http://repub.eur.nl/res/aut/3938/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/8516/ 1999-01-01T00:00:00Z Complex seizure characteristics in patients with a positive family history were studied to define familial phenotype subgroups of febrile seizures. A total of 51 children with one or more affected first degree relatives and 177 without an affected first degree relative were compared for history of complex characteristics of the initial febrile seizure. No difference was found in the frequency of febrile status epilepticus (OR = 1.1 (95% confidence interval (CI) 0.3 to 4.3)), multiple type (OR = 0.6 (CI 0.3 to 1.2)), and focal characteristics (OR = 0.4 (CI 0.2 to 1.2)). The presence of any complex characteristic (OR = 0.5 (CI 0.3 to 1.0)) was higher in those without an affected first degree relative, although differences did not reach significance. The familial type of febrile seizures is not associated with complex characteristics of the initial febrile seizure. Complex seizure characteristics are unlikely to help in discriminating phenotype subgroups for genetic studies of febrile seizures. http://repub.eur.nl/res/pub/17640/ 1998-11-11T00:00:00Z Febrile seizures are described as a temporary seizure disorder of childhood; the attacks occur by definition in association with fever and are usually accompanied by sudden tonic-clonic muscle contractions and reduced consciousness, usually lasting not longer than 5 to 10 minutes. According to the commonly accepted definition of the National Institutes of Health consensus meeting of febrile seizures in 1980, 'a febrile seizure (an abnormal, sudden, excessive electrical discharge of neurons [grey malter] which propagates down the neuronal processes [white matter] to affect an end organ in a clinically measurable fashion) is an event in infancy or childhood, usually occurring between three months and five years of age, associated with fever but without evidence of intracranial infection or defined cause. Seizures with fever in children who have suffered a previous nonfebrile seizure are excluded. Febrile seizures are to be distinguished from epilepsy, which is characterised by recurrent non febrile seizures'. 1 In the context of this thesis, fever has been defined as a rectally measured body temperature of 38.5 °C or higher. Complex febrile seizures have one or more of the foHowing characteristics: the seizure lasts for more than 15 minutes (prolonged) or 30 minutes or more (febrile status epilepticus); there are one or more recurrences within 24 hours (multiple type febrile seizures); the seizure has partial features, i.e. a focal onset of the seizure or a postictal Todd paresis of facial muscles or Iimbs. Seizures are referred to as simple, if they last less than 15 minutes, do not recur within 24 hours (single-type) and are generalised. http://repub.eur.nl/res/pub/8923/ 1998-01-01T00:00:00Z OBJECTIVES: Febrile seizures recur frequently. Factors increasing the risk of febrile seizure recurrence include young age at onset, family history of febrile seizures, previous recurrent febrile seizures, time lapse since previous seizure <6 months, relative low temperature at the initial seizure, multiple type initial seizure, and frequent febrile illnesses. Prevention of seizure recurrences serves two useful purposes: meeting parental fear of recurrent febrile seizures in general and reducing the (small) risk of a long-lasting and eventually injurious recurrent seizure. In daily practice, children with febrile seizures often are treated with antipyretics during fever to prevent febrile seizure recurrences. Thus far, no randomized placebo-controlled trial has been performed to assess the efficacy of intermittent antipyretic treatment in the prevention of seizure recurrence. METHODS: We performed a randomized, double-blind, placebo-controlled trial. Children 1 to 4 years of age who had had at least one risk factor for febrile seizure recurrence were enrolled. They were randomly assigned to either ibuprofen syrup, 20 mg/mL, 0.25 mL (= 5 mg) per kilogram of body weight per dose, or matching placebo, to be administered every 6 hours during fever (temperature, >/=38.5 degrees C). Parents were instructed to take the child's rectal temperature immediately when the child seemed ill or feverish and to promptly administer the study medication when the temperature was >/=38.5 degrees C. Doses were to be administered every 6 hours until the child was afebrile for 24 hours. The parents were instructed not to administer any other antipyretic drug to the child. For measuring rectal temperature, a Philips HP5316 digital thermometer (Philips, Eindhoven, The Netherlands) was distributed. During subsequent treatment of the fever episode, parents had to call the investigator at least once each day to notify the investigator in case of febrile seizure recurrence. The investigator could be contacted by parents 24 hours per day. The primary outcome was the first recurrence of a febrile seizure. Kaplan-Meier curves and Cox regression were used for the statistical analysis. The treatment effect on the course of the temperature was assessed using analysis of covariance, with temperature at fever onset as covariate. Two analyses were performed. In an intention-to-treat analysis, all first recurrences were considered regardless of study medication compliance. A per-protocol analysis was limited to those recurrences that occurred in the context of study medication compliance. RESULTS: Between October 1, 1994, and April 1, 1996, 230 children were randomly assigned to ibuprofen syrup (111 children) or placebo (119 children). Median follow-up time was 1.04 years (25th-75th percentiles; 0.7-1.8 years) in the ibuprofen group and 0.98 years (0.7-1.6 years) in the placebo group. Of all children, 67 had a first febrile seizure recurrence, with 31 in the ibuprofen group and 36 in the placebo group. The 2-year recurrence probabilities were 32% and 39%, respectively. The recurrence risk in the ibuprofen group was 0.9 (95% confidence interval: 0.6-1.5) times the recurrence risk in the placebo group (intention to treat). Adjustment for baseline characteristics did not affect the risk-reduction estimate. Of the 67 recurrences, 30 occurred in the context of study medication compliance (13 ibuprofen, 17 placebo). The per-protocol analysis, which was limited to these events, showed similar results. A significant reduction in temperature (0.7 degrees C) after fever onset in the ibuprofen group compared with the placebo group was demonstrated if all 555 fever episodes were considered. In the fever episodes with a seizure recurrence, a similar temperature increase was shown in both groups, with no significant difference between the intention-to-treat and the per-protocol analysis. DISCUSSION: (ABSTRACT TRUNCATED) http://repub.eur.nl/res/pub/8925/ 1998-01-01T00:00:00Z BACKGROUND: The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children. AIM: To assess the quality of the informed consent process in a paediatric setting. METHODS: A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures. RESULTS: 181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%). CONCLUSIONS: Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent. http://repub.eur.nl/res/pub/8980/ 1998-01-01T00:00:00Z OBJECTIVE: Prediction of a recurrent febrile seizure during subsequent episodes of fever. DESIGN: Study of the data of the temperatures, seizure recurrences, and baseline patient characteristics that were collected at a randomized placebo controlled trial of ibuprofen syrup to prevent febrile seizure recurrences. SETTING: Two pediatric hospitals in the Netherlands. PATIENTS: A total of 230 children with an increased risk of febrile seizure recurrence. MAIN OUTCOME MEASURE: Seizure recurrence during a subsequent fever episode. RESULTS: A total of 509 episodes of fever were registered with 67 recurrences; 35 (52%) recurrences within the first 2 hours after fever of onset had a lower median temperature (39.3 degrees C) than 32 (48%) after more than 2 hours of fever (40.0 degrees C, P<.001). Poisson regression analysis resulted in 3 univariably significant (P<.05) predictors of a recurrence of seizure during a subsequent episode of fever. In a multivariable model, they were corrected for their correlation: interval between the last previous seizure and fever of onset less than 6 months (relative risk= 1.3 [95% confidence interval: 0.8-2.4]), age at fever of onset (relative risk=0.7 [95% confidence interval: 0.5-1.0] per year increase) and temperature at fever of onset (relative risk = 1.7 [95% confidence interval: 1.1-2.8] per degree Celsius increase). CONCLUSIONS: Half of the recurrent seizures occur in the first 2 hours after fever of onset of a subsequent fever episode. If seizure recurs at a later time, the temperature at seizure is higher compared with recurrences occurring in the first 2 hours of fever. Young age at fever of onset, high temperature at fever of onset, and high temperature during the episode of fever are associated with an increased risk of a recurrent febrile seizure at the moment that a child with a history of febrile seizures has fever again.