The Annals of pharmacotherapy
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With the release of the updated pain, agitation, and delirium guidelines by the Society of Critical Care Medicine, a number of new and updated recommendations are provided regarding the pharmacological prevention and treatment of ICU delirium. Whereas this is important to understand the limitations of existing literature in interpreting the guideline recommendations, it also provides an opportunity to identify those areas of practice where we need further knowledge. We discuss 5 of the most critical questions in our view regarding pharmacological therapy for ICU delirium in an attempt to highlight areas of this ICU condition that are much deserving of further research, including the deliriogenic potential of dexmedetomidine, optimal sedative choices for the delirious ICU patient, pharmacological prophylaxis for ICU delirium, optimal treatment duration for ICU delirium, and the impact of pharmacotherapy on long-term cognitive outcomes in ICU survivors. A multitude of opportunities for further research exist in the above areas for clinicians and researchers interested in this ICU condition.
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To review the pharmacology, pharmacokinetics, clinical trials, adverse effects, and formulary considerations of ponatinib, a pan-tyrosine kinase inhibitor (TKI). ⋯ Ponatinib is a potent TKI that can overcome several resistance mechanisms in previously treated patients with CML and Ph+ ALL. Ponatinib should be reserved for patients who have failed first-line therapy, have the T315I mutation, or have progressed.
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To review pharmacokinetic and pharmacodynamic drug-drug interactions (DDIs) involving new oral anticoagulants for atrial fibrillation. ⋯ Awareness of drugs that alter the function of the P-gp efflux transporter protein and CYP3A4 enzymes and provide additive effects should enable prescribers to anticipate and avoid potential DDIs involving the new oral anticoagulants. To this end, briefing documents and prescribing information have applied cautionary measures for individuals treated with these newer anticoagulants.
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Medication-related harm can be detected using the adverse drug event (ADE) trigger tool and the medication module of the Global Trigger Tool (GTT) developed by the Institute for Healthcare Improvement (IHI). In recent years, there has been some controversy on the performance of this method. In addition, there are limited data on the performance of the medication module of the GTT as compared with the ADE trigger tool. ⋯ Applying the trigger tool method proposed by the IHI to a Belgian hospital led to the identification of one ADE out of 4 admissions. To increase performance, refining the list of triggers in the ADE trigger tool and in the medication module of the GTT would be needed. Recording nontriggered events should be encouraged.
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Observational Study
Challenges of anticoagulation for atrial fibrillation in patients with severe sepsis.
Although numerous studies have shown that anticoagulation of nonvalvular atrial fibrillation (AF) significantly decreases the risk of stroke, anticoagulating critically ill patients in the intensive care unit (ICU) poses many challenges and the benefits have not been determined. ⋯ Administration of anticoagulation for elderly patients with a CHADS2 score at 2 or more in the setting of sepsis can be associated with an increased risk of anticoagulation-related complications (eg, bleeding, heparin-induced thrombocytopenia). Managing and targeting a therapeutic goal with warfarin therapy in critically ill patients with sepsis is challenging. Further studies are necessary to provide appropriate recommendations in this setting.