Caregiver Well-Being and Burden: Variations by Race/Ethnicity and Care Recipient Nativity Status

Background and Objectives: Despite growing diversity among the aging population and extensive previous research on racial/ethnic minority caregivers, little research has been conducted on the potentially unique experiences and outcomes of informal caregivers of foreign-born care recipients. Using nationally representative data and the Stress Process Model, the current study examined the differences in caregiver outcomes (care burden, psychological well-being, and self-rated health) by care recipient nativity status (U.S.-born vs. foreign-born) and the extent to which caregiver outcomes vary by care recipient nativity status and caregiver race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, and Others). Research Design and Methods: The current study used Round 5 of the National Health and Aging Trends Study and the National Study of Caregiving (N = 1,436). We conducted ordinary least squares regression to analyze the differences in caregiver’s outcomes by care recipient nativity status and caregiver race/ethnicity and to investigate the impacts of the inclusion of caregiving factors (background factors, primary stressors, secondary stressors, and resources). Results: Regression analyses showed that only care burden significantly varied by care recipient nativity status after controlling for covariates. Caregivers of foreign-born care recipients reported a higher burden. However, when interactions of care recipient nativity status × caregiver race/ethnicity were introduced, non-Hispanic black and Hispanic caregivers of foreign-born care recipients were more likely to report better psychological well-being and self-rated health compared to their counterparts. Across caregiver groups, better caregiver–care recipient relationship quality and less caregiver chronic conditions were associated with less burden and better caregiver psychological well-being and self-rated health. Discussion and Implications: Care recipient nativity status and caregiver race/ethnicity may have complex effects on caregiving experiences. Given the observed significant interaction effects for caregiver psychological well-being and self-rated health, cultural factors may affect the extent to which these caregivers appraise their caregiving. Future research should delve into the appropriate ways to assess care stress as well as resilience among each caregiver group. Our results indicate the need for research, education, and practice that assess cultural and within-group differences among caregivers and inform needed changes to structural barriers

Purification and characterization of platelet aggregation inhibitors from snake venoms

Proteins that inhibit glycoprotein (GP) IIb/IIIa mediated platelet aggregation have been purified from the venom of two snake species. A small platelet aggregation inhibitor (pl.AI), multisquamatin (Mr=5,700), was purified from Echis multisquamatus venom by hydrophobic interaction HPLC and two steps on C18 reverse phase HPLC. A larger pl.AI, contortrostatin (Mr=15,000), was purified by a similar HPLC procedure from the venom of Agkistrodon contortrix contortrix. Both pl.AIs inhibit ADP-induced human, canine and rabbit platelet aggregation using platelet rich plasma (PRP). Multisquamatin has an IC50 of 97 nM, 281 nM and 333 nM for human, canine and rabbit PRP, respectively. Contortrostatin has an IC50 of 49 nM, 120 nM and 1,150 nM for human, canine and rabbit PRP, respectively. In a competitive binding assay using 125I-7E3 (a monoclonal antibody to GPIIb/IIIa that inhibits platelet aggregation) both contortrostatin and multisquamatin demonstrated GPIIb/IIIa specific binding to human and canine platelets. The IC50 for contortrostatin displacement of 7E3 binding to human and canine GPIIb/IIIa is 27 nM and 16 nM, respectively and for multisquamatin it is 3 nM and 63 nM, respectively. Our results indicate that both pl.AIs inhibit platelet aggregation by binding with high affinity to GPIIb/IIIa.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31863/1/0000813.pd

Caregiver Well-Being and Burden: Variations by Race/Ethnicity and Care Recipient Nativity Status

Background and Objectives Despite growing diversity among the aging population and extensive previous research on racial/ethnic minority caregivers, little research has been conducted on the potentially unique experiences and outcomes of informal caregivers of foreign-born care recipients. Using nationally representative data and the Stress Process Model, the current study examined the differences in caregiver outcomes (care burden, psychological well-being, and self-rated health) by care recipient nativity status (U.S.-born vs. foreign-born) and the extent to which caregiver outcomes vary by care recipient nativity status and caregiver race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, and Others). Research Design and Methods The current study used Round 5 of the National Health and Aging Trends Study and the National Study of Caregiving (N = 1,436). We conducted ordinary least squares regression to analyze the differences in caregiver’s outcomes by care recipient nativity status and caregiver race/ethnicity and to investigate the impacts of the inclusion of caregiving factors (background factors, primary stressors, secondary stressors, and resources). Results Regression analyses showed that only care burden significantly varied by care recipient nativity status after controlling for covariates. Caregivers of foreign-born care recipients reported a higher burden. However, when interactions of care recipient nativity status × caregiver race/ethnicity were introduced, non-Hispanic black and Hispanic caregivers of foreign-born care recipients were more likely to report better psychological well-being and self-rated health compared to their counterparts. Across caregiver groups, better caregiver–care recipient relationship quality and less caregiver chronic conditions were associated with less burden and better caregiver psychological well-being and self-rated health. Discussion and Implications Care recipient nativity status and caregiver race/ethnicity may have complex effects on caregiving experiences. Given the observed significant interaction effects for caregiver psychological well-being and self-rated health, cultural factors may affect the extent to which these caregivers appraise their caregiving. Future research should delve into the appropriate ways to assess care stress as well as resilience among each caregiver group. Our results indicate the need for research, education, and practice that assess cultural and within-group differences among caregivers and inform needed changes to structural barriers

Caregiver Well-Being and Burden: Variations by Race/Ethnicity and Care Recipient Nativity Status

Background and Objectives Despite growing diversity among the aging population and extensive previous research on racial/ethnic minority caregivers, little research has been conducted on the potentially unique experiences and outcomes of informal caregivers of foreign-born care recipients. Using nationally representative data and the Stress Process Model, the current study examined the differences in caregiver outcomes (care burden, psychological well-being, and self-rated health) by care recipient nativity status (U.S.-born vs. foreign-born) and the extent to which caregiver outcomes vary by care recipient nativity status and caregiver race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, and Others). Research Design and Methods The current study used Round 5 of the National Health and Aging Trends Study and the National Study of Caregiving (N = 1,436). We conducted ordinary least squares regression to analyze the differences in caregiver’s outcomes by care recipient nativity status and caregiver race/ethnicity and to investigate the impacts of the inclusion of caregiving factors (background factors, primary stressors, secondary stressors, and resources). Results Regression analyses showed that only care burden significantly varied by care recipient nativity status after controlling for covariates. Caregivers of foreign-born care recipients reported a higher burden. However, when interactions of care recipient nativity status × caregiver race/ethnicity were introduced, non-Hispanic black and Hispanic caregivers of foreign-born care recipients were more likely to report better psychological well-being and self-rated health compared to their counterparts. Across caregiver groups, better caregiver–care recipient relationship quality and less caregiver chronic conditions were associated with less burden and better caregiver psychological well-being and self-rated health. Discussion and Implications Care recipient nativity status and caregiver race/ethnicity may have complex effects on caregiving experiences. Given the observed significant interaction effects for caregiver psychological well-being and self-rated health, cultural factors may affect the extent to which these caregivers appraise their caregiving. Future research should delve into the appropriate ways to assess care stress as well as resilience among each caregiver group. Our results indicate the need for research, education, and practice that assess cultural and within-group differences among caregivers and inform needed changes to structural barriers

Nitroglycerin inhibits experimental thrombosis and reocclusion after thrombolysis

Nitroglycerin inhibits platelet aggregation in vitro, but its effect on thrombosis and platelet function in vivo is controversial. This study assessed the effect of nitroglycerin on primary thrombus formation in response to vessel wall injury and secondary thrombus formation, or rethrombosis, after lysis of an existing thrombus. In the first protocol the right carotid artery was instrumented with a flow probe, stenosis, an anodal electrode, and a proximal infusion line. A 300 [mu]A anodal current was used to induce endothelial injury and subsequent thrombotic occlusion of the vessel. Anisoylated plasminogen streptokinase activator complex (APSAC; 0.05 U/kg intraarterially) was injected proximal to the thrombus 30 minutes after occlusion. After APSAC, nitroglycerin (1 [mu]g/kg/min intraarterially, n = 7) or vehicle (n = 6) was infused proximal to the thrombus for 3 hours. Reocclusion occurred in two of seven nitroglycerin-treated dogs and six of six vehicle-treated dogs (p n = 12) artery to determine control times to occlusion. The left carotid artery served as the test vessel, receiving either nitroglycerin (1 [mu]g/kg/min intraarterially, n = 6) or trimethaphan (0.05 mg/kg/hr intraarterially, n = 6). Trimethaphan was used to produce controlled hypotension to match the approximately 10% decrease in mean arterial blood pressure that was observed during nitroglycerin infusion. Control arteries and those treated with trimethaphan formed occlusive thrombi in all instances. Nitroglycerin infusion resulted in a lower incidence of occlusion (1 of 6; p p < 0.05). Local infusion of nitroglycerin reduced the formation of primary thrombi, independent of the hypotensive effect of the drug, and exerted systemic effects on platelet aggregation. Furthermore, platelet inhibition with nitroglycerin reduced the incidence of secondary thrombus formation (rethrombosis) after thrombolysis. The results suggest that a potential benefit of nitroglycerin therapy may be derived from its ability to inhibit thrombotic events in patients with unstable angina or myocardial infarction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31690/1/0000626.pd

Activation of coagulation by administration of recombinant factor VIIa elicits interleukin 6 (IL-6) and IL-8 release in healthy human subjects

The activation of coagulation has been shown to contribute to proinflammatory responses in animal and in vitro experiments. Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma. This increase was absent when the subjects were pretreated with recombinant nematode anticoagulant protein c2, the inhibitor of tissue factor-factor VII

Recombinant nematode anticoagulant protein c2, an inhibitor of the tissue factor/factor VIIa complex, in patients undergoing elective coronary angioplasty

OBJECTIVES We investigated the safety and pharmacodynamics of escalating doses of recombinant nematode anticoagulant protein c2 (rNAPc2) in patients undergoing elective coronary angioplasty. BACKGROUND Recombinant NAPc2 is a potent inhibitor of the tissue factor/factor VIIa complex, which has the potential to reduce the risk of thrombotic complications in coronary artery disease. METHODS In a randomized, double-blinded, dose-escalation, multicenter trial, 154 patients received placebo or rNAPc2 at doses of 3.5, 5.0, 7.5, and 10.0 mug/kg body weight as a single subcutaneous administration 2 to 6 h before angioplasty. All patients received aspirin, unfractionated heparin during angioplasty, and clopidogrel in case of stent implantation. RESULTS Minor bleeding rates for the doses 3.5 to 7.5 mug/kg were comparable to that with placebo (6.7%), whereas an incidence of 26.9% was observed at the 10.0-mug/kg dose level (p <0.01). Major bleedings occurred in the 5.0-mug/kg (n = 3) and 7.5-mug/kg (n = 1) dose groups. The three patients in the 5.0-mug/kg dose group also received a glycoprotein IIb/IIIa receptor inhibitor at the moment of major bleeding. Systemic thrombin generation, as measured by prothrombin fragment 1+2 (F1+2), was suppressed in all rNAPc2 dose groups to levels below pretreatment values for at least 36 h. In the placebo group, a distinct increase of F1+2 levels was observed following cessation of heparin. CONCLUSIONS Inhibition of the tissue factor/factor VIIa complex with rNAPc2, at doses up to 7.5 mug/kg, in combination with aspirin, clopidogrel, and unfractionated heparin appears to be a safe and effective strategy to prevent thrombin generation during coronary angioplasty. (J Am Coll Cardiol 2003;41:2147-53) (C) 2003 by the American College of Cardiology Foundatio

Local activation of the tissue factor-factor VIIa pathway in patients with pneumonia and the effect of inhibition of this pathway in murine pneumococcal pneumonia

OBJECTIVE: The tissue factor (TF)-factor VIIa (FVIIa) complex not only is essential for activation of blood coagulation but also affect the inflammatory response during sepsis. The objective of this study was to determine the role of TF-FVIIa in pneumonia caused by Streptococcus pneumoniae, the most important causative organism in community-acquired pneumonia and a major cause of sepsis. DESIGN: A controlled, in vivo laboratory study. SETTING: Research laboratory of a health sciences university. PATIENTS AND SUBJECTS: Patients with unilateral community-acquired pneumonia and female BALB/c mice. INTERVENTIONS: Bilateral bronchoalveolar lavage was performed in patients with community-acquired pneumonia. In mice, pneumonia was induced by intranasal inoculation with S. pneumoniae with or without concurrent inhibition of TF-FVIIa by subcutaneous injections of recombinant nematode anticoagulant protein (rNAPc2). MEASUREMENTS AND MAIN RESULTS: Patients with unilateral community-acquired pneumonia demonstrated elevated concentrations of FVIIa, soluble TF, and thrombin-antithrombin complexes in bronchoalveolar lavage fluid obtained from the infected site compared with the uninfected site. Mice with S. pneumoniae pneumonia displayed increased TF expression and fibrin deposits in lungs together with elevated thrombin-antithrombin complex levels in bronchoalveolar lavage fluid; inhibition of TF-FVIIa by rNAPc2 attenuated the procoagulant response in the lung but did not affect host defense, as reflected by an unaltered outgrowth of pneumococci and an unchanged survival. CONCLUSIONS: These data suggest that TF-FVIIa activity contributes to activation of coagulation in the lung during pneumococcal pneumonia but does not play an important role in the antibacterial host defense in this murine mode

IgA Nephropathy Patient Baseline Characteristics in the Sparsentan PROTECT Study

Introduction: Sparsentan is a novel single-molecule dual endothelin angiotensin receptor antagonist with hemodynamic and anti-inflammatory properties and is not an immunosuppressant. The ongoing phase 3 PROTECT trial examines sparsentan in adults with IgA nephropathy (IgAN). Methods: The PROTECT trial (NCT03762850) is a multicenter, international, randomized, double-blind, parallel-group, active-controlled study. The efficacy and safety of sparsentan versus the active control irbesartan is being evaluated in adults with biopsy-proven IgAN and proteinuria ≥1.0 g/d despite maximized treatment with an angiotensin-converting enzyme inhibitor (ACEi) and/or angiotensin receptor blocker (ARB) for at least 12 weeks. Blinded and aggregated baseline characteristics are reported descriptively and compared to contemporary phase 3 trials with patients with IgAN. Results: The primary analysis population includes 404 patients who were randomized and received study drug (median age, 46 years). Enrolled patients were from Europe (53%), Asia Pacific (27%), and North America (20%). Baseline median urinary protein excretion was 1.8 g/d. The range of estimated glomerular filtration rate (eGFR) was broad with the largest proportion of patients (35%) in chronic kidney disease (CKD) stage 3B. Before transitioning to study medication, mean systolic/diastolic blood pressure was 129/82 mm Hg, with the majority of patients (63.4%) receiving the maximum labeled ACEi or ARB dose. Patients in Asian versus non-Asian regions included a higher percentage of females, had lower blood pressures, and included lower proportions of patients with a history of hypertension and baseline antihypertensive treatment. Conclusions: Patient enrollment in PROTECT, with differing racial backgrounds and across CKD stages, will allow for important characterization of the treatment effect of sparsentan in patients with IgAN with proteinuria at high risk of kidney failure