Contrast-enhanced CT facilitates rapid, non-destructive assessment of cartilage and bone properties of the human metacarpal.

OBJECTIVE: The aim of this work is to establish the human metacarpal as a new whole joint surface early-stage osteoarthritis (OA) model that enables comparisons of articular cartilage and subchondral bone through high resolution contrast-enhanced CT (CECT) imaging, mechanical testing, and biochemical analysis. DESIGN: The fourth metacarpal was obtained from 12 human cadaveric donors and baseline µCT imaging was followed by indentation testing. The samples were then immersed in anionic (Ioxaglate) and cationic (CA4+) iodinated contrast agent solutions followed by CECT. Cartilage GAG content and distribution was measured using the 1,9 dimethylmethylene blue (DMMB) assay and Safranin-O histology staining. Linear regression was performed to compare cartilage and subchondral bone properties. RESULTS: Strong and significant positive correlations were observed between CA4+ CECT attenuation and both GAG content (R(2) = 0.86) and equilibrium modulus (R(2) = 0.84), while correlations using Ioxaglate were insignificant (R(2) ≤ 0.24, P > 0.05). Subchondral bone plate (SBP) thickness negatively and significantly correlated with SBP mineral density (R(2) = 0.49). Cartilage GAG content significantly correlated with several trabecular bone properties, including positive correlations with bone volume fraction (%BV/TV, R(2) = 0.67), trabecular number (Tb.N, R(2) = 0.60), and trabecular thickness (R(2) = 0.42), and negative relationships with structural model index (SMI, R(2) = 0.78) and trabecular spacing (Tb.Sp, R(2) = 0.56). Similarly, equilibrium modulus correlated positively with %BV/TV (R(2) = 0.50), Tb.N (R(2) = 0.59) and negatively with Tb.Sp (R(2) = 0.55) and SMI (R(2) = 0.60). CONCLUSION: This study establishes the human metacarpal as a new early-stage OA model suitable for rapid, high resolution CECT imaging, mechanical testing, and biochemical analysis of the cartilage and subchondral bone, and for examining their inter-relationships.

Assessment of axial bone rigidity in rats with metabolic diseases using CT-based structural rigidity analysis.

OBJECTIVES: This study aims to assess the correlation of CT-based structural rigidity analysis with mechanically determined axial rigidity in normal and metabolically diseased rat bone. METHODS: A total of 30 rats were divided equally into normal, ovariectomized, and partially nephrectomized groups. Cortical and trabecular bone segments from each animal underwent micro-CT to assess their average and minimum axial rigidities using structural rigidity analysis. Following imaging, all specimens were subjected to uniaxial compression and assessment of mechanically-derived axial rigidity. RESULTS: The average structural rigidity-based axial rigidity was well correlated with the average mechanically-derived axial rigidity results (R(2) = 0.74). This correlation improved significantly (p < 0.0001) when the CT-based Structural Rigidity Analysis (CTRA) minimum axial rigidity was correlated to the mechanically-derived minimum axial rigidity results (R(2) = 0.84). Tests of slopes in the mixed model regression analysis indicated a significantly steeper slope for the average axial rigidity compared with the minimum axial rigidity (p = 0.028) and a significant difference in the intercepts (p = 0.022). The CTRA average and minimum axial rigidities were correlated with the mechanically-derived average and minimum axial rigidities using paired t-test analysis (p = 0.37 and p = 0.18, respectively). CONCLUSIONS: In summary, the results of this study suggest that structural rigidity analysis of micro-CT data can be used to accurately and quantitatively measure the axial rigidity of bones with metabolic pathologies in an experimental rat model. It appears that minimum axial rigidity is a better model for measuring bone rigidity than average axial rigidity.

A pharmacy-based approach to cholesterol management.

OBJECTIVE: To determine the clinical and economic impact of a pharmacy-based cholesterol management program in patients with cardiovascular disease. STUDY DESIGN: Demonstration project. PATIENTS AND METHODS: From January 1, 1999, through June 30, 1999, 300 patients with a documented history of cardiovascular disease were enrolled in a pharmacy-based cholesterol program. A similar group of 150 randomly selected patients receiving usual care during the same period served as the comparator group. The following were collected for both groups: patient demographics, comorbidities, fasting lipid profiles, cholesterol medication, cost of medication, and cardiovascular events. The McNemar symmetry chi2 test was used to compare appropriate laboratory monitoring, receipt of cholesterol medication, and achievement of target low-density lipoprotein cholesterol levels at baseline and 1 year for both groups. Kruskal-Wallis analysis of variance was used to compare the cost of therapy for both groups at baseline and follow-up. RESULTS: Mean +/- SD age of program and usual care patients was 67 +/- 10 and 69 +/- 11 years, respectively. At 1 year, >95% of program patients were receiving appropriate laboratory monitoring. In 1 year, the percentage of patients reaching target low-density lipoprotein cholesterol levels increased from 45% to 72% (P< .01) and from 33% to 43% (P = .26) in program and usual care patients, respectively. Despite increased medication use among program patients, their cost per patient per month was lower at 1-year follow-up vs baseline. CONCLUSION: Regular patient interaction and close patient monitoring allowed the pharmacy-based lipid management program to improve cholesterol management in patients with cardiovascular disease.

Acid-suppressive therapy use associated with antihypertensive agents.

Nitrates and calcium channel blockers (CCBs) have been shown to decrease lower esophageal sphincter pressure and theoretically may precipitate or aggravate gastroesophageal reflux. Thus, the authors hypothesized that patients who receive these agents would have greater use of acid-suppressive drug use, defined as histamine2 antagonists or proton pump inhibitors. A retrospective cohort design was used to assess the use of acid-suppressive drug use in hypertensive patients with respect to both nitrates and antihypertensive therapy. Of 15,662 treated hypertensive patients, 20% received acid-suppressive therapy. An increased use of acid-suppressive therapy was associated with nitrate (odds ratio [OR] = 1.71), CCB (OR = 1.46), and alpha 1 antagonist (OR = 1.32) treatment, which appeared to be additive when patients received two or more of the agents. Within the class of CCBs, there was no significant difference among the individual agents. As the clinical and economic burden may be substantial, further study is warranted.

Treatment of hypertension in a managed care setting.

BACKGROUND: Based on recommendations of the Fifth and Sixth Reports of the Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, Health Care Plan (now Univera Healthcare) Buffalo, NY, developed a clinical guideline to improve the management of patients with hypertension. To increase awareness and utilization, the guideline was distributed as hard copy reports and made available through our electronic information system. OBJECTIVE: To determine blood pressure (BP) control rates and adherence to guideline recommendations. STUDY DESIGN: Retrospective chart review. PATIENTS AND METHODS: We randomly sampled hypertensive patients seen during 1998 to evaluate hypertension management. Computerized medical and pharmacy records were reviewed for patient demographics, antihypertensive medications, comorbid conditions, and BP readings. Patient assessment was based on antihypertensive regimen and achievement of target BP according to the recommendations of the guidelines (< 140/90 mm Hg for the general population and < 130/85 mm Hg for special populations). In addition, we assessed control rates using traditional Health Plan Employer Data and Information Set (HEDIS) measures (< 140/90 mm Hg). RESULTS: Overall, 35% of patients achieved target BP and 68% were treated with agents recommended by our JNC-based guideline. In contrast, using traditional HEDIS measures, 41% of patients achieved BP control. Of 39 patients with compelling indications (primarily diabetic patients), 13% achieved BP target and 67% were treated with recommended agents. CONCLUSIONS: The impact of our clinical guideline is reflected through the relatively high utilization of recommended drugs. However, optimal BP control continues to be problematic. In particular, patients with diabetes warrant focused attention.