Time Trends in Race-Ethnic Differences in Do-Not-Resuscitate Orders After Stroke.

Background and Purpose- Do-not-resuscitate (DNR) orders are common after stroke, though there are limited data on trends over time. We investigated time trends in DNR orders in a community with a large minority population. Methods- Cases of ischemic stroke (IS) or intracerebral hemorrhage (ICH) were identified from the BASIC study (Brain Attack Surveillance in Corpus Christi) from June 2007 through October 2016. Cox proportional hazards models were used to assess time to DNR orders, with an interaction term added to allow separate hazard ratios for early (≤24 hours) and late (>24 hours) DNR. Stroke type-specific calendar trends were assessed with an interaction term between calendar year (linear) and stroke type. Results- Two thousand six hundred seventy-two cases were included (ICH, 14%). Mean age was 69, 50% were female, and race-ethnicity was Mexican American (58%), non-Hispanic white (37%), and African American (5%). Overall, 16% had a DNR order during the hospitalization. For ICH, DNR orders (early and late) were stable over the study period. However, early DNR orders became more common over time after ischemic stroke (hazard ratio for 2016 versus 2007: 1.89; 95% CI, 1.06-3.39), with no change over time for late DNR orders after ischemic stroke. Mexican Americans (hazard ratio, 0.65; 95% CI, 0.50-0.86) and African Americans (hazard ratio, 0.17; 95% CI, 0.04-0.71) were less likely than non-Hispanic whites to have early DNR orders, though there were no race-ethnic differences in late DNR orders. There was no change in race-ethnic difference in DNR orders over the time of the study (interaction P>0.60). Conclusions- Despite revised national guidelines cautioning against early DNR orders in ICH, presence of DNR orders after ICH was stable between 2007 and 2016, with only slight increases in early DNR orders after ischemic stroke. Mexican Americans and African Americans remain less likely than non-Hispanic whites to have early DNR orders after stroke.

Explaining the Process of Determining Futility Increases Lay Public Acceptance.

Rationale: National guidelines have laid out a process to conflict resolution in cases of potentially inappropriate medical interventions. Objectives: To determine the association between information about a process-based approach and lay public perceptions of the appropriateness of withholding medically inappropriate interventions. Methods: Respondents from a nationwide sample completed a survey with two adult intensive care unit-based vignettes: one about advanced cancer where doctors told the family that additional chemotherapy would not be offered, and a second case of multiorgan failure after brain hemorrhage where dialysis would not be offered. Participants were randomly assigned to see or not see information about a detailed process for the determination to withhold (second opinion, ethics consultation, exploring transfer to another institution). The primary outcome was the perceived appropriateness of not providing the treatment (four-point scale, dichotomized for analysis, modified Poisson regression), and the secondary outcome was the negative emotional reaction to the case (positive and negative affect schedule, range 1-5, higher is greater negative emotional response, linear regression). Results: A total of 1,191 respondents were included. Providing detailed process information increased the perceived appropriateness of withholding treatment by approximately 10 percentage points in each vignette: (chemotherapy, 75.7-85.4%; dialysis, 68.0-79.3%). Process information remained associated with perceived appropriateness of withholding treatment after adjustment for order effects and prespecified respondent characteristics (chemotherapy: prevalence ratio, 1.13; 95% confidence interval [CI], 1.07-1.19) (dialysis: prevalence ratio, 1.17; 95% CI, 1.10-1.25). Process information was not associated with emotional response to the cases (chemotherapy: ß = -0.04; 95% CI, -0.16 to 0.09) (dialysis: ß = -0.02; 95% CI, -0.14 to 0.10; both adjusted for order effects). Conclusions: Providing process-based conflict resolution information increased public acceptance of determinations of medical futility, supporting the practice outlined in national consensus statements.

How acceptable is paternalism? A survey-based study of clinician and nonclinician opinions on paternalistic decision making.

We conducted an empirical study to explore clinician and lay opinions on the acceptability of physician paternalism. Respondents read a vignette describing a patient with brain hemorrhage facing urgent surgery that would be lifesaving but would result in long-term severe disability. Cases were randomized to show either low or high surrogate distress and certain or uncertain prognosis, with respondents rating the acceptability of not offering brain surgery. Clinicians (N = 169) were more likely than nonclinicians (N = 649) to find the doctor withholding surgery acceptable (30.2% vs. 11.4%, p ≤ 0.001). Among clinicians, the doctor withholding surgery was more acceptable when prognosis was certain to be poor (odds ratio [OR] 2.04, 95% confidence interval [CI] 1.04, 4.01). There was no effect of surrogate distress on clinician ratings. Responses among lay public were more variable. Given the differences in attitudes across clinicians and lay public, there is an ongoing need to engage stakeholders in the process of end-of-life decision making.

The Voice Is As Mighty As the Pen: Integrating Conversations into Advance Care Planning.

Advance care planning allows patients to articulate preferences for their medical treatment, lifestyle, and surrogate decision-makers in order to anticipate and mitigate their potential loss of decision-making capacity. Written advance directives are often emphasized in this regard. While these directives contain important information, there are several barriers to consider: veracity and accuracy of surrogate decision-makers in making choices consistent with the substituted judgement standard, state-to-state variability in regulations, literacy issues, lack of access to legal resources, lack of understanding of medical options, and cultural disparities. Given these issues, it is vital to increase the use of patient and healthcare provider conversations as an advance care planning tool and to increase integration of such discourse into advance care planning policy as adjuncts and complements to written advance directives. This paper reviews current legislation about written advance directives and dissects how documentation of spoken interactions might be integrated and considered. We discuss specific institutional policy changes required to facilitate implementation. Finally, we explore the ethical issues surrounding the increased usage and recognition of clinician-patient conversations in advance care planning.

Engrailed-2 (En2) deletion produces multiple neurodevelopmental defects in monoamine systems, forebrain structures and neurogenesis and behavior.

Many genes involved in brain development have been associated with human neurodevelopmental disorders, but underlying pathophysiological mechanisms remain undefined. Human genetic and mouse behavioral analyses suggest that ENGRAILED-2 (EN2) contributes to neurodevelopmental disorders, especially autism spectrum disorder. In mouse, En2 exhibits dynamic spatiotemporal expression in embryonic mid-hindbrain regions where monoamine neurons emerge. Considering their importance in neuropsychiatric disorders, we characterized monoamine systems in relation to forebrain neurogenesis in En2-knockout (En2-KO) mice. Transmitter levels of serotonin, dopamine and norepinephrine (NE) were dysregulated from Postnatal day 7 (P7) to P21 in En2-KO, though NE exhibited the greatest abnormalities. While NE levels were reduced ∼35% in forebrain, they were increased 40 -: 75% in hindbrain and cerebellum, and these patterns paralleled changes in locus coeruleus (LC) fiber innervation, respectively. Although En2 promoter was active in Embryonic day 14.5 -: 15.5 LC neurons, expression diminished thereafter and gene deletion did not alter brainstem NE neuron numbers. Significantly, in parallel with reduced NE levels, En2-KO forebrain regions exhibited reduced growth, particularly hippocampus, where P21 dentate gyrus granule neurons were decreased 16%, suggesting abnormal neurogenesis. Indeed, hippocampal neurogenic regions showed increased cell death (+77%) and unexpectedly, increased proliferation. Excess proliferation was restricted to early Sox2/Tbr2 progenitors whereas increased apoptosis occurred in differentiating (Dcx) neuroblasts, accompanied by reduced newborn neuron survival. Abnormal neurogenesis may reflect NE deficits because intra-hippocampal injections of ß-adrenergic agonists reversed cell death. These studies suggest that disruption of hindbrain patterning genes can alter monoamine system development and thereby produce forebrain defects that are relevant to human neurodevelopmental disorders.