Investigating self-efficacy, disease knowledge and adherence to treatment in adolescents with cystic fibrosis.

AIM: Patient adherence is integral to the effectiveness of prescribed treatment, and is associated with beneficial disease outcomes, yet in adolescents with cystic fibrosis, adherence is often sub-optimal. Multiple factors may contribute to treatment adherence, including disease knowledge and self-efficacy. In adolescents with cystic fibrosis: (i) to compare the disease knowledge of adolescents and their parents before transition to adult care; (ii) to determine the relationship between disease knowledge (adolescent, parent) and adherence; and (iii) to evaluate self-efficacy and its association with disease knowledge and adherence. METHODS: Adolescents with cystic fibrosis and their parents were recruited from a tertiary children's hospital. Disease knowledge and self-efficacy was assessed using the Knowledge of Disease Management-CF and General Self-Efficacy Scales respectively. Using pharmacy records, medication possession ratio was calculated to measure treatment adherence in the preceding year. RESULTS: Thirty-nine adolescent (aged 12-17 (median 14) years) and parent pairs were recruited. Adherence to hypertonic saline, but not other medications, was significantly associated with disease knowledge in adolescents (r 2 = 0.40, P = 0.029). Mean (SD) adolescent self-efficacy was 30.8 (4.0), and not associated with disease knowledge or adherence. Mean (SD) disease knowledge was less in adolescents than parents (55 (16)% and 72 (14)% respectively, P < 0.001). CONCLUSION: Disease knowledge is sub-optimal in adolescents with cystic fibrosis, even in the 2 years immediately before transition to adult care. Given that adherence with some treatments has been associated with disease knowledge our results suggest the need for educational interventions in adolescents with cystic fibrosis to optimise self-management and health outcomes.

Polymorphisms in the tissue factor pathway inhibitor gene are not associated with ischaemic stroke.

The present study aimed to determine whether four previously described polymorphisms found within the tissue factor pathway inhibitor (TFPI) gene are associated with free plasma TFPI levels or with TFPI activity as well as the risk of ischaemic stroke in stroke patients and control individuals. We conducted a case-control study of 162 first-ever ischaemic stroke cases and 170 randomly selected community control individuals. The TFPI genotype was determined for the T-287C, C-399T, Intron 7 C-33T, and Val264Met (G874A) polymorphisms. Free plasma TFPI and TFPI activity were measured during the first 7 days and 3-6 months after the acute stroke event. Free plasma TFPI levels were significantly lowered 3-6 months after stroke compared with levels observed in the patient group during the acute phase of the stroke (mean, 16.3 versus 22.46 ng/ml; P = 0.046) and among the control group (mean, 16.3 versus 22.79 ng/ml; P < 0.0001). Conversely, TFPI activity was significantly up-regulated during the acute phase (mean, 1.30 versus 1.11 U/ml; P = 0.0051) and remained elevated 3-6 months later (mean, 1.28 versus 1.11 U/ml; P = 0.03). The TFPI gene polymorphisms studied were not significantly associated with TFPI levels or activity, nor with the risk of ischaemic stroke. In conclusion, the TFPI activity and concentration in plasma varied significantly after an ischaemic stroke; however, these variations were not found to be due to the presence of any of the genetic mutations analysed in this study. Our results are consistent with the emerging model suggesting the lipoprotein-bound portion of TFPI has a significant influence on coagulation and diseases of haemostasis.

The tissue factor pathway in ischemic stroke.

To explore the role of the the tissue factor (TF) pathway in ischemic stroke. We measured blood concentrations of markers of the TF pathway [TF antigen, free tissue factor pathway inhibitor antigen (TFPIf) and activity (TFPIac), and activated factor VII (FVIIa)] within 7 days (acute phase) and after 3-6 months (convalescence) in 150 patients with first-ever ischemic stroke and 150 community controls. During the acute phase, TF antigen and TFPIf were not significantly altered but TFPIac was increased (mean 1.27 versus 1.13 U/ml, P = 0.04) and FVIIa was decreased in cases compared with controls (mean 43.3 versus 57.9 mU/ml, P = 0.0004). After adjusting for baseline differences between cases and controls, increasing quartiles of TFPIf were independently associated with reduced odds of stroke, and reducing quartiles of FVIIa and increasing quartiles of TFPIac with increased odds of stroke. During the convalescent phase, FVIIa and TFPIac returned to normal but TF antigen and TFPIf were significantly decreased compared with controls [median TF antigen, 110 (follow-up) versus 155 pg/ml (controls), P = 0.0008; median TFPIf, 15.5 (follow-up) versus 23.3 ng/ml (controls), P = 0.002]. Alterations of blood concentrations of TF pathway markers are common in patients with acute ischemic stroke. The mechanisms are unclear but may relate to enhanced formation of TF-FVIIa complexes and upregulation and release of TFPI during the acute phase, and ongoing consumption of TF antigen and TFPIf during the chronic phase as the atherosclerotic plaque heals.

Protein Z in ischemic stroke and its etiologic subtypes.

BACKGROUND AND PURPOSE: Protein Z is a vitamin K-dependent plasma protein whose significance in arterial thrombosis remains uncertain. The objectives of this study were to determine the association between protein Z, ischemic stroke, and etiologic subtypes of ischemic stroke. METHODS: We conducted a case-control study of 173 hospital cases of first-ever ischemic stroke and 186 randomly selected community controls. Using established criteria, we classified cases of stroke by etiologic subtype. Protein Z concentrations were measured during the first 7 days and at 3 to 6 months after the acute stroke event. RESULTS: Blood levels of protein Z measured within 7 days of acute stroke were significantly higher in cases than in controls (geometric mean, 1.46 versus 1.16 microg/mL; P<0.0001). Compared with the lowest tertile, the upper 2 tertiles of protein Z were associated with an adjusted odds ratio (OR) of ischemic stroke of 1.75 (95% CI, 1.00 to 3.07) for the second tertile and 3.07 (95% CI, 1.73 to 5.45) for the upper tertile. The adjusted odds of ischemic stroke caused by large-artery atherothrombosis was nearly 8-fold greater for those with protein Z concentrations in the upper tertile compared with the lower tertile (OR, 7.91; 95% CI, 3.11 to 20.14). The adjusted odds of ischemic stroke due to small-artery disease (OR, 1.79; 95% CI, 0.83 to 3.87) and cardioembolism (OR, 1.80; 95% CI, 0.58 to 5.64) was also increased among individuals with protein Z concentrations in the upper tertile compared with the lower tertile, but not significantly so. There was no significant difference between mean protein Z concentrations among cases in the convalescent phase (3 months) after stroke and age- and sex-matched controls. CONCLUSIONS: There is a strong, independent relationship between elevated blood levels of protein Z and ischemic stroke during the acute phase, particularly ischemic stroke due to large-artery atherothromboembolism, which is no longer evident during the convalescent phase. These results are consistent with the notion that protein Z is either an important factor in the pathogenesis of ischemic stroke due to large-artery atherothromboembolism or an acute phase reactant. Further studies are required to elucidate whether protein Z has a causative or prognostic role in acute arterial thrombosis.

Endothelial and platelet activation in acute ischemic stroke and its etiological subtypes.

BACKGROUND AND PURPOSE: Activation of endothelial cells and platelets is an important mediator of atherothrombosis. Markers of endothelial cell and platelet activation such as soluble adhesion molecules can be measured in plasma. We hypothesized that patients with acute ischemic stroke would have increased blood concentrations of soluble E-selectin and von Willebrand factor (vWF), primarily reflecting activation of endothelial cells, and increased concentrations of soluble P-selectin and platelet-derived microvesicles (PDM), primarily reflecting activation of platelets, compared with healthy controls. We also hypothesized that these markers would be differentially elevated in ischemic stroke caused by large- and small-artery atherothrombosis compared with cardiogenic embolism. METHODS: We conducted a case-control study of 200 hospital-referred cases of first-ever ischemic stroke and 205 randomly selected community controls stratified by age, sex, and postal code. Using established criteria, we classified cases of stroke by etiological subtype in a blinded fashion. The prevalence of vascular risk factors and blood concentrations of E-selectin, P-selectin, vWF antigen, and PDM were determined in stroke cases within 7 days and at 3 to 6 months after stroke and in controls. RESULTS: Mean blood concentrations of soluble E-selectin, P-selectin, and PDM within 7 days of stroke onset were all significantly higher in cases compared with controls. At 3 to 6 months after stroke, the mean blood concentrations of E-selectin and P-selectin fell significantly below that of controls, and PDM concentrations remained elevated. There was a strong, graded, and independent (of age, sex, and vascular risk factors) association between increasing blood concentrations of E-selectin during the acute phase and all etiological subtypes of ischemic stroke, particularly ischemic stroke caused by large-artery atherothrombosis. There was also a significant, graded, and independent association between increasing blood concentrations of vWF during the acute phase and ischemic stroke caused by large-artery atherothrombosis. CONCLUSIONS: We have demonstrated significant associations between acute elevation of blood markers of endothelial cell and platelet activation and ischemic stroke and between acute elevation of blood markers of endothelial cell activation and ischemic stroke caused by large-artery atherothrombosis. Persistent elevated blood concentrations of PDM may be a marker of increased risk of ischemic stroke.

C-reactive protein in ischemic stroke and its etiologic subtypes.

The possible role of C-reactive protein (CRP) in the etiology and prognosis of ischemic stroke remains to be clearly defined. The purpose of this study was to determine whether CRP levels are elevated in patients with stroke, whether they remain persistently elevated, and whether CRP levels are higher in patients with etiologic subtypes of stroke caused by large or small artery disease ("atherogenic hypothesis") or whether they may be higher in patients with more extensive cerebral infarction caused by large artery or cardiogenic embolism ("inflammatory hypothesis"). We conducted a case-control study of 199 hospital cases with a first-ever ischemic stroke and 202 randomly selected community controls. Cases of stroke were classified by etiologic subtype and the prevalence of conventional vascular risk factors and CRP levels were determined in cases and controls. Blood levels of CRP measured within 7 days of acute stroke were significantly higher in cases compared with controls (8.50 vs. 2.18 mg/L, P < .0001) and remained elevated in stroke survivors at 3 to 6 months of follow-up (3.35 vs. 2.18 mg/L, P = .003) although levels were significantly lower compared with the first 7 days (3.35 vs. 8.50 mg/L, P < .001-.003). Compared with the lowest quartile of CRP, the upper 3 quartiles were associated with an adjusted odds ratio (OR) of ischemic stroke of 1.9 (95% CI: 1.0-3.8) for the second quartile, 5.8 (95% CI: 2.9-11.4) for the third quartile, and 16.9 (95% CI: 7.9-36.1) for the fourth quartile (P for trend < .0001). Comparing the upper with the lower quartile, the strongest association was with etiologic stroke subtypes caused by large artery disease (OR 52.5; 95% CI: 13.4-205) and embolism from the heart (OR 56.1; 95% CI: 11.3-278), with a much weaker association with small artery disease (OR 2.4; 95% CI: 0.8-6.0). The mean Oxford Handicap Scale score was lowest in small artery, intermediate in large artery and highest in cardioembolic stroke (2.8 vs. 3.1 vs. 3.6, respectively; P = .001) while the mean Barthel Index was highest in small artery, intermediate in large artery, and lowest in cardioembolic stroke (13.5 vs. 11.5 vs. 8.6, respectively; P = .002). Furthermore, there was a significant correlation between CRP levels during the first 7 days and stroke severity, as measured by the Oxford Handicap Scale score (P = .03) and Barthel index (P = .001). We conclude that there is a strong, independent relationship between elevated blood levels of CRP and ischemic stroke, particularly because of more severe strokes caused by large artery disease and embolism from the heart, which remains evident over the long term. These results are consistent with the inflammatory marker hypothesis of CRP as a marker of the extent of ischemic cerebral injury and its complications.