Similar cardiovascular outcomes in patients with diabetes and established or high risk for coronary vascular disease treated with dulaglutide with and without baseline metformin / Desfechos cardiovasculares semelhantes em pacientes com diabetes e risco estabelecido ou alto para doença vascular coronariana tratada com dulaglutida com e sem linha de base metformina

Objective Recent European Guidelines for Diabetes, Prediabetes and Cardiovascular Diseases introduced a shift in managing patients with type 2 diabetes at high risk for or established cardiovascular (CV) disease by recommending GLP-1 receptor agonists and SGLT-2 inhibitors as initial glucose-lowering therapy. This is questioned since outcome trials of these drug classes had metformin as background therapy. In this post hoc analysis, the effect of dulaglutide on CV events was investigated according to the baseline metformin therapy by means of a subgroup analysis of the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial. Research design and methods Patients in REWIND (n = 9901; women: 46.3%; mean age: 66.2 years) had type 2 diabetes and either a previous CV event (31%) or high CV risk (69%). They were randomized (1:1) to sc. dulaglutide (1.5 mg/weekly) or placebo in addition to standard of care. The primary outcome was the first of a composite of nonfatal myocardial infarction, nonfatal stroke, and death from cardiovascular or unknown causes. Key secondary outcomes included a microvascular composite endpoint, all-cause death, and heart failure. The effect of dulaglutide in patients with and without baseline metformin was evaluated by a Cox regression hazard model with baseline metformin, dulaglutide assignment, and their interaction as independent variables. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by a Cox regression model with adjustments for factors differing at baseline between people with vs. without metformin, identified using the backward selection. Results Compared to patients with metformin at baseline (n = 8037; 81%), those without metformin (n = 1864; 19%) were older and slightly less obese and had higher proportions of women, prior CV events, heart failure, and renal disease. The primary outcome occurred in 976 (12%) participants with baseline metformin and in 281 (15%) without. There was no significant difference in the effect of dulaglutide on the primary outcome in patients with vs. without metformin at baseline [HR 0.92 (CI 0.81­1.05) vs. 0.78 (CI 0.61­0.99); interaction P = 0.18]. Findings for key secondary outcomes were similar in patients with and without baseline metformin. Conclusion This analysis suggests that the cardioprotective effect of dulaglutide is unaffected by the baseline use of metformin therapy.

Similar cardiovascular outcomes in patients with diabetes and established or high risk for coronary vascular disease treated with dulaglutide with and without baseline metformin.

OBJECTIVE: Recent European Guidelines for Diabetes, Prediabetes and Cardiovascular Diseases introduced a shift in managing patients with type 2 diabetes at high risk for or established cardiovascular (CV) disease by recommending GLP-1 receptor agonists and SGLT-2 inhibitors as initial glucose-lowering therapy. This is questioned since outcome trials of these drug classes had metformin as background therapy. In this post hoc analysis, the effect of dulaglutide on CV events was investigated according to the baseline metformin therapy by means of a subgroup analysis of the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial. RESEARCH DESIGN AND METHODS: Patients in REWIND (n = 9901; women: 46.3%; mean age: 66.2 years) had type 2 diabetes and either a previous CV event (31%) or high CV risk (69%). They were randomized (1:1) to sc. dulaglutide (1.5 mg/weekly) or placebo in addition to standard of care. The primary outcome was the first of a composite of nonfatal myocardial infarction, nonfatal stroke, and death from cardiovascular or unknown causes. Key secondary outcomes included a microvascular composite endpoint, all-cause death, and heart failure. The effect of dulaglutide in patients with and without baseline metformin was evaluated by a Cox regression hazard model with baseline metformin, dulaglutide assignment, and their interaction as independent variables. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by a Cox regression model with adjustments for factors differing at baseline between people with vs. without metformin, identified using the backward selection. RESULTS: Compared to patients with metformin at baseline (n = 8037; 81%), those without metformin (n = 1864; 19%) were older and slightly less obese and had higher proportions of women, prior CV events, heart failure, and renal disease. The primary outcome occurred in 976 (12%) participants with baseline metformin and in 281 (15%) without. There was no significant difference in the effect of dulaglutide on the primary outcome in patients with vs. without metformin at baseline [HR 0.92 (CI 0.81-1.05) vs. 0.78 (CI 0.61-0.99); interaction P = 0.18]. Findings for key secondary outcomes were similar in patients with and without baseline metformin. CONCLUSION: This analysis suggests that the cardioprotective effect of dulaglutide is unaffected by the baseline use of metformin therapy.

Estimating the potential effects of pesticide seed treatments on the reproductive success of arable birds.

In temperate zones, seeds of spring-sown crops may be an attractive food source for breeding farmland birds. We modelled the effects of pesticide seed treatments on the reproductive success of 4 UK arable bird species (Rook, Linnet, Skylark, Yellowhammer) exposed to treated seeds of 3 spring-sown crops (beans, barley and linseed). We ran three types of model, 1) a "broods-at-risk" model looking at the temporal overlap between nesting and seed-sowing dates, and estimating the proportion of those nests that suffered toxicity-exposure ratios < 5; 2) a "seasonal success" Markov chain model estimating the number of chicks successfully raised in the course of a breeding season.; and 3) the potential effects of pesticides on population growth rates. Based on physiology, Rooks, should be less at risk from treated seeds than smaller species because bigger birds eat less as a proportion of their bodyweights. However, in nearly all our scenarios, Rooks were more vulnerable, followed by Skylark and Linnet, with Yellowhammer being least affected. A principal cause is that Rooks are more likely to be breeding at a time when treated seeds are being sown. Furthermore, whereas the other species may make several breeding attempts and early failures from pesticide exposure may be compensated by later successes, Rooks breed only once in a season. The results are also supported by historical evidence of Rook population declines following pesticide seed treatments.

Reflections on bird and mammal risk assessment for plant protection products in the European Union: Past, present, and future.

The use of plant protection products on agricultural crops can result in exposure of birds and mammals to toxic chemicals. In the European Union, the risks from such exposures are assessed under the current (2009) guidance document from the European Food Safety Authority (EFSA), designed to increase the realism of the theoretical risk assessments in comparison to its predecessor (SANCO/4145/2000). Since its adoption over 7 yr ago, many plant protection products have been evaluated successfully using the 2009 EFSA guidance document. However, there are still significant areas of improvement recommended for future revisions of this guidance. The present Focus article discusses experiences to date with the current scheme, including levels of conservatism in input parameters and interpretation by regulatory authorities together with proposals for how the guidance document could be improved when it is revised in the not too distant future. Several areas for which further guidance is recommended have been identified, such as the derivation of ecologically relevant bird and mammal reproductive endpoints and the use of modeling approaches to contextualize risk assessments. Areas where existing databases could be improved were also highlighted, including the collation of relevant focal species across Europe and expansion of the residue database for food items. To produce a realistic and useable guidance document in the future, it is strongly recommended that there is open and constructive communication between industry, regulatory authorities, and the EFSA. Such collaboration would also encourage harmonization between member states, thus reducing workloads for both industry and regulatory authorities. Environ Toxicol Chem 2017;36:565-575. © 2017 SETAC.

Orthodontic outreach clinics--no marked advantages or disadvantages.

DESIGN: Single centre randomised controlled trial. INTERVENTION: Allocation of referred patients to outreach or main base consultation appointments. OUTCOME MEASURE: The outcome of consultation, the cost and duration of the visit and the carer/patient's perceptions of the visit. RESULTS: There were no differences in outcome of the consultation. While consumer travel costs and the duration of appointments were significantly higher for the main base clinics, these differences were not great. However, consumers preferred to attend an appointment in an outreach clinic. CONCLUSIONS: There do not appear to be marked advantages or disadvantages in providing consultation appointments for orthodontics in outreach clinics.

Dental health educators in general practice have small impact.

DESIGN: A cluster randomised, controlled clinical trial of two years' duration. INTERVENTION: Test group were given visits to a dental health educator over a 2-year period to counsel mothers of at-risk, pre-school children. OUTCOME MEASURE: Caries prevalence of the children and dental health knowledge, attitudes and toothbrushing skills of the parents. The full costs of the exercise were kept throughout. RESULTS: After 2 years, 271 (81%) children and 248 (92%) mothers remained in the study. There was an 18% difference in mean dmft between the groups in favour of the test group children but this was not statistically significant. CONCLUSIONS: The model tested of seconding a qualified dental health educator to general dental practices to counsel mothers of regularly attending, at-risk, young children failed to reveal a substantial improvement in dental health over a 2-year period. However, there were clear benefits in relation to dental health knowledge, attitudes and toothbrushing skills among these mothers.