Clinicians' Use of Choice Framing in ICU Family Meetings.

OBJECTIVES: To quantify the frequency and patterns of clinicians' use of choice frames when discussing preference-sensitive care with surrogate decision-makers in the ICU. DESIGN: Secondary sequential content analysis. SETTING: One hundred one audio-recorded and transcribed conferences between surrogates and clinicians of incapacitated, critically ill adults from a prospective, multicenter cohort study. SUBJECTS: Surrogate decision-makers and clinicians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four coders identified preference-sensitive decision episodes addressed in the meetings, including topics such as mechanical ventilation, renal replacement, and overall goals of care. Prior critical care literature provided specific topics identified as preference-sensitive specific to the critical care context. Coders then examined each decision episode for the types of choice frames used by clinicians. The choice frames were selected a priori based on decision science literature. In total, there were 202 decision episodes across the 101 transcripts, with 20.3% of the decision episodes discussing mechanical ventilation, 19.3% overall goals of care, 14.4% renal replacement therapy, 14.4% post-discharge care (i.e., discharge location such as a skilled nursing facility), and the remaining 32.1% other topics. Clinicians used default framing, in which an option is presented that will be carried out if another option is not actively chosen, more frequently than any other choice frame (127 or 62.9% of decision episodes). Clinicians presented a polar interrogative, or a "yes or no question" to accept or reject a specific care choice, in 43 (21.3%) decision episodes. Clinicians more frequently presented options emphasizing both potential losses and gains rather than either in isolation. CONCLUSIONS: Clinicians frequently use default framing and polar questions when discussing preference-sensitive choices with surrogate decision-makers, which are known to be powerful nudges. Future work should focus on designing interventions promoting the informed use of these and the other most common choice frames used by practicing clinicians.

Engineering Equity Into the Promise of Xenotransplantation.

Two of the greatest challenges facing kidney transplantation are the lack of donated organs and inequities in who receives a transplant. Xenotransplantation holds promise as a treatment approach that could solve the supply problem. Major advances in gene-editing procedures have enabled several companies to raise genetically engineered pigs for organ donation. These porcine organs lack antigens and have other modifications that should reduce the probability of immunological rejection when transplanted into humans. The US Food and Drug Administration and transplantation leaders are starting to chart a path to test xenotransplants in clinical trials and later integrate them into routine clinical care. Here we provide a framework that industry, regulatory authorities, payers, transplantation professionals, and patient groups can implement to promote equity during every stage in this process. We also call for immediate action. Companies developing xenotransplant technology should assemble patient advocacy boards to bring the concerns of individuals with end-stage kidney disease to the forefront. For trials, xenotransplantation companies should partner with transplant programs with substantial patient populations of racial and ethnic minority groups and that have reciprocal relationships with those communities. Those companies and transplant programs should reach out now to those communities to inform them about xenotransplantation and try to address their concerns. These actions have the potential to make these communities full partners in the promise of xenotransplantation.

Prevalence and predictors of shared decision-making in goals-of-care clinician-family meetings for critically ill neurologic patients: a multi-center mixed-methods study.

BACKGROUND: Shared decision-making is a joint process where patients, or their surrogates, and clinicians make health choices based on evidence and preferences. We aimed to determine the extent and predictors of shared decision-making for goals-of-care discussions for critically ill neurological patients, which is crucial for patient-goal-concordant care but currently unknown. METHODS: We analyzed 72 audio-recorded routine clinician-family meetings during which goals-of-care were discussed from seven US hospitals. These occurred for 67 patients with 72 surrogates and 29 clinicians; one hospital provided 49/72 (68%) of the recordings. Using a previously validated 10-element shared decision-making instrument, we quantified the extent of shared decision-making in each meeting. We measured clinicians' and surrogates' characteristics and prognostic estimates for the patient's hospital survival and 6-month independent function using post-meeting questionnaires. We calculated clinician-family prognostic discordance, defined as ≥ 20% absolute difference between the clinician's and surrogate's estimates. We applied mixed-effects regression to identify independent associations with greater shared decision-making. RESULTS: The median shared decision-making score was 7 (IQR 5-8). Only 6% of meetings contained all 10 shared decision-making elements. The most common elements were "discussing uncertainty"(89%) and "assessing family understanding"(86%); least frequent elements were "assessing the need for input from others"(36%) and "eliciting the context of the decision"(33%). Clinician-family prognostic discordance was present in 60% for hospital survival and 45% for 6-month independent function. Univariate analyses indicated associations between greater shared decision-making and younger clinician age, fewer years in practice, specialty (medical-surgical critical care > internal medicine > neurocritical care > other > trauma surgery), and higher clinician-family prognostic discordance for hospital survival. After adjustment, only higher clinician-family prognostic discordance for hospital survival remained independently associated with greater shared decision-making (p = 0.029). CONCLUSION: Fewer than 1 in 10 goals-of-care clinician-family meetings for critically ill neurological patients contained all shared decision-making elements. Our findings highlight gaps in shared decision-making. Interventions promoting shared decision-making for high-stakes decisions in these patients may increase patient-value congruent care; future studies should also examine whether they will affect decision quality and surrogates' health outcomes.

Gut microbiota and systemic immunity in health and disease.

The mammalian intestine is colonized by trillions of microorganisms that have co-evolved with the host in a symbiotic relationship. Although the influence of the gut microbiota on intestinal physiology and immunity is well known, mounting evidence suggests a key role for intestinal symbionts in controlling immune cell responses and development outside the gut. Although the underlying mechanisms by which the gut symbionts influence systemic immune responses remain poorly understood, there is evidence for both direct and indirect effects. In addition, the gut microbiota can contribute to immune responses associated with diseases outside the intestine. Understanding the complex interactions between the gut microbiota and the host is thus of fundamental importance to understand both immunity and human health.

Promoting equity with a multi-principle framework to allocate scarce ICU resources.

We wholeheartedly agree with Schmidt and colleagues' efforts to promote equity in intensive care unit (ICU) triage. We also take issue with their characterisation of the New Jersey (NJ) allocation framework for ICU beds and ventilators, which is modelled after the multi-principle allocation framework we developed early in the pandemic. They characterise it as a two-criterion allocation framework and claim-without evidence-that it will 'compound disadvantage for black patients'. However, the NJ triage framework-like the model allocation policy we developed-actually contains four allocation criteria: the two criteria that the authors mentioned (chances for survival and near-term prognosis) and two criteria that they failed to mention which we included to promote equity: giving priority to frontline essential workers and giving priority to younger patients. These omissions are problematic both for reasons of factual accuracy and because the two criteria they failed to acknowledge would likely mitigate rather than exacerbate racial disparities during triage.

Mitigating Inequities and Saving Lives with ICU Triage during the COVID-19 Pandemic.

The burdens of the coronavirus disease (COVID-19) pandemic have fallen disproportionately on disadvantaged groups, including the poor and Black, Latinx, and Indigenous communities. There is substantial concern that the use of existing ICU triage protocols to allocate scarce ventilators and critical care resources-most of which are designed to save as many lives as possible-may compound these inequities. As governments and health systems revisit their triage guidelines in the context of impending resource shortages, scholars have advocated a range of alternative allocation strategies, including the use of a random lottery to give all patients in need an equal chance of ICU treatment. However, both the save-the-most-lives approach and random allocation are seriously flawed. In this Perspective, we argue that ICU triage policies should simultaneously promote population health outcomes and mitigate health inequities. These ethical goals are sometimes in conflict, which will require balancing the goals of maximizing the number of lives saved and distributing health benefits equitably across society. We recommend three strategies to mitigate health inequities during ICU triage: introducing a correction factor into patients' triage scores to reduce the impact of baseline structural inequities; giving heightened priority to individuals in essential, high-risk occupations; and rejecting use of longer-term life expectancy and categorical exclusions as allocation criteria. We present a practical triage framework that incorporates these strategies and attends to the twin public health goals of promoting population health and social justice.

Ethical Framework for Assessing Manual and Digital Contact Tracing for COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has challenged the traditional public health balance between benefiting the good of the community through contact tracing and restricting individual liberty. This article first analyzes important technical and ethical issues regarding new smartphone apps that facilitate contact tracing and exposure notification. It then presents a framework for assessing contact tracing, whether manual or digital: the effectiveness at mitigating the pandemic; acceptability of risks, particularly privacy; and equitable distribution of benefits and risks. Both manual and digital contact tracing require public trust, engagement of minority communities, prompt COVID-19 testing and return of results, and high adherence with physical distancing and use of masks.

Clinical Medical Ethics: How Did We Start? Where Are We Heading?

The author presents his view of the start of clinical medical ethics and ideas on where the broader field of bioethics is heading. In addition to clinical medical ethics, people with training in clinical ethics can enlarge the scope of their work in order to have additional real-world impact. Important opportunities abound in empirical research on medical ethics, the ethics of healthcare institutions, ethical issues regarding biomedical research, and public policy. Three topics for bioethics scholars to address are artificial intelligence in clinical care, health disparities, and communicating persuasively to broader audiences beyond academia.

The Transcription Factor RORα Preserves ILC3 Lineage Identity and Function during Chronic Intestinal Infection.

Innate lymphoid cells (ILCs) are critical for host defense and tissue repair but can also contribute to chronic inflammatory diseases. The transcription factor RORα is required for ILC2 development but is also highly expressed by other ILC subsets where its function remains poorly defined. We previously reported that Rorasg/sg bone marrow chimeric mice (C57BL/6J) were protected from Salmonella-induced intestinal fibrosis due to defective ILC3 responses. In this study, single-cell RNA analysis of ILCs isolated from inflamed tissues indicates that RORα perturbation led to a reduction in ILC3 lineages. Furthermore, residual Rorasg/sg ILC3s have decreased expression of key signature genes, including Rorc and activating cytokine receptors. Collectively, our data suggest that RORα plays a key role in preserving functional ILC3s by modulating their ability to integrate environmental cues to efficiently produce cytokines.

IL-22 Preserves Gut Epithelial Integrity and Promotes Disease Remission during Chronic Salmonella Infection.

The cytokine IL-22 is rapidly induced at barrier surfaces where it regulates host-protective antimicrobial immunity and tissue repair but can also enhance disease severity in some chronic inflammatory settings. Using the chronic Salmonella gastroenteritis model, Ab-mediated neutralization of IL-22 impaired intestinal epithelial barrier integrity and, consequently, exaggerated expression of proinflammatory cytokines. As disease normally resolved, neutralization of IL-22 caused luminal narrowing of the cecum-a feature reminiscent of fibrotic strictures seen in Crohn disease patients. Corresponding to the exaggerated immunopathology caused by IL-22 suppression, Salmonella burdens in the gut were reduced. This enhanced inflammation and pathogen clearance was associated with alterations in gut microbiome composition, including the overgrowth of Bacteroides acidifaciens Our findings thus indicate that IL-22 plays a protective role by limiting infection-induced gut immunopathology but can also lead to persistent pathogen colonization.

Making Medical Treatment Decisions for Unrepresented Patients in the ICU. An Official American Thoracic Society/American Geriatrics Society Policy Statement.

Background and Rationale: ICU clinicians regularly care for patients who lack capacity, an applicable advance directive, and an available surrogate decision-maker. Although there is no consensus on terminology, we refer to these patients as "unrepresented." There is considerable controversy about how to make treatment decisions for these patients, and there is significant variability in both law and clinical practice.Purpose and Objectives: This multisociety statement provides clinicians and hospital administrators with recommendations for decision-making on behalf of unrepresented patients in the critical care setting.Methods: An interprofessional, multidisciplinary expert committee developed this policy statement by using an iterative consensus process with a diverse working group representing critical care medicine, palliative care, pediatric medicine, nursing, social work, gerontology, geriatrics, patient advocacy, bioethics, philosophy, elder law, and health law.Main Results: The committee designed its policy recommendations to promote five ethical goals: 1) to protect highly vulnerable patients, 2) to demonstrate respect for persons, 3) to provide appropriate medical care, 4) to safeguard against unacceptable discrimination, and 5) to avoid undue influence of competing obligations and conflicting interests. These recommendations also are intended to strike an appropriate balance between excessive and insufficient procedural safeguards. The committee makes the following recommendations: 1) institutions should offer advance care planning to prevent patients at high risk for becoming unrepresented from meeting this definition; 2) institutions should implement strategies to determine whether seemingly unrepresented patients are actually unrepresented, including careful capacity assessments and diligent searches for potential surrogates; 3) institutions should manage decision-making for unrepresented patients using input from a diverse interprofessional, multidisciplinary committee rather than ad hoc by treating clinicians; 4) institutions should use all available information on the patient's preferences and values to guide treatment decisions; 5) institutions should manage decision-making for unrepresented patients using a fair process that comports with procedural due process; 6) institutions should employ this fair process even when state law authorizes procedures with less oversight.Conclusions: This multisociety statement provides guidance for clinicians and hospital administrators on medical decision-making for unrepresented patients in the critical care setting.

A Multicenter Study of the Causes and Consequences of Optimistic Expectations About Prognosis by Surrogate Decision-Makers in ICUs.

OBJECTIVES: Optimistic expectations about prognosis by surrogate decision-makers in ICUs are common, but there are few data about the causes and clinical consequences. Our objective was to determine the causes of optimistic expectations about prognosis among surrogates and whether it is associated with more use of life support at the end of life. DESIGN: Prospective, multicenter cohort study from 2009 to 2012. SETTING: Twelve ICUs from multiple regions of the United States. SUBJECTS: The surrogates and physicians of 275 incapacitated ICU patients at high risk of death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Surrogates and physicians completed a validated instrument assessing their prognostic expectations for hospital survival. We determined the proportion of surrogates with optimistic expectations, defined as a prognostic estimate that was at least 20% more optimistic than the physician's, then determined how frequently this arose from surrogates miscomprehending the physicians' prognosis versus holding more hopeful beliefs compared with the physician. We used multivariable regression to examine whether optimistic expectations were associated with length of stay, stratified by survival status, and time to withdrawal of life support among nonsurvivors. Overall, 45% of surrogates (95% CI, 38-51%) held optimistic expectations about prognosis, which arose from a combination of misunderstanding the physician's prognostic expectations and from holding more hopeful beliefs compared with the physician. Optimistic expectations by surrogates were associated with significantly longer duration of ICU treatment among nonsurvivors before death (ß coefficient = 0.44; 95% CI, 0.05-0.83; p = 0.027), corresponding to a 56% longer ICU stay. This difference was associated with a significantly longer time to withdrawal of life support among dying patients whose surrogates had optimistic prognostic expectations compared with those who did not (ß coefficient = 0.61; 95% CI, 0.16-1.07; p = 0.009). CONCLUSIONS: The prevalent optimism about prognosis among surrogates in ICUs arises both from surrogates' miscomprehension of physicians' prognostications and from surrogates holding more hopeful beliefs. This optimism is associated with longer duration of life support at the end of life.

Resolving Family-Clinician Disputes in the Context of Contested Definitions of Futility.

The word futile has been a touchstone in debates regarding resolution of disputes regarding life-prolonging treatments since the 1980s. Here, we respond to several criticisms of the Multiorganization Policy Statement, "An Official ATS/AACN/ACCP/ESICM/SCCM Policy Statement: Responding to Requests for Potentially Inappropriate Treatments in Intensive Care Units" (Bosslet et al. 2015). This response highlights the need for a strict definition of the word futile in order to avoid undue treatment differences when end-of-life interventions are contested. We also reply to several criticisms of this policy statement that are formulated upon fundamental misunderstandings of the statement and its assertions.

Loss of Vascular CD34 Results in Increased Sensitivity to Lung Injury.

Survival during lung injury requires a coordinated program of damage limitation and rapid repair. CD34 is a cell surface sialomucin expressed by epithelial, vascular, and stromal cells that promotes cell adhesion, coordinates inflammatory cell recruitment, and drives angiogenesis. To test whether CD34 also orchestrates pulmonary damage and repair, we induced acute lung injury in wild-type (WT) and Cd34-/- mice by bleomycin administration. We found that Cd34-/- mice displayed severe weight loss and early mortality compared with WT controls. Despite equivalent early airway inflammation to WT mice, CD34-deficient animals developed interstitial edema and endothelial delamination, suggesting impaired endothelial function. Chimeric Cd34-/- mice reconstituted with WT hematopoietic cells exhibited early mortality compared with WT mice reconstituted with Cd34-/- cells, supporting an endothelial defect. CD34-deficient mice were also more sensitive to lung damage caused by influenza infection, showing greater weight loss and more extensive pulmonary remodeling. Together, our data suggest that CD34 plays an essential role in maintaining vascular integrity in the lung in response to chemical- and infection-induced tissue damage.

Reframing Consent for Clinical Research: A Function-Based Approach.

Although informed consent is important in clinical research, questions persist regarding when it is necessary, what it requires, and how it should be obtained. The standard view in research ethics is that the function of informed consent is to respect individual autonomy. However, consent processes are multidimensional and serve other ethical functions as well. These functions deserve particular attention when barriers to consent exist. We argue that consent serves seven ethically important and conceptually distinct functions. The first four functions pertain principally to individual participants: (1) providing transparency; (2) allowing control and authorization; (3) promoting concordance with participants' values; and (4) protecting and promoting welfare interests. Three other functions are systemic or policy focused: (5) promoting trust; (6) satisfying regulatory requirements; and (7) promoting integrity in research. Reframing consent around these functions can guide approaches to consent that are context sensitive and that maximize achievable goals.