28 research outputs found
Managing Edit Checks and Database Cleaning with Stata
We have developed a set of ado-files for use in data management, specifically designed to manage user-written edit checks and to complement the process of data cleaning. Collectively, these tools enable us to identify, distribute, and track edit-checks in several large multi-center clinical trials using Stata software. Our approach is successful because the coding is simple and the entire process is visible and familiar to most users. It does not depend on any particular database structure. The framework approximates an object-oriented environment, with the objects being (a) the database, open at the time a command is called, (b) an edit-check, consisting of a Stata do-file, a query message and a list of variables to be identified for review, and (c) the edit-check history, implemented as a Stata dataset. These objects can be manipulated directly or by using a command in Stata. Actions managed by command include creating or modifying an edit-check, generating a query-clean dataset, preparing and tracking a set of edit-check documents, and summarizing the edit-check history. Here, we present a brief overview of our process and describe the use of the commands in the context of clinical research.
Chemotherapy weakly contributes to predicted neoantigen expression in ovarian cancer
Abstract Background Patients with highly mutated tumors, such as melanoma or smoking-related lung cancer, have higher rates of response to immune checkpoint blockade therapy, perhaps due to increased neoantigen expression. Many chemotherapies including platinum compounds are known to be mutagenic, but the impact of standard treatment protocols on mutational burden and resulting neoantigen expression in most human cancers is unknown. Methods We sought to quantify the effect of chemotherapy treatment on computationally predicted neoantigen expression for high grade serous ovarian carcinoma patients enrolled in the Australian Ovarian Cancer Study. In this series, 35 of 114 samples were collected after exposure to chemotherapy; 14 are matched with an untreated sample from the same patient. Our approach integrates whole genome and RNA sequencing of bulk tumor samples with class I MHC binding prediction and mutational signatures extracted from studies of chemotherapy-exposed Caenorhabditis elegans and Gallus gallus cells. We additionally investigated the relationship between neoantigens, tumor infiltrating immune cells estimated from RNA-seq with CIBERSORT, and patient survival. Results Greater neoantigen burden and CD8+ T cell infiltration in primary, pre-treatment samples were independently associated with improved survival. Relapse samples collected after chemotherapy harbored a median of 78% more expressed neoantigens than untreated primary samples, a figure that combines the effects of chemotherapy and other processes operative during relapse. The contribution from chemotherapy-associated signatures was small, accounting for a mean of 5% (range 0–16) of the expressed neoantigen burden in relapse samples. In both treated and untreated samples, most neoantigens were attributed to COSMIC Signature (3), associated with BRCA disruption, Signature (1), associated with a slow mutagenic process active in healthy tissue, and Signature (8), of unknown etiology. Conclusion Relapsed ovarian cancers harbor more predicted neoantigens than primary tumors, but the increase is due to pre-existing mutational processes, not mutagenesis from chemotherapy
Effect of prasugrel versus clopidogrel on outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention without stent implantation: A TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel (TRITON)-Thrombolysis in Myocardial Infarction (TIMI) 38 Substudy
Background Prasugrel led to a significant reduction in ischemic cardiovascular events among patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PC]) with stent implantation compared to clopidogrel. Whether this benefit extends to patients undergoing PCI without stent implantation is unknown
Additional file 4 of Chemotherapy weakly contributes to predicted neoantigen expression in ovarian cancer
Supplemental figures. Figures S1Ă¢Â€Â“S11. (PDF 798 kb
Additional file 3 of Chemotherapy weakly contributes to predicted neoantigen expression in ovarian cancer
HLA types. Patient HLA types. (CSV 5 kb
Revue de l'instruction publique en France et dans les pays Ă©trangers
28 juin 18551855/06/28 (A15,N13)-1855/06/28