Generating Practice-Based Evidence in the Use of Guideline-Recommended Combination Therapy for Secondary Prevention of Acute Myocardial Infarction

Background: Clinical guidelines recommend beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers, and statins for the secondary prevention of acute myocardial infarction (AMI). It is not clear whether variation in real-world practice reflects poor quality-of-care or a balance of outcome tradeoffs across patients. Methods: The study cohort included Medicare fee-for-service beneficiaries hospitalized 2007–2008 for AMI. Treatment within 30-days post-discharge was grouped into one of eight possible combinations for the three drug classes. Outcomes included one-year overall survival, one-year cardiovascular-event-free survival, and 90-day adverse events. Treatment effects were estimated using an Instrumental Variables (IV) approach with instruments based on measures of local-area practice style. Pre-specified data elements were abstracted from hospital medical records for a stratified, random sample to create “unmeasured confounders” (per claims data) and assess model assumptions. Results: Each drug combination was observed in the final sample (N = 124,695), with 35.7% having all three, and 13.5% having none. Higher rates of guideline-recommended treatment were associated with both better survival and more adverse events. Unmeasured confounders were not associated with instrumental variable values. Conclusions: The results from this study suggest that providers consider both treatment benefits and harms in patients with AMIs. The investigation of estimator assumptions support the validity of the estimates

Reconstruction of fish allergenicity from the content and structural traits of the component β-parvalbumin isoforms

12 pages, 7 figures.-- This article is licensed under a Creative Commons Attribution 4.0 International LicenseMost fish-allergic patients have anti-β-parvalbumin (β-PV) immunoglobulin E (IgE), which cross-reacts among fish species with variable clinical effects. Although the β-PV load is considered a determinant for allergenicity, fish species express distinct β-PV isoforms with unknown pathogenic contributions. To identify the role various parameters play in allergenicity, we have taken Gadus morhua and Scomber japonicus models, determined their β-PV isoform composition and analyzed the interaction of the IgE from fish-allergic patient sera with these different conformations. We found that each fish species contains a major and a minor isoform, with the total PV content four times higher in Gadus morhua than in Scomber japonicus. The isoforms showing the best IgE recognition displayed protease-sensitive globular folds, and if forming amyloids, they were not immunoreactive. Of the isoforms displaying stable globular folds, one was not recognized by IgE under any of the conditions, and the other formed highly immunoreactive amyloids. The results showed that Gadus morhua muscles are equipped with an isoform combination and content that ensures the IgE recognition of all PV folds, whereas the allergenic load of Scomber japonicus is under the control of proteolysis. We conclude that the consideration of isoform properties and content may improve the explanation of fish species allergenicity differencesThis work was supported by grants from the Spanish AEI/EU-FEDER SAF2014-52661-C3 (MG) and BFU2015- 72271-EXP (MG), Angulas Aguinaga (MG, RRP) contract and the Ramón Areces Foundation (MC). MC is a Ramón y Cajal fellowPeer reviewe