Randomization

ObjectivesTo compare the efficacy, safety and tolerability of a novel rivastigmine transdermal patch with conventional rivastigmine capsules and placebo in patients with Alzheimer's disease (AD).To compare the efficacy, safety and tolerability of a novel rivastigmine transdermal patch with conventional rivastigmine capsules and placebo in patients with Alzheimer's disease (AD).MethodsIn this 24-week, multicenter, double-blind, double-dummy, placebo- and active-controlled trial, patients with probable AD were randomized to one of four treatment groups: 12 mg/day rivastigmine capsules; 10 cm2 (9.5 mg/24 h) rivastigmine patch; 20 cm2 (17.4 mg/24 h) rivastigmine patch; or placebo. Primary efficacy measures were the Alzheimer's Disease Assessment Scale—Cognitive subscale (ADAS-Cog) and Alzheimer's Disease Cooperative Study––Clinical Global Impression of Change (ADCS-CGIC).In this 24-week, multicenter, double-blind, double-dummy, placebo- and active-controlled trial, patients with probable AD were randomized to one of four treatment groups: 12 mg/day rivastigmine capsules; 10 cm2 (9.5 mg/24 h) rivastigmine patch; 20 cm2 (17.4 mg/24 h) rivastigmine patch; or placebo. Primary efficacy measures were the Alzheimer's Disease Assessment Scale—Cognitive subscale (ADAS-Cog) and Alzheimer's Disease Cooperative Study––Clinical Global Impression of Change (ADCS-CGIC).ResultsOne thousand one hundred and ninety five AD patients from 21 countries participated in the study. Treatment differences (vs placebo) on the ADAS-Cog at Week 24 in 10 cm2 patch, 20 cm2 patch and capsule groups were 1.6 (p = 0.005), 2.6 (p < 0.001) and 1.6 (p = 0.003). Treatment differences on the ADCS-CGIC were 0.3 (p = 0.01), 0.2 (p = 0.054) and 0.3 (p = 0.009). Comparison between the 10 cm2 patch and the capsule revealed non-inferiority. Rates of nausea in the 10 cm2 patch and capsule groups were 7.2% and 23.1%, respectively; rates of vomiting were 6.2% and 17.0%, respectively. Moderate or severe skin irritation occurred in ≤10% patients across the four patch sizes (5, 10, 15 and 20 cm2).One thousand one hundred and ninety five AD patients from 21 countries participated in the study. Treatment differences (vs placebo) on the ADAS-Cog at Week 24 in 10 cm2 patch, 20 cm2 patch and capsule groups were 1.6 (p = 0.005), 2.6 (p < 0.001) and 1.6 (p = 0.003). Treatment differences on the ADCS-CGIC were 0.3 (p = 0.01), 0.2 (p = 0.054) and 0.3 (p = 0.009). Comparison between the 10 cm2 patch and the capsule revealed non-inferiority. Rates of nausea in the 10 cm2 patch and capsule groups were 7.2% and 23.1%, respectively; rates of vomiting were 6.2% and 17.0%, respectively. Moderate or severe skin irritation occurred in ≤10% patients across the four patch sizes (5, 10, 15 and 20 cm2).ConclusionsThe target dose of 10 cm2 rivastigmine patch provides efficacy similar to the highest doses of capsules with a superior tolerability profile. The transdermal patch with rivastigmine may offer convenience important to many caregivers and patients. Copyright © 2007 John Wiley & Sons, Ltd.The target dose of 10 cm2 rivastigmine patch provides efficacy similar to the highest doses of capsules with a superior tolerability profile. The transdermal patch with rivastigmine may offer convenience important to many caregivers and patients. Copyright © 2007 John Wiley & Sons, Ltd.

Objective: The aim of this trial was to investigate whether a routine of allowing normal food at will increases morbidity after major upper gastrointestinal (GI) surgery. Summary Background Data: Nil-by-mouth with enteral tube feeding is widely practiced for several days after major upper GI surgery. After other abdominal operations, normal food at will has been shown to be safe and to improve gut function. Methods: Patients were randomly assigned to a routine of nil-bymouth and enteral tube feeding by needle-catheter jejunostomy (ETF group) or normal food at will from the first day after major upper GI surgery. Primary end point was rate of major complications and death. Secondary outcomes were minor complications and adverse events, bowel function, and length of stay. All patients were invited to a follow-up at 8 weeks after discharge from the hospital. Results: Four hundred fifty-three patients who underwent major open upper GI surgery in 5 centers were enrolled between 2001 and 2006. Four hundred forty-seven patients were correctly randomized. Of 227 patients 76 (33.5%) had major complications in the ETF group compared with 62 (28.2%) of 220 patients allowed normal food at will (P ϭ 0.26, 95% CI for the difference in rate from Ϫ3.3 to 13.9). In the ETF group, 36 (15.9%) patients were reoperated compared with 29 (13.2%) in the group allowed normal food at will (P ϭ 0.50) and 30-day mortality was 10 (4.4%) of 227 and 11 (5.0%) of 220 patients, respectively (P ϭ 0.83). Time to resumed bowel function was significantly in favor of allowing normal food at will (P ϭ 0.01), as were the total number of major complications, length of stay, and rate of postdischarge complications. Conclusions: Allowing patients to eat normal food at will from the first day after major upper GI surgery does not increase morbidity compared with traditional care with nil-by-mouth and enteral feeding. (Ann Surg 2008;247: 721-729) From the

Background: Eperisone hydrochloride, a centrally acting muscle relaxant, is a calcium antagonist that causes vasodilation and antispastic actions. Aceclofenac, an anti-inflammatory analgesic and antipyretic drug, has similar efficacy and improved gastrointestinal tolerance compared with other nonsteroidal antiinflammatory drugs, such as diclofenac. Although eperisone hydrochloride and aceclofenac are frequently coadministered, no published studies have reported on the pharmacokinetic interactions between these 2 drugs.