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Objective: To assess whether vascular activity seen on 18F‐fluorodeoxyglucose–positron emission tomography (FDG‐PET) scan is associated with angiographic change in large vessel vasculitis (LVV). Methods: Patients with LVV were recruited into a prospective cohort. All patients underwent magnetic resonance angiography or computed tomography angiography and FDG‐PET imaging. Follow‐up imaging using the same imaging modalities was obtained ≥6 months later per a standardized imaging protocol. Arterial damage, defined as stenosis, occlusion, or aneurysm, and corresponding FDG uptake were evaluated in 17 arterial territories. On follow‐up, development of new lesions was recorded, and existing lesions were characterized as improved, worsened, or unchanged. Results: A total of 1,091 arterial territories from 70 patients with LVV (38 patients with Takayasu arteritis, 32 patients with giant cell arteritis) were evaluated. Over a median 1.6 years of follow‐up, new lesions developed only in 8 arterial territories in 5 patients with Takayasu arteritis. Arterial lesions improved in 16 territories and worsened in 6 territories. Most arterial territories that did not have vascular activity on FDG‐PET scan at baseline had no angiographic change over the follow‐up period (787 [99%] of 793). Few territories with baseline FDG‐PET activity had angiographic change over time (24 [8%] of 298), but of the territories that developed angiographic change, 80% had FDG‐PET activity at baseline. Within the same patient, an arterial territory with baseline FDG‐PET activity had significantly increased risk for angiographic change compared to a paired arterial territory without FDG‐PET activity (odds ratio 19.49 [95% confidence interval 2.44–156.02]; P < 0.01). Concomitant edema and wall thickening further increased risk for angiographic change. Conclusion: Development of angiographic change was infrequent in this cohort of patients with LVV. A lack of baseline FDG‐PET activity was strongly associated with stable angiographic disease. In cases of angiographic progression, change was preceded by the presence of FDG‐PET activity. [ABSTRACT FROM AUTHOR]

Background: Statistical methods for modeling longitudinal and time-to-event data has received much attention in medical research and is becoming increasingly useful. In clinical studies, such as cancer and AIDS, longitudinal biomarkers are used to monitor disease progression and to predict survival. These longitudinal measures are often missing at failure times and may be prone to measurement errors. More importantly, time-dependent survival models that include the raw longitudinal measurements may lead to biased results. In previous studies these two types of data are frequently analyzed separately where a mixed effects model is used for the longitudinal data and a survival model is applied to the event outcome.Methods: In this paper we compare joint maximum likelihood methods, a two-step approach and a time dependent covariate method that link longitudinal data to survival data with emphasis on using longitudinal measures to predict survival. We apply a Bayesian semi-parametric joint method and maximum likelihood joint method that maximizes the joint likelihood of the time-to-event and longitudinal measures. We also implement the Two-Step approach, which estimates random effects separately, and a classic Time Dependent Covariate Model. We use simulation studies to assess bias, accuracy, and coverage probabilities for the estimates of the link parameter that connects the longitudinal measures to survival times.Results: Simulation results demonstrate that the Two-Step approach performed best at estimating the link parameter when variability in the longitudinal measure is low but is somewhat biased downwards when the variability is high. Bayesian semi-parametric and maximum likelihood joint methods yield higher link parameter estimates with low and high variability in the longitudinal measure. The Time Dependent Covariate method resulted in consistent underestimation of the link parameter. We illustrate these methods using data from the Framingham Heart Study in which lipid measurements and Myocardial Infarction data were collected over a period of 26 years.Conclusions: Traditional methods for modeling longitudinal and survival data, such as the time dependent covariate method, that use the observed longitudinal data, tend to provide downwardly biased estimates. The two-step approach and joint models provide better estimates, although a comparison of these methods may depend on the underlying residual variance. [ABSTRACT FROM AUTHOR]

Objective: Osteoarthritis (OA) and pain are both made more severe by low‐grade inflammation. This study was undertaken to examine whether visceral fat, a major source of inflammatory cytokines and adipokines, is associated with an increased risk of knee OA or musculoskeletal pain. Methods: Subjects in the Multicenter Osteoarthritis Study cohort, who were age 50–79 years and had or were at high risk of knee OA, underwent whole‐body dual x‐ray absorptiometry (DXA) at baseline. At baseline, 30 months, and 60 months radiographs and magnetic resonance images (MRIs) of the knees were obtained, and patients were asked to score the severity of their knee pain and to identify sites of joint pain using a body homunculus. Baseline DXA scans were used to measure total body fat and visceral and subcutaneous fat in the torso. The association of fat depot size with structural outcomes (incident radiographic OA and cartilage loss and synovitis on MRI) and with pain outcomes (worsening knee pain, number of painful joints, and widespread pain) was assessed. Regression analyses were adjusted for age, sex, race, education level, smoking status, physical activity, body mass index (BMI), and depressive symptoms. Results: Of the 2,961 participants at baseline, 60.7% were women. The mean age was 62.5 years and mean BMI was 30.5 kg/m2. After adjustment for covariates, no fat measures were associated with any structural outcomes. However, total and visceral, but not subcutaneous, fat were positively associated with worsening knee pain (P = 0.0005 for total fat and P = 0.007 for visceral fat) and widespread pain (P = 0.001 for total fat and P = 0.02 for visceral fat), and the amount of visceral fat was associated with the number of painful joints (P = 0.07). Conclusion: Our findings indicate that visceral fat is associated with an increased risk of musculoskeletal and widespread pain. [ABSTRACT FROM AUTHOR]

Background: The impact of back pain on disability in older women is well-understood, but the influence of back pain on mortality is unclear.Objective: To examine whether back pain was associated with all-cause and cause-specific mortality in older women and mediation of this association by disability.Design: Prospective cohort study.Setting: The Study of Osteoporotic Fractures.Participants: Women aged 65 or older.Measurement: Our primary outcome, time to death, was assessed using all-cause and cause-specific adjusted Cox models. We used a four-category back pain exposure (no back pain, non-persistent, infrequent persistent, or frequent persistent back pain) that combined back pain frequency and persistence across baseline (1986-1988) and first follow-up (1989-1990) interviews. Disability measures (limitations of instrumental activities of daily living [IADL], slow chair stand time, and slow walking speed) from 1991 were considered a priori potential mediators.Results: Of 8321 women (mean age 71.5, SD = 5.1), 4975 (56%) died over a median follow-up of 14.1 years. A higher proportion of women with frequent persistent back pain died (65.8%) than those with no back pain (53.5%). In the fully adjusted model, women with frequent persistent back pain had higher hazard of all-cause (hazard ratio [HR] = 1.24 [95% CI, 1.11-1.39]), cardiovascular (HR = 1.34 [CI, 1.12-1.62]), and cancer (HR = 1.33, [CI 1.03-1.71]) mortality. No association with mortality was observed for other back pain categories. In mediation analyses, IADL limitations explained 47% of the effect of persistent frequent back pain on all-cause mortality, slow chair stand time, and walking speed, explained 27% and 24% (all significant, p < 0.001), respectively.Limitations: Only white women were included.Conclusion: Frequent persistent back pain was associated with increased mortality in older women. Much of this association was mediated by disability. [ABSTRACT FROM AUTHOR]

Objectives: Smoking is associated with an increased risk of psoriatic arthritis (PsA) in the general population, but not among patients with psoriasis. We sought to clarify the possible methodological mechanisms behind this paradox.Methods: Using 1995-2015 data from The Health Improvement Network, we performed survival analysis to examine the association between smoking and incident PsA in the general population and among patients with psoriasis. We clarified the paradox using mediation analysis and conducted bias sensitivity analyses to evaluate the potential impact of index event bias and quantify its magnitude from uncontrolled/unmeasured confounders.Results: Of 6.65 million subjects without PsA at baseline, 225 213 participants had psoriasis and 7057 developed incident PsA. Smoking was associated with an increased risk of PsA in the general population (HR 1.27; 95% CI 1.19 to 1.36), but with a decreased risk among patients with psoriasis (HR 0.91; 95% CI 0.84 to 0.99). Mediation analysis showed that the effect of smoking on the risk of PsA was mediated almost entirely through its effect on psoriasis. Bias-sensitivity analyses indicated that even when the relation of uncontrolled confounders to either smoking or PsA was modest (both HRs=~1.5), it could reverse the biased effect of smoking among patients with psoriasis (HR=0.9).Conclusions: In this large cohort representative of the UK general population, smoking was positively associated with PsA risk in the general population, but negatively associated among patients with psoriasis. Conditioning on a causal intermediate variable (psoriasis) may even reverse the association between smoking and PsA, potentially explaining the smoking paradox for the risk of PsA among patients with psoriasis. [ABSTRACT FROM AUTHOR]

Objective: Older adults with knee osteoarthritis (OA) who live in environments with mobility barriers may be at greater risk of developing participation restrictions, defined as difficulties in engagement in life situations. We investigated the risk of participation restriction over 5 years due to self-reported environmental features among older adults with knee OA.Methods: Participants from the Multicenter Osteoarthritis (MOST) Study self-reported participation at baseline, 30 months, and 60 months using the instrumental role subscale of the Late Life Disability Index (LLDI). Data on self-reported environmental features were from the Home and Community Environment questionnaire administered in the MOST Knee Pain and Disability study, an ancillary study of MOST. The relative risks (RRs) of developing participation restriction at 60 months, indicated by an LLDI score <67.6 out of a possible 100, due to reported high community mobility barriers and high transportation facilitators, were calculated using robust Poisson regression, adjusting for covariates.Results: Sixty-nine of the 322 participants (27%) developed participation restriction by 60 months. Participants reporting high community mobility barriers at baseline had 1.8 times the risk (95% confidence interval [95% CI] 1.2-2.7) of participation restriction at 60 months, after adjusting for covariates. Self-report of high transportation facilitators at baseline resulted in a reduced but statistically nonsignificant risk of participation restriction at 60 months (RR 0.7, 95% CI 0.4-1.1).Conclusion: Higher perceived environmental barriers impact the risk of long-term participation restriction among older adults with or at risk of knee OA. Approaches aimed at reducing the development of participation restrictions in this population should consider decreasing environmental barriers. [ABSTRACT FROM AUTHOR]

Background: Previous studies have found an association between uterine leiomyomata (UL) and uterine malignancies. This relation has not been studied in black women, who are disproportionately affected by UL.Methods: We investigated prospectively the association between self-reported physician-diagnosed UL and endometrial cancer in the Black Women's Health Study. During 1995-2013, 47,267 participants with intact uteri completed biennial health questionnaires. Reports of endometrial cancer were confirmed by pathology data from medical records and cancer registries. Cox regression was used to derive incidence rate ratios (IRR) and 95% confidence intervals (CI).Results: There were 300 incident endometrial cancer cases during 689,546 person-years of follow-up. In multivariable models, UL history was associated with a 42% greater incidence of endometrial cancer compared with no such history (95% CI 1.12-1.80). IRRs for cancer diagnosed 0-2, 3-9, and ≥10 years after UL diagnosis were 3.20 (95% CI 2.06-4.98), 0.95 (95% CI 0.60-1.52), and 1.35 (95% CI 1.03-1.77), respectively. Stronger overall associations between UL history and endometrial cancer were observed for later stages at cancer diagnosis (IRR = 2.25, 95% CI 1.09-4.63) and type II/III cancers (IRR = 3.13, 95% CI 1.64-5.99).Conclusions: In this large cohort of black women, a history of UL was positively associated with endometrial cancer, particularly type II/III tumors. The strongest association was observed for cancer diagnosed within 2 years of UL diagnosis, a finding that might be explained by greater surveillance of women with UL or misdiagnosis of cancer as UL. However, an association was also observed for cancer reported ≥10 years after UL diagnosis. [ABSTRACT FROM AUTHOR]

Background. The ability to walk for short and prolonged periods of time is often measured with separate walking tests. It is unclear whether decline in the 2-minute walk coincides with decline in a shorter 20-m walk among older adults. Objective. The aim of this study was to describe patterns of change in the 20-m walk and 2-minute walk over 8 years among a large cohort of older adults. Should change be similar between tests of walking ability, separate retesting of prolonged walking may need to be reconsidered. Design. A longitudinal, observational cohort study was conducted. Methods. Data were from 1,893 older adults who were well-functioning (≥70 years of age). The 20-m walk and 2-minute walk were repeatedly measured over 8 years to measure change during short and prolonged periods of walking, respectively. Change was examined using a dual group-based trajectory model (dual model), and agreement between walking trajectories was quantified with a weighted kappa statistic. Results. Three trajectory groups for the 20-m walk and 2-minute walk were identified. More than 86% of the participants were in similar trajectory groups for both tests from the dual model. There was high chance-corrected agreement (kappa =.84; 95% confidence interval=.82, .86) between the 20-m walk and 2-minute walk trajectory groups. Limitations. One-third of the original Health, Aging and Body Composition (Health ABC) study cohort was excluded from analysis due to missing clinic visits, followed by being excluded for health reasons for performing the 2-minute walk, limiting generalizability to healthy older adults. Conclusions. Patterns of change in the 2-minute walk are similar to those in the 20-m walk. Thus, separate retesting of the 2-minute walk may need to be reconsidered to gauge change in prolonged walking. INSET: The Bottom Line. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine whether the effects of weight loss on arterial function are differentially modified by insulin status. Background: Clinical studies suggest that plasma insulin levels may predict the extent of cardiovascular benefit achieved with weight loss in obese individuals, but mechanisms are currently unknown. Methods: We prospectively followed 208 overweight or obese patients (body mass index [BMI] ≥25 kg/m2) receiving medical/dietary (48%) or bariatric surgical (52%) weight-loss treatment during a median period of 11.7 months (interquartile range: 4.6 to 13 months). We measured plasma metabolic parameters and vascular endothelial function using ultrasound at baseline and following weight-loss intervention and stratified analyses by median plasma insulin levels. Results: Patients age 45 ± 1 years, with BMI 45 ± 9 kg/m2, experienced 14 ± 14% weight loss during the study period. In individuals with higher baseline plasma insulin levels (above median >12 μIU/ml; n = 99), ≥10% weight loss (compared with <10%) significantly improved brachial artery macrovascular flow-mediated vasodilation and microvascular reactive hyperemia (p < 0.05 for all). By contrast, vascular function did not change significantly in the lower insulin group (≤12 μIU/ml; n = 109) despite a similar degree of weight loss. In analyses using a 5% weight loss cut point, only microvascular responses improved in the higher insulin group (p = 0.02). Conclusions: Insulin status is an important determinant of the positive effect of weight reduction on vascular function with hyperinsulinemic patients deriving the greatest benefit. Integrated improvement in both microvascular and macrovascular function was associated with ≥10% weight loss. Reversal of insulin resistance and endothelial dysfunction may represent key therapeutic targets for cardiovascular risk reduction in obesity. [ABSTRACT FROM AUTHOR]