Integrating Narrative Goals of Care in the Medical Intensive Care Unit: Impact on Educational and Clinical Outcomes.

Background: High-quality goals of care (GOC) communication is fundamental to providing excellent critical care. Objective: Educate medical intensive care unit (MICU) clinicians, design and implement workflows relating to GOC communication, and measure the impact on communication proficiency and rate of GOC documentation. Methods: Guided by Lean Six Sigma principles, an interprofessional team from palliative and critical care tailored a multicomponent intervention-the 3-Act Model communication training and workflow modification-to equip and empower the pulmonary and critical care medicine (PCCM) fellow as the clinical lead for GOC discussions. Fellows' education included in-person narrative reflection, asynchronous online didactic and demonstration videos of the 3-Act Model, online roleplays, and direct observation leading GOC discussions in the ICU. PCCM fellows were objectively evaluated for proficiency using the Goals of Care Assessment Tool. To evaluate the impact of our intervention on documented GOC conversations, we performed a retrospective chart review over two 3-month periods (before and after intervention) when the MICU cared exclusively for critically ill patients with coronavirus disease (COVID-19). Results: All PCCM fellows demonstrated proficiency in GOC communication via online simulated roleplays, as well as in observed bedside GOC communication. Per chart review of patients with a minimum of 7 consecutive days in the MICU, documented GOC conversations were found for 5.55% (2/36) of patients during the preintervention period and for 28.89% (13/45) of patients in the postintervention period. Palliative care consults increased in the pre- versus postintervention period: for all patients, 4.85% versus 14.52% (P < 0.05); for patients age ⩾80 years, 3.54% versus 29.41% (P < 0.05); and for patients with MICU length of stay ⩾7 days, 2.78% versus 24.44% (P < 0.05). Conclusion: Combining 3-Act Model education for PCCM fellows with Lean Six Sigma quality improvement resulted in effective GOC communication training and improved palliative care integration in the ICU.

Charged nucleobases and their potential for RNA catalysis.

Catalysis in living cells is carried out by both proteins and RNA. Protein enzymes have been known for over 200 years, but RNA enzymes, or "ribozymes", were discovered only 30 years ago. Developing insight into RNA enzyme mechanisms is invaluable for better understanding both extant biological catalysis as well as the primitive catalysis envisioned in an early RNA-catalyzed life. Natural ribozymes include large RNAs such as the group I and II introns; small RNAs such as the hepatitis delta virus and the hairpin, hammerhead, VS, and glmS ribozymes; and the RNA portion of the ribosome and spliceosome. RNA enzymes use many of the same catalytic strategies as protein enzymes, but do so with much simpler side chains. Among these strategies are metal ion, general acid-base, and electrostatic catalysis. In this Account, we examine evidence for participation of charged nucleobases in RNA catalysis. Our overall approach is to integrate direct measurements on catalytic RNAs with thermodynamic studies on oligonucleotide model systems. The charged amino acids make critical contributions to the mechanisms of nearly all protein enzymes. Ionized nucleobases should be critical for RNA catalysis as well. Indeed, charged nucleobases have been implicated in RNA catalysis as general acid-bases and oxyanion holes. We provide an overview of ribozyme studies involving nucleobase catalysis and the complications involved in developing these mechanisms. We also consider driving forces for perturbation of the pK(a) values of the bases. Mechanisms for pK(a) values shifting toward neutrality involve electrostatic stabilization and the addition of hydrogen bonding. Both mechanisms couple protonation with RNA folding, which we treat with a thermodynamic formalism and conceptual models. Furthermore, ribozyme reaction mechanisms can be multichannel, which demonstrates the versatility of ribozymes but makes analysis of experimental data challenging. We examine advances in measuring and analyzing perturbed pK(a) values in RNA. Raman crystallography and fluorescence spectroscopy have been especially important for pK(a) measurement. These methods reveal pK(a) values for the nucleobases A or C equal to or greater than neutrality, conferring potential histidine- and lysine/arginine-like behavior on them. Structural support for ionization of the nucleobases also exists: an analysis of RNA structures in the databases conducted herein suggests that charging of the bases is neither especially uncommon nor difficult to achieve under cellular conditions. Our major conclusions are that cationic and anionic charge states of the nucleobases occur in RNA enzymes and that these states make important catalytic contributions to ribozyme activity. We conclude by considering outstanding questions and possible experimental and theoretical approaches for further advances.