Catabolism of newly synthesized decorin in vitro by human peritoneal mesothelial cells.

OBJECTIVE: Previous studies have shown that decorin and biglycan account for over 70% of the proteoglycans (PGs) synthesized by human peritoneal mesothelial cells (HPMCs). Since these PGs are involved in the control of cell growth, cell differentiation, and matrix assembly, we investigated their turnover in cultured HPMCs. METHODS: Confluent HPMCs were metabolically labeled with [35S]-sulfate and the labeled products isolated from the cell medium and the cell layer characterized by sensitivity to bacterial eliminases. Experiments were undertaken with exogenous labeled decorin, and its metabolic state was studied. RESULTS: In a 24-hour labeling period, 75% of the newly synthesized chondroitin sulfate/dermatan sulfate (CS/DS) PGs appeared in the culture medium, the majority of which (90%) was decorin. In the cell layer, protein-free glycosaminoglycan (GAG) chains accounted for 21% of the total CS/DS at 24 hours and exhibited constant specific activity at 12-16 hours. The latter material was turned over with a half-life of approximately 2.5 hours. Exogenous decorin underwent receptor-mediated endocytosis and subsequent intracellular degradation. Uptake but not degradation could be inhibited by heparin. CONCLUSIONS: HPMCs are distinguished by a rapid turnover of decorin. A characteristic metabolic feature is the existence of a large intracellular pool of protein-free DS-GAGs. Understanding the control of decorin turnover in HPMCs might lead to delineation of its potential role in both the physiology and pathophysiology of the membrane in PD patients.     

Predictors of non-spine fracture in elderly men: the MrOS study.

We examined determinants of nonvertebral fracture in elderly men from six U.S. communities followed an average of 4.1 years. Six clinical risk factors predicted fracture risk independent of hip BMD: tricyclic antidepressant use, previous fracture, inability to complete a narrow walk trial, falls in previous year, age > or =80 years, and depressed mood. INTRODUCTION: There are few prospective studies of fracture determinants in men. We examined the associations between a comprehensive set of clinical risk factors and risk of nonspine fracture in older men and whether determinants of fracture risk were independent of total hip BMD. MATERIALS AND METHODS: A total of 5995 men > or =65 years of age were recruited from six communities in the Unites States and followed prospectively for an average of 4.1 years. Baseline assessments of demographic, lifestyle, medical history, functional status, anthropometry, and cognitive, visual, and neuromuscular function were assessed by questionnaire or examination. Triannual mailed questionnaires ascertained incident fracture; reported fractures were adjudicated by physicians using medical records and X-ray reports. Proportional hazards models were used to develop multivariable models, selecting variables and controlling for BMD. RESULTS: Of 5876 men, 4.7% (N = 275) reported an incident nonspine fracture during follow-up (11.46/1000 person-years). Tricyclic antidepressant use (hazard ratio [HR], 2.36; 95% CI, 1.25-4.46), history of fracture at or after age 50 (HR, 2.07; 95% CI, 1.62-2.65), inability to complete a narrow walk trial (HR, 1.70; 95% CI, 1.23-2.34), falls in previous year (HR, 1.59; 95% CI, 1.23-2.05), age > or =80 years (HR, 1.33; 95% CI, 1.01-1.76), depressed mood (HR, 1.72; 95% CI, 1.00-2.95), and decreased total hip BMD (HR, 1.53; 95% CI, 1.34-1.74) were independently related to increased risk. Compared with having none (48.0% of men), having three or more of the clinical risk factors (4.9% of men) increased fracture risk 5-fold, independent of BMD. Having three or more risk factors and being in the lowest tertile of BMD was associated with a 15-fold greater risk than having no risk factors and being in the highest BMD tertile. CONCLUSIONS: Several clinical risk factors were independently associated with nonspine fractures in elderly men. The combination of multiple risk factors and low BMD was a very powerful indicator of fracture risk.     

Association Between Outpatient Follow-Up and Pediatric Emergency Department Asthma Visits

Background. The National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend that patients receive a follow-up outpatient asthma visit after being discharged from an emergency department (ED) for asthma. Objective. To measure the frequency of follow-up outpatient asthma visits and its association with repeat ED asthma visit. Design. We conducted a retrospective cohort study of children with asthma using claims data from a university-based managed care organization from 01 1998 to 10 2000. We performed a multivariate survival analysis using Cox proportional hazards model to determine the effect of follow-up outpatient asthma visits on the likelihood of a repeat ED asthma visit, after controlling for severity of illness, patient age, gender, insurance, and the specialty of the primary care provider. Results: A total of 561 children had 780 ED asthma visits. Of these, 103 (17%) had a repeat ED asthma visit within 1 year. Almost two-thirds of children (66%) did not receive outpatient follow-up for asthma within 30 days of an ED asthma visit. Outpatient asthma visits within 30 days of an ED asthma visit are associated with an increased likelihood (relative risk = 1.80; 95% confidence interval 1.19, 2.72) for repeat ED asthma visits within 1 year. Conclusions. Most patients do not have outpatient follow-up after an ED asthma visit. However, those patients that present for outpatient follow-up have an increased likelihood for repeat ED asthma visits. For the primary care provider, these outpatient follow-up visits signal an increased risk that a patient will return to the ED for asthma and are a key opportunity to prevent future ED asthma visits.     

Implementation of Evidence-Based Tobacco Use Cessation Guidelines in Managed Care Organizations

Background: Although managed care organizations (MCOs) may be optimal settings for implementing tobacco use cessation clinical guidelines, such guidelines remain poorly implemented in many MCO settings.Purpose: We examined issues related to the implementation of guidelines in MCOs, to provide examples of studies that have addressed issues related to guideline implementation and to suggest ways behavioral medicine researchers can play a role in examining issues of how guidelines can be better implemented.Methods: Surveys of clinical guideline implementation, studies from the Robert Wood Johnson Foundation addressing tobacco use cessation in a managed care database, selected to illustrate issues related to system-wide implementation.Results: Surveys show that effective tobacco use cessation interventions remain underutilized in MCOs. A few studies have evaluated and shown the benefit of insurance coverage for tobacco use and dependence treatments, clinician reimbursement and leadership incentives, practice feedback, and leveraging administrative data to create tobacco use tracking systems. The studies also point to the need for large-scale, multidisciplinary, methodologically rigorous studies that allow one to isolate the effects of promising strategies as well as to explore synergistic effects as different system changes are combined.Conclusions: Tobacco use cessation guidelines need to be better implemented in MCOs. Behavioral medicine research needs to move beyond treatment efficacy and effectiveness studies to focus on rigorous evaluations of these and other strategies to enhance guideline implementation and dissemination. This research was supported by grants from the Tobacco-Related Disease Research Program (Taylor) and from the Robert Wood Johnson Foundation (Taylor and Curry).