Serum sclerostin: the missing link in the bone-vessel cross-talk in hemodialysis patients?

UNLABELLED: We found for the first time that in maintenance hemodialysis patients, higher sclerostin serum level was associated with severe abdominal aortic calcification (AAC). In addition, cortical bone microarchitecture (density and thickness) assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at tibia was also independently associated with severe AAC. These results suggest that sclerostin may be involved in the association of mineral and bone disorder with vascular calcification in hemodialysis patients. INTRODUCTION: Severe abdominal aortic calcifications are predictive of high cardiovascular mortality in maintenance hemodialysis (MHD) patients. In patients with end-stage renal disease, a high aortic calcification score was associated with lower bone turnover on bone biopsies. Thus, we hypothesized that sclerostin, a Wnt pathway inhibitor mainly secreted by osteocytes and acting on osteoblasts to reduce bone formation, may be associated with vascular calcifications in MHD patients. METHODS: Fifty-three MHD patients, aged 53 years [35-63] (median [Q1-Q3]) were included. Serum was sampled before the MHD session to assay sclerostin. Framingham score was computed and the abdominal aortic calcification (AAC) score was assessed according to Kauppila method on lateral spine imaging using DEXA. Tibia bone status was evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Patients were distributed into two groups according to their AAC score: patients with mild or without AAC (score below 6) versus patients with severe AAC (score of 6 and above). RESULTS: In multivariate analysis, after adjustment on age, dialysis duration and diabetes, serum sclerostin and cortical thickness were independently associated with severe AAC (odds ratio (OR) = 1.43 for each 0.1 ng/mL increase [95 % confidence interval (CI) 1.10-1.83]; p = 0.006 and 0.16 for 1 SD increase [0.03-0.73]; p = 0.018, respectively). A second cardiovascular model adjusted on Framingham score and the above mentioned confounders showed similar results. CONCLUSIONS: Elevated sclerostin serum level and poorer tibia cortical bone structure by HR-pQCT were positively and independently associated with higher odds of severe AAC in MHD patients. Serum sclerostin may become a biomarker of mineral and bone disorder and vascular risk in MHD patients.

Shear wave elastography: An accurate technique to stage liver fibrosis in chronic liver diseases.

OBJECTIVES: The goals of this study were to assess the diagnostic accuracy of shear wave elastography (SWE) using the results of histopathological analysis as a standard of reference and compare the results of SWE and those of transient elastography (TE) to the degree of fibrosis as evaluated by histomorphometry. PATIENTS AND METHODS: Adult patients who were scheduled to undergo liver biopsy were prospectively enrolled in the study. The diagnostic performances of SWE were assessed using AUROC curve analysis according to fibrosis thresholds defined by ≥F2 (significant fibrosis), ≥F3 (advanced fibrosis) and F4 (cirrhosis). Additional analyses using the Obuchowski measures for pairwise comparisons of fibrosis stages were performed. In a subgroup of 55 patients, the relationships between stiffness as measured using SWE and TE and the percentage of fibrosis were compared using Spearman's rank coefficient. RESULTS: Among the initially enrolled 170 patients, 148/170 (87%) had successful SWE acquisition and formed the study population. SWE sensitivity and specificity were respectively 85.1% and 82.7% (≥F2), 88.9% and 90.3% (≥F3), 93.3% and 98.3% (F4). The AUROC curves of SWE along with their 95% confidence intervals (CI) were respectively 0.904 (95%CI: 0.845-0.946) for fibrosis ≥F2; 0.958 (95%CI: 0.912-0.984) for fibrosis ≥F3 and 0.988 (95%CI: 0.955-0.999) for fibrosis=F4. The global Obuchowski measure was 0.953±0.007. In the subgroup study, a significant correlation was found between the percentage of fibrosis and stiffness as assessed by SWE (r=0.77; 95%CI: 0.63-0.86; P<0.0001) and by TE (r=0.65; 95%CI: 0.47-0.78; P<0.01). CONCLUSION: SWE is accurate to assess liver fibrosis in patients with chronic liver disease.

A controlled trial of two forms of self-management education for adults with asthma.

PURPOSE: Excess morbidity and mortality due to asthma, aggravated by demonstrably poor patient self-management practices, suggest the need for formal patient education programs. Individual and group asthma education programs were developed and evaluated to determine their cognitive, behavioral, and clinical effects. PATIENTS AND METHODS: We compared changes in asthma symptoms, utilization of medical services, knowledge about asthma, metered-dose inhaler (MDI) technique, and self-management behaviors for 323 adult Kaiser Permanente patients with moderate to severe asthma who were randomly assigned to small-group education, individual teaching, or 1 of 2 control conditions--an information (workbook) control or usual control (no formal asthma education). Data were collected from patients by questionnaire, diary, and physical examination at enrollment and at 5 months and 1 year after intervention. Medical record data on these patients were abstracted for a total 3-year period, from 1 year before to 2 years after enrollment. RESULTS: Compared with the usual control, the self-management education programs were associated with significant improvements in control of asthma symptoms (reduced "bother" due to asthma and increased symptom-free days), MDI technique, and environmental control practices. Small-group education also was associated with significant improvements in physician evaluation of the patients' asthma status and in patients' level of physical activity. For both group and individual education recipients, improvement in MDI technique was positively correlated with improved control of symptoms; however, the degree of improvement in symptoms was greater than that which could be accounted for on the basis of improvement in MDI technique alone. The time course over which changes occurred in the various outcome measures suggests the mechanism by which education resulted in improvement in the patient's status. Significant improvements in MDI technique and environmental control practices were manifest immediately following education (5-month follow-up) and at the 1-year follow-up. Significant improvements in symptom measures were not apparent until the 1-year follow-up. The rate of utilization of medical care for acute exacerbations decreased between baseline and the 2-year follow-up period, but this decrease did not differ significantly among treatment conditions. However, there was a trend toward greater reduction in patients receiving small-group education. An ad hoc finding of a significant difference favoring small-group education between the baseline and the second follow-up year acute visit rates was observed. This result must be regarded as tentative, since it is not clear that unambiguous statistical significance is attained in the light of multiplicity issues. However, this trend is consistent with the antecedent benefits of the small-group education, and appears to warrant further investigation. CONCLUSIONS: Carefully designed asthma education programs for adults can improve patients' understanding of their condition and its treatment and increase their motivation and confidence that the condition can be controlled, thereby increasing their adherence to the treatment regimen and management of symptoms, and, in turn, improving control of symptoms. Both small-group education and individual education were associated with significant benefits, but the group program was simpler to administer, better received by patients and educators, and more cost-effective. The results show promise for improving clinical outcomes, through well-designed educational programs, for patients with asthma and other chronic health problems.

An evaluation of approaches to asthma self-management education for adults: the AIR/Kaiser-Permanente Study.

The purpose of the AIR/Kaiser-Permanente asthma project is to evaluate various approaches to the education of adults with asthma, identifying those types of patients for whom particular approaches are most cost effective. Critical self-management practices for adults with asthma were identified using the critical incident technique. An individualized and a group administered educational program are being developed to teach the identified critical skills, using the instructional models previously employed in AIR WISE and AIR POWER programs for children with asthma. Three hundred patients with moderate to severe asthma from Northern California Kaiser-Permanente Medical Group clinics will participate in a trial of these programs. Patients will be randomly assigned to one of four conditions: One of two educational programs, an information/attention control, or a data-only control condition. Data will be collected on all patients for 15 months; health care utilization data covering a two-year period will be available from medical records. Program effectiveness will be evaluated in terms of pre-post changes in the patients' knowledge, attitudes, self-management practices, medical condition, daily functioning, and utilization of services. Cost effectiveness will be evaluated, paying specific attention to the cost effectiveness of different educational approaches for different types of patients.