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At Stanford University, all clinical notes (both inpatient and outpatient) have been transcribed and recorded electronically since 1994. These data are warehoused for research use in the Stanford Translational Research Integrated Database Environment (STRIDE). The de-identified subset of PF data used in our analysis contained data on 1.

The GenePAD cohort is comprised of individuals who underwent an elective, non-emergent coronary angiogram amoxicare 250 angina, shortness of breath or an Sofosbuvir and Velpatasvir Fixed-dose Combination Tablets (Epclusa)- Multum stress test at Stanford University or Mount Sinai Medical Centers.

Cardiovascular mortality was defined as that from myocardial infarction, cardiac arrest, stroke, heart failure or aneurysm rupture. Cardiovascular outcomes were assessed through medical record review and confirmed by contacting the patient or next of kin directly. Sofosbuvir and Velpatasvir Fixed-dose Combination Tablets (Epclusa)- Multum form of dual follow-up was specifically implemented to limit detection bias from differential frequencies in physician contact between groups.

Finally, all deaths were confirmed and cross-referenced to the SSDI to minimize detection bias. The study cohort commenced in 2004 and included 1,503 individuals. Note that such a data-mining procedure is not the same as performing an epidemiological study. Our data-mining approach, which aims to minimize false positives, has 97.

Drug terms were normalized to active ingredients using RxNorm, and classified according to the Anatomical Therapeutical Chemical classification system. Disease terms were normalized and Sofosbuvir and Velpatasvir Fixed-dose Combination Tablets (Epclusa)- Multum according to the hierarchical relationships from the Unified Medical Language System Metathesaurus and BioPortal.

The matrix (for STRIDE) comprises nearly a trillion pieces of data-roughly, 1. GERD is the primary indication for PPIs, so we used the presence of this indication to define the baseline population in our pipeline. Sofosbuvir and Velpatasvir Fixed-dose Combination Tablets (Epclusa)- Multum excluded all patients under the age of 18 at their first GERD mention. We defined GERD by International Classification of Diseases, Ninth Revision (ICD-9) codes for esophageal reflux (530.

The main outcome of interest, MI, was defined central core acute myocardial infarction (ICD-9 code 410), and more than 18 different UMLS codes including myocardial infarction (C0027051) and silent myocardial infarction (C0340324). See S1 Table for full definitions. The study period included all data from 1994 through 2011 in STRIDE and 2007 through 2012 in PF. We defined two study groups within the GERD baseline population in this period.

The primary study group was the subset defined by patients taking PPIs, including a sub-group of those patients who were not on clopidogrel. We considered six PPIs (omeprazole, lansoprazole, pantoprazole, esomeprazole, rabeprazole, and dexlansoprazole) individually and as a class. We excluded dexlansoprazole from individual analysis because of insufficient exposure (The summary of the data-mining pipeline shown in the S1 Fig outlines the decisions used in the data-mining pipeline to populate a contingency table for each of the associations tested.

For example, a mention of PPI use after a GERD indication would be counted as an exposure. A subsequent mention of MI counts as an associated outcome.

First we compute a raw association, followed by adjustment which involves matching on age, gender, race, length of observation, and, as proxies for health status, the number Somatropin [rDNA origin] (Genotropin)- Multum unique drug and disease concepts mentioned in the full record.

The first step Sofosbuvir and Velpatasvir Fixed-dose Combination Tablets (Epclusa)- Multum useful for flagging fertility signals, and the second step in reducing false alarms. As in prior work, we attempted to match up to 5 controls.

In cases where there are not enough controls to draw from, we tried either 1:3 or finally 1:1 matching (Table 1). The balance of variables before and after matching for the PPI study group is shown in Table 2. The balance of variables for the H2Bs study group is shown in Table 3. Adjusted models included age, gender, race, total Sofosbuvir and Velpatasvir Fixed-dose Combination Tablets (Epclusa)- Multum, high-density lipoprotein cholesterol, systolic blood pressure, use of anti-hypertension medications, and lifetime pack-years.

In our study the primary population of interest is patients with GERD. We find that the class-level association of PPIs with MI in patients treated for GERD exists across two independent datasets and is independent of clopidogrel use and high-risk age groups.

By comparison, we find no association with MI in GERD patients treated with H2Bs in the same dataset. All patients with GERD above the age of 18, representing the general population likely to take a PPI, comprise the baseline population for our studies. The two study groups include patients exposed to PPIs, and, for comparison, patients exposed to H2Bs. Table 1 summarizes the characteristics of the baseline and study populations for the primary dataset from Stanford, called STRIDE.



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