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In this international, randomized trial, patients with minor stroke or TIA who received clopidogrel plus aspirin had a lower risk of major ischemic events but a higher risk of major hemorrhage at 90 days than those who received aspirin alone.

In this double-blind, randomized trial involving 13,199 patients with ischemic stroke or transient ischemic attack, ticagrelor was not superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. Ischemic stroke and transient ischemic attack are common, and the risk of subsequent ischemic events is particularly high during the first 90 days after the index cerebrovascular event. 1 – 4 Aspirin at a dose of 50 to 325 mg daily is commonly used in this context. 5 – 7 However, the benefit of aspirin in the secondary prevention of ischemic stroke is limited; even with concurrent aspirin treatment, the rate of recurrent stroke is 10 to 15% in the first 90 days, and the rate of new ischemic events when aspirin is used in the long term is only 22% lower than the . . .

A trial involving 11,016 patients showed that the combination of ticagrelor and aspirin after a stroke or high-risk transient ischemic attack was better than aspirin alone in preventing a stroke or death within 30 days. Severe bleeding was rare but occurred more frequently in the dual antiplatelet group.

In a trial in China, patients with a minor stroke or transient ischemic attack with CYP2C19 loss-of-function alleles as determined by point-of-care testing had modestly fewer second strokes with ticagrelor than with clopidogrel but also had more total bleeding events.

Social distancing orders have been enacted worldwide to slow the coronavirus disease (COVID-19) pandemic, reduce strain on healthcare systems, and prevent deaths. To estimate the impact of the timing and intensity of such measures, we built a mathematical model of COVID-19 transmission that incorporates age-stratified risks and contact patterns and projects numbers of hospitalizations, patients in intensive care units, ventilator needs, and deaths within US cities. Focusing on the Austin metropolitan area of Texas, we found that immediate and extensive social distancing measures were required to ensure that COVID-19 cases did not exceed local hospital capacity by early May 2020. School closures alone hardly changed the epidemic curve. A 2-week delay in implementation was projected to accelerate the timing of peak healthcare needs by 4 weeks and cause a bed shortage in intensive care units. This analysis informed the Stay Home-Work Safe order enacted by Austin on March 24, 2020.

Inbreeding depression is ubiquitous, but we still know little about its genetic architecture and precise effects in wild populations. Here, we combine long-term life-history data with 417 K imputed SNP genotypes for 5952 wild Soay sheep to explore inbreeding depression on a key fitness component, annual survival. Inbreeding manifests in long runs of homozygosity (ROH), which make up nearly half of the genome in the most inbred individuals. The ROH landscape varies widely across the genome, with islands where up to 87% and deserts where only 4% of individuals have ROH. The fitness consequences of inbreeding are severe; a 10% increase in individual inbreeding F ROH is associated with a 60% reduction in the odds of survival in lambs, though inbreeding depression decreases with age. Finally, a genome-wide association scan on ROH shows that many loci with small effects and five loci with larger effects contribute to inbreeding depression in survival. Without understanding the genetic architecture of inbreeding depression, its effects are hard to pinpoint. Long-term data from wild Soay sheep shows that inbreeding manifests in long runs of homozygosity, which made up nearly half of the genome in the most inbred individuals with severe fitness consequences.

Decision makers must have sufficient confidence in models if they are to influence their decisions. We propose three screening questions to critically evaluate models with respect to their purpose, organization, and evidence. They enable a more transparent, robust, and secure use of model outputs.

New stroke occurred in 7% of patients who received clopidogrel–aspirin and in 9% who received only aspirin up to 72 hours after atherothrombotic stroke. Bleeding incidence was low but higher with dual antiplatelet treatment.

In this trial involving patients with minor stroke or transient ischemic attack, treatment with a combination of clopidogrel and aspirin within 24 hours after onset reduced the risk of stroke in the next 90 days, as compared with aspirin alone. Transient ischemic attack (TIA) and acute minor ischemic stroke are common and often lead to disabling events. In China, there are approximately 3 million new strokes every year, and approximately 30% of them are minor ischemic strokes. 1 , 2 The incidence of TIA in China has not been determined, but on the basis of the incidence in other countries, there are probably more than 2 million TIAs annually in China. 3 – 5 The risk of another stroke occurring after a TIA or minor stroke is high, with approximately 10 to 20% of patients having a stroke within 3 months after the index . . .

AbstractObjectiveTo test the hypothesis that ticagrelor plus aspirin is safe and superior to clopidogrel plus aspirin for reducing high platelet reactivity at 90 days and stroke recurrence in patients with minor stroke or transient ischaemic attack, particularly in carriers of the CYP2C19 loss-of-function allele and patients with large artery atherosclerosis.DesignOpen label, blinded endpoint, randomised controlled phase II trial.SettingProspective studies conducted at 26 centres in China, August 2015 to March 2017.Participants675 patients with acute minor stroke or transient ischaemic attack.InterventionTicagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 mg loading dose, 75 mg daily thereafter) on a background of aspirin (100 mg daily for the first 21 days) within 24 hours of symptom onset.Main outcome measuresPrimary outcome was the proportion of patients with high platelet reactivity at 90 days. High platelet reactivity was defined as P2Y12 reaction units of more than 208. Secondary outcomes included high platelet reactivity at 90 days (7 days either way) in patients carrying genetic variants that would affect clopidogrel metabolism, and any stroke (ischaemic or haemorrhagic) recurrence at 90 days (7 days either way), six months, and one year.ResultsAt 90 days, high platelet reactivity occurred in 35 (12.5%) of 280 patients in the ticagrelor/aspirin group and 86 (29.7%) of 290 patients in the clopidogrel/aspirin group (risk ratio 0.40; 95% confidence interval 0.28 to 0.56; P<0.001), and in 10.8% versus 35.4% (0.31; 0.18 to 0.49; P<0.001) of patients carrying CYP2C19 loss-of-function alleles. Stroke occurred in 21 (6.3%) of 336 patients in the ticagrelor/aspirin group and 30 (8.8%) of 339 patients in the clopidogrel/aspirin group (hazard ratio 0.70; 95% confidence interval 0.40 to 1.22; P=0.20). Patients with large artery atherosclerosis in the ticagrelor/aspirin group had a lower stroke recurrence at 90 days than those in the clopidogrel/aspirin group (6.0% v 13.1%; hazard ratio 0.45, 95% confidence interval 0.20 to 0.98; P=0.04). No difference was seen in the rates of major or minor haemorrhagic events between the ticagrelor/aspirin and clopidogrel/aspirin groups (4.8% v 3.5%; P=0.42).ConclusionPatients with minor stroke or transient ischaemic attack who are treated with ticagrelor plus aspirin have a lower proportion of high platelet reactivity than those who are treated with clopidogrel plus aspirin, particularly for those who are carriers of the CYP2C19 loss-of-function allele. The results of this study should be evaluated further in large scale, phase III trials and in different populations.Trial registrationClinicaltrials.gov NCT02506140.