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treatment","volume":"24","author":"G Kose","year":"2009","journal-title":"J Child Neurol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1111\/j.1528-1167.2006.00596.x","article-title":"Risk of aplastic anemia in patients using antiepileptic drugs","volume":"47","author":"KB Handoko","year":"2006","journal-title":"Epilepsia"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1136\/adc.71.2.153","article-title":"Bone marrow suppression induced by high dose valproic acid","volume":"71","author":"T Kishi","year":"1994","journal-title":"Arch Dis Child"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/BF01957735","article-title":"Fatal pancytopenia during high-dose valproate monotherapy","volume":"151","author":"J Rajantie","year":"1992","journal-title":"Eur J Pediatr"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1016\/S0140-6736(98)05418-X","article-title":"Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis during first weeks of antiepileptic therapy: a case-control study. Study Group of the International Case Control Study on Severe Cutaneous Adverse Reactions","volume":"353","author":"B Rzany","year":"1999","journal-title":"Lancet"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jaad.2009.06.085","article-title":"Stevens-Johnson syndrome and toxic epidermal necrolysis in Asian children","volume":"62","author":"MJ-A Koh","year":"2010","journal-title":"J AM ACAD DERMATOL"},{"key":"ref30","unstructured":"Uppsala Monitoring Centre. WHO Collaborating Centre for International Drug Monitoring. Caveat document. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.who-umc.org\/graphics\/25300.pdf\" xlink:type=\"simple\">http:\/\/www.who-umc.org\/graphics\/25300.pdf<\/ext-link>. Accessed 26 Sep 2013."},{"key":"ref31","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1177\/014107689108400612","article-title":"Spontaneous adverse drug reaction reporting vs event monitoring: a comparison","volume":"84","author":"AP Fletcher","year":"1991","journal-title":"J R Soc Med"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"385","DOI":"10.2165\/00002018-200629050-00003","article-title":"Under-reporting of adverse drug reactions: a systematic review","volume":"29","author":"L Hazell","year":"2006","journal-title":"Drug Saf"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ejpn.2008.12.003","article-title":"Social and medical care of preschool children with epilepsy in Croatia: population-based survey","volume":"14","author":"L Cvitanovic-Sojat","year":"2010","journal-title":"Eur J Paediatr Neurol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1111\/j.1528-1167.2009.02331.x","article-title":"Comparison of antiepileptic drug prescribing in children in three European countries","volume":"51","author":"Y Hsia","year":"2010","journal-title":"Epilepsia"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1111\/j.2042-7174.2012.00215.x","article-title":"Access to antiepileptic drug therapy in children in Camaguey Province, Cuba","volume":"20","author":"ZB Arencibia","year":"2012","journal-title":"Int J Pharm Pract"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1001\/archpedi.153.12.1267","article-title":"Treatment of newly diagnosed pediatric epilepsy: a community-based study","volume":"153","author":"AT Berg","year":"1999","journal-title":"Arch Pediatr Adolesc Med"},{"key":"ref37","first-page":"19","article-title":"Prevalence of epilepsy in school children in El-Manyal Island","volume":"46","author":"F Talaat","year":"2009","journal-title":"Egypt J Neurol Psychiatr Neurosurg"},{"key":"ref38","unstructured":"Electronic Medicines Compendium. Summary of Product Characteristics for Epilim Chronosphere. 2014; <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.medicines.org.uk\/emc\/medicine\/26144\" xlink:type=\"simple\">http:\/\/www.medicines.org.uk\/emc\/medicine\/26144<\/ext-link>. 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