Equity in Clinical Care and Research Involving Persons with Disorders of Consciousness.

People with disorders of consciousness (DoC) are characteristically unable to synchronously participate in decision-making about clinical care or research. The inability to self-advocate exacerbates preexisting socioeconomic and geographic disparities, which include the wide variability observed across individuals, hospitals, and countries in access to acute care, expertise, and sophisticated diagnostic, prognostic, and therapeutic interventions. Concerns about equity for people with DoC are particularly notable when they lack a surrogate decision-maker (legally referred to as "unrepresented" or "unbefriended"). Decisions about both short-term and long-term life-sustaining treatment typically rely on neuroprognostication and individual patient preferences that carry additional ethical considerations for people with DoC, as even individuals with well thought out advance directives cannot anticipate every possible situation to guide such decisions. Further challenges exist with the inclusion of people with DoC in research because consent must be completed (in most circumstances) through a surrogate, which excludes those who are unrepresented and may discourage investigators from exploring questions related to this population. In this article, the Curing Coma Campaign Ethics Working Group reviews equity considerations in clinical care and research involving persons with DoC in the following domains: (1) access to acute care and expertise, (2) access to diagnostics and therapeutics, (3) neuroprognostication, (4) medical decision-making for unrepresented people, (5) end-of-life decision-making, (6) access to postacute rehabilitative care, (7) access to research, (8) inclusion of unrepresented people in research, and (9) remuneration and reciprocity for research participation. The goal of this discussion is to advance equitable, harmonized, guideline-directed, and goal-concordant care for people with DoC of all backgrounds worldwide, prioritizing the ethical standards of respect for autonomy, beneficence, and justice. Although the focus of this evaluation is on people with DoC, much of the discussion can be extrapolated to other critically ill persons worldwide.

Non-Psychiatric Treatment Refusal in Patients with Depression: How Should Surrogate Decision-Makers Represent the Patient's Authentic Wishes?

Patients with mental illness, and depression in particular, present clinicians and surrogate decision-makers with complex ethical dilemmas when they refuse life-sustaining non-psychiatric treatment. When treatment rejection is at variance with the beliefs and preferences that could be expected based on their premorbid or "authentic" self, their capacity to make these decisions may be called into question. If capacity cannot be demonstrated, medical decisions fall to surrogates who are usually advised to decide based on a substituted judgment standard or, when that is not possible, best interest. We propose that in cases where the patient meets the widely accepted cognitive criteria for capacity but is making decisions that appear inauthentic, the surrogate may best uphold patient autonomy by following a "restorative representation" model. We see restorative representation as a subset of substituted judgement in which the decision-maker retains responsibility for deciding as the patient would have, but discerns the decision their "truest self" would make, rather than inferring their current wishes, which are directly influenced by illness. Here we present a case in which the patient's treatment refusal and previously undiagnosed depression led to difficulty determining the patient's authentic wishes and placed a distressing burden on the surrogate decision-maker. We use this case to examine how clinicians and ethicists might better advise surrogates who find themselves making these clinically and emotionally challenging decisions.

Ethics Along the Continuum of Research Involving Persons with Disorders of Consciousness.

Interest in disorders of consciousness (DoC) has grown substantially over the past decade and has illuminated the importance of improving understanding of DoC biology; care needs (use of monitoring, performance of interventions, and provision of emotional support); treatment options to promote recovery; and outcome prediction. Exploration of these topics requires awareness of numerous ethics considerations related to rights and resources. The Curing Coma Campaign Ethics Working Group used its expertise in neurocritical care, neuropalliative care, neuroethics, neuroscience, philosophy, and research to formulate an informal review of ethics considerations along the continuum of research involving persons with DoC related to the following: (1) study design; (2) comparison of risks versus benefits; (3) selection of inclusion and exclusion criteria; (4) screening, recruitment, and enrollment; (5) consent; (6) data protection; (7) disclosure of results to surrogates and/or legally authorized representatives; (8) translation of research into practice; (9) identification and management of conflicts of interest; (10) equity and resource availability; and (11) inclusion of minors with DoC in research. Awareness of these ethics considerations when planning and performing research involving persons with DoC will ensure that the participant rights are respected while maximizing the impact and meaningfulness of the research, interpretation of outcomes, and communication of results.

Ethics Priorities of the Curing Coma Campaign: An Empirical Survey.

BACKGROUND: The Curing Coma Campaign (CCC) is a multidisciplinary global initiative focused on evaluation, diagnosis, treatment, research, and prognostication for patients who are comatose due to any etiology. To support this mission, the CCC Ethics Working Group conducted a survey of CCC collaborators to identify the ethics priorities of the CCC and the variability in priorities based on country of practice. METHODS: An electronic survey on the ethics priorities for the CCC was developed using rank-choice questions and distributed between May and July 2021 to a listserv of the 164 collaborators of the CCC. The median rank for each topic and subtopic was determined. Comparisons were made on the basis of country of practice. RESULTS: The survey was completed by 93 respondents (57% response rate); 67% practiced in the United States. On the basis of respondent ranking of each topic, the prioritization of ethics topics across respondents was as follows: (1) clinical care, (2) diagnostic definitions, (3) clinical research, (4) implementation/innovation, (5) family, (6) data management, (7) public engagement/perceptions, and (8) equity. Respondents who practiced in the United States were particularly concerned about public engagement, the distinction between clinical care and research, disclosure of results from clinical research to families, the definition of "personhood," and the distinction between the self-fulfilling prophecy/nihilism and medical futility. Respondents who practiced in other countries were particularly concerned about diagnostic modalities for clinical care, investigational drugs/devices for clinical research, translation of research into practice, and the definition of "minimally conscious state." CONCLUSIONS: Collaborators of the CCC considered clinical care, diagnostic definitions, and clinical research the top ethics priorities of the CCC. These priorities should be considered as the CCC explores ways to improve evaluation, diagnosis, treatment, research, and prognostication of patients with coma and associated disorders of consciousness. There is some variability in ethics priorities based on country of practice.

Magnesium, hemostasis, and outcomes in patients with intracerebral hemorrhage.

OBJECTIVE: We tested the hypothesis that admission serum magnesium levels are associated with hematoma volume, hematoma growth, and functional outcomes in patients with intracerebral hemorrhage (ICH). METHODS: Patients presenting with spontaneous ICH were enrolled in an observational cohort study that prospectively collected demographic, clinical, laboratory, radiographic, and outcome data. We performed univariate and adjusted multivariate analyses to assess for associations between serum magnesium levels and initial hematoma volume, final hematoma volume, and in-hospital hematoma growth as radiographic measures of hemostasis, and functional outcome measured by the modified Rankin Scale (mRS) at 3 months. RESULTS: We included 290 patients for analysis. Admission serum magnesium was 2.0 ± 0.3 mg/dL. Lower admission magnesium levels were associated with larger initial hematoma volumes on univariate (p = 0.02), parsimoniously adjusted (p = 0.002), and fully adjusted models (p = 0.006), as well as greater hematoma growth (p = 0.004, p = 0.005, and p = 0.008, respectively) and larger final hematoma volumes (p = 0.02, p = 0.001, and p = 0.002, respectively). Lower admission magnesium level was associated with worse functional outcomes at 3 months (i.e., higher mRS; odds ratio 0.14, 95% confidence interval 0.03-0.64, p = 0.011) after adjustment for age, admission Glasgow Coma Scale score, initial hematoma volume, time from symptom onset to initial CT, and hematoma growth, with evidence that the effect of magnesium is mediated through hematoma growth. CONCLUSIONS: These data support the hypothesis that magnesium exerts a clinically meaningful influence on hemostasis in patients with ICH.

Post-traumatic Stress Disorder and Complicated Grief are Common in Caregivers of Neuro-ICU Patients.

BACKGROUND: To explore the effect of end of life and other palliative decision making scenarios on the mental health of family members of patients in the neuro-intensive care unit. METHODS: Decision makers of patients in the neuro-ICU at a large, urban, academic medical center meeting palliative care triggers were identified from November 10, 2014, to August 27, 2015. Interviews were conducted at 1 and 6 months post-enrollment. At 1 month, the Inventory of Complicated Grief-Revised (ICG-R), Impact of Events Scale-Revised (IES-R), and the Family Satisfaction-ICU (FS-ICU) were performed along with basic demographic questionnaires. At 6 months, only the ICG-R and IES-R were repeated. RESULTS: At 1 month, 9 (35%) subjects had significant symptoms in at least one of the three domains of traumatic response. Two (7.7%) subjects met full criteria for PTSD (IES-R ≥ 1.5). At 6 months, 5 (22%) subjects met criteria for PTSD and 5 (22%) for Complicated Grief (ICG-R ≥ 36). Fifteen (50%) had at least one domain of PTSD symptoms identified in follow-up. Time spent at bedside and lower household income were associated with PTSD at 1 and 6 months, respectively. In all, clinically significant psychological outcomes were identified in 9 (30%) of subjects. CONCLUSIONS: Clinically significant grief and stress reactions were identified in 30% of decision makers for severely ill neuro-ICU patients. Though factors including time at bedside during hospitalization and total household income may have some predictive value for these disorders, further evaluation is required to help identify family members at risk of psychopathology following neuro-ICU admissions.

The Epidemiology of Global Epilepsy.

The International League Against Epilepsy defines epilepsy as at least 2 unprovoked seizures more than 24 hours apart. It is a wide-reaching and complex illness affecting more than 70 million people worldwide and can take on a variety of forms, patterns, and severities. Geographic differences in the illness are often related to its etiology. A host of endemic illnesses and parasitic infections can lead to epilepsy syndromes. Management varies by region due to the availability of diagnostic modalities and medications. Treatment gaps in epilepsy care often are related to social and cultural factors that must also be understood.

Epidemiology of Multiple Sclerosis.

The epidemiology of multiple sclerosis (MS) includes a consideration of genetic and environmental factors. Comparative studies of different populations have revealed prevalence and incidence rates that vary with geography and ethnicity. With a prevalence ranging from 2 per 100,000 in Japan to greater than 100 per 100,000 in Northern Europe and North America, the burden of MS is similarly unevenly influenced by longevity and comorbid disorders. Well-powered genome-wide association studies have investigated the genetic substrate of MS, providing insight into autoimmune mechanisms involved in the etiopathogenesis of MS and elucidating possible avenues of biological treatment.

Communication, Leadership, and Decision-Making in the Neuro-ICU.

The Neuro-ICU is a multidisciplinary location that presents peculiar challenges and opportunities for patients with life-threatening neurological disease. Communication skills are essential in supporting caregivers and other embedded providers (e.g., neurosurgeons, advanced practice providers, nurses, pharmacists), through leadership. Limitations to prognostication complicate how decisions are made on behalf of non-communicative patients. Cognitive dysfunction and durable reductions in health-related quality of life are difficult to predict, and the diagnosis of brain death may be challenging and confounded by medications and comorbidities. The Neuro-ICU team, as well as utilization of additional consultants, can be structured to optimize care. Future research should explore how to further improve the composition, communication and interactions of the Neuro-ICU team to maximize outcomes, minimize caregiver burden, and promote collegiality.