Long-Term Psychological Distress Among Surrogate Decision Makers for Mexican American and Non-Hispanic White Patients With Severe Stroke.

BACKGROUND AND OBJECTIVES: During acute hospitalizations, physicians often focus on the stroke patient and not family who may be traumatized by this sudden change to their loved one. We investigated long-term psychological distress among family surrogate decision makers for Mexican American (MA) and non-Hispanic White (NHW) severe stroke patients. Previous work in other diseases suggested worse psychological outcomes in MA than NHW caregivers. METHODS: This was a population-based, prospective cohort study in Nueces County, TX. Stroke patient participants and their surrogate decision makers were enrolled soon after any stroke between April, 2016, and October, 2020, if surrogates had made decisions about life-sustaining treatments. Surrogates completed validated measures of posttraumatic stress, National Stressful Events Survey for Posttraumatic Stress Disorder Short Scale; anxiety, Generalized Anxiety Disorder-7; and depression, Patient Health Questionnaire-8 at discharge, 3, 6, and 12 months. Ethnic differences were assessed with multilevel linear mixed models, sequentially adjusted for prespecified patient and surrogate demographic, socioeconomic, and clinical covariates. RESULTS: There were 301 family surrogates for 241 severe stroke patients. The mean follow-up was 315 days. High scores on measures of psychological distress ranged between 17% and 28% of surrogates. One or more high levels of the psychological outcomes were found in 17%-43% of surrogates; 2 or more were found in 12%-27%; and all 3 were found in 5%-16% of surrogates. All psychological outcomes were worse among MAs on unadjusted analyses. In fully adjusted models, posttraumatic stress remained worse among MAs (0.36, 95% CI 0.17-0.56); ethnic differences were attenuated and no longer significant in the final model for anxiety (0.59, 95% CI -0.55 to 1.74) and depression (0.97, 95% CI -0.25 to 2.19). The trajectory for depression did differ by ethnicity (interaction p = 0.03), with depression score improving more rapidly over time among NHWs than MAs. Advance care plans did not seem to confound any ethnic differences. DISCUSSION: Psychological distress is common among family surrogate decision makers in the year after stroke and may be worse among MAs. Efforts are needed to support family members of all ethnic groups after severe stroke.

Surrogate Decision-Making After Stroke in a Community Setting: The OASIS Project.

BACKGROUND: Patients with severe stroke often rely on surrogate decision-makers for life-sustaining treatment decisions. We investigated ethnic differences between Mexican Americans (MAs) and non-Hispanic White (NHW) individuals in surrogate reports of physician quality of communication and shared decision-making from the OASIS study (Outcomes Among Surrogate Decision Makers in Stroke) project. METHODS: Patients had ischemic stroke or intracerebral hemorrhage in Nueces County, TX. Surrogates self-identified as being involved in decisions about do-not-resuscitate orders, brain surgery, ventilator, feeding tube, or hospice/comfort care. Surrogate reports of physician quality of communication (scale score, range from 0 to 10) and shared decision-making (CollaboRATE scale score, binary score 1 versus 0) were compared by ethnicity with linear or logistic regression using generalized estimating equations, adjusted for prespecified demographics, clinical factors, and confounders. RESULTS: Between April 2016 and September 2020, 320 surrogates for 257 patients with stroke enrolled (MA, 158; NHW, 85; and other, 14). Overall quality of communication score was better among surrogates of MA patients than NHW individuals after adjustment for demographics, stroke severity, and patient survival though the ethnic difference was attenuated (ß, 0.47 [95% CI, -0.17 to 1.12]; P=0.15) after adjustment for trust in the medical profession and frequency of personal prayer. High CollaboRATE scale scores were more common among surrogates of MA patients than NHW individuals (unadjusted odds ratio, 1.75 [95% CI, 1.04-2.95]). This association persisted after adjustment for demographic and clinical factors though there was an interaction between patient age and ethnicity (P=0.04), suggesting that this difference was primarily in older patients. CONCLUSIONS: Surrogate decision-makers of MA patients generally reported better outcomes on validated measures of quality of communication and shared decision-making than NHW individuals. Further study of outcomes among diverse populations of stroke surrogate decision-makers may help to identify sources of strength and resiliency that may be broadly applicable.

Barriers to Surrogate Application of Patient Values in Medical Decisions in Acute Stroke: Qualitative Study in a Biethnic Community.

BACKGROUND: The objective of this study was to identify barriers to surrogate decision-maker application of patient values on life-sustaining treatments after stroke in Mexican American (MA) and non-Hispanic White (NHW) patients. METHODS: We conducted a qualitative analysis of semistructured interviews with stroke patient surrogate decision-makers completed approximately 6 months after hospitalization. RESULTS: Forty-two family surrogate decision-makers participated (median age: 54.5 years; female: 83%; patients were MA [60%] and NHW [36%], and 50% were deceased at the time of the interview). We identified three primary barriers to surrogates' applications of patient values and preferences when making decisions on life-sustaining treatments: (1) a minority of surrogates had no prior discussion of what the patient would want in the event of a serious medical illness, (2) surrogates struggled to apply prior known values and preferences to the actual decisions made, and (3) surrogates felt guilt or burden, often even in the setting of some knowledge of patient values or preferences. The first two barriers were seen to a similar degree in MA and NHW participants, though guilt or burden was reported more commonly among MA (28%) than NHW (13%) participants. Maintaining patient independence (e.g., ability to live at home, avoid a nursing home, make their own decisions) was the most important priority for decision-making for both MA and NHW participants; however, MA participants were more likely to list spending time with family as an important priority (24% vs. 7%). CONCLUSIONS: Stroke surrogate decision-makers may benefit from (1) continued efforts to make advance care planning more common and more relevant, (2) assistance in how to apply their knowledge of patient values to actual treatment decisions, and (3) psychosocial support to reduce emotional burden. Barriers to surrogate application of patient values were generally similar in MA and NHW participants, though the possibility of greater guilt or burden among MA surrogates warrants further investigation and confirmation.

Advance Care Planning and Transitions to Comfort Measures after Stroke.

Background: Advance care planning (ACP) is recommended to align treatment with patient goals, although there has been little study of the impact of ACP on in-hospital stroke treatment. Objective: To examine the association between ACP and transitions to comfort measures after stroke. Design: Prospective cohort study. Setting/Subjects: Hospitalized stroke patients 45 years and older and surrogate decision makers from a population-based study in Corpus Christi, TX. Measurements: Surrogates were interviewed to assess presence of patient prestroke ACP, categorized as none, informal conversations only, or formal documentation. Patient records were reviewed for time from admission to transition to comfort measures only (CMO) (defined as in-hospital comfort measures or discharge with hospice services). Cox proportional-hazards models assessed the relationship between ACP and time to transition to CMO. Results: Of 148 included stroke patients, 37% transitioned to CMO (median time five days). For ACP, 44% had only informal conversations, 38% had formal documentation (98% of which also reported informal conversations), and 18% had neither. After adjustment for age, severity, and baseline disability, informal conversations alone (hazard ratio [HR] 3.55; 95% confidence interval [CI]: 1.35-9.33) and formal documentation (HR 2.85; 95% CI: 1.05-7.72) were associated with earlier transition to comfort measures compared to no ACP. There was no difference between formal documentation and informal conversations on time to comfort measures (HR 0.80, 95% CI: 0.40-1.63). Conclusions: There was no additional association of formal ACP documentation over informal conversations on time to transition to comfort measures after stroke. Further study of formal ACP is warranted.

Family Perceptions of Quality of End-of-Life Care in Stroke.

Background: Most end-of-life decisions after stroke are made by a surrogate decision maker, yet there has been limited study of surrogate assessment of the quality of end-of-life stroke care. Objective: To assess surrogate perceptions of quality of end-of-life care (QEOLC) in stroke and explore factors associated with quality. Design: Cross-sectional analysis of interviewer-administered survey. Settings/subjects: Surrogate decision makers for deceased stroke patients in a population-based study. Measurements: The primary outcome was the validated 10-item family version of the QEOLC scale. The univariate association between prespecified patient and surrogate factors and dichotomized QEOLC score (high: 8-10, low: 0-7) was explored with logistic regression fit using generalized estimating equations. Results: Seventy-nine surrogates for 66 deceased stroke cases were enrolled (median patient age: 76, female patient: 53%, Mexican American patient: 59%, median time from stroke to death: seven days, median surrogate age: 59, and female surrogate: 72%). The overall QEOLC was generally high (median 8.3, quartiles 6.1, 9.6) although several individual items had a high proportion (∼30%-50%) of surrogates who felt that the questions did not apply to the patient's situation. No hypothesized factors were associated with QEOLC score, including demographics, stroke type, location/timing of death, advance directives, health literacy, or understanding of patient wishes. Conclusions: Surrogates reported generally high QEOLC. Although this finding is encouraging, modifications to the QEOLC may be needed in stroke as some surrogates were unable to provide a valid response for certain items.

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.

Ethnic Differences in 90-Day Poststroke Medication Adherence.

Background and Purpose- We assessed ethnic differences in medication adherence 3 months poststroke in a population-based study as an initial step in investigating the increased stroke recurrence risk in Mexican Americans compared with non-Hispanic whites. Methods- Ischemic stroke cases from 2008 to 2015 from the Brain Attack Surveillance in Corpus Christi project in Texas were followed prospectively for 3 months poststroke to assess medication adherence. Medications in 5 drug classes were analyzed: statins, antiplatelets, anticoagulants, antihypertensives, and antidepressants. For each drug class, patients were considered adherent if they reported never missing a dose in a typical week. The χ2 tests or Kruskal-Wallis nonparametric tests were used for ethnic comparisons of demographics, risk factors, and medication adherence. A multivariable logistic regression model was constructed for the association of ethnicity and medication nonadherence. Results- Mexican Americans (n=692) were younger (median 65 years versus 68 years, P<0.001), had more diabetes mellitus ( P<0.001) and hypertension ( P<0.001) and less atrial fibrillation ( P=0.003), smoking ( P=0.003), and education ( P<0.001) than non-Hispanic whites (n=422). Sex, insurance status, high cholesterol, previous stroke/transient ischemic attack history, excessive alcohol use, tPA (tissue-type plasminogen activator) treatment, National Institutes of Health Stroke Scale score, and comorbidity index did not significantly differ by ethnicity. There was no significant difference in medication adherence for any of the 5 drug classes between Mexican Americans and non-Hispanic whites. Conclusions- This study did not find ethnic differences in medication adherence, thus challenging this patient-level factor as an explanation for stroke recurrence disparities. Other reasons for the excessive stroke recurrence burden in Mexican Americans, including provider and health system factors, should be explored.

Recurrent stroke in midlife is associated with not having a primary care physician.

OBJECTIVE: To determine using a population-based study whether midlife stroke patients having a primary care physician (PCP) at the time of first stroke have a lower risk of stroke recurrence and mortality than those who do not have a PCP. METHODS: First-ever ischemic stroke patients 45 to 64 years of age at stroke onset were ascertained through the Brain Attack Surveillance in Corpus Christi (BASIC) project from 2000 to 2013 in Texas. Cox proportional hazards models were used to examine the association between not having a PCP and stroke recurrence or all-cause mortality in separate models. Cases were followed up for up to 5 years or until December 31, 2013, whichever came first. Cases were censored for recurrence if they died before experiencing a recurrent event. We adjusted for clinical risk factors that could be associated with having a PCP and recurrence or mortality. RESULTS: There were 663 first-occurrence ischemic stroke cases. Of these, 77% had a PCP, 43% were female, and average age was 55.6 years. Five-year recurrence risk was 14.6%, and mortality risk was 19.2%. Not having a PCP was associated with higher recurrence risk (adjusted hazard ratio 1.75, 95% confidence interval 1.02-3.02). Having a PCP was not associated with mortality. Sensitivity analyses showed that results were robust to different ways to adjust for chronic conditions. CONCLUSION: This study found lower rates of stroke recurrence among those with a PCP at the time of first stroke. Future studies could determine the value of establishing a PCP before stroke hospital discharge for secondary stroke prevention.

An Epigenetic Spin to ALS and FTD.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two devastating and lethal neurodegenerative diseases seen comorbidly in up to 15% of patients. Despite several decades of research, no effective treatment or disease-modifying strategies have been developed. We now understand more than before about the genetics and biology behind ALS and FTD, but the genetic etiology for the majority of patients is still unknown and the phenotypic variability observed across patients, even those carrying the same mutation, is enigmatic. Additionally, susceptibility factors leading to neuronal vulnerability in specific central nervous system regions involved in disease are yet to be identified. As the inherited but dynamic epigenome acts as a cell-specific interface between the inherited fixed genome and both cell-intrinsic mechanisms and environmental input, adaptive epigenetic changes might contribute to the ALS/FTD aspects we still struggle to comprehend. This chapter summarizes our current understanding of basic epigenetic mechanisms, how they relate to ALS and FTD, and their potential as therapeutic targets. A clear understanding of the biological mechanisms driving these two currently incurable diseases is urgent-well-needed therapeutic strategies need to be developed soon. Disease-specific epigenetic changes have already been observed in patients and these might be central to this endeavor.

Conserved DNA methylation combined with differential frontal cortex and cerebellar expression distinguishes C9orf72-associated and sporadic ALS, and implicates SERPINA1 in disease.

We previously found C9orf72-associated (c9ALS) and sporadic amyotrophic lateral sclerosis (sALS) brain transcriptomes comprise thousands of defects, among which, some are likely key contributors to ALS pathogenesis. We have now generated complementary methylome data and combine these two data sets to perform a comprehensive "multi-omic" analysis to clarify the molecular mechanisms initiating RNA misregulation in ALS. We found that c9ALS and sALS patients have generally distinct but overlapping methylome profiles, and that the c9ALS- and sALS-affected genes and pathways have similar biological functions, indicating conserved pathobiology in disease. Our results strongly implicate SERPINA1 in both C9orf72 repeat expansion carriers and non-carriers, where expression levels are greatly increased in both patient groups across the frontal cortex and cerebellum. SERPINA1 expression is particularly pronounced in C9orf72 repeat expansion carriers for both brain regions, where SERPINA1 levels are strictly down regulated across most human tissues, including the brain, except liver and blood, and are not measurable in E18 mouse brain. The altered biological networks we identified contain critical molecular players known to contribute to ALS pathology, which also interact with SERPINA1. Our comprehensive combined methylation and transcription study identifies new genes and highlights that direct genetic and epigenetic changes contribute to c9ALS and sALS pathogenesis.