Mapping the process of ICU care delivery to improve treatment decisions in acute respiratory failure.

Evidence suggests system-level norms and care processes influence individual patients' medical decisions, including end-of-life decisions for patients with critical illnesses like acute respiratory failure. Yet, little is known about how these processes unfold over the course of a patient's critical illness in the intensive care unit (ICU). Our objective was to map current-state ICU care delivery processes for patients with acute respiratory failure and to identify opportunities to improve the process. We conducted a process mapping study at two academic medical centers, using focus groups and semi-structured interviews. The 70 participants represented 17 distinct roles in ICU care, including interprofessional medical ICU and palliative care clinicians, surrogate decision makers, and patient survivors. Participants refined and endorsed a process map of current-state care delivery for all patients admitted to the ICU with acute respiratory failure requiring mechanical ventilation. The process contains four critical periods for active deliberation about the use of life-sustaining treatments. However, active deliberation steps are inconsistently performed and frequently disrupted, leading to prolongation of life-sustaining treatment by default, without consideration of patients' individual goals and priorities. Interventions to standardize active deliberation in the ICU may improve treatment decisions for ICU patients with acute respiratory failure.

Design thinking to improve healthcare delivery in the intensive care unit: Promise, pitfalls, and lessons learned.

Design thinking is a problem-solving approach characterized by the empathetic lens through which designers integrate perspectives of end-users and key stakeholders throughout the entire process of developing solutions. This approach is rooted in diverse fields including engineering, computer science, psychology, and business and is increasingly widespread in healthcare. Herein, we describe the promise of design thinking to help solve intractable problems in healthcare delivery, including those within the complex social and technical intensive care unit system. We highlight our team's experience using design thinking to address the complex problem of aligning the delivery of life-sustaining treatments with patients' individual goals, values, and preferences. However, given the high stakes of design failure in healthcare, we also discuss the limitations of this approach and the potential consequences of inadequate application. Finally, we suggest a pathway forward that combines the philosophy and tools of design thinking with existing methods within healthcare delivery science, such as qualitative research, quality improvement methods, and implementation science. Ultimately, we argue that design thinking is a valuable approach to guide designers, clinicians, researchers, and administrators towards a more genuine understanding of the healthcare experience, through the lens of patients, their families, and frontline clinicians.

Evaluation of automated specialty palliative care in the intensive care unit: A retrospective cohort study.

INTRODUCTION: Automated specialty palliative care consultation (SPC) has been proposed as an intervention to improve patient-centered care in the intensive care unit (ICU). Existing automated SPC trigger criteria are designed to identify patients at highest risk of in-hospital death. We sought to evaluate common mortality-based SPC triggers and determine whether these triggers reflect actual use of SPC consultation. We additionally aimed to characterize the population of patients who receive SPC without meeting mortality-based triggers. METHODS: We conducted a retrospective cohort study of all adult ICU admissions from 2012-2017 at an academic medical center with five subspecialty ICUs to determine the sensitivity and specificity of the five most common SPC triggers for predicting receipt of SPC. Among ICU admissions receiving SPC, we assessed differences in patients who met any SPC trigger compared to those who met none. RESULTS: Of 48,744 eligible admissions, 1,965 (4.03%) received SPC; 979 (49.82%) of consultations met at least 1 trigger. The sensitivity and specificity for any trigger predicting SPC was 49.82% and 79.61%, respectively. Patients who met no triggers but received SPC were younger (62.71 years vs 66.58 years, mean difference (MD) 3.87 years (95% confidence interval (CI) 2.44-5.30) p<0.001), had longer ICU length of stay (11.43 days vs 8.42 days, MD -3.01 days (95% CI -4.30 --1.72) p<0.001), and had a lower rate of in-hospital death (48.68% vs 58.12%, p<0.001). CONCLUSION: Mortality-based triggers for specialty palliative care poorly reflect actual use of SPC in the ICU. Reliance on such triggers may unintentionally overlook an important population of patients with clinician-identified palliative care needs.

Group II mGluR agonist LY354740 and NAAG peptidase inhibitor effects on prepulse inhibition in PCP and D-amphetamine models of schizophrenia.

RATIONALE: Group II metabotropic glutamate receptor (mGluR) agonists represent a novel approach to the treatment of schizophrenia. Inasmuch as the peptide neurotransmitter N-acetylaspartylglutamate (NAAG) activates these receptors, NAAG peptidase inhibitors conceptually represent a parallel path toward development of new antipsychotic drugs. While group II agonists are effective in several animal models of schizophrenia, they are reported to lack efficacy in moderating the effects of phencyclidine (PCP) on prepulse inhibition of acoustic startle in animal models of sensory processing deficits found in this disorder. OBJECTIVE: The objective of this study was to re-examine the efficacy of a group II metabotropic glutamate agonist and NAAG peptidase inhibitors in prepulse inhibition models of schizophrenia across two strains of mice. METHODS: The method used was an assay to determine the efficacy of these drugs in moderating the reduction in prepulse inhibition of acoustic startle in mice treated with PCP and D: -amphetamine. RESULTS: The group II agonist LY354740 (5 and 10 mg/kg) moderated the effects of PCP on prepulse inhibition of acoustic startle in DBA/2 but not C57BL/6 mice. In contrast, two NAAG peptidase inhibitors, ZJ43 (150 mg/kg) and 2-PMPA (50, 100, and 150 mg/kg), did not significantly affect the PCP-induced reduction in prepulse inhibition in either strain. CONCLUSIONS: These data demonstrate that the efficacy of group II agonists in this model of sensory motor processing is strain-specific in mice. The difference between the effects of the group II agonist and the peptidase inhibitors in the DBA/2 mice may relate to the difference in efficacy of NAAG and the agonist at mGluR2.

Phencyclidine and dizocilpine induced behaviors reduced by N-acetylaspartylglutamate peptidase inhibition via metabotropic glutamate receptors.

BACKGROUND: N-methyl-D-aspartate (NMDA) receptor open channel blockers phencyclidine (PCP) and dizocilpine (MK-801) elicit schizophrenia-like symptoms in humans and in animal models. Group II metabotropic glutamate receptor agonists reverse the behavioral effects of PCP and MK-801 in animal models. N-acetylaspartylglutamate (NAAG), the third most prevalent neurotransmitter in the mammalian nervous system, is a selective group II metabotropic glutamate receptor agonist. We previously reported that ZJ43, a potent inhibitor of the enzymes that inactivate synaptically released NAAG, reduced motor and stereotypic effects of PCP in the rat. METHODS: To confirm the efficacy of NAAG peptidase inhibition in decreasing motor behaviors induced by PCP and MK-801, ZJ43 was tested in additional schizophrenia models. RESULTS: ZJ43 reduced MK-801-induced motor activation in a mouse model that has been used to characterize the efficacy of a wide range of pharmacotherapies for this human disorder. In a second mouse strain, the peptidase inhibitor reduced PCP-induced stereotypic movements. ZJ43 also reduced PCP-induced negative symptoms in a resident-intruder assay. The group II metabotropic glutamate receptor antagonist, LY341495, blocked the effect of NAAG peptidase inhibition in these mouse models of positive and negative PCP- and MK-801-induced behaviors. Additionally, LY341495 alone increased some PCP-induced behaviors suggesting that normal levels of NAAG act to moderate the effect of PCP via a group II mGluR. CONCLUSIONS: These data support the proposal that NAAG peptidase inhibition and elevation of synaptic NAAG levels represent a new therapeutic approach to treating the positive and negative symptoms of schizophrenia that are modeled by open channel NMDA receptor antagonists.