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Background Children on the ketogenic diet must limit carbohydrate intake to maintain ketosis and reduce seizure burden. Patients on ketogenic diet are vulnerable to harm in the hospital setting where carbohydrate-containing medications are commonly prescribed. We developed clinical decision support to reduce inappropriate prescription of carbohydrate-containing medications in hospitalized children on ketogenic diet. Methods A clinical decision support alert was developed through formative and summative usability testing. The alert warned prescribers when they entered an order for a carbohydrate-containing medication in patients on ketogenic diet. The alert was implemented using a quasi-experimental design with sequential crossover from control to intervention at two tertiary care pediatric hospitals within a single health system. The primary outcome was carbohydrate-containing medication orders per patient-day. Results During the study period, there were 280 ketogenic diet patient admissions totaling 1219 patient-days. The carbohydrate-containing medication order rate declined from 0.69 to 0.35 orders per patient-day (absolute rate reduction 0.34, 95% confidence interval 0.25-0.43), corresponding to 256 inappropriate orders prevented. The alert fired 398 times and was accepted (i.e., the order was removed) 227 times for an overall acceptance rate of 57%. Conclusions Implementation of a clinical decision support alert at order-entry resulted in a sustained reduction in carbohydrate-containing medication orders for hospitalized patients on ketogenic diet without an increase in alert burden. Clinical decision support developed with user-centered design principles can improve patient safety for children on ketogenic diet by influencing prescriber behavior.

A basic challenge in drug development and clinical trial is the need to achieve throughput across numerous concurrent projects. Each project may operate under unique conditions and present numerous management challenges that cross organizational boundaries. This issue goes beyond complexity. Management in this environment requires a sort of organizational and operational calculus for controlling and understanding large volumes of clinical data gathered to serve project momentum leading, ideally, to a new drug application. In a traditional model, data are sampled and analyzed through various reporting and representation techniques as business or operational processes generate them. This yields indicators on which some decision can be based. Business intelligence is a phrase commonly identified with these methodologies. In the pharmaceutical industry, common business intelligence models offer only a partial solution. This paper outlines a more comprehensive methodology based on process intelligence. Process intelligence represents an understanding of key business data in the context of its relationship to strategy, organizational priorities, and work process momentum, Organizations exercising process intelligence are flexibly adaptive and oriented toward maximizing business throughput and quality. Several attributes identify process intelligence: integration, aggregation, transformation, communication, and orchestration. Each of these attributes is described and analyzed in this paper.

Objective Seek information about spinal cord safety for children with Down syndrome positioned for ear surgery. Study Design Prospective consecutive patients, each serving as his or her own control. Methods Somatosensory evoked potentials were recorded from 17 children who were undergoing elective otolaryngological surgery. None of the patients had neurological symptoms or physical examination findings suggesting cervical spinal cord embarrassment. Specifically, muscle tone was normal or mildly reduced globally, consistent with Down syndrome, and deep tendon reflexes were normal and not appreciably different in the upper and lower extremities. On plain lateral radiographs obtained in the neutral, flexed, and extended positions, the patients' cervical spines were normal. Results When the anesthetized children had their necks placed in either right or left 60° rotation, no significant change in somatosensory latency or amplitude was found. With more than 99.999% certainty, neurologically intact children with Down syndrome with normal plain cervical spine radiographs were not exposed to extra risks by 60° neck rotation during surgery. Conclusion Patients with Down syndrome who are neurologically intact and who have normal lateral neck radiographs do not appear at great risk with neck rotation.

Newer antiepileptic drugs are reported to have better side-effect profiles than traditional antiepileptics, although the evidence to this effect and their efficacy is limited. We compare the efficacy and tolerability of levetiracetam and carbamazepine monotherapy in children with partial epilepsy ≤ 16 years of age. We identified 86 patients (66 levetiracetam, 20 carbamazepine) treated with initial monotherapy for partial epilepsy and followed for ≥ 6 months. Efficacy was based on the number of patients achieving seizure freedom of ≥ 6 months. Tolerability was based on parent-and patient-reported side effects. Forty-eight (73%) subjects on levetiracetam and 13 (65%) subjects on carbamazepine achieved 6 months of seizure freedom. A total of 70% of patients on carbamazepine and 45% of those on levetiracetam had at least 1 adverse event while on monotherapy ( P = .07). Levetiracetam and carbamazepine monotherapy demonstrate similar efficacy for treatment of partial epilepsy and are well tolerated in children.

Benign familial neonatal convulsions (BFNC) is an epileptic disorder caused by dominant mutations in the genes KCNQ2 and KCNQ3 encoding the K+ channels K(V)7.2 and K(V)7.3. We identified two novel KCNQ2 mutations in two BFNC families. One mutation predicted a truncated protein (S247X) that lacks the channel's pore region, the other resulted in the amino acid substitution S122L in the S2 segment of K(V)7.2. In comparison to wild-type (WT) K(V)7.2, functional analysis of S122L mutant channels in Xenopus oocytes revealed a significant positive shift and increased slope of the activation curve leading to significant current reduction in the subthreshold range of an action potential (75% reduction at -50 mV). Our results establish an important role of the K(V)7.2 S2 segment in voltage-dependent channel gating and demonstrate in a human disease that subthreshold voltages are likely to represent the physiologically relevant range for this K+ channel to regulate neuronal firing.

Various paraneoplastic autoantibodies have been linked to discrete neurologic syndromes and tumors in adults, but little is known about their incidence in children. We report a cross-sectional study of known paraneoplastic antibodies in 59 children with opsoclonus-myoclonus-ataxia, 86% of whom were moderately or severely symptomatic, and 68% of whom had relapsed at the time of testing. This total number of patients includes 18 children with low-stage neuroblastoma (tested after tumor resection), six of whom had never been treated with immunosuppressants. All were seronegative for anti-Hu, anti-Ri, and anti-Yo, the three paraneoplastic antibodies most associated with opsoclonus-myoclonus or ataxia in adults. These data contrast with reports of anti-Hu-positive sera in children with high-stage tumors and suggest that anti-Hu, anti-Ri, and anti-Yo do not explain relapses in pediatric opsoclonus-myoclonus-ataxia. They underscore the need to search for unique autoantibodies, as well as cellular mechanisms of pediatric paraneoplastic disease.

Summary: Purpose: To describe three cases of refractory status epilepticus (RSE) in children responsive to topiramate (TPM). Methods: Patients with SE refractory to therapeutic doses of at least two antiepileptic medications were given TPM, 10 mg/kg/d, for 2 consecutive days, followed by maintenance doses of 5 mg/kg/d. Results: This protocol has been used in three cases of RSE at our institution. In each case, SE was aborted within 21 h of the initial dose of TPM. Two patients avoided pharmacologic coma, and one was rapidly weaned from continuous benzodiazepine infusion. Conclusions: Our experience indicates that TPM loading can be effective in the treatment of RSE in children.

The cervical spine in Down syndrome patients is often lax, at least at radiographic imaging, and the risk of spinal cord embarrassment is increased. This study was performed to obtain information that would help identify patients at risk for this problem and reduce the risk of endotracheal intubation and other surgical procedures in patients with Down syndrome. Somatosensory evoked potential studies were performed in 15 consecutive children who were undergoing elective otolaryngic surgery. None had neurologic symptoms or the physical examination finding of cervical spinal cord embarrassment, and their cervical spines were considered normal by plain radiographs obtained in the neutral, flexed, and extended positions. No significant change in latency (P = .16) or amplitude (P = .19) was found when the anesthetized children had their necks placed in either full flexion or full extension. With more than 90% certainty, the authors believe that children with Down syndrome who have "normal" plain cervical spine radiographs are exposed to no extra risks from neck flexion or extension during surgery.

A prospective study was undertaken using a range-gated, pulsed Doppler velocimeter to study flowpressure relationships in the anterior cerebral artery. Serial velocity and pressure studies were performed with each infant serving as his or her own control. The hypothesis tested was that ill preterm infants sustaining subependymal/intraventricular hemorrhage would have absent autoregulation. The hypothesis has been tested in 88 studies on 32 infants. Of 32 infants studied, 15 were judged to be pressure passive; nine of these children bled. The other 17 infants were not pressure passive; eight of these children bled (P > .05). From these studies, it may be concluded that the pressure passive state is not the final common link in the genesis of subependymal/intravertricular hemorrhage. Pulsed Doppler ultrasound may provide an extremely useful noninvasive technique for studing both the arterial and venous sides of the cerebral circulation.

• Infants with periventricular-intraventricular hemorrhage (PV-IVH) were followed up with weekly ultrasound sector scans to define the natural history of late ventricular dilation (ie, dilation in excess of that seen at the time of diagnosis of PV-IVH). Infants fell into two groups: (1) posthemorrhagic hydrocephalus (PHH), dilation that produced an increase in occipitofrontal circumference greater than 2 cm per week and/or clinical symptoms of increased intracranial pressure; and (2) ventriculomegaly (VM), dilation that stabilized or reversed without producing these effects. The former was directly related to the severity of hemorrhage. The diameter of the lateral ventricle was significantly greater in PHH. In 26 of 48 infants at risk, late dilation developed; 14 had VM and 12 had PHH. Thus, late ventricular dilation stabilized or resolved spontaneously in 54%. Only three infants eventually required a ventriculoperitoneal shunt. Clinical changes in addition to ventricular size should be used in assessing the need for treatment of ventricular dilation after PV-IVH. ( Am J Dis Child 1982;136:589-593)