Weight change during childhood acute lymphoblastic leukemia induction therapy predicts obesity: a report from the Children's Oncology Group.

BACKGROUND: Obesity is a well documented problem associated with childhood acute lymphoblastic leukemia (ALL) with increasing body mass index often observed during therapy. This study aims to evaluate if weight gain, early in therapy, is predictive of obesity at the end of treatment. PROCEDURE: In this secondary analysis, data from 1,017 high-risk ALL patients previously treated on a Children's Oncology Group protocol (CCG study 1961) were reviewed. Logistic regression was used to examine whether change in BMI z-score at Induction or Delayed Intensification (DI) 1 were predictive of obesity at the end of therapy. RESULTS: The BMI z-score at the beginning of Induction and the change in BMI z-score during Induction were both significant predictors of obesity at the end of therapy. The change in BMI z-score during cycle 1 of DI was not found to be associated with obesity. CONCLUSIONS: It is well know that obesity at the beginning of therapy is predictive of obesity at the end of ALL therapy. The new, and more important, finding from this study is that even after adjusting for baseline weight, the increase in BMI z-scores during induction was an independent predictor of obesity at the end of therapy. Most researchers agree that prevention is the best form of treatment for obesity as it is difficult to reverse once it is present. This study suggests that monitoring weight trends during Induction may be useful in guiding healthcare practitioners in identifying which patients are at highest risk for obesity development so that early intervention may occur.

Adiponectin, Interleukin-18 (IL-18), and Visceral Adipose Tissue in Filipino Americans: Biomarkers and Risk of Type 2 Diabetes.

Introduction: Filipino Americans (FAs) are at high risk for developing type 2 diabetes despite other Asian phenotypes. Evidence suggests that pro-inflammatory interleukin-18 (IL-18) and anti-inflammatory adiponectin biomarkers associated with visceral adipose tissue (VAT) may explain this risk. Objectives: This study aimed to quantify the biomarkers in relation to standard ranges of VAT or typical circulating concentration ranges reported in the literature of IL-18 and adiponectin, examine relationships of these markers, and determine if they were different among those participants without diabetes, prediabetes, and diabetes. Methods: A cross-sectional study was used to enroll FAs without diabetes, prediabetes, or diabetes. VAT was measured using the InBody 570© Body Composition Analyzer. Blood samples were obtained to assess plasma concentrations of IL-18 and adiponectin using enzyme-linked immunosorbent assay. All analyses were conducted using a 5% type I error rate. Mean ±SD and percentages were used to describe the sample and data where appropriate. Pearson's correlations (R) were calculated to determine the relationships between VAT and IL-18 in each group. Analysis of variance was used to determine differences in VAT, IL-18, and adiponectin among groups. Further, nonparametric procedures examined the differences in adiponectin among those within groups. Results: Seventy-five participants were enrolled. Biomarkers above the typical concentration range were observed for VAT, IL-18, and adiponectin. Adiponectin significantly differed among groups with lower values in the diabetes group vs. the nondiabetes group. Conclusions: The findings indicate that while inflammation-related biomarkers, such as adiponectin, correlate with VAT and may serve as indicators of increased risk of type 2 diabetes in FAs, correlation alone does not establish causality.

Curcuminoids limit neutrophil-mediated reperfusion injury in experimental stroke by targeting the endothelium.

OBJECTIVE: We sought to test the hypothesis that turmeric-derived curcuminoids limit reperfusion brain injury in an experimental model of stroke via blockade of early microvascular inflammation during reperfusion. METHODS: Male Sprague Dawley rats subjected to MCAO/R were treated with turmeric-derived curcuminoids (vs. vehicle) 1 hour prior to reperfusion (300 mg/kg ip). Neutrophil adhesion to the cerebral microcirculation and measures of neutrophil and endothelial activation were assayed during early reperfusion (0-4 hours); cerebral infarct size, edema, and neurological function were assessed at 24 hours. Curcuminoid effects on TNFα-stimulated human brain microvascular endothelial cell (HBMVEC) were assessed. RESULTS: Early during reperfusion following MCAO, curcuminoid treatment decreased neutrophil rolling and adhesion to the cerebrovascular endothelium by 76% and 67% and prevented >50% of the fall in shear rate. The increased number and activation state (CD11b and ROS) of neutrophils were unchanged by curcuminoid treatment, while increased cerebral expression of TNFα and ICAM-1, a marker of endothelial activation, were blocked by >30%. Curcuminoids inhibited NF-κB activation and subsequent ICAM-1 gene expression in HBMVEC. CONCLUSION: Turmeric-derived curcuminoids limit reperfusion injury in stroke by preventing neutrophil adhesion to the cerebrovascular microcirculation and improving shear rate by targeting the endothelium.

Early Skin Temperature Characteristics of the Kennedy Lesion (Kennedy Terminal Ulcer).

BACKGROUND: Pressure injuries are associated with skin temperature changes, but little is known about skin temperature characteristics of the Kennedy Lesion (KL). PURPOSE: The purpose of this study was to describe early skin temperature changes in KLs using long-wave infrared thermography. METHODS: KLs were identified from chart review in 10 ICU patients. Skin assessments were performed within 24 hours of new skin discoloration. Temperature measurements were performed using a long-wave infrared thermography imaging system. Relative Temperature Differential (RTD) between the discolored area and a selected control point was calculated. RTDs of > +1.2 degrees C and < -1.2 degrees C were considered abnormal. Demographic data and observable characteristics of the KL were collected when available. Descriptive statistics (Mean plus/minus SD; % ) were used. RESULTS: The major finding of this study was that there were no early skin temperature differences between the KLs and surrounding skin. CONCLUSION: The early stage of the KL may be limited to microvascular injury which results in a normal skin temperature. More studies are needed to verify this finding and to ascertain whether KL skin temperature changes over time. The study also supports the bedside use of thermography in skin temperature assessment.

A cultural perspective of Samoans' perceived risk of cardiovascular disease and diabetes.

BACKGROUND: Cardiovascular disease (CVD) and diabetes, which are leading causes of morbidity and mortality in the United States, have a high incidence among Pacific Islanders. Risk of these conditions increases in the presence of metabolic syndrome. Risk-reducing behaviors for CVD and diabetes are driven partly by perceived risk of health threats and their consequences. Perceived risk is influenced by sociocultural beliefs and is a component of some health behavior models, yet it is understudied in Pacific Islanders. OBJECTIVE: This mixed-methods study explored the perceived risk of CVD and diabetes in at-risk Samoan Pacific Islanders. SUBJECTS AND METHODS: We used culturally sensitive strategies to recruit and enroll 43 adult Samoans from a community setting in Hawaii. Participants were obese with at least 1 other component of metabolic syndrome. Their objective risk was determined by the National Cholesterol Education Program Adult Treatment Program III risk categories. Participants provided demographic and health history information and answered 2 quantitative perceived risk questions. They also participated in 1 of 7 focus groups--the source of perceived risk qualitative data. Quantitative and qualitative data were analyzed using descriptive statistics and content analysis, respectively. The mixed-methods analysis targeted points of data convergence and complementarity for the 2 methods. RESULTS: More than 80% of participants who were at moderately high (10%-20%) objective risk for CVD and diabetes had high (>20%) perceived risk of these conditions. There was high concordance of perceived risk for CVD and diabetes (P < .05). Qualitative data revealed bidirectional codes that influenced and were influenced by perceived risk within the participants' cultural perspective: current and planned health behavior, physical health, and family history of CVD or diabetes. CONCLUSION: Using mixed methods facilitated better understanding of cultural perspectives of perceived risk of CVD and diabetes. These results provide a foundation for developing culturally appropriate interventions targeting CVD and diabetes risk reduction in Samoans.

Stroke-Specific Refinements to Naylor's Transitional Care Model to Address the Storm of Uncertainty and Unmet Survivor and Caregiver Needs.

ABSTRACT: BACKGROUND: By 2030, there will be approximately 7.6 million stroke survivors (SSs) in the United States, yet comprehensive transitional care (TC) for stroke is not widely available. Stroke strikes without warning and leaves in its wake a "storm" of uncertainty for SSs and caregivers (CGs) as they encounter a myriad of unmet physical, mental, emotional, and financial needs that are not wholly addressed by passive healthcare delivery systems. Needed is a stroke-specific TC model that bridges this storm to active delivery of SS and CG postacute care. Naylor's Transitional Care Model (NTCM) has not been examined for how it can frame comprehensive stroke care. The purpose of this study was to solicit SS and CG descriptions of TC experiences to inform the NTCM with refined operational definitions and exemplars specific to stroke. METHODS: Focus groups conducted for this qualitative descriptive study were guided by interview questions based on the 8 NTCM operational definitions. Data were analyzed using inductive and deductive qualitative content analysis methods. RESULTS: Post-acute-stroke care does not comprehensively meet the needs of SSs and CGs. Participants described TC deficits across all 8 NTCM components. Two new subcomponents that could be applied for a stroke-specific NTCM emerged: psychological and transportation challenges. CONCLUSION: Unmet needs identified by SSs and CGs were used to extend NTCM specific to the stroke population and to develop the Recommendations and Exemplars for Stroke Specific Comprehensive Transitional Care Delivery (see Supplementary Digital Content, available at http://links.lww.com/JNN/A385). Researchers and practitioners can use the findings to develop and deliver more comprehensive TC to SSs and CGs.

The Economic Burden of Multiple Sclerosis in the United States: Estimate of Direct and Indirect Costs.

BACKGROUND AND OBJECTIVES: A recent report estimated that approximately 1 million adults were living with multiple sclerosis (MS) in the United States. Although MS is rarely the direct cause of death, its debilitating effects on normal body functions can result in considerable disruption to daily living and life roles including work, physical independence, mobility, social interaction, and participation in leisure activities. This study estimated the total economic burden of MS in the United States in 2019. METHODS: This study used a prevalence-based approach to estimate the national economic burden of MS. Claims from 3 sources (Medicare Current Beneficiary Survey, Medicare Standard Analytical File, and Optum de-identified Normative Health Information System) were used to obtain direct costs and a survey was developed to collect indirect costs (e.g., labor market productivity losses, costs of paid and unpaid caregivers, home modification) from 946 patients with MS (PwMS). Direct medical costs reflected the difference in the total average annual amount paid for PwMS vs matched controls without MS. Future earnings loss due to premature death attributable to MS was calculated using Centers for Disease Control and Prevention mortality data and Medicare claims data. RESULTS: The estimated total economic burden was $85.4 billion, with a direct medical cost of $63.3 billion and indirect and nonmedical costs of $22.1 billion. Retail prescription medication (54%); clinic-administered drugs, medication, and administration (12%); and outpatient care (9%) were the 3 largest components of the direct costs. The average excess per-person annual medical costs for PwMS was $65,612; at $35,154 per person, disease-modifying therapies (DMTs) accounted for the largest proportion of this cost. The cost per DMT user ranged from $57,202 to $92,719, depending on sex-age strata. The average indirect and nonmedical costs were $18,542 per PwMS and $22,875 per PwMS if caregivers' costs were included. Lost earnings due to premature death, presenteeism, and absenteeism losses were the largest indirect cost components. DISCUSSION: MS is a costly chronic disease, with direct costs of prescription drugs and indirect productivity loss being important cost drivers. Our findings suggested that the burden of MS in the United States has been underestimated.

Exaggerated neutrophil-mediated reperfusion injury after ischemic stroke in a rodent model of type 2 diabetes.

OBJECTIVE: We tested the hypothesis that both chronic and acute inflammatory processes contribute to worse reperfusion injury and stroke outcome in an experimental model of T2DM. MATERIALS AND METHODS: Twelve- to thirteen-week-old male Zucker Diabetic Fatty (ZDF) rats vs. Zucker Lean Controls (ZLC) rats were tested at baseline and after middle cerebral artery occlusion (ischemia) and reperfusion (I-R). Neutrophil adhesion to the cerebral microcirculation, neutrophil expression of CD11b, infarction size, edema, neurologic function, sICAM, and cerebral expression of neutrophil-endothelial inflammatory genes were measured. RESULTS: At baseline, CD11b and sICAM were significantly increased in ZDF vs. ZLC animals (p < 0.05). After I-R, significantly more neutrophil adhesion and cell aggregates were observed in ZDF vs. ZLC (p < 0.05); infarction size, edema, and neurologic function were significantly worse in ZDF vs. ZLC (p < 0.05). CD11b and sICAM-1 remained significantly increased in ZDFs (p < 0.05), and cerebral expression of IL-1ß, GRO/KC, E-selectin, and sICAM were significantly induced in ZDF, but not ZLC groups (p < 0.05) after 2.5 hours of reperfusion. CONCLUSION: Both sides of the neutrophil-endothelial interface appear to be primed prior to I-R, and remain significantly more activated during I-R in an experimental model of T2DM. Consequently, reperfusion injury appears to play a significant role in poor stroke outcome in T2DM.

Diseasome: an approach to understanding gene-disease interactions.

Using bioinformatics computational tools, network maps that integrate the complex interactions of genetics and diseases have been developed. The purpose of this review is to introduce the reader to new approaches in understanding disease-gene associations using network maps, with an emphasis on how the human disease network (HDN) map (or diseasome) was constructed. A search was conducted in PubMed using the years 1999-2011 and using key words diseasome, molecular interaction, interactome, protein-protein interaction, and gene. The information reviewed included journal reviews, open source and web-based databases, and open source computational tools. A review of the literature revealed the complexity of molecular, genetic, and protein structures that contribute to cellular function and possible disease, and how network mapping can help the clinician and scientist gain a better understanding of this complexity Using computational tools and databases of genetics, protein interactions, and diseases, scientists have developed a network map of human genes and human diseases referred to as a diseasome. The diseasome is composed of 22 disease classes represented in different colored circular nodes. Lines connecting nodes indicate shared genes among diseases. Thus, the diseasome map provides a colorfully visual display that helps the user conceptualize gene-disease relationships. This review provides an overview of the use of network maps to understand the interrrelationships of genomics and disease. One such map, the diseasome, could be used as a reference for biomedical researchers and multidiscipline health care providers, including nurse practitioners and genetic counselors, to enhance their conceptualization and understanding of the genetic origins of disease.

Central nervous system genomics.

In the past 25 years, remarkable progress has been made in our understanding of genomics and its influence on central nervous system diseases. In this chapter, common diseases of the central nervous system will be reviewed along with the genomics associated with these diseases. The diseases/injuries that will be investigated include neurovascular disorders such as ischemic stroke, hemorrhagic stroke, subarachnoid hemorrhage, and traumatic brain injury. This chapter will also explore Apolipoprotein E (APOE), a 299-aminoacid protein encoded by the APOE gene, and its associations with many of the previously named diseases. APOE was first tied to the risk of Alzheimer's disease and has since then been investigated in traumatic brain injury and hemorrhagic strokes. In addition, we will discuss the future of genomic research in central nervous system diseases.

Perspectives for practice: translating estimated average glucose (eAG) to promote diabetes self-management capacity.

PURPOSE: The purpose of this article is to facilitate translation of the Consensus Statement to practice for diabetes educators and other professionals who contribute to the care of individuals with diabetes. METHODS: The 2007 Consensus Statement from the American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), and International Diabetes Federation (IDF) called for the standardization of glycated hemoglobin measurement in reporting and use of average glucose values in clinical practice. RESULTS: Conversion of glycated hemoglobin percentage to average blood glucose was anchored historically in early laboratory techniques linked to disease outcomes rather than to definitive laboratory standardization. Recently, the A1C-Derived Average Glucose (ADAG) study demonstrated that A1C values can be accurately expressed as estimated average glucose (eAG) and endorsed eAG as the best way to standardize the expression of laboratory values of glycated hemoglobin. CONCLUSIONS: Adoption of the 2007 Consensus Statement will influence clinical practice and decision making and subsequently influence self-management for individuals with diabetes.

Patterns of Recovery From Aphasia in the First 2 Weeks After Stroke.

Purpose Recovery from aphasia after stroke has a decelerating trajectory, with the greatest gains taking place early and the slope of change decreasing over time. Despite its importance, little is known regarding evolution of language function in the early postonset period. The goal of this study was to characterize the dynamics and nature of recovery of language function in the acute and early subacute phases of stroke. Method Twenty-one patients with aphasia were evaluated every 2-3 days for the first 15 days after onset of acute ischemic or hemorrhagic stroke. Language function was assessed at each time point with the Quick Aphasia Battery (Wilson, Eriksson, Schneck, & Lucanie, 2018), which yields an overall summary score and a multidimensional profile of 7 different language domains. Results On a 10-point scale, overall language function improved by a mean of 1.07 points per week, confidence interval [0.46, 1.71], with 19 of 21 patients showing positive changes. The trajectory of recovery was approximately linear over this time period. There was significant variability across patients, and patients with more impaired language function at Day 2 poststroke experienced greater improvements over the subsequent 2 weeks. Patterns of recovery differed across language domains, with consistent improvements in word finding, grammatical construction, repetition, and reading, but less consistent improvements in word comprehension and sentence comprehension. Conclusion Overall language function typically improves substantially and steadily during the first 2 weeks after stroke, driven mostly by recovery of expressive language. Information on the trajectory of early recovery will increase the accuracy of prognoses and establish baseline expectations against which to evaluate the efficacy of interventions. Supplemental Material https://doi.org/10.23641/asha.7811876.

Caspase inhibition of platelet activation.

The role of caspases in platelet function is not well understood. When platelets are activated, they express phosphatidylserine on the outer plasma membrane, form platelet microparticles, and aggregate (Pag). The aims of this study were to determine if caspases play a role in the platelet activation seen in type 2 diabetes. Diabetic rats (Zucker diabetic fatty) were treated with a broad-spectrum caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone, in vivo and platelets were evaluated for phosphatidylserine expression, platelet microparticle formation, and Pag. We found a decreased phosphatidylserine exposure in zVAD-Zucker diabetic fatty rats compared to Zucker diabetic fatty-phosphate-buffered saline when activated with 20 micromol/l ADP. Zucker diabetic fatty rats treated with benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone decreased platelet microparticle numbers compared to phosphate-buffered saline control Zucker diabetic fatty rats. Further, treatment with benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone significantly decreased Pag. These results indicate that caspases play a role in platelet activation, suggesting a unique physiologic role of these proteases and perhaps the underlying mechanisms involved in the chronic platelet activation observed in type 2 diabetes.

Whole blood aggregation and coagulation in db/db and ob/ob mouse models of type 2 diabetes.

Type 2 diabetes in humans is associated with a significant hypercoagulable state; however, the effects of this on stroke and cardiovascular disease are not completely understood. The genetic mutations in db/db and ob/ob mice produce metabolic abnormalities similar to type 2 diabetes, but little is known about their platelet or coagulation properties. The objective of this study was therefore to examine platelet function and coagulation in db/db and ob/ob mice to determine the degree of alteration induced by type 2 diabetes. Male db/db and ob/ob mice, 8-16 weeks old, and their respective genetic control mice were used for all experiments. To examine platelet function and coagulation, we measured ADP-induced whole blood aggregation at baseline and after inhibition with aspirin and fucoidan, whole blood coagulation by thromboelastography, and platelet CD61 expression by flow cytometry. Both db/db and ob/ob mice demonstrated significantly less ADP-induced whole blood aggregation compared with control mice (db/db mice, P < 0.001; ob/ob mice, P < 0.01). Aggregation was significantly inhibited with aspirin in all groups; however, fucoidan inhibited aggregation only in control mice. The db/db and ob/ob mice demonstrated significantly less maximal clot strength compared with control mice (P < 0.01), and ob/ob mice demonstrated premature clot fibrinolysis measured by thromboelastography. In conclusion, the db/db and ob/ob type 2 diabetes mouse models do not demonstrate a hypercoagulable state similar to humans with this disease. We caution their use for studying cardiovascular and cerebrovascular disease in the setting of type 2 diabetes.

Comparison of sample fixation and the use of LDS-751 or anti-CD45 for leukocyte identification in mouse whole blood for flow cytometry.

Flow cytometry methods used to measure leukocyte function often entail sample preparation procedures that cause artifactual cell activation. To avoid leukocyte activation by isolation techniques, some preparation methods use fluorescent markers to discriminate leukocytes from erythrocytes in whole blood. One of these markers, laser dye styryl-751(LDS-751), has been used to distinguish leukocytes by staining nucleic acid, but has been found to stain other blood cells and dead cells indiscriminately. Thus, LDS-751 may not be an appropriate reagent for leukocyte identification in whole blood. Fixing samples with formaldehydes increases cell permeability and causes surface protein cross-linking that may alter staining of both intra- and extracellular markers. The degree of this sample alteration by formaldehyde fixation, however, remains in question. In addition, little is known about flow cytometry and sample preparation methods in mouse whole blood. The purpose of this study was to determine if labeling leukocytes with a monoclonal antibody specific to leukocyte common antigen (CD45) was superior to labeling with LDS-751 and to determine the effect of sample fixation on a mouse whole blood preparation for flow cytometry. Samples were incubated with CD16/CD32 Fc receptor blocker, and either 10 microg/ml LDS-751 or phosphate buffered saline (PBS). The samples were then fixed with paraformaldehyde or diluted with PBS followed by incubation with 5 microg/ml PerCP-conjugated anti-CD45, 5 microg/ml FITC-conjugated anti-CD11b, or 80 microM dichlorofluorescein diacetate. We found that samples labeled with LDS-751 demonstrated decreased fluorescence intensity for granulocyte CD11b expression and ROS production compared to samples labeled with anti-CD45. In addition, sample fixation decreased mean fluorescence intensity in samples labeled with either LDS-751 or anti-CD45. We conclude that labeling leukocytes with monoclonal antibody CD45 in a mouse whole blood preparation is preferable, as it provides improved measurement of leukocyte indices compared to LDS-751. Also, while sample fixation prior to antibody staining caused a decrease in overall fluorescence; it can be used to successfully identify extra-cellular markers.

Leukocyte-platelet aggregates in rat peripheral blood after ischemic stroke and reperfusion.

Ischemic stroke and reperfusion (ISR) is associated with an inflammatory response characterized, in part, by the formation of leukocyte-platelet aggregates (LPA). Aggregate formation may amplify the immunologic and hemostatic functions of both cell types and thus exacerbate reperfusion injury after ischemic stroke. LPA formation in peripheral blood may also serve as a biomarker of the severity of injury. However, it is not fully known whether ISR causes LPA formation that can be detected in the peripheral blood. Therefore, the purpose of this study was to measure LPA in the peripheral blood after ISR using a rat model. The filament method was used to perform ISR. Blood was collected from the jugular vein before ischemia, after 4 hours of ischemia, and after 1 hour of reperfusion. Flow cytometry was used to quantify LPA in peripheral blood. Separate ISR groups were treated with tirofiban, a platelet GPIIb/IIIa inhibitor, and fucoidan, a selectin adhesion molecule inhibitor, and analyzed for LPA. Leukocyte CD11b expression and reactive oxygen species production were also analyzed to note the role of polymorphonuclear neutrophilic (PMN) activation on LPA formation. After ISR, LPA levels in peripheral blood were twice as large as preischemic levels. Both GPIIb/IIIa and selectin adhesion molecule inhibition (p < .05) decreased LPA to preischemic values. PMN CD11b expression was increased above baseline but did not differ between groups. Reactive oxygen species production did not differ between groups during reperfusion. These data suggest that ischemic stroke and reperfusion results in an increase in LPA that can be consistently measured in peripheral blood. LPA formation may be a useful biomarker and potential therapeutic target after ischemic stroke and reperfusion.

Transitions of care for stroke and TIA.

PURPOSE: The purpose of this study was to identify elements of a stroke population that may affect transitions of care (TOC). DATA SOURCES: A retrospective analysis of the demographic characteristics of patients from an urban primary stroke center with an admitting diagnosis of transient ischemic attack, acute ischemic stroke, subarachnoid hemorrhage, or intracerebral hemorrhage was performed over an 8-month period (N = 276). A subset of this patient sample participated in a telephone survey 1 month after discharge. CONCLUSION: Hospital length of stay, age, insurance status, discharge disposition, comorbidities, and readmission rates were identified as important elements affecting TOC for stroke and TIA. Information from patient surveys indicated that emotional health, follow-up with care providers, stroke education, and point of contact are important elements during the transition periods after stroke and TIA. IMPLICATIONS FOR PRACTICE: Both providers and patients should inform the development of a comprehensive TOC program that spans in-hospital to multiple care settings, including the home, which is essential. The advanced practice nurse is ideally suited to successfully lead these programs.

Identification of Barriers to Stroke Awareness and Risk Factor Management Unique to Hispanics.

Barriers to risk factor control may differ by race/ethnicity. The goal of this study was to identify barriers to stroke awareness and risk factor management unique to Hispanics as compared to non-Hispanic whites (NHWs). We performed a prospective study of stroke patients from an academic Stroke Center in Arizona and surveyed members of the general community. Questionnaires included: the Duke Social Support Index (DSSI), the Multidimensional Health Locus of Control (MHLC) Scale, a stroke barriers questionnaire, and a Stroke Awareness Test. Of 145 stroke patients surveyed (72 Hispanic; 73 NHW), Hispanics scored lower on the Stroke Awareness Test compared to NHWs (72.5% vs. 79.1%, p = 0.029). Hispanic stroke patients also reported greater barriers related to medical knowledge, medication adherence, and healthcare access (p < 0.05 for all). Hispanics scored higher on the "powerful others" sub-scale (11.3 vs. 10, p < 0.05) of the MHLC. Of 177 members of the general public surveyed, Hispanics had lower stroke awareness compared to NHWs and tended to have lower awareness than Hispanic stroke patients. These results suggest that Hispanic stroke patients perceive less control over their health, experience more healthcare barriers, and demonstrate lower rates of stroke literacy. Interventions for stroke prevention and education in Hispanics should address these racial/ethnic differences in stroke awareness and barriers to risk factor control.

Ethnic Differences in Withdrawal of Life Support After Intracerebral Hemorrhage.

Minorities are less likely to decide on withdrawal of life support (WOLS) after acute severe illness. However, the decision-making process for WOLS after intracerebral hemorrhage (ICH) among Native Hawaiians and other Pacific Islanders (NHOPI) has not been described. To address this gap in the literature, a retrospective study was conducted on consecutive spontaneous ICH patients admitted to a tertiary center in Honolulu between 2006 and 2010. The occurrence of WOLS and time-to-WOLS were the outcome measures. Unadjusted and multivariable logistic regression models were performed to determine associations between NHOPI ethnicity and WOLS. This study assessed 396 patients (18% NHOPI, 63% Asians, 15% non-Hispanic whites [NHW], 4% others) with ICH. NHOPI was associated with lower rate of WOLS than NHW in the univariate analysis (OR 0.35, 95% CI: 0.15, 0.80). However, NHOPI ethnicity was no longer significant when adjusted for age (OR 0.59, 95% CI: 0.25, 1.43) and in the fully adjusted model (OR 0.68, 95% CI: 0.20, 2.39). Although NHOPI with ICH were initially perceived to have less WOLS compared to NHW, this observed difference was largely driven by the younger age of NHOPI rather than from underlying cultural differences that are inherent to their ethnicity.

Caspase inhibition decreases both platelet phosphatidylserine exposure and aggregation: caspase inhibition of platelets.

Apoptosis of nucleated cells is regulated by caspases, a group of cysteine proteases, and is characterized by phosphatidylserine expression on the outer leaflet of the plasma membrane. Reports indicate that platelets contain caspases. However, the role of caspases in platelet function is not well understood. When platelets become activated, they express phosphatidylserine (PS) on the outer leaflet of the plasma membrane. In addition, platelets aggregate when activated. The aims of this study were to determine if caspase inhibition (using the pan-caspase inhibitor zVAD-fmk): (1) decreased PS expression and (2) decreased platelet aggregation following activation. Flow cytometry was used to determine PS expression and a platelet aggregometer was used to assess aggregation. We found that platelets treated with zVAD-fmk significantly decreased both A23187-induced PS exposure (total fluorescence index, TFI: A23187=791.42+/-174; zVAD+A23187=92.97+/-57, p<==0.05) and ADP-induced PS exposure (TFI: ADP=669.24+/-145, zVAD+ADP=174.6+/-151, p<==0.05). Further, treatment with zVAD-fmk significantly decreased ADP-induced platelet aggregation (%: untreated=80+/-1.5, zVAD treated=69+/-3.0, p<==0.05). These results indicate that caspases play a role in platelet activation, suggesting a unique physiologic role for these proteases.