Frequency and spatial distribution of cartilage thickness change in knee osteoarthritis and its relation to clinical and radiographic covariates - data from the osteoarthritis initiative.

OBJECTIVE: Estimate the frequency and spatial location of rapid femorotibial cartilage thinning or thickening in knees with, or at risk of, osteoarthritis (OA) and examine their association with clinical and radiographic covariates. DESIGN: Knee cartilage thickness change over 12 months was measured using magnetic resonance imaging in the right knee of 757 Osteoarthritis Initiative (OAI) participants that had radiographic findings of osteophytes or joint space narrowing (JSN). Thickness changes in individual knees were classified as having rapid thinning or thickening or no detectable OA-related change when compared to asymptomatic OAI Control cohort knees. RESULTS: Cartilage thinning, found in 18.5% of subjects, was more frequent in knees with OAI calculated Kellgren-Lawrence grade (cKLG) > 2 (P < 0.001) and with frequent pain (P = 0.047). No link was found between body mass index, sex, and age and cartilage thinning (P > 0.15). The percent of knees with thickening was small (4.4%), but greater in knees with frequent pain (P = 0.02). Rapid thinning was most common in the central (36.4%) and external (32.1%) subregions of the medial weight-bearing femur. Mean cartilage loss in rapidly thinning subregions ranged from 11.2%/y to 24.6%/y. Knees with cKLG > 2, but classified as having no detectable OA-related change had mean cartilage loss rates significantly >0 (0.4%/y-1.3%/y) in 10 subregions. CONCLUSION: Most observed subregional changes in OA knees were indistinguishable from changes found in an asymptomatic cohort, but a fraction of subregions showed rapid progression. The relative frequency of rapid thinning increases when cKLG > 2, a classification closely associated with JSN and/or frequent knee pain are present.

Direct comparison of fixed flexion, radiography and MRI in knee osteoarthritis: responsiveness data from the Osteoarthritis Initiative.

OBJECTIVE: Minimum radiographic joint space width (mJSW) represents the Food and Drug Administration (FDA) standard for demonstrating structural therapeutic benefits for knee osteoarthritis (KOA), but only shows moderate responsiveness (sensitivity to change). We directly compare the responsiveness of magnetic resonance imaging (MRI)-based cartilage thickness and JSW measures from fixed-flexion radiography (FFR) and explore the correlation of region-matched changes between both methods. METHODS: Nine hundred and sixty-seven knees of Osteoarthritis Initiative participants with radiographic KOA were studied: 445 over 1 year with coronal FLASH MRI and FFR, and 375/522 over 1/2 years with sagittal DESS MRI and FFR. Standardized response means (SRM) of cartilage thickness and mJSW were compared using the sign-test. RESULTS: With FLASH MRI, SRM was -0.28 for medial femorotibial compartment (MFTC) cartilage loss vs -0.15 for mJSW, and -0.32 vs -0.22 for the most sensitive MRI subregion (central MFTC) vs the most sensitive fixed-location JSW(x = 0.25). With DESS MRI, 1-year SRM was -0.34 for MFTC vs -0.22 for mJSW and -0.44 vs -0.28 for central MFTC vs JSW(x = 0.225). Over 2 years, the SRM was significantly greater for MFTC than for mJSW (-0.43 vs -0.31, P = 0.017) and for central MFTC than for JSW(x = 0.225) (-0.51 vs -0.44, P < 0.001). Correlations between changes in spatially matched MRI subregions and fixed-location JSW were not consistently higher (r = 0.10-0.51) than those between non-matched locations (r = 0.15-0.50). CONCLUSIONS: MRI displays greater responsiveness in KOA than JSW FFR-based JSW, with the greatest SRM observed in the central medial femorotibial compartment. Fixed-location radiographic measures appear not capable of determining the spatial distribution of femorotibial cartilage loss.

Using ordered values of subregional cartilage thickness change increases sensitivity in detecting risk factors for osteoarthritis progression.

OBJECTIVE: To examine whether ordered values of (sub)regional femorotibial cartilage thickness change are superior to region-based approaches in detecting risk factors for cartilage loss in osteoarthritis (OA). METHODS: 58 women with knee OA had 3 Tesla MR images acquired at baseline and 24 months. Changes in cartilage thickness (∆ThCtAB) were determined in eight medial femorotibial subregions. An ascending sort of individual ∆ThCtAB measurements was done to create "ordered values". Risk factors for cartilage loss considered were: age, BMI, anatomical knee axis (AAA), minimal (medial) joint space width (mJSW), and percent of medial tibial plateau covered by the meniscus (percent cover). All change metrics were tested for association with the risk factors using Kendall's τ and relative sensitivity of multiple tests of subregions and ordered values were compared with single metrics of change from plate and compartment summaries and the first ordered value. RESULTS: The associations between subregion ∆ThCtAB and AAA (P=0.0002), mJSW (P=0.016), and age (P=0.011) were significant, but only AAA (at α=0.05) and age (at α=0.1) remained significant after adjusting for multiple subregions. In contrast, cMFTC had P-values<0.05 for AAA (P=0.0001), mJSW (P=0.016), and meniscus subluxation (0.04). The first ordered value had significant associations with AAA (P=0.0004), mJSW (P=0.003), meniscus subluxation (P=0.02) and percent cover (P=0.031) all of which were significant at α=0.05 after adjusting for tests on multiple risk factors. CONCLUSION: Ordered values of ∆ThCtAB were more sensitive in detecting risk factors of cartilage loss than subregional ∆ThCtAB. Sensitivity was further enhanced by considering the minimum ordered value as a single test, thus not requiring adjustment for multiple tests. Using ordered values there was a significant association between ∆ThCtAB and baseline AAA, mJSW, meniscus subluxation and meniscus percent cover. This study provides an important step in validating ordered values of cartilage change.

Osteoarthritis may not be a one-way-road of cartilage loss--comparison of spatial patterns of cartilage change between osteoarthritic and healthy knees.

OBJECTIVE: To explore whether longitudinal change in cartilage thickness in femorotibial subregions of knees with radiographic osteoarthritis (ROA) differs from that in healthy knees. METHODS: 3T coronal magnetic resonance (MR) images were acquired in 152 women at seven clinical centers at baseline (BL) and 24 months. Knees from 75 women with signs of ROA in either anterior-posterior or Lyon schuss radiographs were compared with those from 77 asymptomatic healthy controls without ROA to identify knees showing greater change in cartilage thickness than expected based on observations in healthy knees. The femorotibial cartilage thickness was determined in BL and follow-up MR images across five tibial and three femoral subregions in the medial/lateral compartment, respectively. RESULTS: A substantial portion of knees with ROA were classified as having longitudinal cartilage thinning (28%) or thickening (20%) in at least one medial femorotibial subregion based on comparisons to longitudinal changes observed in healthy knees; only 5% showed both subregional thinning and thickening across (different) medial subregions at the same time. Whereas the estimated proportion of Kellgren Lawrence grade (KLG) 3 knees (n=28) with significant medial cartilage thinning (46%) was substantially greater than that with cartilage thickening (18%), the estimated percentages of KLG2 knees (n=30) with significant medial thinning (20%) and thickening (23%) were similar. CONCLUSION: This exploratory study indicates that OA may not be a one-way-road of cartilage loss. Subregional analysis suggests that, compared with healthy knees, cartilage changes in ROA may occur in both directions. Medial femorotibial cartilage thickening was observed as frequently as cartilage thinning in KLG2 knees.

Change in regional cartilage morphology and joint space width in osteoarthritis participants versus healthy controls: a multicentre study using 3.0 Tesla MRI and Lyon-Schuss radiography.

OBJECTIVE: Cartilage morphology displays sensitivity to change in osteoarthritis (OA) with quantitative MRI (qMRI). However, (sub)regional cartilage thickness change at 3.0 Tesla (T) has not been directly compared with radiographic progression of joint space narrowing in OA participants and non-arthritic controls. METHODS: A total of 145 women were imaged at 7 clinical centres: 86 were non-obese and asymptomatic without radiographic OA and 55 were obese with symptomatic and radiographic OA (27 Kellgren-Lawrence grade (KLG)2 and 28 KLG3). Lyon-Schuss (LS) and fixed flexion (FF) radiographs were obtained at baseline, 12 and 24 months, and coronal spoiled gradient echo MRI sequences at 3.0 T at baseline, 6, 12 and 24 months. (Sub)regional, femorotibial cartilage thickness and minimum joint space width (mJSW) in the medial femorotibial compartment were measured and the standardised response means (SRMs) determined. RESULTS: At 6 months, qMRI demonstrated a -3.7% "annualised" change in cartilage thickness (SRM -0.33) in the central medial femorotibial compartment (cMFTC) of KLG3 subjects, but no change in KLG2 subjects. The SRM for mJSW in 12-month LS/FF radiographs of KLG3 participants was -0.68/-0.13 and at 24 months was -0.62/-0.20. The SRM for cMFTC changes measured with qMRI was -0.32 (12 months; -2.0%) and -0.48 (24 months; -2.2%), respectively. CONCLUSIONS: qMRI and LS radiography detected significant change in KLG3 participants at high risk of progression, but not in KLG2 participants, and only small changes in controls. At 12 and 24 months, LS displayed greater, and FF less, sensitivity to change in KLG3 participants than qMRI.

Subregional femorotibial cartilage morphology in women--comparison between healthy controls and participants with different grades of radiographic knee osteoarthritis.

OBJECTIVE: To identify subregional differences in femorotibial cartilage morphology between healthy controls and women with different grades of radiographic knee osteoarthritis (OA). DESIGN: 158 women aged > or =40 years were studied. Weight-bearing extended anterior-posterior (AP) and Lyon schuss radiographs were obtained and the Kellgren Lawrence grade (KLG) determined. 97 women had a body mass index (BMI)< or =28, no symptoms, and were AP KLG0. 61 women had a BMI> or =30, symptoms in the target knee, and mild (KLG2=31) to moderate (KLG3=30) medial femorotibial radiographic OA in the AP views. Coronal spoiled gradient echo water excitation sequences were acquired at 3.0 Tesla. Total plate and regional measures of cartilage morphology of the weight-bearing femorotibial joint were quantified. RESULTS: KLG2 participants displayed, on average, thicker cartilage than healthy controls in the medial femorotibial compartment (particularly anterior subregion of the medial tibia (MT) and peripheral [external, internal] subregions of the medial femur), and in the lateral femur. KLG3 participants displayed significantly thinner cartilage than KLG0 participants in the medial weight-bearing femur (central subregion), in the external subregion of the MT, and in the internal subregion of the lateral tibia. These differences were generally unaffected when possible effects of demographic covariates were considered. CONCLUSIONS: The results indicate that in femorotibial OA regional cartilage thickening and thinning may occur, dependent on the (radiographic) disease status of the joint. These changes appear to display a heterogeneous spatial pattern, where certain subregions are more strongly affected than others.

Precision of 3.0 Tesla quantitative magnetic resonance imaging of cartilage morphology in a multicentre clinical trial.

OBJECTIVE: Quantitative MRI (qMRI) of cartilage morphology is a promising tool for disease-modifying osteoarthritis drug (DMOAD) development. Recent studies at single sites have indicated that measurements at 3.0 Tesla (T) are more reproducible (precise) than those at 1.5 T. Precision errors and stability in multicentre studies with imaging equipment from various vendors have, however, not yet been evaluated. METHODS: A total of 158 female participants (97 Kellgren and Lawrence grade (KLG) 0, 31 KLG 2 and 30 KLG 3) were imaged at 7 clinical centres using Siemens Magnetom Trio and GE Signa Excite magnets. Double oblique coronal acquisitions were obtained at baseline and at 3 months, using water excitation spoiled gradient echo sequences (1.0x0.31x0.31 mm3 resolution). Segmentation of femorotibial cartilage morphology was performed using proprietary software (Chondrometrics GmbH, Ainring, Germany). RESULTS: The precision error (root mean square coefficient of variation (RMS CV)%) for cartilage thickness/volume measurements ranged from 2.1%/2.4% (medial tibia) to 2.9%/3.3% (lateral weight-bearing femoral condyle) across all participants. No significant differences in precision errors were observed between KLGs, imaging sites, or scanner manufacturers/types. Mean differences between baseline and 3 months ranged from <0.1% (non-significant) in the medial to 0.94% (p<0.01) in the lateral femorotibial compartment, and were 0.33% (p<0.02) for the total femorotibial subchondral bone area. CONCLUSIONS: qMRI performed at 3.0 T provides highly reproducible measurements of cartilage morphology in multicentre clinical trials with equipment from different vendors. The technology thus appears sufficiently robust to be recommended for large-scale multicentre trials.

Modeled estimates of chlorpyrifos exposure and dose for the Minnesota and Arizona NHEXAS populations.

This paper presents a probabilistic, multimedia, multipathway exposure model and assessment for chlorpyrifos developed as part of the National Human Exposure Assessment Survey (NHEXAS). The model was constructed using available information prior to completion of the NHEXAS study. It simulates the distribution of daily aggregate and pathway-specific chlorpyrifos absorbed dose in the general population of the State of Arizona (AZ) and in children aged 3-12 years residing in Minneapolis-St. Paul, Minnesota (MSP). Pathways included were inhalation of indoor and outdoor air, dietary ingestion, non-dietary ingestion of dust and soil, and dermal contact with dust and soil. Probability distributions for model input parameters were derived from the available literature, and input values were chosen to represent chlorpyrifos concentrations and demographics in AZ and MSP to the extent possible. When the NHEXAS AZ and MSP data become available, they can be compared to the distributions derived in this and other prototype modeling assessments to test the adequacy of this pre-NHEXAS model assessment. Although pathway-specific absorbed dose estimates differed between AZ and MSP due to differences in model inputs between simulated adults and children, the aggregate model results and general findings for simulated AZ and MSP populations were similar. The major route of chlorpyrifos intake was food ingestion, followed by indoor air inhalation. Two-stage Monte Carlo simulation was used to derive estimates of both inter-individual variability and uncertainty in the estimated distributions. The variability in the model results reflects the difference in activity patterns, exposure factors, and concentrations contacted by individuals during their daily activities. Based on the coefficient of variation, indoor air inhalation and dust ingestion were most variable relative to the mean, primarily because of variability in concentrations due to use or no-use of pesticides. Uncertainty analyses indicated a factor of 10-30 for uncertainty of model predictions of 10th, 50th, and 90th percentiles. The greatest source of uncertainty in the model stems from the definition of no household pesticide use as no use in the past year. Because chlorpyrifos persists in the residential environment for longer than a year, the modeled estimates are likely to be low. More information on pesticide usage and environmental concentrations measured at different post-application times is needed to refine and evaluate this and other pesticide exposure models.

Reducing costs of laparoscopic hysterectomy.

STUDY OBJECTIVE: To establish the role of laparoscopic hysterectomy using reuseable surgical equipment. DESIGN: Prospective, observational study (Canadian Task Force classification II-2). SETTING: Tertiary major teaching hospital. PATIENTS: Fifty consecutive women carefully selected for laparoscopic hysterectomy. INTERVENTIONS: The ultrasonically activated (harmonic) scalpel was used for coagulative cutting of pedicles and ligaments attached to the uterus and adnexa, backed by bipolar diathermy. No nonabsorbable material was left in the pelvis at the conclusion of the procedures. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, uterine weight, histology, operating time, recovery, analgesic requirements, and hospital stay were recorded. Complications were noted and critically assessed for constructive quality assurance appraisal. Outcomes were satisfactory according to both patients and gynecologists. CONCLUSION: This pilot study suggests that the method is an efficacious, cost-effective, and well-controlled technique of laparoscopic hysterectomy.

The effects of danazol after endometrial resection--results of a randomized, placebo-controlled, double-blind study.

We report the results of a controlled, randomized, prospective, 'double blind' evaluation of the effect of danazol treatment in 120 patients after hysteroscopic endometrial resection. After endometrial resection, the women were allocated to 1 of 3 groups: Group A- placebo; Group B - high-dose danazol (600 mg daily); Group C - low-dose danazol (200 mg daily) plus placebo tablets. Tablets were specifically manufactured for the study, were identical in appearance, and were supplied in individual prepackaged boxes. The duration of treatment was 3 months and patients' compliance was noted. Amenorrhoea, dysmenorrhoea and premenstrual tension symptoms were assessed for each group by 1 or 2 independent gynaecologists at follow-up intervals of 6 weeks, 3, 6 and 12 months. A statistically-significant increased rate of amenorrhoea was found in patients who received treatment with the higher-dose danazol (600 mg day) following endometrial resection. While not statistically significant, the same trend was noted with the low-dose danazol. This result should influence our clinical management of women with menorrhagia, and the long-term results on the same cohort of patients are awaited with interest.

Estimating long-term exposures from short-term measurements.

Many health problems are related to chronic exposure of individuals to pollutants in the environment. The level of exposure of a specified population is typically represented by the mean level of exposure of the population, the variation in exposure between individuals within the population, and levels of exposure for selected percentiles of the population, such as the 50th and 98th percentiles. However, the day-to-day level of exposure for individuals varies, and direct measurement of total exposure for long periods of time is impractical. The problem is to estimate the quantities listed above using incomplete sampling of the time period of interest. This paper looks at the effect of using estimates of long-term exposure for individuals on estimating the exposure distribution of the population. A simple and apparently robust estimate for the upper percentiles of the exposure distribution is proposed. Problems related to estimating an individual's long-term exposure, including sample size, are also discussed. The length of time defined as long-term in this paper is one year; however, the results are generalizable to any period of time desired.

Digestive parameters in young turkeys fed yucca saponin.

Yucca saponin fed in a concentration of 63 ppm to turkey poults at 6 to 14 weeks of age did not significantly improve weight gains, feed conversion, or digestive coefficients. Compared with nonstressed control groups, saponin-fed poults did not have significantly greater average weight gains or feed intakes when stressed by crowding (3 poults per cage) or by adding ammonia to the atmosphere (30 to 35 ppm).