Nuisance Bleeding With Prolonged Dual Antiplatelet Therapy After Acute Myocardial Infarction and its Impact on Health Status

ObjectivesThe purpose of this study was to examine the incidence of nuisance bleeding after AMI and its impact on QOL.BackgroundProlonged dual antiplatelet therapy (DAPT) is recommended after acute myocardial infarction (AMI) to reduce ischemic events, but it is associated with increased rates of major and minor bleeding. The incidence of even lesser degrees of post-discharge “nuisance” bleeding with DAPT and its impact on quality of life (QOL) are unknown.MethodsData from the 24-center TRIUMPH (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status) study of 3,560 patients, who were interviewed at 1, 6, and 12 months after AMI, were used to investigate the incidence of nuisance bleeding (defined as Bleeding Academic Research Consortium type 1). Baseline characteristics associated with “nuisance” bleeding and its association with QOL, as measured by the EuroQol 5 Dimension visual analog scale, and subsequent re-hospitalization were examined.ResultsNuisance (Bleeding Academic Research Consortium type 1) bleeding occurred in 1,335 patients (37.5%) over the 12 months after AMI. After adjusting for baseline bleeding and mortality risk, ongoing DAPT was the strongest predictor of nuisance bleeding (rate ratio [RR]: 1.44, 95% confidence interval [CI]: 1.17 to 1.76 at 1 month; RR: 1.89, 95% CI: 1.35 to 2.65 at 6 months; and RR: 1.39, 95% CI: 1.08 to 1.79 at 12 months; p < 0.01 for all comparisons). Nuisance bleeding at 1 month was independently associated with a decrement in QOL at 1 month (−2.81 points on EuroQol 5 Dimension visual analog scale; 95% CI: 1.09 to 5.64) and nonsignificantly toward higher re-hospitalization (hazard ratio: 1.20; 95% CI: 0.95 to 1.52).ConclusionsNuisance bleeding is common in the year after AMI, associated with ongoing use of DAPT, and independently associated with worse QOL. Improved selection of patients for prolonged DAPT may help minimize the incidence and adverse consequences of nuisance bleeding

Nuisance Bleeding With Prolonged Dual Antiplatelet Therapy After Acute Myocardial Infarction and its Impact on Health Status

ObjectivesThe purpose of this study was to examine the incidence of nuisance bleeding after AMI and its impact on QOL.BackgroundProlonged dual antiplatelet therapy (DAPT) is recommended after acute myocardial infarction (AMI) to reduce ischemic events, but it is associated with increased rates of major and minor bleeding. The incidence of even lesser degrees of post-discharge “nuisance” bleeding with DAPT and its impact on quality of life (QOL) are unknown.MethodsData from the 24-center TRIUMPH (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status) study of 3,560 patients, who were interviewed at 1, 6, and 12 months after AMI, were used to investigate the incidence of nuisance bleeding (defined as Bleeding Academic Research Consortium type 1). Baseline characteristics associated with “nuisance” bleeding and its association with QOL, as measured by the EuroQol 5 Dimension visual analog scale, and subsequent re-hospitalization were examined.ResultsNuisance (Bleeding Academic Research Consortium type 1) bleeding occurred in 1,335 patients (37.5%) over the 12 months after AMI. After adjusting for baseline bleeding and mortality risk, ongoing DAPT was the strongest predictor of nuisance bleeding (rate ratio [RR]: 1.44, 95% confidence interval [CI]: 1.17 to 1.76 at 1 month; RR: 1.89, 95% CI: 1.35 to 2.65 at 6 months; and RR: 1.39, 95% CI: 1.08 to 1.79 at 12 months; p < 0.01 for all comparisons). Nuisance bleeding at 1 month was independently associated with a decrement in QOL at 1 month (−2.81 points on EuroQol 5 Dimension visual analog scale; 95% CI: 1.09 to 5.64) and nonsignificantly toward higher re-hospitalization (hazard ratio: 1.20; 95% CI: 0.95 to 1.52).ConclusionsNuisance bleeding is common in the year after AMI, associated with ongoing use of DAPT, and independently associated with worse QOL. Improved selection of patients for prolonged DAPT may help minimize the incidence and adverse consequences of nuisance bleeding

CRT-100.12 Risk of Bleeding Among Cangrelor-Treated Patients Administered Upstream P2Y12 Inhibitor Therapy

Introduction: Little is known about the use of cangrelor in patients with MI who are treated with an oral P2Y12 inhibitor upstream prior to cardiac catheterization. Methods: CAMEO (Cangrelor in Acute MI: Effectiveness and Outcomes) is a 12-hospital observational registry studying platelet inhibition for MI patients undergoing cardiac cath. Upstream oral P2Y12 inhibition was defined as receipt of an oral P2Y12 inhibitor within 24 hours prior to hospitalization or in-hospital prior to cath. Among cangrelor-treated patients, we compared bleeding after cangrelor use through 7 days post-discharge between patients with and w/o upstream oral P2Y12 inhibitor exposure using logistic regression. We examined rates of bleeding among patients with a shorter (\u3c1 hour) vs. longer (1-3 hours or \u3e3 hours) duration between the last oral dose and cangrelor start. Results: Among 1,775 cangrelor-treated MI patients, 433 (24.4%) had upstream oral P2Y12 inhibitor treatment prior to cath. Of these, 165 patients (38%) started cangrelor within 1 hour, 109 (25%) between 1-3 hours, and 134 (31%) \u3e 3 hours after the in-hospital oral P2Y12 inhibitor dose. Cangrelor-treated patients who received upstream treatment were more likely to have a history of prior PCI, MI, PAD, and diabetes and to be clopidogrel-treated (all p\u3c0.01) compared w/o upstream treatment. There was no significant difference in risk of bleeding among cangrelor-treated patients with and w/o upstream oral P2Y12 inhibitor exposure (Table). While bleeding events were higher in patients with longer delays to cangrelor initiation, bleeding risk was not significant after adjustment (Table). Conclusions: Bleeding risk was not observed to be higher in cangrelor-treated patients after upstream oral P2Y12 inhibitor exposure compared with patients treated with cangrelor w/o upstream oral P2Y12 inhibitor exposure

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

The full-of-bacteria gene is required for phagosome maturation during immune defense in Drosophila

Drosophila fob encodes a homolog of the Vps16 HOPS complex subunit, required for phagosome maturation and digestion of engulfed pathogens

The Neurocognition of Prosody

Prosody is one of the most undervalued components of language, despite its fulfillment of manifold purposes. It can, for instance, help assign the correct meaning to compounds such as “white house” (linguistic function), or help a listener understand how a speaker feels (emotional function). However, brain-based models that take into account the role prosody plays in dynamic speech comprehension are still rare. This is probably due to the fact that it has proven difficult to fully denote the neurocognitive architecture underlying prosody. This review discusses clinical and neuroscientific evidence regarding both linguistic and emotional prosody. It will become obvious that prosody processing is a multistage operation and that its temporally and functionally distinct processing steps are anchored in a functionally differentiated brain network