For term infants with PPHN, early I-NO as the sole adjunct to conventional management produced an acute and sustained improvement in oxygenation for 24 hours without short-term side effects (5 and 20 ppm doses), and the suggestion that ECMO use may be reduced.

OBJECTIVETo evaluate efficacy and safety of switching from twice-daily exenatide to once-daily liraglutide or of 40 weeks of continuous liraglutide therapy.RESEARCH DESIGN AND METHODSWhen added to oral antidiabetes drugs in a 26-week randomized trial (Liraglutide Effect and Action in Diabetes [LEAD]-6), liraglutide more effectively improved A1C, fasting plasma glucose, and the homeostasis model of β-cell function (HOMA-B) than exenatide, with less persistent nausea and hypoglycemia. In this 14-week extension of LEAD-6, patients switched from 10 μg twice-daily exenatide to 1.8 mg once-daily liraglutide or continued liraglutide.RESULTSSwitching from exenatide to liraglutide further and significantly reduced A1C (0.32%), fasting plasma glucose (0.9 mmol/l), body weight (0.9 kg), and systolic blood pressure (3.8 mmHg) with minimal minor hypoglycemia (1.30 episodes/patient-year) or nausea (3.2%). Among patients continuing liraglutide, further significant decreases in body weight (0.4 kg) and systolic blood pressure (2.2 mmHg) occurred with 0.74 episodes/patient-year of minor hypoglycemia and 1.5% experiencing nausea.CONCLUSIONSConversion from exenatide to liraglutide is well tolerated and provides additional glycemic control and cardiometabolic benefits.

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This multicenter, randomized, open-label, parallel-group, phase-1 study assessed the pharmacokinetics (PK), safety, and tolerability of the investigational intramuscular paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia or schizoaffective disorder. A total of 328 patients (men or women, aged 18-65 years) were enrolled in 1 of 4 separately conducted panels (A to D). Each panel had 2 single-dose treatment periods (period 1, 1 mg intramuscular paliperidone immediate release [IR]; period 2, intramuscular PP3M 75-525 mg eq) separated by a washout of 7-21 days. Overall, 245 of 308 (79.5%) PP3M-dosed patients completed the study. Because the PK studies of panels A and C were compromised by incomplete injection in some patients, PK data from only panels B and D are presented. Safety data from all panels are presented. Peak paliperidone plasma concentration was achieved between 23 and 34 days, and apparent half-life was ∼2-4 months. Mean plasma AUC∞ and Cmax of paliperidone appeared to be dose-proportional. Relative bioavailability in comparison with paliperidone was ∼100% independent of the dose and injection site. Headache and nasopharyngitis were the most common (>7%) treatment-emergent adverse events. Overall, safety and tolerability were similar to those of the 1-month formulation. Results support a once-every-3-months dosing interval in patients with schizophrenia or schizoaffective disorder.

A novel recursive algorithm for discrete Fourier transform (DFT) and its inverse transform (IDFT) is proposed in this brief. It was found that the proposed algorithm and its implementation outperformed other existing recursive algorithms. The proposed algorithm was found to 1) reduce multiplication computations by 50.5% using the symmetric identity of coefficients and a resource-sharing technique and register-splitting scheme; 2) decrease read-only memory sizes by 50% compared with conventional algorithms; 3) reduce the number of multipliers implemented by 80% compared with the latest algorithm; and 4) increase data throughput by 100% per transformation. This design is suitable for communication systems and digital radio mondiale (DRM) systems, such as dual-tone multifrequency detection and coded orthogonal frequency-division-multiplexing modulation. The algorithm was designed and fabricated using a 0.18 μm 1P6M complementary metal-oxide-semiconductor process. The core area is 397 × 388 μm 2 , including the DFT and IDFT modules. For modern applications (voice over packet and DRM), this processor only consumes 2.96 mW at 25 MHz. Furthermore, it can calculate the 212/165/106/288/256/176/112-point DFTs and IDFTs.

For infants classified as treatment successes, a dose response between the I-NO dose and decrease in PaO(2) after discontinuing I-NO was found. A reduction in I-NO to 1 ppm before discontinuation of the drug seems to minimize the decrease in PaO(2) seen. For infants failing treatment, discontinuation of I-NO could pose a life-threatening reduction in oxygenation should extracorporeal membrane oxygenation not be readily available or I-NO cannot be continued on transport.

This study was a randomized, double-blind, 12-week comparison of the pharmacokinetics, safety, and tolerability of two cyclosporine (CsA) formulations, cyclosporine emulsion capsules and oral solution for microemulsion and cyclosporine, in the postoperative management of renal transplant patients. Of the 101 patients, aged 18 to 65, who entered the study, 89 were evaluable for pharmacokinetics. Initial dosage was 10 mg/kg per day, administered twice daily in two equal doses. Dosages were adjusted to achieve target CsA concentrations. The pharmacokinetic (PK) parameters (dose-normalized) of greatest interest were maximum blood concentration (C(max)/dose), time to reach maximum concentration (t(max), area under the blood concentration-vs.-time curve (AUC/dose), and trough blood concentrations (Co h/dose). The relative CsA bioavailabilty was found to be significantly enhanced with cyclosporine emulsion compared with cyclosporine with a 16% to 31% increase in AUC and a 32% to 42% increase in C(max). Intrapatient variability of PK parameters was significantly lower with cyclosporine emulsion than with cyclosporine for AUC, C(oh), t(max), and C(max) in many instances. This indicates a more consistent, rapid, and more complete total absorption of CsA. Despite higher CsA C(max) levels and AUCs with cyclosporine emulsion, safety and tolerability (detailed in a parallel report) were comparable to those of cyclosporine. The PK advantages of cyclosporine emulsion over cyclosporine are either independent of food conditions or possibly reflective of more consistent absorption of CsA with cyclosporine emulsion. The findings suggest that de novo use of cyclosporine emulsion may simplify and improve management of organ transplant recipients and that the PK advantages of cyclosporine emulsion may translate into clinical benefits.

OBJECTIVE -The safety and efficacy of insulin aspart continuous subcutaneous insulin infusion (CSII) was compared with that of insulin lispro CSII in children and adolescents with type 1 diabetes.RESEARCH DESIGN AND METHODS -Children and adolescents aged 4 -18 years with diagnosed type 1 diabetes Ն1 year previously and treated with insulin analog in a CSII Ն3 months were randomly assigned 2:1 to 16 weeks of insulin aspart CSII (n ϭ 198) or insulin lispro CSII (n ϭ 100) in this open-label, parallel-group, multicenter study. Standard diabetes safety and efficacy parameters were assessed.RESULTS -Baseline demographics, subject characteristics, and diabetes history were similar between treatment groups. After 16 weeks of treatment, insulin aspart CSII was noninferior to insulin lispro CSII as measured by change in A1C from baseline (aspart, Ϫ0.15 Ϯ 0.05%; lispro, Ϫ0.05 Ϯ 0.07% [95% CI of the treatment difference Ϫ0.27 to 0.07]; P ϭ 0.241). No significant differences between treatment groups were observed in fasting plasma glucose, hyperglycemia, and rates of hypoglycemic episodes. At week 16, 59.7% of subjects in the aspart group and 43.8% of subjects in the lispro groups achieved age-specific American Diabetes Association A1C goals (Ͻ8.5% for subjects aged Ͻ6 years; Ͻ8% for subjects aged 6 -18 years) (P ϭ 0.040, corrected for baseline). Daily insulin dose (units per kilogram) was significantly lower at week 16 for subjects treated with aspart compared with those treated with lispro (0.86 Ϯ 0.237 vs. 0.94 Ϯ 0.233, P ϭ 0.018).CONCLUSIONS -Insulin aspart was as safe and effective as insulin lispro for use in a CSII in children and adolescents with type 1 diabetes. Diabetes Care 31:210-215, 2008