherapy will be determined. Additionally, discontinuation rates due to ADRs will be determined. The data will assist clinicians in choosing AEDs with the least toxicity.

6.
Children (Basel) ; 3(1)2016 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-27417239

RESUMO

Drug toxicity is, unfortunately, a significant problem in children both in the hospital and in the community. Drug toxicity in children is different to that seen in adults. At least one in 500 children will experience an adverse drug reaction each year. For children in hospital, the risk is far greater (one in ten). Additionally, different and sometimes unique adverse drug reactions are seen in the paediatric age groups. Some of the major cases of drug toxicity historically have occurred in neonates. It is important that we understand the mechanism of action of adverse drug reactions. Greater understanding alongside rational prescribing should hopefully reduce drug toxicity in children in the future.

7.
Expert Rev Clin Pharmacol ; 9(8): 1117-27, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27171366

RESUMO

INTRODUCTION: Herbal medicines (HMs) have been well known to people of the European Union (EU) and Russia for centuries. Currently, Western HMs can be classified into two categories, plant-derived conventional medicines and dietary supplements. Interest to HMs has grown rapidly in all countries during the past two decades. AREAS COVERED: The main goal of this review article is to present the history of HMs in the EU and Russia, forms of modern HMs, including Oriental Medicines that are popular among consumers of both countries. Additional discussion points comprise safety and adulteration issues associated with HMs, including regulatory changes and new legislative measures undertaken by the authorities. Materials available from legislative and governmental websites, PubMed and news media were used. Expert commentary: Due to cultural diversities in the EU and Russia, traditional HMs of other regions, particularly Chinese Traditional and Ayurvedic medicines, are also popular. Recently, dietary supplements containing multiple herbal and other natural products have flooded the EU and Russian markets. Pharmacovigilance in these markets is challenging in terms of establishing quality and safety of ingredients, determining efficacy, and defining risks of herb-herb and herb-drug interactions. Both the EU and Russia have introduced new legislation aimed to overcome these deficiencies.


Assuntos
Fitoterapia/métodos , Preparações de Plantas/uso terapêutico , Plantas Medicinais/química , Animais , Suplementos Nutricionais/efeitos adversos , Suplementos Nutricionais/normas , União Europeia , Interações Ervas-Drogas , Humanos , Legislação de Medicamentos , Medicina Tradicional/métodos , Preparações de Plantas/efeitos adversos , Preparações de Plantas/normas , Federação Russa
10.
Arch Dis Child ; 100(10): 928-31, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26272911

RESUMO

BACKGROUND: The UK has a high child mortality rate, whereas Sweden's is lower (under-five mortality rates of five and three, respectively, in 2011).We therefore wished to compare causes of death in young children aged <5 years in the two countries. METHODS: Under-five mortality data were obtained from the Office of National Statistics for each of the individual countries within the UK for 3 years (2006-2008). Data for Sweden for the same period were obtained from the National Board of Health and Welfare. Causes of death were compared statistically using χ(2) test. RESULTS: There were a total of 14,104 and 1036 deaths aged <5 years in the UK and Sweden, respectively, between 2006 and 2008. The total numbers of live births during the same period were 2,295,964 and 315,884, respectively. The overall mortality rate in the UK was 614 per 100,000 children which was significantly higher than that in Sweden (328; p<0.001). The mortality rates for the three main causes of death in the UK (prematurity, congenital malformations and infections) were 138.5, 112.1 and 63.9, respectively, per 100,000 children. The mortality rates for the same three conditions in Sweden were 10.1, 88.6 and 34.8, respectively. They were all significantly more frequent in the UK than in Sweden (p<0.001), as were the majority of the disorders. Treatable infections, such as pneumonia, meningitis and septicaemia, in both neonates and young children had significantly higher mortality rates in the UK than in Sweden (p<0.001). CONCLUSIONS: In order to reduce the mortality rate in the UK, we need to try and reduce the causes of prematurity. Additionally, the care of children with treatable infections should be reviewed to understand ways in which to reduce the differences in mortality seen.


Assuntos
Causas de Morte , Mortalidade da Criança/tendências , Mortalidade Infantil/tendências , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Suécia/epidemiologia , Reino Unido/epidemiologia
11.
BMJ Open ; 5(6): e007711, 2015 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-26070796

RESUMO

OBJECTIVES: To identify adverse drug reactions associated with lamotrigine in children and compare the safety profile with other antiepileptic drugs. SETTING: Databases EMBASE (1974-April 2015), MEDLINE (1946-April 2015), PubMed and the Cochrane library for randomised controlled trials were searched for studies on safety of lamotrigine. PARTICIPANTS: All studies involving paediatric patients aged ≤ 18 years who have received at least a single dose of lamotrigine with safety as an outcome measure were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was safety of lamotrigine. Drug interaction of lamotrigine was the secondary outcome. RESULTS: A total of 78 articles involving 3783 paediatric patients were identified. There were 2222 adverse events (AEs) reported. Rash was the most commonly reported AE, occurring in 7.3% of the patients. Stevens-Johnson syndrome was rarely reported, with a risk of 0.09 per 100 patients. Discontinuation due to an adverse drug reaction (ADR) was recorded in 72 children (1.9% of all treated patients). Fifty-eight per cent of treatment discontinuation was attributed to different forms of rash and 21% due to increased seizures. Children on lamotrigine monotherapy had lower incidences of AEs. Headache (p=0.02), somnolence (<0.001), nausea (p=0.01), vomiting (p<0.001), dizziness (p<0.001) and abdominal pain (p=0.01) were significantly lower among children on monotherapy. CONCLUSIONS: Rash was the most common ADR of lamotrigine and the most common reason for treatment discontinuation. Children receiving polytherapy have a higher risk of AEs than monotherapy users. TRIAL REGISTRATION NUMBER: CRD42013006910.


Assuntos
Anticonvulsivantes/efeitos adversos , Triazinas/efeitos adversos , Dor Abdominal/induzido quimicamente , Anticonvulsivantes/administração & dosagem , Criança , Tontura/induzido quimicamente , Quimioterapia Combinada , Exantema/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Lamotrigina , Náusea/induzido quimicamente , Triazinas/administração & dosagem , Vômito/induzido quimicamente
13.
J Adv Nurs ; 69(3): 655-63, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22671021

RESUMO

AIM: This study examined children's opinions on the taste of three analgesic medicines: paracetamol, ibuprofen and codeine. BACKGROUND: Many medicines for children are unpleasant and unacceptable. Research has shown that children's taste preferences differ to adults, in whom palatability is often tested. Little British research exists on children's opinions on the palatability of medicines. This study aimed to address this gap in knowledge. DESIGN: Prospective observational study. METHODS: Between May-September 2008, hospital inpatients aged 5-16 years rated the taste of required analgesics on a 100-mm visual analogue scale. This incorporated a 5-point facial hedonic scale. They were also asked their favourite flavour and colour for a medicine. RESULTS: A total of 159 children took part. Eighty-five males (53·5%) and 74 females (46·5%). The median age was 8 years (Inter-quartile range 6-11). The taste of ibuprofen was significantly preferred to paracetamol or codeine. Significant differences were observed depending if the medicine rated was taken first or second (for example pre-medication with paracetamol and ibuprofen). Younger children (5-8 years) were more likely to choose the extremes of the scale when grading than older children were. Preferred flavours on questioning were strawberry 44% and banana 17%. Favourite colours were pink 25·8% and red 20·8%, with girls more likely to choose pink and boys blue. CONCLUSION: Ibuprofen was the most palatable analgesic medicine tested. Children reported they preferred fruit flavours and colour was sex dependent. Nurses when administering two medicines together should consider giving the least palatable first, for example paracetamol before ibuprofen for pre-medication.


Assuntos
Analgésicos não Entorpecentes/uso terapêutico , Analgésicos Opioides/uso terapêutico , Cor , Paladar , Acetaminofen/uso terapêutico , Adolescente , Criança , Pré-Escolar , Codeína/uso terapêutico , Feminino , Humanos , Ibuprofeno/uso terapêutico , Masculino , Estudos Prospectivos , Reino Unido
14.
Eur J Clin Pharmacol ; 68(2): 189-94, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21858432

RESUMO

BACKGROUND: There is now greater involvement of children in drug trials to ensure that paediatric medicines are supported by sound scientific evidence. The safety of the participating children is of paramount importance. Previous research shows that these children can suffer moderate and severe adverse drug reactions (ADRs) in clinical trials, yet very few of the trials designated a data safety monitoring board (DSMB) to oversee the trial. METHODS: Safety data from a systematic review of paediatric drug randomised controlled trials (RCTs) published in 2007 were analysed. All reported adverse events (AEs) were classified and assessed to determine whether an ADR had been experienced. ADRs were then categorised according to severity. Each trial report was examined as to whether an independent DSMB was in place. RESULTS: Of the 582 paediatric drug RCTs analysed, 210 (36%) reported that a serious AE had occurred, and in 15% mortality was reported. ADRs were detected in more than half of the RCTs (305); 66 (11%) were severe, and 79 (14%) were moderate. Severe ADRs involved a wide range of organ systems and were frequently associated with cytotoxic drugs, antiparasitics, anticonvulsants and psychotropic drugs. Two RCTs reported significantly higher mortality rates in the treatment group. Only 69 (12%) of the RCTs stated there was a DSMB. DSMBs terminated five RCTs and changed the protocol in one. CONCLUSIONS: Children participating in drug RCTs experience a significant amount and a wide range of ADRs. DSMBs are needed to ensure the safety of paediatric participants in clinical drug trials.


Assuntos
Ensaios Clínicos como Assunto/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Pediatria/estatística & dados numéricos , Comitês de Monitoramento de Dados de Ensaios Clínicos , Humanos
15.
J Popul Ther Clin Pharmacol ; 18(1): e10-6, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21317441

RESUMO

BACKGROUND: Due to ethical concerns and constraints inherent to research in children, the conduct of clinical trials in children has often been difficult. The views of medical professionals and trainees towards conducting clinical trials in children have been largely unexplored and are potentially important towards working to increase the number of appropriate trials conducted in children. OBJECTIVE: To explore the views of Canadian medical school trainees towards paediatric clinical trials and to compare these views with that of an earlier pilot study conducted amongst Canadian and British health care professionals. METHODS: Participants were given a questionnaire which consisted of direct questions as well as scenarios with ethical dilemmas. Responders were asked to state whether they would enter children in the trial documented in the scenario and to justify their reasons. RESULTS: 89 questionnaires were collected (74% response rate). 42% had formal teaching regarding paediatric ethical dilemmas but only 2% had formal teaching on pharmaceutical testing in children. The students were divided on whether children should only participate in trials where they receive direct benefit. Most students (85%; 95% CI: 77% to 91%) were comfortable with non-inferiority trials even with post-hoc consent. Only a third (33%; 95% CI: 24% to 43%) agreed with the use of placebo in an analgesia trial. CONCLUSION: Teaching on the ethics of paediatric clinical trials still appears to be lacking amongst medical trainees. However, there does seem to be increased willingness on the part of trainees compared to practicing medical professionals in enrolling children in clinical trials.


Assuntos
Atitude do Pessoal de Saúde , Ensaios Clínicos como Assunto/ética , Pediatria , Estudantes de Medicina , Adulto , Canadá , Criança , Feminino , Humanos , Masculino , Inquéritos e Questionários , Reino Unido
17.
Eur J Clin Pharmacol ; 66(10): 1025-35, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20552179

RESUMO

OBJECTIVE: protein energy malnutrition (PEM) is a nutritional problem affecting many children world-wide. Its association with a wide spectrum of infections necessitates multiple drug therapies. A systematic review was performed to determine the effects of PEM on drug pharmacokinetics. METHODS: literature searches in the MEDLINE and EMBASE databases (January 1960 to December 2009) were performed. Malnutrition, undernutrition, underweight, protein-energy malnutrition, protein-calorie malnutrition, marasmus, marasmic-kwashiorkor or kwashiorkor was the medical subject heading (MeSH) descriptor used. Inclusion criteria were abstracts that assessed or discussed absorption, distribution, metabolism, elimination, clearance, pharmacokinetics or pharmacodynamics of drugs, except micronutrients and appetite-stimulating drugs. RESULTS: altogether, 41 publications were identified. A total of 34 drugs were studied. The absorption of 18 drugs was studied; the extent of absorption (AUC) was unaffected for 10 drugs. The plasma protein binding of 20 drugs was evaluated; it was significantly reduced for 12 drugs. The volume of distribution (Vd) of 13 drugs was evaluated; it was, however, unaffected for most of the drugs. The effect of PEM on total clearance and the half-life of drugs primarily metabolised by the liver was studied for 8 drugs. There was decreased total clearance and an associated increased half-life of 5 drugs. For 2 drugs (chloramphenicol and quinine), different degrees of PEM affected total clearance differently. The total clearance of six drugs primarily eliminated by the kidneys was studied; it was unaffected for four drugs, but significantly decreased for two drugs (cefoxitin and penicillin). CONCLUSIONS: considering the proportion of children affected with PEM world-wide, there have been relatively few pharmacokinetic studies of drugs frequently used for their treatment. More studies are therefore required to establish the appropriate dose and safety of these drugs for PEM children. The studies need to recognise that PEM is a disease spectrum and should further look at the differential effects of kwashiorkor and marasmus on drug pharmacokinetics in children.


Assuntos
Farmacocinética , Desnutrição Proteico-Calórica/metabolismo , Adolescente , Criança , Pré-Escolar , Meia-Vida , Humanos , Lactente , Kwashiorkor/metabolismo , Fígado/metabolismo
18.
Arch Dis Child ; 95(6): 469-73, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20501540

RESUMO

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.


Assuntos
Tratamento Farmacológico/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Adolescente , Fatores Etários , Criança , Pré-Escolar , Países em Desenvolvimento , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Lactente , Recém-Nascido , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos
19.
Paediatr Drugs ; 12(2): 99-103, 2010 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-20218746

RESUMO

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.


Assuntos
Comitês de Monitoramento de Dados de Ensaios Clínicos/organização & administração , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Criança , Países em Desenvolvimento , Desenvolvimento Humano , Humanos , Classificação Internacional de Doenças , MEDLINE , Preparações Farmacêuticas/administração & dosagem , Organização Mundial da Saúde
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