Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

Background Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens — aspirin plus extendedrelease dipyridamole (ASA–ERDP) versus clopidogrel. Methods In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. Results A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA–ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA–ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA–ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA–ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). Conclusions The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA–ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)

An evolutionary squeaky wheel optimisation approach to personnel scheduling

The quest for robust heuristics that are able to solve more than one problem is ongoing. In this paper, we present, discuss and analyse a technique called Evolutionary Squeaky Wheel Optimisation and apply it to two different personnel scheduling problems. Evolutionary Squeaky Wheel Optimisation improves the original Squeaky Wheel Optimisation’s effectiveness and execution speed by incorporating two additional steps (Selection and Mutation) for added evolution. In the Evolutionary Squeaky Wheel Optimisation, a cycle of Analysis-Selection-Mutation-Prioritization-Construction continues until stopping conditions are reached. The aim of the Analysis step is to identify below average solution components by calculating a fitness value for all components. The Selection step then chooses amongst these underperformers and discards some probabilistically based on fitness. The Mutation step further discards a few components at random. Solutions can become incomplete and thus repairs may be required. The repair is carried out by using the Prioritization step to first produce priorities that determine an order by which the following Construction step then schedules the remaining components. Therefore, improvements in the Evolutionary Squeaky Wheel Optimisation is achieved by selective solution disruption mixed with iterative improvement and constructive repair. Strong experimental results are reported on two different domains of personnel scheduling: bus and rail driver scheduling and hospital nurse scheduling.