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Article: Mortality rates and causes of death in children with epilepsy prescribed antiepileptic drugs: A retrospective cohort study using the uk general practice research database

TitleMortality rates and causes of death in children with epilepsy prescribed antiepileptic drugs: A retrospective cohort study using the uk general practice research database
Authors
Issue Date2011
PublisherAdis International Ltd. The Journal's web site is located at http://drugsafety.adisonline.com/
Citation
Drug Safety, 2011, v. 34 n. 5, p. 403-413 How to Cite?
AbstractBackground: Patients with epilepsy, including children, have an increased risk of mortality compared with the general population. Antiepileptic drugs (AEDs) were the most frequent class of drugs reported in a study looking at fatal suspected adverse drug reactions in children in the UK. Objective: The objective of the study was to identify cases and causes of death in a paediatric patient cohort prescribed AEDs with an associated epilepsy diagnosis. Methods: This was a retrospective cohort study supplemented with general practitioner-completed questionnaires, post-mortem reports and death certificates. The setting was UK primary care practices contributing to the General Practice Research Database. Participants were children and adolescents aged 0-18 years prescribed AEDs between 1993 and 2005. Causality assessment was undertaken by a consensus panel comprising paediatric specialists in neuropathology, neurology, neuropsychiatry, paediatric epilepsy, pharmacoepidemiology and pharmacy to determine crude mortality rate (CMR) and standardized mortality ratios (SMRs), and the likelihood of an association between AED(s) and the event of death. Results: There were 6190 subjects in the cohort (contributing 26 890 personyears of data), of whom 151 died. Median age at death was 8.0 years. CMR was 56.2 per 10 000 person-years and the SMR was 22.4 (95% CI 18.9, 26.2). The majority of deceased subjects had severe underlying disorders. Death was attributable to epilepsy in 18 subjects; in 9 the cause of death was sudden unexpected death in epilepsy (SUDEP) [3.3 per 10 000 person-years (95% CI 1.5, 6.4)]. AEDs were probably (n = 2) or possibly (n = 3) associated causally with death in five subjects. Two status epilepticus deaths were associated causally with AED withdrawal. Conclusions: Children prescribed AEDs have an increased risk of mortality relative to the general population. Most of the deaths were in children with serious underlying disorders. A small number of SUDEP cases were identified. AEDs are not a major cause of death but in a small proportion of cases, a causal relationship between death and AEDs could not be excluded. © 2011 Adis Data Information BV. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/171419
ISSN
2015 Impact Factor: 3.206
2015 SCImago Journal Rankings: 1.359
References

 

DC FieldValueLanguage
dc.contributor.authorAckers, Ren_US
dc.contributor.authorBesag, FMCen_US
dc.contributor.authorHughes, Een_US
dc.contributor.authorSquier, Wen_US
dc.contributor.authorMurray, MLen_US
dc.contributor.authorWong, ICKen_US
dc.date.accessioned2012-10-30T06:14:03Z-
dc.date.available2012-10-30T06:14:03Z-
dc.date.issued2011en_US
dc.identifier.citationDrug Safety, 2011, v. 34 n. 5, p. 403-413en_US
dc.identifier.issn0114-5916en_US
dc.identifier.urihttp://hdl.handle.net/10722/171419-
dc.description.abstractBackground: Patients with epilepsy, including children, have an increased risk of mortality compared with the general population. Antiepileptic drugs (AEDs) were the most frequent class of drugs reported in a study looking at fatal suspected adverse drug reactions in children in the UK. Objective: The objective of the study was to identify cases and causes of death in a paediatric patient cohort prescribed AEDs with an associated epilepsy diagnosis. Methods: This was a retrospective cohort study supplemented with general practitioner-completed questionnaires, post-mortem reports and death certificates. The setting was UK primary care practices contributing to the General Practice Research Database. Participants were children and adolescents aged 0-18 years prescribed AEDs between 1993 and 2005. Causality assessment was undertaken by a consensus panel comprising paediatric specialists in neuropathology, neurology, neuropsychiatry, paediatric epilepsy, pharmacoepidemiology and pharmacy to determine crude mortality rate (CMR) and standardized mortality ratios (SMRs), and the likelihood of an association between AED(s) and the event of death. Results: There were 6190 subjects in the cohort (contributing 26 890 personyears of data), of whom 151 died. Median age at death was 8.0 years. CMR was 56.2 per 10 000 person-years and the SMR was 22.4 (95% CI 18.9, 26.2). The majority of deceased subjects had severe underlying disorders. Death was attributable to epilepsy in 18 subjects; in 9 the cause of death was sudden unexpected death in epilepsy (SUDEP) [3.3 per 10 000 person-years (95% CI 1.5, 6.4)]. AEDs were probably (n = 2) or possibly (n = 3) associated causally with death in five subjects. Two status epilepticus deaths were associated causally with AED withdrawal. Conclusions: Children prescribed AEDs have an increased risk of mortality relative to the general population. Most of the deaths were in children with serious underlying disorders. A small number of SUDEP cases were identified. AEDs are not a major cause of death but in a small proportion of cases, a causal relationship between death and AEDs could not be excluded. © 2011 Adis Data Information BV. All rights reserved.en_US
dc.languageengen_US
dc.publisherAdis International Ltd. The Journal's web site is located at http://drugsafety.adisonline.com/en_US
dc.relation.ispartofDrug Safetyen_US
dc.subject.meshAdolescenten_US
dc.subject.meshAdverse Drug Reaction Reporting Systems - Statistics & Numerical Dataen_US
dc.subject.meshAnticonvulsants - Adverse Effects - Therapeutic Useen_US
dc.subject.meshCause Of Deathen_US
dc.subject.meshChilden_US
dc.subject.meshChild, Preschoolen_US
dc.subject.meshCohort Studiesen_US
dc.subject.meshData Collectionen_US
dc.subject.meshDatabases, Factualen_US
dc.subject.meshEpilepsy - Drug Therapy - Mortality - Physiopathologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshGreat Britain - Epidemiologyen_US
dc.subject.meshHumansen_US
dc.subject.meshInfanten_US
dc.subject.meshMaleen_US
dc.subject.meshRetrospective Studiesen_US
dc.subject.meshStatus Epilepticus - Etiology - Mortalityen_US
dc.subject.meshSubstance Withdrawal Syndrome - Physiopathologyen_US
dc.titleMortality rates and causes of death in children with epilepsy prescribed antiepileptic drugs: A retrospective cohort study using the uk general practice research databaseen_US
dc.typeArticleen_US
dc.identifier.emailWong, ICK:wongick@hku.hken_US
dc.identifier.authorityWong, ICK=rp01480en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.2165/11588480-000000000-00000en_US
dc.identifier.pmid21513363-
dc.identifier.scopuseid_2-s2.0-79955372251en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955372251&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume34en_US
dc.identifier.issue5en_US
dc.identifier.spage403en_US
dc.identifier.epage413en_US
dc.publisher.placeNew Zealanden_US
dc.identifier.scopusauthoridAckers, R=16308666600en_US
dc.identifier.scopusauthoridBesag, FMC=7004367676en_US
dc.identifier.scopusauthoridHughes, E=21334732800en_US
dc.identifier.scopusauthoridSquier, W=6603853552en_US
dc.identifier.scopusauthoridMurray, ML=7403583537en_US
dc.identifier.scopusauthoridWong, ICK=7102513915en_US

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