Physical activity is associated with changes in knee cartilage microstructure.

OBJECTIVE: The purpose of this study was to determine if there is an association between objectively measured physical activity and longitudinal changes in knee cartilage microstructure. METHODS: We used accelerometry and T2-weighted magnetic resonance imaging (MRI) data from the Osteoarthritis Initiative, restricting the analysis to men aged 45-60 years, with a body mass index (BMI) of 25-27 kg/m2 and no radiographic evidence of knee osteoarthritis. After computing 4-year changes in mean T2 relaxation time for six femoral cartilage regions and mean daily times spent in the sedentary, light, moderate, and vigorous activity ranges, we performed canonical correlation analysis (CCA) to find a linear combination of times spent in different activity intensity ranges (Activity Index) that was maximally correlated with a linear combination of regional changes in cartilage microstructure (Cartilage Microstructure Index). We used leave-one-out pre-validation to test the robustness of the model on new data. RESULTS: Nineteen subjects satisfied the inclusion criteria. CCA identified an Activity Index and a Cartilage Microstructure Index that were significantly correlated (r = .82, P < .0001 on test data). Higher levels of sedentary time and vigorous activity were associated with greater medial-lateral differences in longitudinal T2 changes, whereas light activity was associated with smaller differences. CONCLUSIONS: Physical activity is better associated with an index that contrasts microstructural changes in different cartilage regions than it is with univariate or cumulative changes, likely because this index separates the effect of activity, which is greater in the medial loadbearing region, from that of patient-specific natural aging.

Modeling and predicting osteoarthritis progression: data from the osteoarthritis initiative.

OBJECTIVE: The goal of this study was to model the longitudinal progression of knee osteoarthritis (OA) and build a prognostic tool that uses data collected in 1 year to predict disease progression over 8 years. DESIGN: To model OA progression, we used a mixed-effects mixture model and 8-year data from the Osteoarthritis Initiative (OAI)-specifically, joint space width measurements from X-rays and pain scores from the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire. We included 1243 subjects who at enrollment were classified as being at high risk of developing OA based on age, body mass index (BMI), and medical and occupational histories. After clustering subjects based on radiographic and pain progression, we used clinical variables collected within the first year to build least absolute shrinkage and selection (LASSO) regression models for predicting the probabilities of belonging to each cluster. Areas under the receiver operating characteristic curve (AUC) represent predictive performance on held-out data. RESULTS: Based on joint space narrowing, subjects clustered as progressing or non-progressing. Based on pain scores, they clustered as stable, improving, or worsening. Radiographic progression could be predicted with high accuracy (AUC = .86) using data from two visits spanning 1 year, whereas pain progression could be predicted with high accuracy (AUC = .95) using data from a single visit. Joint space narrowing and pain progression were not associated. CONCLUSION: Statistical models for characterizing and predicting OA progression promise to improve clinical trial design and OA prevention efforts in the future.

An analysis of gestational age, neonatal size and neonatal death using nonparametric logistic regression.

The relationship between gestational age, neonatal size and neonatal death is complex. To date, most authors have used birth weight as a proxy for neonatal size and have neglected to examine head circumference and crown heel length. In addition, they have assumed the size and gestational age were linearly related to neonatal death. In this study we use nonparametric multiple logistic regression to examine the relationship between gestational age, neonatal size and neonatal death. On its own, gestational age was nonlinearly associated with neonatal death. This nonlinearity disappeared with the addition of birth weight, crown heel length and head circumference. Birth weight, head circumference and crown heel length all had significant nonlinear associations with neonatal death in univariate analysis. With all factors in the model, birth weight and head circumference were nonlinearly associated with neonatal death and crown heel length was linearly associated with neonatal death. The complex relations between gestational age, neonatal size and neonatal death were explored with greater ease with nonparametric logistic regression.

[Survey of antibiotic resistance in gram-negative bacteria using the cross product ratio]. / Untersuchung der Antibiotika-Resistenz in gram-negativen Bakterien unter Verwendung der Cross Product Ratio.

Antibiotic resistance pattern in clinical isolates of selected gram-negative bacteria at Groote Schuur Hospital during two three-month periods with a ten year interval were investigated. The antibiotic resistance is represented by means of the cross product, or odds ratio, using the log-linear model. This was found to be a simple method of monitoring the change or increase of antibiotic resistance, and enabled an overall analysis, catering for antibiotic and organism effects, to be performed

Regression with an ordered categorical response.

A survey on Mseleni joint disease in South Africa involved the scoring of pelvic X-rays of women to measure osteoporosis. The scores were ordinal by construction and ranged from 0 to 12. It is standard practice to use ordinary regression techniques with an ordinal response that has that many categories. We give evidence for these data that the constraints on the response result in a misleading regression analysis. McCullagh's proportional-odds model is designed specifically for the regression analysis of ordinal data. We demonstrate the technique on these data, and show how it fills the gap between ordinary regression and logistic regression (for discrete data with two categories). In addition, we demonstrate non-parametric versions of these models that do not make any linearity assumptions about the regression function.

Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials.

BACKGROUND: Low-molecular-weight heparins may simplify the management of deep venous thrombosis. A critical clinical issue is whether this more convenient therapy is as safe and effective as treatment with unfractionated heparin. PURPOSE: To compare the safety and efficacy of low-molecular-weight heparins with those of unfractionated heparin for treatment of acute deep venous thrombosis. DATA SOURCES: Reviewers identified studies by searching MEDLINE, reviewing references from retrieved articles, scanning abstracts from conference proceedings, and contacting investigators and pharmaceutical companies. STUDY SELECTION: Randomized, controlled trials that compared a low-molecular-weight heparin preparation with unfractionated heparin for treatment of acute deep venous thrombosis. DATA EXTRACTION: Two reviewers extracted data independently. Reviewers evaluated study quality using a validated four-item instrument. DATA SYNTHESIS: Eleven of 37 studies met inclusion criteria for three major outcomes. Most studies used proper randomization procedures, but only one was double-blinded. Compared with unfractionated heparin, low-molecular-weight heparins reduced mortality rates over 3 to 6 months of patient follow-up (odds ratio, 0.71 [95% CI, 0.53 to 0.94]; P = 0.02). For major bleeding complications, the odds ratio favored low-molecular-weight heparins (0.57 [CI, 0.33 to 0.99]; P = 0.047), but the absolute risk reduction was small and not statistically significant (0.61% [CI, -0.04% to 1.26%]; P = 0.07). For preventing thromboembolic recurrences, low-molecular-weight heparins seemed as effective as unfractionated heparin (odds ratio, 0.85 [CI, 0.63 to 1.14]; P > 0.2). CONCLUSIONS: Low-molecular-weight heparin treatment reduces mortality rates after acute deep venous thrombosis. These drugs seem to be as safe as unfractionated heparin with respect to major bleeding complications and appear to be as effective in preventing thromboembolic recurrences.

Quantitative determination of age-related geometric changes in the normal abdominal aorta.

PURPOSE: We conducted a novel quantitative three-dimensional analysis of computed tomography (CT) angiograms to establish the relationship between aortic geometry and age, sex, and body surface area in healthy subjects. METHODS: Abdominal helical CT angiograms from 77 healthy potential renal donors (33 men/44 women; mean age, 44 years; age range, 19-67 years) were selected. In each dataset, orthonormal cross-sectional area and diameter measurements were obtained at 1-mm intervals along the automatically calculated central axis of the abdominal aorta. The aorta was subdivided into six consecutive anatomic segments (supraceliac, supramesenteric, suprarenal, inter-renal, proximal infrarenal, and distal infrarenal). The interrelated effects of anatomic segment, age, sex, and body surface area on cross-sectional dimensions were analyzed with linear mixed-effects and varying-coefficient statistical models. RESULTS: We found that significant effects of sex and of body surface area on aortic diameters were similar at all anatomic levels. The effect of age, however, was interrelated with anatomic position, and gradually decreasing slopes of significant diameter-versus-age relationships along the aorta, which ranged from 0.14 mm/y (P <.0001) proximally to 0.03 mm/y (P =.013) distally in the abdominal aorta, were shown. CONCLUSION: The abdominal aorta undergoes considerable geometric changes when a patient is between 19 and 67 years of age, leading to an increase of aortic taper with time. The hemodynamic consequences of this geometric evolution for the development of aortic disease still need to be established.