Open-label, long-term safety study of zonisamide administered to children and adolescents with epilepsy

BACKGROUND: Zonisamide is licensed in the EU and USA for the adjunctive treatment of partial-onset seizures in adults but there are few data about its use in children. AIMS: To assess the long-term safety and efficacy of zonisamide in children and adolescents. METHODS: Zonisamide-na?ve patients (n=109, aged 3-15 years, weight >or=12.5 kg) with a clinical diagnosis of epilepsy (>or=4 seizures/month, receiving 1-2 antiepileptic drugs [AEDs] daily) received zonisamide once or twice daily in an open-label trial. The starting dose was 1mg/kg/day, increased by 2 mg/kg/day every 1-2 weeks at the investigator's discretion to an initial maximum of 12 mg/kg/day. The occurrence of adverse events (AEs) was the primary safety measure. Efficacy was measured via the reductions in seizure frequency and via investigator- and carer-rated global assessment ratings. RESULTS: The mean dose received was 8.5 mg/kg/day. Of the 109 children, 52 (48%) completed 15 months' treatment. Treatment-related AEs, mostly mild-to-moderate in severity, were reported by 58 patients. Seven patients discontinued due to treatment-related AEs. Serious AEs (pancreatitis, decreased sweating, and vertigo) were reported by three patients. A significant (p=0.033) median reduction in 'all seizure' frequency of 2.60 seizures per week was observed. Additionally, a significant (p=0.029) median reduction of 1.80 seizures/week in 'complex partial' seizures was reported. Improvements in investigator- and carer-rated global assessments were noted. CONCLUSIONS: Zonisamide treatment was generally well tolerated and was associated with significant reductions in seizure frequency in this pediatric population with a variety of both partial and generalized medically refractory epilepsy syndromes.     

Intra-patient reproducibility of myocardial SPECT imaging with 201Tl

Background  To define the physical and clinical reproducibility of ²⁰¹Tl myocardial perfusion SPECT (MPS), this study assesses the variation between two repeated rest ²⁰¹Tl MPS with repositioning only, with a two-hour time interval and with phantom measurements as a reference. Methods  Three anthropomorphic thorax phantoms were filled with ²⁰¹Tl. For each phantom five repeated ²⁰¹Tl MPS were obtained. In addition, in 20 patients repeated ²⁰¹Tl rest-MPS and in 26 patients early and delayed ²⁰¹Tl rest-MPS were performed. Quantitative analysis was done using MunichHeart. Statistical methods were used to calculate variability. Visual analysis was performed by 2 independent observers. Results  The average variation between repeated phantom MPS was 0.5% (95% confidence interval (CI): −0.4% to 1.4%). For patient scans this was −5.0% (95% CI: −2.5% to −7.5%) and between early and delayed ²⁰¹Tl MPS −15.5% (95% CI: −11.7% to −19.3%). Visual assessment revealed no clinical significant differences between rest ²⁰¹Tl and repeated or delayed ²⁰¹Tl MPS. Conclusions  Repositioning in phantom ²⁰¹Tl MPS does not cause significant variation. Repeated ²⁰¹Tl MPS in patients shows 5.0% decrease of ²⁰¹Tl in 30 minutes, which increases to 15% during a two-hour time interval without quantitative or visual regional differences. This decrease indicates a time-related washout of ²⁰¹Tl, but does not change clinical diagnosis.     

Health‐related quality of life and its determinants in children and adolescents born with oesophageal atresia

Aim: Following surgical correction in the neonatal period, patients born with oesophageal atresia have significant co‐morbidity, particularly in childhood. This study evaluates health‐related quality of life and its determinants such as concomitant anomalies and the presence of respiratory and/or gastro‐intestinal symptoms 6–18 years after repair of oesophageal atresia. Methods: Parents of 24 patients with oesophageal atresia completed the child health questionnaire for parents and 37 patients completed the child form. Gastro‐intestinal symptoms were assessed by a validated standardized reflux questionnaire. Results were compared with a healthy reference population. Results: Parents as well as patients themselves scored significantly lower on the domain general health perception. According to parents, general health perception was negatively affected by age at follow‐up and concomitant anomalies. Patients reported that reflux symptoms reduced general health perception. Conclusion: In this first study describing health‐related quality of life in children and adolescents born with oesophageal atresia, we demonstrated that general health remains impaired because of a high incidence of concomitant anomalies and gastrointestinal symptoms in patients with oesophageal atresia when compared with the healthy reference population.     

Rizatriptan wafer–sublingual vs. placebo at the onset of acute migraine

Rizatriptan wafer is a 5HT_1B/1D agonist for use in the acute treatment of migraine. It is a freeze-fried formulation, approved for oral administration, which dissolves on the tongue and is swallowed with saliva. In this study the efficacy of sublingually administered rizatriptan 10-mg wafer was evaluated in a randomized, double-blind, placebo-controlled, out-patient study involving 39 migraineurs. Patients were instructed to treat a migraine at the onset of pain in order to evaluate time of onset of pain relief and pain relief at 1 h. The average time to onset of relief was 25 min for patients treated with rizatriptan wafer and 27 min for patients treated with placebo. At 1 h, 50% of the patients receiving rizatriptan wafer and 50% of the patients receiving placebo experienced significant relief. Implications and potential reasons for a high placebo response are discussed.