Excessive alcohol consumption and the risk of knee osteoarthritis: a prospective study from the Osteoarthritis Initiative.

OBJECTIVE: To examine the association of alcohol consumption with risk of incident knee osteoarthritis (OA) in a large prospective cohort study. DESIGN: In the Osteoarthritis Initiative, 2,846 participants aged 45-79 years and free from radiographic knee OA in at least one knee at baseline were followed up to 96 months. Information on baseline alcohol consumption was obtained from the Block Brief Food Frequency Questionnaire. Incident cases of radiographic knee OA (ROA) were defined as Kellgren-Lawrence grade changing from zero or one to ≥ two during the follow-up time. Incident symptomatic OA (SxOA) was defined as ROA with knee pain worsening. The Cox proportional hazards models were used to assess the independent association between alcohol consumption and risk of knee. RESULTS: During 96 months' follow-up, we identified 691 knees with incident ROA, and 496 knees with incident SxOA among 2,846 subjects. Compared to non-drinkers, excessive alcohol consumption was significantly associated with increased risk of ROA (HR ≥ 30  g/d vs none = 1.93, 95% CI: 1.28-2.89) and SxOA (HR ≥ 30 g/d vs none = 1.61, 95% CI: 1.04-2.48). Similar association was observed for liquor consumption (HR liquor≥15 g/d vs none = 1.71, 95% CI: 1.16-2.52 for ROA; HR liquor≥15 g/d vs none = 1.59, 95% CI: 1.04-2.39 for SxOA). Light to moderate alcohol consumption was not associated with knee OA risk. CONCLUSION: Our results suggest that excessive alcohol drinking was associated with an increased risk of knee OA. Further studies are needed in other populations.

Dietary patterns and risk of developing knee osteoarthritis: data from the osteoarthritis initiative.

OBJECTIVE: Some studies have examined the association between dietary factors and risk of knee osteoarthritis (OA). We aimed to examine the prospective association of major dietary patterns with the risk of developing knee OA. METHOD: We followed 2,842 participants in Osteoarthritis Initiative (OAI) aged 45-79 years and with at least one knee free from radiographic knee OA at baseline for up to 72 months. We defined knee OA incidence as Kellgren and Lawrence grade ≥2 during follow-up visits. Using principal component analysis, Western and prudent dietary patterns were derived. Cox proportional hazards models were used to assess the association between dietary patterns and incident knee OA. RESULTS: Among study participants, 385 (418 knees) developed knee OA within 72 months. Following a Western dietary pattern was associated with an increased risk of knee OA (HR quartile 4 vs 1 = 1.69, 95% CI: 1.13 to 2.52, p trend: 0.03), while adherence to the prudent pattern was associated with a reduced risk of knee OA (HR quartile 4 vs 1 = 0.70, 95% CI: 0.50 to 0.98, p trend: 0.05). The observed associations attenuated after additionally adjusting for body mass index (BMI). The observed associations were mediated through BMI by approximately 30%. CONCLUSION: Following a Western diet was associated with increased risk of knee OA, whereas following a prudent pattern was associated with a reduced risk of knee OA. The associations were partially mediated through BMI.

Racial and ethnic disparities in utilization of total knee arthroplasty among older women.

OBJECTIVE: To evaluate racial and ethnic disparities in utilization of total knee arthroplasty (TKA) in relation to demographic, health, and socioeconomic status variables. DESIGN: Prospective study of 102,767 Women's Health Initiative postmenopausal women initially aged 50-79, examining utilization rates of primary TKA between non-Hispanic Black/African American, non-Hispanic White, and Hispanic/Latina women (hereafter referred to as Black, White, and Hispanic). A total of 8,942 Black, 3,405 Hispanic, and 90,420 White women with linked Medicare claims data were followed until time of TKA, death, or transition from fee-for-service coverage. Absolute disparities were determined using utilization rates by racial/ethnic group and relative disparities quantified using multivariable hazards models in adjusting for age, arthritis, joint pain, mobility disability, body mass index, number of comorbidities, income, education, neighborhood socioeconomic status (SES), and geographic region. RESULTS: TKA utilization was higher among White women (10.7/1,000 person-years) compared to Black (8.5/1,000 person-years) and Hispanic women (7.6/1,000 person-years). Among women with health indicators for TKA including diagnosis of arthritis, moderate to severe joint pain, and mobility disability, Black and Hispanic women were significantly less likely to undergo TKA after adjusting for age [Black: HR (95% confidence interval) = 0.70 (0.63-0.79); Hispanic: HR = 0.58 (0.44-0.77)]. Adjustment for SES modestly attenuated the measured disparity, but significant differences remained [Black: HR = 0.75 (0.67-0.89); Hispanic: HR = 0.65 (0.47-0.89)]. CONCLUSIONS: Compared to White women, Black and Hispanic women were significantly less likely to undergo TKA after considering need and appropriateness for TKA and SES. Further investigation into personal-level and provider-level factors that may explain these disparities is warranted.

Implementation of an active, clinic-based child tuberculosis contact management strategy in western Kenya.

Tuberculosis (TB) is a leading cause of childhood mortality. Isoniazid preventive therapy significantly reduces progression to TB disease. The World Health Organization recommends that high TB burden countries conduct child contact management (CCM) to identify exposed child contacts aged <5 years for screening and appropriate treatment. An active, clinic-based CCM strategy incorporating transport/screening reimbursement, monitoring and evaluation tools, and health care worker education was implemented in western Kenya. Among 169 identified child contacts aged <5 years, 146 (86%) underwent successful screening, of whom 43 (29%) were diagnosed with active TB. We describe our CCM strategy and its potential for enhancing screening and treatment efforts.

La tuberculose (TB) est une cause majeure de mortalité des enfants. Le traitement préventif par isoniazide réduit significativement la progression vers la TB maladie. L'Organisation Mondiale de la Santé recommande aux pays durement frappés par la TB de réaliser une prise en charge des enfants contacts (CCM) afin d'identifier les enfants contacts âgés de <5 ans exposés en vue d'un dépistage et d'un traitement appropriés. Une stratégie active de CCM basée sur la clinique incorporant le transport/le remboursement du dépistage, les outils de suivi et évaluation et l'éducation du personnel de santé a été mise en œuvre dans l'Ouest du Kenya. Sur 169 enfants contacts identifies âgés de <5 ans, 146 (86%) ont eu un dépistage réussi, dont 43 (29%) ont eu un diagnostic de TB active. Nous décrivons notre stratégie de CCM et son potentiel d'aMÉlioration des efforts de dépistage et de traitement.

La tuberculosis (TB) es una causa mayor de mortalidad en la niñez. El tratamiento preventivo con isoniazida disminuye de manera considerable la progresión hacia la enfermedad activa. La Organización Mundial de la Salud recomienda a los países con alta carga de morbilidad por TB que practiquen la gestión de los contactos pediátricos (CCM), con el fin de reconocer a los niños menores de 5 años de edad expuestos, realizar la detección de la TB y ofrecer el tratamiento apropiado. En Kenya occidental se introdujo en los consultorios una estrategia activa de gestión de los contactos pediátricos, que comportaba el reembolso de los gastos de transporte y detección, instrumentos de supervisión y evaluación y educación de los profesionales de salud. De los 169 contactos pediátricos menores de 5 años de edad encontrados, se practicó una detección adecuada en 146 (86%) y se diagnosticó TB activa en 43 (29%). En el presente artículo se describe la estrategia CCM y se analiza su capacidad para fortalecer los esfuerzos de detección sistemática y tratamiento.

Prospective associations of C-reactive protein (CRP) levels and CRP genetic risk scores with risk of total knee and hip replacement for osteoarthritis in a diverse cohort.

OBJECTIVE: To examine associations of high-sensitivity C-reactive protein (CRP) levels and polygenic CRP genetic risk scores (GRS) with risk of end-stage hip or knee osteoarthritis (OA), defined as incident total hip (THR) or knee replacement (TKR) for OA. DESIGN: This study included a cohort of postmenopausal white, African American, and Hispanic women from the Women's Health Initiative. Women were followed from baseline to date of THR or TKR, death, or December 31, 2014. Medicare claims data identified THR and TKR. Hs-CRP and genotyping data were collected at baseline. Three CRP GRS were constructed: 1) a 4-SNP GRS comprised of genetic variants representing variation in the CRP gene among European populations; 2) a multilocus 18-SNP GRS of genetic variants significantly associated with CRP levels in a meta-analysis of genome-wide association studies; and 3) a 5-SNP GRS of genetic variants significantly associated with CRP levels among African American women. RESULTS: In analyses conducted separately among each race and ethnic group, there were no significant associations of ln hs-CRP with risk of THR or TKR, after adjusting for age, body mass index, lifestyle characteristics, chronic diseases, hormone therapy use, and non-steroidal anti-inflammatory drug use. CRP GRS were not associated with risk of THR or TKR in any ethnic group. CONCLUSIONS: Serum levels of ln hs-CRP and genetically-predicted CRP levels were not associated with risk of THR or TKR for OA among a diverse cohort of women.

Patterns of intra-articular injection use after initiation of treatment in patients with knee osteoarthritis: data from the osteoarthritis initiative.

OBJECTIVE: We sought to describe and evaluate longitudinal use of intra-articular injections after treatment initiation among adults with radiographically confirmed knee osteoarthritis (OA). METHOD: Using data from the Osteoarthritis Initiative (OAI), we included participants with radiographically confirmed OA (Kellgren-Lawrence grade (K-L) ≥ 2) in ≥1 knee at baseline. With 9 years of data, 412 participants newly initiating hyaluronic acid or corticosteroid injections with their index visit were identified. For each type of injection initiated, socio-demographic and clinical characteristics were described by patterns of treatments (one-time use, switched, or continued injections). Multinomial logistic models estimated the extent to which patient-reported symptoms (post-initial injection and changes over time) were associated with patterns of injection use. RESULTS: Of those initiating injections, ∼19% switched, ∼21% continued injection type, and ∼60% did not report any additional injections. For participants initiating corticosteroid injections, greater symptoms post-initial injection were associated with lower odds of continued use compared to one-time users (adjusted odds ratio (aOR) for Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain: 0.91; 95%, confidence interval (CI): 0.83 to 0.99; aORstiffness: 0.77; CI: 0.63 to 0.94; aORphysical function: 0.97; CI: 0.94 to 1.00). Symptom changes over time (e.g., worsened or improved) were not associated with patterns of injections use. CONCLUSION: After treatment initiation, the proportion of patients switching injection use and one-time users was substantial. Symptoms post-initial injection appear to be associated with patterns of injection use. The extent to which these patterns are an indication of lack of impact on patient-reported symptoms should be explored.

The relationship between meniscal pathology and osteoarthritis depends on the type of meniscal damage visible on magnetic resonance images: data from the Osteoarthritis Initiative.

OBJECTIVE: To determine the association of different types of meniscal pathology with knee pain, bone marrow lesion (BML) volume, and end-stage knee osteoarthritis (esKOA). DESIGN: Participants were selected from an ancillary project to the Osteoarthritis Initiative (OAI) who had at least one knee with symptomatic osteoarthritis. Baseline magnetic resonance images (MRI) were evaluated for meniscal pathology using a modified International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine (ISAKOS) classification system. We collapsed 10 types of meniscal pathology into five categories: normal, intrameniscal signal, morphological deformity/extrusion (altered meniscal shape and/or extrusion but no apparent substance loss), tear, and maceration. Outcomes included Western Ontario and McMaster Universities osteoarthritis index (WOMAC) knee pain and BML volume at baseline and after 2 years. We defined the prevalence of esKOA based on a validated algorithm. We performed logistic regression and adjusted for age, sex, and body mass index (BMI). RESULTS: The 463 participants (53% male) included in the analysis had mean age 63 (9.2) years, BMI 29.6 (4.6) kg/m2, and 71% had Kellgren-Lawrence grade ≥2. Morphological deformity/extrusion and maceration, but no other types of meniscal pathology, were associated with BML volume (morphological deformity/extrusion odds ratio [OR] = 2.47, 95% CI: 1.49, 4.09, maceration OR = 5.85, 95% CI: 3.40, 10.06) and change in BML volume (morphological deformity/extrusion OR = 2.17, 95% CI: 1.37, 3.45, maceration OR = 3.12, 95% CI: 1.87, 5.19). Only maceration was associated with baseline WOMAC knee pain (OR = 2.82, 95% CI: 1.79, 4.43) and prevalence of esKOA (OR = 7.53, 95% CI: 4.25, 13.31). CONCLUSIONS: Based on MRI, morphologic deformity/extrusion and maceration rather than intrameniscal signal or tear were associated with osteoarthritis severity and progression, which highlights the importance of differentiating distinct types of meniscal pathology.

The relationship between smoking and knee osteoarthritis in the Osteoarthritis Initiative.

OBJECTIVE: To estimate the extent that smoking history is associated with symptoms and disease progression among individuals with radiographically confirmed knee Osteoarthritis (OA). METHOD: Both cross-sectional (baseline) and longitudinal studies employed data from the Osteoarthritis Initiative (OAI) (n = 2250 participants). Smoking history was assessed at baseline with 44% current or former smokers. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was used to measure knee pain, stiffness, and physical function. Disease progression was measured using joint space width (JSW). We used adjusted multivariable linear models to examine the relationship between smoking status and exposure in pack years (PY) with symptoms and JSW at baseline. Changes in symptoms and JSW over time were further assessed. RESULTS: In cross-sectional analyses, compared to never-smokers high PY (≥15 PY) was associated with slightly greater pain (beta 0.36, 95% CI: 0.01-0.71) and stiffness (beta 0.20, 95% CI: 0.03-0.37); and low PY (<15 PY) was associated with better JSW (beta 0.15, 95% CI: 0.02-0.28). Current smoking was associated with greater pain (beta 0.59, 95% CI: 0.04-1.15) compared to never-smokers. These associations were not confirmed in the longitudinal study. Longitudinally, no associations were found between high or low PY or baseline smoking status with changes in symptoms (at 72 months) or JSW (at 48 months). CONCLUSION: Cross-sectional findings are likely due residual confounding. The more robust longitudinal analysis found no associations between smoking status and symptoms or JSW. Long-term smoking provides no benefits to knee OA patients while exposing them to other well-documented serious health risks.

Bone marrow lesions are associated with altered trabecular morphometry.

OBJECTIVE: Bone marrow lesions (BMLs) are a common magnetic resonance (MR) feature in patients with osteoarthritis, however their pathological basis remains poorly understood and has not been evaluated in vivo. Our aim was to evaluate the trabecular structure associated with the presence and size of BMLs present in the same regions of interest (ROI) using quantitative MR-based trabecular morphometry. DESIGN: 158 participants in the Osteoarthritis Initiative (OAI) were imaged with a coronal 3D fast imaging with steady state precession (FISP) sequence for trabecular morphometry in the same session as the OAI 3 T MR knee evaluation. The proximal medial tibial subchondral bone in the central weight-bearing ROI on these knee 3D FISP images were quantitatively evaluated for apparent bone volume fraction, trabecular number, spacing, and thickness. BMLs were also evaluated in the subchondral bone immediately adjacent to the articular cartilage. BML volume was also evaluated within the same trabecular morphometry ROI and semi-quantitatively classified as none, small, or large. Kruskal-Wallis test was used to determine if mean apparent bone volume fraction, trabecular number, spacing, or thickness differed by BML score. RESULTS: Compared to knees with ROIs containing no BMLs, knees with small or large BMLs had statistically higher apparent bone volume fraction (P < 0.01), trabecular number (P < 0.01), and thickness (P = 0.02), and lower trabecular spacing (P < 0.01). CONCLUSIONS: Compared to knees with ROIs containing no BMLs, knees with ROIs containing small or large BMLs had higher apparent bone volume fraction, trabecular number and thickness, but lower trabecular spacing. These findings may represent areas of locally increased bone remodeling or compression.

Genome-wide meta-analyses of smoking behaviors in African Americans.

The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (ß = 0.040, s.e. = 0.007, P = 1.84 × 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.

Use of complementary and alternative medicine among patients with radiographic-confirmed knee osteoarthritis.

OBJECTIVE: To examine use of complementary and alternative medicine (CAM) among individuals with radiographic-confirmed osteoarthritis (OA) of the knee. METHODS: We included 2679 participants of the Osteoarthritis Initiative with radiographic tibiofemoral knee OA in at least one knee at baseline. Trained interviewers asked a series of specific questions relating to current OA treatments including CAM therapies (seven categories - alternative medical systems, mind-body interventions, manipulation and body-based methods, energy therapies, and three types of biologically based therapies) and conventional medications. Participants were classified as: (1) conventional medication users only, (2) CAM users only; (3) users of both; and (4) users of neither. Polytomous logistic regression identified correlates of treatment approaches including sociodemographics and clinical/functional correlates. RESULTS: CAM use was prevalent (47%), with 24% reporting use of both CAM and conventional medication approaches. Multi-joint OA was correlated with all treatments (adjusted odds ratios (aOR) conventional medications only: 1.62; CAM only: 1.37 and both: 2.16). X-ray evidence of severe narrowing (OARSI grade 3) was associated with use of glucosamine/chondroitin (aOR: 2.20) and use of both (aOR: 1.98). The Western Ontario and McMaster Universities (WOMAC)-Pain Score was correlated with conventional medication use, either alone (aOR: 1.28) or in combination with CAM (aOR: 1.41 per one standard deviation change). Knee Outcomes in Osteoarthritis Survey (KOOS)-Quality of Life (QOL) and Short Form (SF)-12 Physical Scale scores were inversely related to all treatments. CONCLUSION: CAM is commonly used to treat joint and arthritis pain among persons with knee OA. The extent to which these treatments are effective in managing symptoms and slowing disease progression remains to be proven.

Health utilities associated with hemoglobin levels and blood loss in postmenopausal women: the Women's Health Initiative.

OBJECTIVES: The purpose of our study was to use health-related quality of life data from the Women's Health Initiative to calculate health-related utility weights and examine differences in these health utility weights across different hemoglobin (Hgb) levels. These utility weights could then be used in future cost-effectiveness studies. METHODS: Health utility weights were measured by the Short Form-6D (SF-6D), a health utility index derived from the Short Form Medical Outcomes questionnaire. Adjusted least square means were calculated for each level of Hgb at baseline and in longitudinal regression analysis the relationship between change in Hgb and change in the SF-6D was examined. Both baseline and longitudinal analyses were performed for all postmenopausal women and separately for those with self-reported heart failure, cancer, and osteoarthritis. RESULTS: Women with Hgb in the anemic range had lower health utility weights than those with higher Hgb levels. Longitudinally, a loss of of 2 g/dl Hgb or more was associated with a statistically significant and clinically meaningfully decline in SF-6D in all participants and also in the group of participants with cancer and osteoarthritis, but not in those with heart failure. CONCLUSIONS: Lower levels of Hgb and a loss of Hgb are associated with a statistically significant and clinically meaningful decrement in health utility in all postmenopausal women we studied and also in those with chronic conditions.

Comparison of BLOKS and WORMS scoring systems part I. Cross sectional comparison of methods to assess cartilage morphology, meniscal damage and bone marrow lesions on knee MRI: data from the osteoarthritis initiative.

OBJECTIVE: To compare two semiquantitative scoring systems for assessing the prevalence and severity of morphologic cartilage lesions, meniscal damage and bone marrow lesions (BMLs) from Magnetic Resonance Imagings (MRIs) of knees with osteoarthritis (OA). METHODS: From participants in the OA Initiative (OAI), a sample of 115 knees with radiographic OA at high risk of cartilage loss, were selected based on risk factors for progression. Knee MRIs were read separately using both Whole Organ MR Scoring (WORMS) and Boston-Leeds OA Knee Scoring (BLOKS), and a subset was fed back to readers for reliability. Baseline readings were used for comparison of the two methods for inter-reader reliability as well as agreement on presence/absence and severity of MRI features at both the compartment level and finer anatomical subregion levels. RESULTS: Both methods had high inter-reader agreement for all features studied (kappa for WORMS 0.69-1.0 and for BLOKS 0.65-1.0). Although the methods agreed well on presence and severity of morphological cartilage lesions (inter-method kappas from 0.66 to 0.95), BLOKS was more sensitive for full thickness defects. The two methods gave equivalent results for extent (kappa 0.74-0.80) and number (Spearman's Rho=0.85) of BMLs, and little extra information was obtained using the more complex BLOKS BML scoring. Similar results were also obtained for the common types of meniscal damage and extrusion (inter-method kappa 0.85-0.94), but the inclusion in BLOKS of meniscal signal abnormality and uncommon types of tear may be an advantage if these prove clinically meaningful. CONCLUSION: Both WORMS and BLOKS had high reliability. The two methods gave similar results in this sample for prevalence and severity of cartilage loss, BMLs and meniscal damage. Selecting between, or combining, the two methods should be based on factors such as reader effort, appropriateness for the goals of a study, and longitudinal performance.

Can cartilage loss be detected in knee osteoarthritis (OA) patients with 3-6 months' observation using advanced image analysis of 3T MRI?

PURPOSE: Prior investigations of magnetic resonance imaging (MRI) biomarkers of cartilage loss in knee osteoarthritis (OA) suggest that trials of interventions which affect this biomarker with adequate statistical power would require large clinical studies of 1-2 years duration. We hypothesized that smaller, shorter duration, "Proof of Concept" (PoC) studies might be achievable by: (1) selecting a population at high risk of rapid medial tibio-femoral (TF) progression, in conjunction with; (2) high-field MRI (3T), and; (3) using advanced image analysis. The primary outcome was the cartilage thickness in the central medial femur. METHODS: Multi-centre, non-randomized, observational cohort study at four sites in the US. Eligible participants were females with knee pain, a body mass index (BMI)> or =25 kg/m(2), symptomatic radiographic evidence of medial TF OA, and varus mal-alignment. The 29 participants had a mean age of 62 years, mean BMI of 36 kg/m(2), with eight index knees graded as Kellgren-Lawrence (K&L)=2 and 21 as K&L=3. Eligible participants had four MRI scans of one knee: two MRIs (1 week apart) were acquired as a baseline with follow-up MRI at 3 and 6 months. A trained operator, blind to time-point but not subject, manually segmented the cartilage from the Dual Echo Steady State water excitation MR images. Anatomically corresponding regions of interest were identified on each image by using a three-dimensional statistical shape model of the endosteal bone surface, and the cartilage thickness (with areas denuded of cartilage included as having zero thickness - ThCtAB) within each region was calculated. The percentage change from baseline at 3 and 6 months was assessed using a log-scale analysis of variance (ANOVA) model including baseline as a covariate. The primary outcome was the change in cartilage thickness within the aspect of central medial femoral condyle exposed within the meniscal window (w) during articulation, neglecting cartilage edges [nuclear (n)] (nwcMF x ThCtAB), with changes in other regions considered as secondary endpoints. RESULTS: Anatomical mal-alignment ranged from -1.9 degrees to 6.3 degrees , with mean 0.9 degrees . With one exception, no changes in ThCtAB were detected at the 5% level for any of the regions of interest on the TF joint at 3 or 6 months of follow-up. The change in the primary variable (nwcMF x ThCtAB) from (mean) baseline at 3 months from the log-scale ANOVA model was -2.1% [95% confidence interval (CI) (-4.4%, +0.2%)]. The change over 6 months was 0.0% [95% CI (-2.7%, +2.8%)]. The 95% CI for the change from baseline did not include zero for the cartilage thickness within the meniscal window of the lateral tibia (wLT x ThCtAB) at 6 month follow-up (-1.5%, 95% CI [-2.9, -0.2]), but was not significant at the 5% level after correction for multiple comparisons. CONCLUSIONS: The small inconsistent compartment changes, and the relatively high variabilities in cartilage thickness changes seen over time in this study, provide no additional confidence for a 3- or 6-month PoC study using a patient population selected on the basis of risk for rapid progression with the MRI acquisition and analyses employed.

Region of interest analysis: by selecting regions with denuded areas can we detect greater amounts of change?

INTRODUCTION: Based on recent analyses, the measures of short-term responsiveness of magnetic resonance imaging (MRI) derived cartilage morphometry may not be as large as earlier studies had suggested. We examined if by selecting regions of interest with denuded cartilage, the remaining cartilage within this region of interest was susceptible to greater rates of cartilage loss. METHODS: Subjects included for this analysis are a subset of the approximately 4700 participants in the Osteoarthritis Initiative (OAI) Study. Bilateral radiographs and 3T MRI (Siemens Trio) of the knees and clinical data are obtained at baseline and annually in all participants. Hundred and fifty subjects from the OAI progression subcohort all of whom had both frequent symptoms and, in the same knee, radiographic osteoarthritis (ROA defined as definite tibio-femoral osteophytes on X-ray) based on a screening reading done at the OAI clinics. One knee from each subject was selected for analysis. Using sagittal 3D DESSwe MR images from the baseline and 12-month follow-up visit, a segmentation algorithm was applied to the cartilage plates of the index knee to compute the cartilage volume, normalized cartilage volume (volume normalized to bone surface interface area), and percent denuded area (Total Cartilage Bone Interface area denuded of cartilage). Summary statistics of the changes (absolute and percentage) from baseline at 1 year and the standardized response mean (SRM), i.e., mean change divided by the standard deviation (SD) of that change were calculated. Analyses are stratified into three groups according to baseline assessment of denuded area: those with no denuded area in the region of interest at baseline, and then two groups (intermediate denuded area (or=median) denuded area) of equal sample size. RESULTS: On average the subjects were 60.9 years of age and obese with a mean body mass index (BMI) of 30.3 kg/m(2). For the combined central medial femur and tibia the mean volume change for the whole sample was -48.2 (SD 159.8) mm(3), which gives an SRM of -0.30. In the subsample of knees with no denuded area the SRM was -0.25, in the knees with intermediate denuded area the SRM was -0.30, and in knees with severe denuded area the SRM was -1.00. For normalized volume of the central medial femur in the subsample of knees with no denuded area the SRM was -0.22, in the knees with intermediate denuded area the SRM was -0.26, and in knees with severe denuded area (n=23) the SRM was -0.71. The magnitude of the SRMs was generally smaller in participants with no denuded area. In contrast, the SRMs in participants with denuded area were larger. CONCLUSION: By selecting participants with the presence of cartilage regions with denuded area the ability to demonstrate change in cartilage loss in that specific location is markedly improved compared to persons without a full thickness lesion in that cartilage plate. This option for screening during recruitment in clinical trials could facilitate the detection of participants at greater risk of subsequent cartilage loss.

The relation of femoral notch stenosis to ACL tears in persons with knee osteoarthritis.

OBJECTIVE: A significant risk factor for anterior cruciate ligament (ACL) tears in young athletes is a reduced femoral Notch Width Index (NWI). The purpose of this study was to test if persons with knee osteoarthritis (OA) and ACL tears have smaller NWI independent of prior joint injury and osteophyte volume. METHODS: We included 160 participants from the progression sub-cohort of the Osteoarthritis Initiative (OAI) Study, an ongoing 4-year, multi-center study, focusing on knee OA. The femoral notch width, the condylar notch width at 2/3 of the notch depth, and the intercondylar notch angle (beta) were measured on sagittal and coronal MR-images. NWI=notch width/condylar width at 2/3 of the notch depth, was calculated and outcome of ACL tear frequency was compared between two groups; NWI0.20. The NWI and beta were analyzed as continuous variables. RESULTS: Of the 160 subjects [51% female, age 62.1 (+/-9.9), BMI 30.3 (+/-4.7)kg/m(2)] 14.4% showed an ACL tear. Osteophyte bone volume was available for 150 participants, of which 13% had an ACL tear. The continuous measure of NWI on the coronal images was significantly (P=0.01) smaller in participants with ACL tear [0.246, 95% confidence interval (CI) 0.234-0.258] compared to those without (0.263, 95% CI 0.258-0.268). Adjustment for demographic variables still showed significant results (P=0.03, mean difference 0.015 95% CI -0.001-0.030) and adjustment for demographic variables and osteophyte bone volume were borderline significant (P=0.06, mean difference 0.015 95% CI 0.001-0.029). CONCLUSIONS: We identified a smaller NWI in participants with knee OA and ACL tears. Further longitudinal investigation is necessary to determine this as an independent risk factor.

Magnetic resonance image segmentation using semi-automated software for quantification of knee articular cartilage---initial evaluation of a technique for paired scans.

PURPOSE: Software-based image analysis is important for studies of cartilage changes in knee osteoarthritis (OA). This study describes an evaluation of a semi-automated cartilage segmentation software tool capable of quantifying paired images for potential use in longitudinal studies of knee OA. We describe the methodology behind the analysis and demonstrate its use by determination of test-retest analysis precision of duplicate knee magnetic resonance imaging (MRI) data sets. METHODS: Test-retest knee MR images of 12 subjects with a range of knee health were evaluated from the Osteoarthritis Initiative (OAI) pilot MR study. Each subject was removed from the magnet between the two scans. The 3D DESS (sagittal, 0.456 mm x 0.365 mm, 0.7 mm slice thickness, TR 16.5 ms, TE 4.7 ms) images were obtained on a 3-T Siemens Trio MR system with a USA Instruments quadrature transmit-receive extremity coil. Segmentation of one 3D-image series was first performed and then the corresponding retest series was segmented by viewing both image series concurrently in two adjacent windows. After manual registration of the series, the first segmentation cartilage outline served as an initial estimate for the second segmentation. We evaluated morphometric measures of the bone and cartilage surface area (tAB and AC), cartilage volume (VC), and mean thickness (ThC.me) for medial/lateral tibia (MT/LT), total femur (F) and patella (P). Test-retest reproducibility was assessed using the root-mean square coefficient of variation (RMS CV%). RESULTS: For the paired analyses, RMS CV % ranged from 0.9% to 1.2% for VC, from 0.3% to 0.7% for AC, from 0.6% to 2.7% for tAB and 0.8% to 1.5% for ThC.me. CONCLUSION: Paired image analysis improved the measurement precision of cartilage segmentation. Our results are in agreement with other publications supporting the use of paired analysis for longitudinal studies of knee OA.

Does cardiovascular risk reduction alleviate erectile dysfunction in men with type II diabetes mellitus?

Veterans (N=41) with type II diabetes were enrolled in a behavioral and pharmacologic intervention for cardiac risk reduction for 4 weeks at the Providence Veterans Affairs Medical Center during 2004-2007 and were followed up 3 months post intervention. Erectile dysfunction (ED) was assessed using the 5-item version of the International Index of Erectile Function (IIEF-5). Participants experienced significant improvements in hemoglobin A1c (HbA1c), diastolic blood pressure and total cholesterol levels over the course of the intervention. Change in systolic and diastolic blood pressure and reduction in or maintenance of HbA1c below 7.0% were significantly associated with change in IIEF-5 (P=0.01, P=0.01, P=0.04, respectively). These results suggest that improved blood pressure and glycemic control in men with diabetes may lead to an improvement in ED.

Two year longitudinal change and test-retest-precision of knee cartilage morphology in a pilot study for the osteoarthritis initiative.

OBJECTIVE: Fast low angle shot (FLASH) and double echo steady state (DESS) magnetic resonance imaging (MRI) acquisitions were recently cross-calibrated for quantification of cartilage morphology at 3T. In this pilot study for the osteoarthritis (OA) initiative we compare their test-retest-precision and sensitivity to longitudinal change. METHOD: Nine participants with mild to moderate clinical OA were imaged twice each at baseline, year 1 (Y1) and year 2 (Y2). Coronal 1.5mm FLASH and sagittal 0.7mm DESS sequences were acquired; 1.5mm coronal multiplanar reformats (MPR) were obtained from the DESS. Patellar, femoral and tibial cartilage plates were quantified in a paired fashion, with blinding to time point. RESULTS: In the weight-bearing femorotibial joint, average precision errors across plates were 1.8% for FLASH, 2.6% for DESS, and 3.0% for MPR-DESS. Volume loss at Y1 was not significant; at Y2 the average change across the femorotibial cartilage plates was -1.7% for FLASH, -2.8% for DESS, and -0.3% for MPR-DESS. Volume change in the lateral tibia (-5.5%; P<0.03), and in the medial (-2.9%; P<0.04) and lateral femorotibial compartments (-3.8%; P<0.03) were significant for DESS. CONCLUSIONS: FLASH, DESS and MPR-DESS all displayed adequate test-retest precision. Although the comparison between protocols is limited by the small number of participants and by the relatively small longitudinal change in cartilage morphology in this pilot study, the data suggest that significant change can be detected with MRI in a small sample of OA subjects over 2 years.

A retrospective study of the relationship between biomarkers of atherosclerosis and erectile dysfunction in 988 men.

Erectile dysfunction (ED) is associated with clinical atherosclerosis and several atherosclerotic risk factors including smoking, hypertension, dyslipidemia, diabetes mellitus, obesity and sedentary lifestyle. Clinical atherosclerosis is also associated with these same risk factors and with biomarkers of inflammation, thrombosis, endothelial cell activation. We evaluated the cross-sectional association between the degree of ED and levels of atherosclerotic biomarkers. A subcohort of 988 US male health professionals between the ages 46 and 81 years as part of an ongoing epidemiologic study had atherosclerotic biomarkers measured from blood collected in 1994-1995. These same men had in 2000, been retrospectively asked about erectile function in 1995 and in 2000. Biennial questionnaires since 1986 assessed medical conditions, medications, smoking, physical activity, body mass index, alcohol intake. The retrospective assessment of erectile function in 2000 for 1995 in these 988 men ranged from very good - 28.2%, good - 25.1%, fair - 19.2%, poor - 13.6%, to very poor - 13.9%. Men with poor to very poor erectile function compared to men with good and very good erectile function had 2.9 the odds of having elevated Factor VII levels (P=0.03), 1.9 times the odds of having elevated vascular cell adhesion molecule (P=0.13) and 2.0 times the odds of having elevated intracellular adhesion molecule (P=0.06) and 2.1 times the odds of having elevated total cholesterol/high-density lipoprotein ratio (P=0.02) comparing the top to bottom quintiles for each atherosclerotic biomarker after multivariate adjustment. Lipoprotein(a), homocysteine, interleukin-6 and tumor necrosis factor receptor, C-reactive protein and fibrinogen were not associated with the degree of erectile function after adjustment. We conclude that selected biomarkers for endothelial function, thrombosis and dyslipidemia but not inflammation are associated with the degree of ED in this cross-sectional analysis. Future studies evaluating the prospective association of ED, endothelial function and cardiovascular disease appear warranted.