ASCEND-Eye: Effects of Aspirin on Diabetic Retinopathy.

PURPOSE: Preclinical studies support a protective role for aspirin in early diabetic retinopathy (DR), but the findings from randomized trials are limited. We present randomized evidence for the efficacy and safety of aspirin on DR outcomes. DESIGN: A substudy of the A Study of Cardiovascular Events in Diabetes (ASCEND) double-masked, randomized, placebo-controlled trial of 100 mg aspirin daily for the primary prevention of serious cardiovascular events in people with diabetes. PARTICIPANTS: Fifteen thousand four hundred eighty United Kingdom adults at least 40 years of age with diabetes. METHODS: Linkage to electronic National Health Service Diabetic Eye Screening Programme records in England and Wales and confirmation of participant-reported eye events via medical record review were carried out. Log-rank methods were used for intention-to-treat analyses of time until the first primary efficacy and safety outcomes. MAIN OUTCOME MEASURES: The primary efficacy end point was the first record of referable disease after randomization, a composite of referable retinopathy or referable maculopathy based on the grading criteria defined by the United Kingdom National Screening Committee. The primary safety outcome was the first sight-threatening eye bleed, defined as clinically significant bleeding in the eye that resulted in unresolved visual loss or required an urgent intervention such as laser photocoagulation, vitreoretinal surgery, intraocular injection, or a combination thereof. RESULTS: Linkage data were obtained for 7360 participants (48% of those randomized in ASCEND). During the mean follow-up of 6.5 years, 539 participants (14.6%) experienced a referable disease event in the aspirin group, compared with 522 participants (14.2%) in the placebo group (rate ratio, 1.03; 95% confidence interval [CI], 0.91-1.16; P = 0.64). No statistically significant between-group difference was found in the proportions of sight-threatening eye bleed events (57 participants [0.7%] and 64 participants [0.8%], respectively; rate ratio, 0.89; 95% CI, 0.62-1.27). DISCUSSION: These data exclude any clinically meaningful benefits of aspirin for DR, but give reassurance regarding the ophthalmologic safety of aspirin. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

ASCEND-Eye: Effects of Omega-3 Fatty Acids on Diabetic Retinopathy.

PURPOSE: Preclinical studies support a protective role for omega-3 fatty acids (FAs) on diabetic retinopathy (DR), but these observations have not been confirmed in randomized trials. We present randomized evidence for the effects of omega-3 FAs on DR outcomes. DESIGN: A substudy of the A Study of Cardiovascular Events iN Diabetes (ASCEND) double-blind, randomized, placebo-controlled trial of 1 g omega-3 fatty acids (containing 460 mg eicosapentaenoic acid and 380 mg docosahexaenoic acid) daily for the primary prevention of serious cardiovascular events, in 15 480 UK adults at least 40 years of age, with diabetes. PARTICIPANTS: Fifteen thousand four hundred eighty adults at least 40 years of age from the United Kingdom with diabetes from the ASCEND cohort. METHODS: Linkage to electronic National Health Service Diabetic Eye Screening Programme records in England and Wales and confirmation of participant-reported eye events via medical record review. Log-rank and stratified log-rank methods were used for intention-to-treat analyses of time until the main outcomes of interest. MAIN OUTCOME MEASURES: The primary efficacy endpoint was time to the first postrandomization recording of referable disease, a composite of referable retinopathy (R2 or R3a/s) or referable maculopathy (M1) based on the grading criteria defined by the United Kingdom National Screening Committee. Secondary and tertiary outcomes included the referable disease outcome stratified by the severity of DR at baseline, any progression in retinopathy grade, and incident diabetic maculopathy. RESULTS: Linkage data were obtained for 7360 participants (48% of those who were randomized in ASCEND). During their mean follow-up of 6.5 years, 548 participants (14.8%) had a referable disease event in the omega-3 FAs group, compared with 513 participants (13.9%) in the placebo group (rate ratio, 1.07; 95% confidence interval, 0.95-1.20; P = 0.29). There were no statistically significant between-group differences in the proportion of events for either of the secondary or tertiary outcomes. CONCLUSIONS: Representing the largest prospective test of its kind to date, these data exclude any clinically meaningful benefits of 1 g daily omega-3 FAs on DR. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comparison of Methods for Xenomonitoring in Vectors of Lymphatic Filariasis in Northeastern Tanzania.

Monitoring Wuchereria bancrofti infection in mosquitoes (xenomonitoring) can play an important role in determining when lymphatic filariasis has been eliminated, or in focusing control efforts. As mosquito infection rates can be low, a method for collecting large numbers of mosquitoes is necessary. Gravid traps collected large numbers of Culex quinquefasciatus in Tanzania, and a collection method that targets mosquitoes that have already fed could result in increased sensitivity in detecting W. bancrofti-infected mosquitoes. The aim of this experiment was to test this hypothesis by comparing U.S. Centers for Disease Control and Prevention (CDC) light traps with CDC gravid traps in northeastern Tanzania, where Cx. quinquefasciatus is a vector of lymphatic filariasis. After an initial study where small numbers of mosquitoes were collected, a second study collected 16,316 Cx. quinquefasciatus in 60 gravid trap-nights and 240 light trap-nights. Mosquitoes were pooled and tested for presence of W. bancrofti DNA. Light and gravid traps collected similar numbers of mosquitoes per trap-night, but the physiological status of the mosquitoes was different. The estimated infection rate in mosquitoes collected in light traps was considerably higher than in mosquitoes collected in gravid traps, so light traps can be a useful tool for xenomonitoring work in Tanzania.

Time-dependent wave selection for information processing in excitable media.

We demonstrate an improved technique for implementing logic circuits in light-sensitive chemical excitable media. The technique makes use of the constant-speed propagation of waves along defined channels in an excitable medium based on the Belousov-Zhabotinsky reaction, along with the mutual annihilation of colliding waves. What distinguishes this work from previous work in this area is that regions where channels meet at a junction can periodically alternate between permitting the propagation of waves and blocking them. These valvelike areas are used to select waves based on the length of time that it takes waves to propagate from one valve to another. In an experimental implementation, the channels that make up the circuit layout are projected by a digital projector connected to a computer. Excitable channels are projected as dark areas and unexcitable regions as light areas. Valves alternate between dark and light: Every valve has the same period and phase, with a 50% duty cycle. This scheme can be used to make logic gates based on combinations of or and and-not operations, with few geometrical constraints. Because there are few geometrical constraints, compact circuits can be implemented. Experimental results from an implementation of a four-bit input, two-bit output integer square root circuit are given.