Ticagrelor Versus Clopidogrel in Patients With STEMI Treated With Fibrinolysis: TREAT Trial

BackgroundThe efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.ObjectivesThe purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.MethodsThis international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months.ResultsThe combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.ConclusionAmong patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088)     

Dose optimization of moxifloxacin and linezolid against tuberculosis using mathematical modeling and simulation

Introduction

There is an urgent need for new anti-tuberculosis (TB) drugs and optimization of current TB treatment. Moxifloxacin and linezolid are valuable options for the treatment of drug-resistant TB; however, it is crucial to find a dose at which these drugs not only show high efficacy but also suppress the development of further drug resistance.

Treatment Experiences,Information Needs,Pain and Quality of Life in Men with Metastatic Castrate-resistant Prostate Cancer: Results from the EXTREQOL Study

Aims

Delaying progression, ameliorating symptoms and maintaining quality of life (QoL) are primary aims of treatment for metastatic castrate-resistant prostate cancer (mCRPC). Real-world rather than clinical trial data about symptoms and side-effects are sparse. In EXTREQOL, patients' QoL, pain and information needs were recorded during treatment.

Prediction modelling using routine clinical parameters to stratify survival in Malignant Pleural Mesothelioma patients undergoing cytoreductive surgery

Introduction

Malignant pleural mesothelioma (MPM) is an uncommon cancer with a poor prognosis and heterogeneous survival. Surgery for MPM is offered in some specialist centers to highly selected patients. A previously described classification and regression tree (CART) model stratified survival in unselected MPM patients using routinely collected clinical data. This study aimed to examine the performance of this CART model on a highly selected surgical population.

locStra: Fast analysis of regional/global stratification in whole‐genome sequencing studies

locStra is an ‐package for the analysis of regional and global population stratification in whole‐genome sequencing (WGS) studies, where regional stratification refers to the substructure defined by the loci in a particular region on the genome. Population substructure can be assessed based on the genetic covariance matrix, the genomic relationship matrix, and the unweighted/weighted genetic Jaccard similarity matrix. Using a sliding window approach, the regional similarity matrices are compared with the global ones, based on user‐defined window sizes and metrics, for example, the correlation between regional and global eigenvectors. An algorithm for the specification of the window size is provided. As the implementation fully exploits sparse matrix algebra and is written in C++, the analysis is highly efficient. Even on single cores, for realistic study sizes (several thousand subjects, several million rare variants per subject), the runtime for the genome‐wide computation of all regional similarity matrices does typically not exceed one hour, enabling an unprecedented investigation of regional stratification across the entire genome. The package is applied to three WGS studies, illustrating the varying patterns of regional substructure across the genome and its beneficial effects on association testing.     

Standardizing Postoperative Complications—Validating the Clavien-Dindo Complications Classification in Cardiac Surgery

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A hotspot mutation in transcription factor IKZF3 drives B cell neoplasia via transcriptional dysregulation

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Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

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