Anesthesiology
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Design, Synthesis, and Pharmacological Evaluation of Ultrashort- to Long-acting Opioid Analgetics. By Feldman PL, James MK, Brackeen MF, Bilotta JM, Schuster SV, Lahey AP, Lutz MW, Johnson MR, Leighton HJ. J Med Chem 1991; 34:2202-8. ⋯ The discrepancies between the in vitro and in vivo activities and variations in duration of action are probably due to different rates of ester hydrolysis by blood esterase(s). The [structure-activity relationships] with respect to analgesic activity and duration of action as a function of the various esters synthesized is discussed. It was also demonstrated that the duration of action for the ultrashort-acting analgetic, 8, does not change upon prolonged infusion or administration of multiple bolus injections.
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Making good decisions in the era of Big Data requires a sophisticated approach to causality. We are acutely aware that association ≠ causation, yet untangling the two remains one of our greatest challenges. This realization has stimulated a Causal Revolution in epidemiology, and the lessons learned are highly relevant to anesthesia research. ⋯ We also illustrate how controlling for the wrong variables can introduce, rather than eliminate, bias; and how directed acyclic graphs can help us diagnose this problem. This is a rapidly evolving field, and we cover only the most basic elements. The true promise of these techniques is that it may become possible to make robust statements about causation from observational studies-without the expense and artificiality of randomized controlled trials.