Cognitive Impairment and Dementia After Stroke: Design and Rationale for the DISCOVERY Study

Stroke ◽  
2021 ◽  
Author(s):  
Natalia S. Rost ◽  
James F. Meschia ◽  
Rebecca Gottesman ◽  
Lisa Wruck ◽  
Karl Helmer ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Acute Stroke ◽  
Clinical Performance ◽  
The United States ◽  
Mediating Effect ◽  
Stroke Event ◽  
Vascular Effects ◽  
Targeted Interventions ◽  
Index Stroke ◽  
Brain Resilience

Stroke is a leading cause of the adult disability epidemic in the United States, with a major contribution from poststroke cognitive impairment and dementia (PSCID), the rates of which are disproportionally high among the health disparity populations. Despite the PSCID’s overwhelming impact on public health, a knowledge gap exists with regard to the complex interaction between the acute stroke event and highly prevalent preexisting brain pathology related to cerebrovascular and Alzheimer disease or related dementia. Understanding the factors that modulate PSCID risk in relation to index stroke event is critically important for developing personalized prognostication of PSCID, targeted interventions to prevent it, and for informing future clinical trial design. The DISCOVERY study (Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on Recovery), a collaborative network of thirty clinical performance clinical sites with access to acute stroke populations and the expertise and capacity for systematic assessment of PSCID will address this critical challenge. DISCOVERY is a prospective, multicenter, observational, nested-cohort study of 8000 nondemented ischemic and hemorrhagic stroke patients enrolled at the time of index stroke and followed for a minimum of 2 years, with serial cognitive evaluations and assessments of functional outcome, with subsets undergoing research magnetic resonance imaging and positron emission tomography and comprehensive genetic/genomic and fluid biomarker testing. The overall scientific objective of this study is to elucidate mechanisms of brain resilience and susceptibility to PSCID in diverse US populations based on complex interplay between life-course exposure to multiple vascular risk factors, preexisting burden of microvascular and neurodegenerative pathology, the effect of strategic acute stroke lesions, and the mediating effect of genomic and epigenomic variation.

scholarly journals Neurocognitive effects associated with proprotein convertase subtilisin-kexin type 9 inhibitor use: a narrative review

2021 ◽  
Vol 12 ◽  
pp. 204209862095927
Author(s):  
Wei C. Yuet ◽  
Didi Ebert ◽  
Michael Jann
Keyword(s):  
Cognitive Impairment ◽  
Adverse Events ◽  
The United States ◽  
Narrative Review ◽  
Lipid Lowering ◽  
Patient Specific ◽  
Proprotein Convertase ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
Receptor Modulation

Neurocognitive adverse events have been observed with the widespread use of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors or “statins,” which reduce low-density lipoprotein cholesterol (LDL-C) levels and subsequently cardiovascular risk. The United States Food and Drug Association directed manufacturers of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors to monitor for neurocognitive adverse events due to their potent effects on LDL-C reduction, which is a proposed mechanism for neuronal cell dysfunction. Other proposed mechanisms for PCSK9 inhibitor-associated neurocognitive adverse events include N-methyl-d-aspartate receptor modulation, dysregulation of lipid and glucose metabolism, and patient-specific risk factors for cognitive impairment. The purpose of this narrative review article is to describe the proposed mechanisms, incidence of neurocognitive adverse events from phase II and III trials for PCSK9 inhibitors, neurocognitive assessments utilized in clinical trials, and clinical implications. Given the increasing prevalence of PCSK9 inhibitor use and the neurocognitive adverse events observed with prior lipid-lowering therapies, clinicians should be aware of the risks associated with PCSK9 inhibitors, especially when therapy is indicated for patients at high risk for cardiovascular events. Overall, the incidence of PCSK9 inhibitor-associated neurocognitive appears to be uncommon. However, additional prospective studies evaluating cognitive impairment may be beneficial to determine the long-term safety of these agents.

scholarly journals Paliperidone to Treat Psychotic Disorders

2021 ◽  
Vol 13 (3) ◽  
pp. 343-358
Author(s):  
Hormazd D. Minwalla ◽  
Peter Wrzesinski ◽  
Allison Desforges ◽  
Joshua Caskey ◽  
Brittany Wagner ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Schizoaffective Disorder ◽  
Negative Symptoms ◽  
Psychotic Disorders ◽  
Drug Information ◽  
The United States ◽  
Mental Illnesses ◽  
Positive Symptoms ◽  
Review Of The Literature ◽  
Second Generation Antipsychotics

Purpose of Review: This is a comprehensive review of the literature regarding the use of paliperidone in the treatment of schizophrenia and schizoaffective disorder. It covers the background and presentation of schizophrenia and schizoaffective disorder, as well as the mechanism of action and drug information for paliperidone. It covers the existing evidence of the use of paliperidone for the treatment of schizophrenia and schizoaffective disorder. Recent Findings: Schizophrenia and schizoaffective disorder lead to significant cognitive impairment. It is thought that dopamine dysregulation is the culprit for the positive symptoms of schizophrenia and schizoaffective disorder. Similar to other second-generation antipsychotics, paliperidone has affinity for dopamine D2 and serotonin 5-HT2A receptors. Paliperidone was granted approval in the United States in 2006 to be used in the treatment of schizophrenia and in 2009 for schizoaffective disorder. Summary: Schizophrenia and schizoaffective disorder have a large impact on cognitive impairment, positive symptoms and negative symptoms. Patients with either of these mental illnesses suffer from impairments in everyday life. Paliperidone has been shown to reduce symptoms of schizophrenia and schizoaffective disorder.

scholarly journals Same-Sex Couples and Cognitive Impairment: Evidence From the Health and Retirement Study

2020 ◽  
Author(s):  
Hui Liu ◽  
Ning Hsieh ◽  
Zhenmei Zhang ◽  
Yan Zhang ◽  
Kenneth M Langa
Keyword(s):  
Cognitive Impairment ◽  
The United States ◽  
Population Based ◽  
Cognitive Status ◽  
Health And Retirement Study ◽  
Sex Partners ◽  
Physical And Mental Health ◽  
Same Sex ◽  
Same Sex Couples ◽  
Retirement Study

Abstract Objectives We provide the first nationally representative population-based study of cognitive disparities among same-sex and different-sex couples in the United States. Methods We analyzed data from the Health and Retirement Study (2000–2016). The sample included 23,669 respondents (196 same-sex partners and 23,473 different-sex partners) aged 50 and older who contributed to 85,117 person-period records (496 from same-sex partners and 84,621 from different-sex partners). Cognitive impairment was assessed using the modified version of the Telephone Interview for Cognitive Status. Mixed-effects discrete-time hazard regression models were estimated to predict the odds of cognitive impairment. Results The estimated odds of cognitive impairment were 78% (p < .01) higher for same-sex partners than for different-sex partners. This disparity was mainly explained by differences in marital status and, to a much lesser extent, by differences in physical and mental health. Specifically, a significantly higher proportion of same-sex partners than different-sex partners were cohabiting rather than legally married (72.98% vs. 5.42% in the study sample), and cohabitors had a significantly higher risk of cognitive impairment than their married counterparts (odds ratio = 1.53, p < .001). Discussion The findings indicate that designing and implementing public policies and programs that work to eliminate societal homophobia, especially among older adults, is a critical step in reducing the elevated risk of cognitive impairment among older same-sex couples.

scholarly journals THE MEDIATING ROLE OF CORPORATE ENTREPRENEURSHIP FOR EXTERNAL ENVIRONMENT EFFECTS ON PERFORMANCE

2013 ◽  
Vol 14 (Supplement_1) ◽  
pp. S328-S357 ◽  
Author(s):  
Claudine Kearney ◽  
Robert D. Hisrich ◽  
Bostjan Antoncic
Keyword(s):  
Public Sector ◽  
Private Sector ◽  
Organizational Performance ◽  
External Environment ◽  
Corporate Entrepreneurship ◽  
The United States ◽  
Mediating Effect ◽  
Integrative Model ◽  
The Public ◽  
Private Sector Organizations

A model is proposed that tests the antecedents and the mediating effect of corporate entrepreneurship on the external environment-performance relationship within private and public sector organizations. Hypotheses were tested using data from a sample of chief executive officers in 51 private sector organizations in the United States, 141 private sector organizations in Slovenia and 134 public sector state and semi-state enterprises in Ireland. Data was analyzed using hierarchical regression analysis. The results show that dynamism and munificence effects on performance are mediated by an organization's corporate entrepreneurship in the private sector and munificence effects on performance are mediated by an organization's renewal in the public sector and that renewal must be in place to maximize the effect of munificence on performance. The results support a model that incorporates an extensive and diverse literature into a single model and helps illuminate similarities and differences of corporate entrepreneurship between the private sector and the public sector. The study shows that an integrative model and the interplay among the constructs yields new insights unavailable to single and focused approaches. It offers new insights about corporate entrepreneurship, not only as a discrete pursuit, but also as a construct that shapes and extends organizational performance.

Abstract 78: Factors Associated with Thrombotic Events During Pregnancy in the United States: NIS 2000-2010

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Ali Razmara ◽  
Steven Cen ◽  
Diana L Jin ◽  
Nerses Sanossian ◽  
Amytis Towfighi
Keyword(s):  
Risk Factors ◽  
The United States ◽  
The South ◽  
Targeted Interventions ◽  
Factors Associated ◽  
Thrombosis Risk ◽  
Significant Difference ◽  
Acute Mi ◽  
Hospital Factors ◽  
Peripartum Period

Intro: Thrombosis risk is increased during pregnancy and puerperium. There are no recent data on nationwide trends in thrombotic events during the delivery period. Objective: To determine risk factors for thrombotic events in women hospitalized for deliveries. Methods: Data from the Nationwide Inpatient Sample (2000-2010) were used to identify deliveries. Weighted proportion of pregnancy hospitalizations with comorbid thrombotic events, including TIA, ischemic stroke, hemorrhagic stroke, acute MI, and venous thromboembolism, was determined. Poisson regression was used to identify risk factors for thrombotic events. The first multivariable model adjusted for sociodemographic and hospital factors. The second model in addition adjusted for comorbid conditions. Results: There were 4,305,561 women hospitalized for delivery (21.5 million US deliveries), of which 7,242 (0.17%) had thrombotic events in the peripartum period. From 2000-2010, there was an increase in deliveries with associated thrombotic events observed from 7.46/10K to 34.8/10K. Compared to 2000, deliveries with thromboses was 8-fold more likely in 2010 (RR 7.94, 95% CI 1.98-31.93). There was no significant difference in rates from 2000 to 2010 after adjustment for sociodemographic and hospital factors. From 2000-2010, pregnant women with thrombotic events were older, more likely to be White, to smoke, to lack insurance, to be admitted to rural hospitals, and to be admitted in the South or Midwest. After multivariable adjustment for sociodemographics, hospital factors, and comorbidities, admissions in the South (RR 1.26, 95% CI 1.02-1.55) or Midwest (1.33, 95% CI 1.05-1.68), atrial fibrillation (1.28, 95% CI 1.01-1.62), pre-/eclampsia (5.78, 95% CI 4.37-7.66), dyslipidemia (1.72, 95% CI 1.42-2.09), atrial septal defect (14.38, 95% CI 6.76-30.58), and valvular heart disease (1.67, 95% CI 1.25-2.24) were independently associated with higher risk of thrombotic events. Conclusions: From 2000-2010, there was a sizeable increase in deliveries with associated thrombosis. Identification of factors associated with thrombotic events for women hospitalized for normal pregnancies will aid in targeted interventions to screen for, prevent and treat thrombosis related to pregnancy.

Valuing Diversity and Inclusion in Healthcare: Pathways to Equip Workforces in the Post-COVID-19 New Normal (Preprint)

2021 ◽  
Author(s):  
Jiban Khuntia ◽  
Xue Ning ◽  
Wayne Cascio ◽  
Rulon Stacey
Keyword(s):  
United States ◽  
Health System ◽  
Health Systems ◽  
The United States ◽  
Mediating Effect ◽  
New Normal ◽  
Diversity And Inclusion ◽  
Healthcare Workforce ◽  
The Us ◽  
Service Oriented

BACKGROUND The COVID-19 pandemic, with all its virus variants, remains a serious situation. Health systems across the United States are trying their best to respond. The healthcare workforce remains relatively homogenous, even though they are caring for a highly diverse array of patients (6-12). It is a perennial problem in the US healthcare workforce that has only been accentuated during the COVID-19 pandemic. Medical workers should reflect the variety of patients they care for and strive to understand their mindsets within the larger contexts of culture, gender, sexual orientation, religious beliefs, and socioeconomic realities. Along with talent and skills, diversity and inclusion (D&I) are essential for maintaining a workforce that can treat the myriad needs and populations that health systems serve. Developing hiring strategies in a post-COVID-19 “new normal” that will help achieve greater workforce diversity remains a challenge for health system leaders. OBJECTIVE Our primary objectives are (1) to explore the characteristics and perceived benefits of US health systems that value D&I; (2) to examine the influence of a workforce strategy designed to balance talent and D&I; and (3) to explore three pathways to better equip workforces and their relative influences on business- and service-oriented benefits: (a) improving D&I among existing employees (IMPROVE), (b) using multiple channels to find and recruit a workforce (RECRUIT), and (c) collaborating with universities to find new talent and establish plans to train students (COLLABORATE). METHODS During February–March 2021, we surveyed 625 health system chief executive officers, in the United States, 135 (22%) of whom responded. We assessed workforce talent and diversity-relevant factors. We collected secondary data from the Agency for Healthcare Research and Quality’s (AHRQ) Compendium of the US. Health Systems, leading to a matched data set of 124 health systems for analysis. We first explored differences in talent and diversity benefits across the health systems. Then, we examined the relationship between IMPROVE, RECRUIT, and COLLABORATE pathways to equip the workforce. RESULTS Health system characteristics, such as size, location, ownership, teaching, and revenue, have varying influences on D&I and business and service outcomes. RECRUIT has the most substantial mediating effect on diversity-enabled business- and service-oriented outcomes of the three pathways. This is also true of talent-based workforce acquisitions. CONCLUSIONS Diversity and talent plans can be aligned to realize multiple desired benefits for health systems. However, a one-size-fits-all approach is not a viable strategy for improving D&I. Health systems need to follow a multipronged approach based on their characteristics. To get D&I right, proactive plans and genuine efforts are essential.

Abstract WP178: Acute Stroke Ischemic Symptom Onset-to-Arrival Time in Michigan Hospitals

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Muhammad U Farooq ◽  
Kathie Thomas
Keyword(s):  
African American ◽  
Ischemic Stroke ◽  
Acute Stroke ◽  
Patient Outcomes ◽  
Symptom Onset ◽  
Arrival Time ◽  
Heart Association ◽  
The United States ◽  
Stroke Patients ◽  
White Patients

Objectives: Stroke is the fifth-leading cause of death and the leading cause of disability in the United States. One of the primary goals of the American Heart Association/American Stroke Association is to increase the number of acute stroke patients arriving at emergency departments (EDs) within 1-hour of symptom onset. Earlier treatment with thrombolysis in patients with acute ischemic stroke translates into improved patient outcomes. The objective of this abstract is to examine the association between the use of emergency medical services (EMS) and symptom onset-to-arrival time in patients with ischemic stroke. Methods: A retrospective review of ischemic stroke patients (n = 8873) from 25 Michigan hospitals from January 2012-December 2014 using Get With the Guidelines databases was conducted. Symptom onset-to-ED arrival time and arrival mode were examined. Results: It was found that 17.4% of ischemic stroke patients arrived at the hospitals within 1-hour of symptom onset. EMS transported 69.1% of patients who arrived within 1-hour of symptom onset. During this 1-hour period African American patients (22%) were less likely to use EMS transportation as compared to White patients (72%). The majority of patients, 41.8%, arrived after 6-hours of symptom onset. EMS transported only 40% of patients who arrived after 6-hours of symptom onset. As before, during this 6-hour period African American patients (20%) were also less likely to use EMS transportation as compared to White patients (75%). Symptom onset-to-ED arrival time was shorter for those patients who used EMS. The median pre-hospital delay time was 2.6 hours for those who used EMS versus 6.2 hours for those who did not use EMS. Conclusions: The use of EMS is associated with a decreased pre-hospital delay, early treatment with thrombolysis and improved patient outcomes in ischemic stroke patients. Community interventions should focus on creating awareness especially in minority populations about stroke as a neurological emergency and encourage EMS use amongst stroke patients.

Abstract WP340: Prevalence and Influence of Chronic Obstructive Pulmonary Disease on Stroke Outcomes in Hospitalized Stroke Patients

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Oladimeji Akinboro ◽  
Odunayo Olorunfemi ◽  
Stanley Holstein ◽  
Daniel Pomerantz ◽  
Stephen Jesmajian ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Hospital Mortality ◽  
The United States ◽  
Mortality Rates ◽  
Chronic Obstructive ◽  
Stroke Patients ◽  
Obstructive Pulmonary Disease ◽  
Index Stroke ◽  
Nationally Representative ◽  
Shared Risk

Background: COPD recently overtook stroke as the third leading cause of death in the United States. Intriguingly, smoking is an important shared risk factor for both stroke and COPD; COPD patients have baseline cerebral hypoxia and hypercapnia that could potentially exacerbate vascular brain injury; and stroke patients with COPD are at higher risk of aspiration than those without COPD. Yet, relatively little is known about the prevalence of COPD among stroke patients or its impact on outcomes after an index stroke. Objective: To assess prevalence of COPD among hospitalized stroke patients in a nationally representative sample and examine the effect of COPD with risk of dying in the hospital after a stroke. Methods: Data were obtained for patients, 18 years and older, from the National Inpatient Sample from 2004-2009 (n=48,087,002). Primary discharge diagnoses of stroke were identified using ICD-9 diagnosis codes 430-432 and 433-436, of which a subset with comorbid COPD were defined with secondary ICD-9 diagnoses codes 490-492, 494, and 496. In-hospital mortality rates were calculated, and independent associations of COPD with in-hospital mortality following stroke were evaluated with logistic regression. All analysis were survey-weighted. Results: 11.71% (95% CI 11.48-11.94) of all adult patients hospitalized for stroke had COPD. The crude and age-adjusted in-hospital mortality rates for these patients were 6.33% (95% CI 6.14-6.53) and 5.99% (95% CI 4.05-7.94), respectively. COPD was independently and modestly associated with overall stroke mortality (OR 1.03, 95% CI 1.01-1.06; p=0.02). However, when analyzed by subtype, greater risks of mortality were seen in those with intracerebral hemorrhage (OR 1.12, 95% CI 1.03-1.20; p<0.01), and ischemic stroke (OR 1.08; 95% CI 1.03-1.13, p<0.01), but not subarachnoid hemorrhage (OR 0.98, 95% CI 0.85-1.13; p=0.78). There were no statistically significant interactions between COPD and age, gender, or race. Conclusion: 12% of hospitalized stroke patients have COPD. Presence of COPD is independently associated with higher odds of dying during ischemic stroke hospitalization. Prospective studies are needed to identify any modifiable risk factors contributing to this deleterious relationship.

Abstract P164: The Impact of the Expanded EVT Window on Acute Stroke Services: A Large Northwest Telestroke Network Experience

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Theodore Lowenkopf ◽  
Leslie Corless ◽  
Elizabeth Baraban
Keyword(s):  
Acute Stroke ◽  
Rural Areas ◽  
Treatment Time ◽  
Time Window ◽  
Tertiary Care ◽  
The United States ◽  
Geographic Region ◽  
Anterior Circulation ◽  
Stroke Subtypes ◽  
The Impact

Background: Telestroke has led the technological revolution in providing acute medical services to rural areas in the United States since the beginning of this century. In January 2018 the American Stroke Association made a level IA recommendation to expand the treatment time window for endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) from 6 to 24 hours for anterior circulation stroke based on perfusion imaging. Our study is the first to our knowledge to report the effect of the expanded time window on acute stroke consult and treatment volumes in a large rural supporting telestroke network. Methods: Stroke registry data from two tertiary care facilities from a 22 hospital telestroke network supporting a large (> 78,000 mi 2 ) primarily rural Northwest geographic region were used. Data included stroke patients arriving within 24 hours of last known well (LKW) between January 2017 and March 2019. Patients arriving January 2017 to December 2017 were grouped into the PRE-expanded time window and those arriving April 2018 to March 2019 into the POST-expanded time window. Stroke subtypes, transfers, telestroke consults (via phone or video), and EVT treatments were compared across time periods. Analyses were performed using Pearson’s chi square test, corrected for multiple comparisons. Results: A total of 1117 patients arrived with stroke symptoms within 24 hours of LKW, 567 (50.8%) in PRE and 550 (49.2%) in POST-window. The percentage of all stroke subtypes were not significantly different in the PRE and POST patient groups (p=.720). However, the percent of telestroke consults increased by 12.1% from 62.3% to 74.4% (p<.001) but the percent of video consults remained similar (25.9% vs 25.8%). The total number of transfers (142 vs 141) and percentage of transfers among AIS patients (25.0% vs 25.6%) from partner to hub did not change. The percentage of thrombectomies among transfers rose by 8.7% with the expanded time window, but was not statistically significant [p=0.118]. Conclusions: In a large Northwest telestroke rural network the expanded EVT treatment time window led to a marked increase in all telestroke consults but did not impact video consults, transfer, or percentage of patients treated.

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