Search

Objective: Hip abductors, important for controlling pelvic and femoral orientation during gait, may affect knee pain. Our objective was to evaluate the relation of hip abductor strength to worsened or new‐onset frequent knee pain. Given previously noted associations of knee extensor strength with osteoarthritis in women, we performed sex‐specific analyses. Methods: We used data from the Multicenter Osteoarthritis study. Hip abductor and knee extensor strength was measured. Knee pain was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire and a question about frequent knee pain at baseline (144‐month visit), and 8, 16, and 24 months thereafter. Knee pain outcomes were worsened knee pain (2‐point increase in WOMAC pain) and incident frequent knee pain (answering yes to the frequent knee pain question among those without frequent knee pain at baseline). Leg‐specific analyses tested hip abductor strength as a risk factor for worsened and new frequent knee pain, adjusting for potential covariates. Additionally, we stratified by knee extensor strength (high versus low). Results: Among women, compared to the highest quartile of hip abductor strength, the lowest quartile had 1.7 (95% confidence interval [95% CI] 1.1–2.6) times the odds of worsened knee pain; significant associations were limited to women with high knee extensor strength (odds ratio 2.0 [95% CI 1.1–3.5]). We found no relation of abductor strength to worsening knee pain in men or with incident frequent knee pain in men or women. Conclusion: Hip abductor weakness was associated with worsening knee pain in women with strong knee extensors, but not with incident frequent knee pain in men or women. Knee extensor strength may be necessary, but not sufficient, to prevent pain worsening. [ABSTRACT FROM AUTHOR]

Objective: To assess the reliability of wearable sensors for at‐home assessment of walking and chair stand activities in people with knee osteoarthritis (OA). Methods: Baseline data from participants with knee OA (n = 20) enrolled in a clinical trial of an exercise intervention were used. Participants completed an in‐person laboratory visit and a video conference–enabled at‐home visit. In both visits, participants performed walking and chair stand tasks while fitted with 3 inertial sensors. During the at‐home visit, participants self‐donned the sensors and completed 2 sets of acquisitions separated by a 15‐minute break, when they removed and redonned the sensors. Participants completed a survey on their experience with the at‐home visit. During the laboratory visit, researchers placed the sensors on the participants. Spatiotemporal metrics of walking gait and chair stand duration were extracted from the sensor data. We used intraclass correlation coefficients (ICCs) and the Bland‐Altman plot for statistical analyses. Results: For test–retest reliability during the at‐home visit, all ICCs were good to excellent (0.85–0.95). For agreement between at‐home and laboratory visits, ICCs were moderate to good (0.59–0.87). Systematic differences were noted between at‐home and laboratory data due to faster task speed during the laboratory visits. Participants reported a favorable experience during the at‐home visit. Conclusion: Our method of estimating spatiotemporal gait measures and chair stand duration function remotely was reliable, feasible, and acceptable in people with knee OA. Wearable sensors could be used to remotely assess walking and chair stand in participant's natural environments in future studies. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore the cross‐sectional relation of unilateral knee pain severity and temporal asymmetry during walking and to determine relations of temporal asymmetry during walking to 2‐year changes in ipsilateral and contralateral knee pain in those with mild‐to‐moderate unilateral knee pain. Methods: The Multicenter Osteoarthritis Study is a prospective cohort study of adults with or at risk for knee osteoarthritis. The current study included participants with unilateral knee pain. Gait was assessed during self‐selected and fast walking at baseline. Knee pain was assessed at baseline and 2 years. We calculated limb symmetry indices (LSIs; nonpainful limb/painful limb × 100) for stance, single‐limb support time, and double‐limb support time, then examined their relations to unilateral knee pain severity, incident contralateral knee pain, and persistent ipsilateral knee pain. Results: Unilateral knee pain severity was not associated with temporal asymmetry during self‐selected or fast walking. At 2 years, 17.1% of participants had incident contralateral knee pain and 51.4% had persistent ipsilateral knee pain. For self‐selected walking, greater LSIs (i.e., longer time on the nonpainful limb) for stance and single‐limb support time were associated with decreased odds of incident contralateral knee pain. Measures of temporal asymmetry were not associated with persistent ipsilateral knee pain, except for single‐limb support time during fast walking. Conclusion: For those with unilateral knee pain, temporal asymmetry during walking is not associated with pain severity. However, select measures of stance and single‐limb support time during self‐selected and fast walking relate to longitudinal knee pain outcomes. [ABSTRACT FROM AUTHOR]

Objective: Diagnosis of pulmonary hypertension (PH) in systemic sclerosis (SSc) requires an invasive right heart catheterization (RHC), often based on an elevated estimated pulmonary artery systolic pressure on screening echocardiography. However, because of the poor specificity of echocardiography, a greater number of patients undergo RHC than necessary, exposing patients to potentially avoidable complication risks. The development of improved prediction models for PH in SSc may inform decision‐making for RHC in these patients. Methods: We conducted a retrospective study of 130 patients with SSc; 66 (50.8%) were diagnosed with PH by RHC. We used data from pulmonary function testing, electrocardiography, echocardiography, and computed tomography to identify and compare the performance characteristics of 3 models predicting the presence of PH: 1) random forest, 2) classification and regression tree, and 3) logistic regression. For each model, we generated receiver operating curves and calculated sensitivity and specificity. We internally validated models using a train‐test split of the data. Results: The random forest model performed best with an area under the curve of 0.92 (95% confidence interval [95% CI] 0.83–1.00), sensitivity of 0.95 (95% CI 0.75–1.00), and specificity of 0.80 (95% CI 0.56–0.94). The 2 most important variables in our random forest model were pulmonary artery diameter on chest computed tomography and diffusing capacity for carbon monoxide on pulmonary function testing. Conclusions: In patients with SSc, a random forest model can aid in the detection of PH with high sensitivity and specificity and may allow for better patient selection for RHC, thereby minimizing patient risk. [ABSTRACT FROM AUTHOR]

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]

Patients with systemic sclerosis complicated by both pulmonary hypertension (SSc- PH) and interstitial lung disease (SSc-PH-ILD) have poor prognosis compared to those with SSc-PH or SSc-ILD alone. Little is known of how ILD severity affects outcomes in those with SSc-PH, or how PH severity affects outcomes in thosewith SSc-ILD. Herein, we aimed to delineate clinical features of patients with SSc-PH and SSc-ILD and determine to what degree PH and ILD severity contribute to mortality in patients with SSc. We conducted parallel retrospective studies in cohorts of patients with SSc-PH and SSc-ILD. We categorized ILD severity by pulmonary function testing and PH severity by cardiopulmonary hemodynamics. Our primary outcome was all-cause mortality from time of PH or ILD diagnosis for the SSc-PH and SSc-ILD cohorts, respectively. We calculated adjusted risks of time to all-cause mortality using Cox proportional hazards models. In patients with SSc- PH, severe ILD (HR: 3.54; 95% CI: 1.05, 11.99) was associated with increased hazards for all-cause mortality. By contrast, mild and moderate ILD were not associated with increased mortality risk. In patients with SSc-ILD, both moderate (HR: 2.65; 95% CI: 1.12, 6.31) and severe PH (HR: 6.60; 95% CI: 2.98, 14.61) were associated with increased hazards for all-cause mortality, while mild PH was not. Through our parallel study design, the risk of all-cause mortality increases as severity of concomitant ILD or PH worsens. Therapies that target slowing disease progression earlier in the disease course may be beneficial. [ABSTRACT FROM AUTHOR]

The Finkelstein and Schoenfeld (FS) test is a popular generalized pairwise comparison approach to analyze prioritized composite endpoints (eg, components are assessed in order of clinical importance). Power and sample size estimation for the FS test, however, are generally done via simulation studies. This simulation approach can be extremely computationally burdensome, compounded by increasing number of composite endpoints and with increasing sample size. Here we propose an analytical solution to calculate power and sample size for commonly encountered two‐component hierarchical composite endpoints. The power formulas are derived assuming underlying distributions in each of the component outcomes on the population level, which provide a computationally efficient and practical alternative to the standard simulation approach. Monte Carlo simulation results demonstrate that performance of the proposed power formulas are consistent with that of the simulation approach, and have generally desirable objective properties including robustness to mis‐specified distributional assumptions. We demonstrate the application of the proposed formulas by calculating power and sample size for the Transthyretin Amyloidosis Cardiomyopathy Clinical Trial. [ABSTRACT FROM AUTHOR]

Objective: Systemic sclerosis–related pulmonary hypertension (SSc‐PH) is a common complication of SSc associated with accelerated mortality. The present study was undertaken to investigate whether cardiac axis deviation indicates abnormalities in cardiac function allowing for prognostication of disease severity and mortality. Methods: This was a retrospective study in which electrocardiograms (ECGs) were reviewed for cardiac axis deviation and their association with echocardiography and cardiopulmonary hemodynamics on right‐sided heart catheterization. The primary outcome observed was all‐cause mortality from the time of PH diagnosis. Results: ECG results were reviewed from 169 patients with SSc‐PH. Right axis deviation (RAD) and left axis deviation (LAD) occurred in 28.4% and 30.8% of patients with SSc‐PH, respectively. Compared to those without RAD, patients with RAD exhibited predominantly right‐sided cardiac disease on echocardiography and increased PH severity by cardiopulmonary hemodynamics including a greater mean ± SD pulmonary artery pressure (42.0 ± 12.5 mm Hg versus 29.8 ± 7.0 mm Hg) and mean ± SD pulmonary vascular resistance (645.6 ± 443.2 dynes · seconds/cm5 versus 286.3 ± 167.7 dynes · seconds/cm5). LAD was associated with predominantly left‐sided cardiac disease on echocardiography but was not associated with PH severity on cardiopulmonary hemodynamics. Both RAD (hazard ratio 10.36 [95% confidence interval 4.90–21.93], P < 0.001) and LAD (hazard ratio 2.94 [95% confidence interval 1.53–5.68], P = 0.001) were associated with an increased hazard for all‐cause mortality. Conclusion: RAD and LAD reflect structural cardiac abnormalities and are associated with poor prognosis in patients with SSc‐PH. These findings support the importance of electrocardiography, an inexpensive, widely available noninvasive test, in risk stratification. [ABSTRACT FROM AUTHOR]

Objective: We developed and validated a set of composite scores that combine quantitative magnetic resonance imaging (MRI)–based measurements of hyaline cartilage damage, bone marrow lesions (BMLs), and effusion‐synovitis into composite scores. Methods: We selected 300 participants (n = 100 for development cohort; n = 200 for validation cohort) from the Osteoarthritis Initiative with complete clinical, radiographic, and MRI data at baseline and 24 months. We used semiautomated programs to quantify tibiofemoral and patellar cartilage damage, BML volume, and whole‐knee effusion‐synovitis volume. The candidate composite scores were formed by summing changes from baseline to 24 months based on prespecified methods. We evaluated the candidate composite scores for 1) the ability to differentiate groups with and without knee osteoarthritis progression (17 radiographic and patient‐reported definitions), 2) sensitivity to change (standardized response means), and 3) relative performance relating to legacy outcome measures of knee osteoarthritis progression. Results: Three of 13 developed composite scores qualified for testing in the validation cohort (ranked by sensitivity to change): whole‐knee cumulative cartilage damage, unweighted total knee score, and BML plus effusion‐synovitis volume. Change in cumulative cartilage damage associated with radiographic progression (Kellgren/Lawrence grade: odds ratio [OR] 1.84; joint space width progression: OR 2.11). Changes in the unweighted total knee score (OR 1.97) and BML plus effusion‐synovitis score (OR 1.92) associated with Western Ontario and McMaster Universities Osteoarthritis Index knee pain progression. Conclusion: Two composite scores emerged, reflecting discrete domains of knee osteoarthritis progression. First, cumulative damage, which is measured by a whole‐knee cartilage damage score, reflects the damage accrued over time. Second, dynamic disease activity, which is measured by a BML plus effusion‐synovitis score, relates to changes in a patient's state of disease and symptoms. [ABSTRACT FROM AUTHOR]

By the early 2000s, disease remission had become a realistic goal, although the definition of remission varied widely, making it hard to compare treatment strategies and gauge how often remission occurred. Conclusion With remission achievable in RA, making the definition of remission stringent will ensure that patients benefit from comprehensive control of their disease. Lee et al (5) reported that joint pain was present and persisted in patients with RA in DAS28 remission but was absent if patients were in Boolean remission. Reexamining Remission Definitions in Rheumatoid Arthritis: Considering Disease Activity Score in 28 Joints, C-Reactive Protein, and Patient Global Assessment. [Extracted from the article]

The editors address concerns regarding the provisional remission criteria in rheumatoid arthritis (RA). The issues include the use in trials of the 28-joint Disease Activity Score thresholds to define remission, the use of C-reactive protein as an element of remission definitions, as well as the appropriateness of including patient global assessment in defining RA remission. They also discuss the history of the development of remission definitions in RA.

Objective: To evaluate the association of fatty infiltration of the quadriceps and vastus medialis (VM) with an increase in knee cartilage, meniscus, or bone marrow lesions, using magnetic resonance imaging (MRI) in knee osteoarthritis (OA) over 3 years. Methods: Participants (n = 69) with and without radiographic knee OA underwent MRI at baseline and 3 years later. Chemical shift–based water/fat MRI was used to quantify the intramuscular fat fraction and the lean anatomical cross‐sectional area (ACSA) for the VM and entire quadriceps muscles. MRI images of the knee were analyzed using the semiquantitative modified whole‐organ MRI score (mWORMS) grading to assess change in lesions in the articular cartilage, meniscus, and bone marrow. Logistic regression was used to assess whether baseline quadriceps and VM fat fraction and lean ACSA were associated with an increase in mWORMS scores. Odds ratios (ORs) were adjusted for age, sex, and body mass index. Results: Overall, of the 69 subjects, 43 (62%) had an increase in cartilage lesions (26 of 43), meniscus lesions (19 of 43), or bone marrow lesions (22 of 43) scores. The quadriceps (OR 2.13 [95% confidence interval (95% CI) 1.09–4.15]) and VM (OR 2.05 [95% CI 1.25–3.36]) fat fraction were both associated with an increase in cartilage, meniscus, or bone marrow lesion scores over 3 years. The association of quadriceps or VM lean ACSA with the outcomes was not significant. Conclusion: These longitudinal findings using quantitative MRI methods for assessment of muscle adiposity highlight the role of quadriceps adiposity, specifically in the VM, in knee OA progression. However, studies in larger cohorts are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between weight change from young adulthood to midlife and the risk of incident arthritis.Methods: Using data from the National Health and Nutrition Examination Survey, we categorized participants into weight-change categories based on their recalled weight during young adulthood and midlife. We estimated the association of weight change and developing an arthritis condition over 10 years using adjusted Cox models. Findings were extrapolated to the US population to determine the proportion of incident arthritis cases that could be averted if the entire population maintained a normal body mass index (BMI) in young adulthood and midlife.Results: Among our sample of adults who were ages 40-69 years at their midlife weight measure (n = 13,669), 3,603 developed an arthritis condition. Compared with adults who maintained a normal-normal BMI, the normal-overweight, normal-obese, overweight-obese, and obese-obese groups had a significantly elevated risk of incident arthritis conditions. The obese-overweight group had a lower risk of incident arthritis conditions compared with the obese-obese group and a comparable risk to the overweight-overweight group. Nearly one-fourth of incident arthritis cases, corresponding to 2.7 million individuals, would have been averted under the hypothetical scenario where all individuals maintained normal weight from young adulthood to midlife.Conclusion: Weight loss from young adulthood to midlife was associated with a substantially reduced risk of developing an arthritis condition. We found no evidence of residual risk from having been heavier earlier in life. Our findings highlight the critical need to expand obesity treatment and prevention to achieve meaningful reductions in the burden of arthritis. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the Boston Overcoming Osteoarthritis through Strength Training Telephone-Linked Communication (BOOST-TLC) program, a novel telephone-based, motivational, strength-training exercise-adherence counseling intervention, improved adherence to a strength-training exercise program over 2 years.Methods: Participants were recruited for this 2-year, single-blind, parallel-arm randomized controlled trial from knee osteoarthritis patient registries, community newspapers, and online websites in Massachusetts. Eligibility criteria included age 50 years or older, painful knee osteoarthritis, and ability to use a telephone. Exclusion criteria included medical conditions precluding exercise, inflammatory arthritis, current regular strength training, planned knee replacement surgery, dementia, inability to follow exercise instructions, and inability to use the TLC system. After participating in a group exercise class, participants were randomized to receiving motivational telephone calls through the BOOST-TLC program for 24 months or the control. Both control and intervention participants received a monthly automated phone message reminder to continue the program. Exercise adherence was ascertained by a single self-report item scored 0-10, where 10 represented complete adherence. Outcomes were evaluated at 6, 12, 18, and 24 months.Results: A total of 104 subjects were randomized, and 89 subjects (44 control, 45 TLC) completed the 24-month follow-up. There was no significant difference in adherence at 24 months between groups (mean for control group 4.01 [95% confidence interval (95% CI) 3.03, 4.99], mean for TLC subjects 3.63 [95% CI 2.70, 4.56]; P = 0.57).Conclusion: In those with knee osteoarthritis who had participated in an exercise program, frequent motivational telephone reminders did not increase adherence to strength-training exercise. [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]

Objective: To explore the feasibility, fidelity, safety, and preliminary outcomes of a physical therapist-administered physical activity (PA) intervention after total knee replacement (TKR).Methods: People who had undergone a unilateral TKR and were receiving outpatient physical therapy (PT) were randomized to a control or intervention group. Both groups received standard PT for TKR. The intervention included being provided with a Fitbit Zip, step goals, and 1 phone call a month for 6 months after discharge from PT. Feasibility was measured by rates of recruitment and retention, safety was measured by the frequency of adverse events, and fidelity was measured by adherence to the weekly steps/day goal created by the physical therapist and participant monitoring of steps/day. An Actigraph GT3X measured PA, which was quantified as steps/day and minutes/week of engaging in moderate-to-vigorous PA. Our preliminary outcome was the difference in PA 6 months after discharge from PT between the control and intervention groups.Results: Of the 43 individuals who were enrolled, 53.4% were women, the mean ± SD age was 67.0 ± 7.0 years, and the mean ± SD body mass index was 31.5 ± 5.9 kg/m2 . For both the control and intervention groups, the recruitment and retention rates were 64% and 83.7%, respectively, and adherence to the intervention ranged from 45% to 60%. No study-related adverse events occurred. The patients in the intervention group accumulated a mean 1,798 more steps/day (95% confidence interval [95% CI] 240, 3,355) and spent 73.4 more minutes/week (95% CI -14.1, 160.9) engaging in moderate-to-vigorous PA at 6 months than those in the control group.Conclusion: A physical therapist-administered PA intervention is feasible and safe, demonstrates treatment fidelity, and may increase PA after TKR. Future research is needed to establish the effectiveness of the intervention. [ABSTRACT FROM AUTHOR]

In observational studies with censored data, exposure-outcome associations are commonly measured with adjusted hazard ratios from multivariable Cox proportional hazards models. The difference in restricted mean survival times (RMSTs) up to a pre-specified time point is an alternative measure that offers a clinically meaningful interpretation. Several regression-based methods exist to estimate an adjusted difference in RMSTs, but they digress from the model-free method of taking the area under the survival function. We derive the adjusted RMST by integrating an adjusted Kaplan-Meier estimator with inverse probability weighting (IPW). The adjusted difference in RMSTs is the area between the two IPW-adjusted survival functions. In a Monte Carlo-type simulation study, we demonstrate that the proposed estimator performs as well as two regression-based approaches: the ANCOVA-type method of Tian et al and the pseudo-observation method of Andersen et al. We illustrate the methods by reexamining the association between total cholesterol and the 10-year risk of coronary heart disease in the Framingham Heart Study. [ABSTRACT FROM AUTHOR]

Objective: To investigate thresholds of strength below which individuals with knee osteoarthritis (OA) may have more difficulty carrying out physical functions of daily life. Individuals below such thresholds might benefit more from strengthening interventions than those with greater strength.Methods: We studied individuals with symptomatic OA at baseline in the Multicenter Osteoarthritis Study who had knee extensor strength measured isokinetically at 60º/second. Participants underwent a 20-meter walk test and a sit-to-stand test and answered questions from the Western Ontario and McMaster Universities Osteoarthritis Index. Physical function results were plotted against measures of quadriceps strength (Nm) (and as strength:body weight) for the worst knee. Loess technique was used to examine inflection points. Nonlinear relationships were examined in piecewise linear regression models. Differences were tested using linear and logistic regression models.Results: The study had 834 participants (65.8% women). The mean ± SD age of the participants was 62.9 ± 7.9 years. In women, there were thresholds of strength below which the slope of strength versus function was steeper: walking speed (<58 Nm), chair stand time (<32 Nm), and the McMaster Universities Osteoarthritis Index functions of rising from a chair and getting on/off the toilet (<38 Nm). We found no thresholds in men. Loess analyses using strength:weight showed similar results.Conclusion: In individuals with symptomatic knee OA, thresholds in the strength function relationship may help identify individuals, especially women, at the brink of disability insofar as strength and capacity for daily tasks. In those with low strength, small increments in strength may be associated with improvement in function and greater ease with common daily life, emphasizing the importance of preventing loss of strength. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether women with surgical menopause have a higher risk of frailty than naturally menopausal women. Design: Prospective cohort study with up to 18 years of follow‐up. Setting: Four U.S clinical centers. Participants: Community‐dwelling white women aged 65 and older (mean 71.2±5.2) enrolled in the Study of Osteoporotic Fractures (N=7,699). Measurements: Surgical menopause was based on participant self‐report of having undergone bilateral oophorectomy before menopause. The outcome was incident frailty, classified as robust, prefrail, frail, or death at 4 follow‐up interviews, conducted 6 to 18 years after baseline. Information on baseline serum total testosterone concentrations was available for 541 participants. Results: At baseline, 12.6% reported surgical menopause. Over the follow‐up period, 22.0% died, and 10.1% were classified as frail, 39.7% as prefrail, and 28.3% as robust. Surgically menopausal women had significantly lower total serum testosterone levels (13.2 ± 7.8 ng/dL) than naturally menopausal women (21.7 ± 14.8 ng/dL) (p=0.000), although they were not at greater risk of frailty (adjusted odds ratio (aOR)=0.94, 95% confidence interval (CI)=0.72–1.22), prefrailty (aOR=0.96, 95% CI=0.80–1.10), or death (aOR=1.17, 95% CI=0.97–1.42) after adjusting for age, body mass index, and number of instrumental activity of daily living impairments. There was no evidence that oral estrogen use modified these associations. Conclusion: In postmenopausal women, surgical menopause was not associated with greater risk for frailty than natural menopause, even in the absence of estrogen therapy. Future prospective studies are needed to investigate hormonal mechanisms involved in development of frailty in older postmenopausal women. J Am Geriatr Soc 66:2172–2177, 2018. [ABSTRACT FROM AUTHOR]

Objective: To evaluate changes in pain (at the knee and elsewhere) and pain sensitization in obese subjects with knee pain who were having bariatric surgery compared with similarly obese individuals who were undergoing medical management.Methods: This study included a cohort of subjects who were having bariatric surgery and those undergoing medical management. Knee pain severity of the more painful knee (index knee) was assessed at baseline and at 12 months using the Western Ontario and McMaster Universities Osteoarthritis Index. The pressure pain threshold (PPT) was evaluated at the index patella and the right wrist. Low patella PPT may reflect peripheral and/or central sensitization, and low wrist PPT may reflect central sensitization. The mean change in measures of pain and pain sensitization was analyzed in the surgery and medical management groups separately.Results: A total of 45 subjects in the surgery group and 22 in the medical management group completed baseline and follow-up visits. The mean weight loss was 32.7 kg (29.0%) and 4.6 kg (4.1%) in the surgery and medical management groups, respectively. Knee pain decreased only in the surgery group, in which the PPT at the patella improved by 38.5% (P = 0.0007) and at the wrist by 30.9% (P = 0.005). There was no significant change in PPT in the medical management group.Conclusion: Persons who underwent bariatric surgery experienced an improvement in pain sensitization, reflected by improvements in PPT. This improvement was observed not only at the patella, but also at the wrist, suggesting that central sensitization improved after bariatric surgery. [ABSTRACT FROM AUTHOR]

Objective: Work disability rates are high among people with rheumatic and musculoskeletal conditions. Effective disability preventive programs are needed. We examined the efficacy of a modified vocational rehabilitation approach delivered by trained occupational therapists and physical therapists on work limitation and work loss over 2 years among people with rheumatic and musculoskeletal conditions.Methods: Eligibility criteria for this single-blind, parallel-arm randomized trial included ages 21-65 years, 15 or more hours/week employment, a self-reported doctor-diagnosed rheumatic or musculoskeletal condition, and concern about staying employed. The intervention consisted of a 1.5-hour meeting, an action plan, written materials on employment supports, and telephone calls at 3 weeks and 3 months. Control group participants received the written materials. The primary outcome was the Work Limitations Questionnaire (WLQ) output job demand subscale. The secondary outcome was work loss. Intent-to-treat analyses were performed.Results: Between October 2011 and January 2014, 652 individuals were assessed for eligibility. A total of 287 participants were randomized: 143 intervention and 144 control participants. In total, 264 participants (92%) completed 2-year data collection. There was no difference in the mean ± SD WLQ change scores from baseline to 2-year followup (-8.6 ± 1.9 intervention versus -8.3 ± 2.2 control; P = 0.93). Of the 36 participants who experienced permanent work loss at 2 years, 11 (8%) were intervention participants and 25 (18%) control participants (P = 0.03).Conclusion: The intervention did not have an effect on work limitations but reduced work loss. The intervention can be delivered by trained rehabilitation therapists. [ABSTRACT FROM AUTHOR]

Objective: Participation restriction, common among people with knee osteoarthritis (OA), may be influenced by affect. We examined the risk of incident participation restriction over 84 months conferred by positive and negative affect among people with knee OA.Methods: Participants were from the Multicenter Osteoarthritis Study and had or were at high risk of knee OA. Participation restriction was measured using the Instrumental Role Limitation subscale of the Late-Life Disability Index, and affect was measured using the positive affect and depressed mood subscales of the Center for Epidemiologic Studies Depression Scale. Robust Poisson regression was used to calculate the risk of incident participation restriction over 84 months conferred by combinations of low and high positive and negative affect, adjusting for covariates.Results: Of 1,810 baseline participants (mean age 62.1 years, 56% female), 470 (26%) had incident participation restriction over 84 months. Participants with low positive affect had 20% greater risk of incident participation restriction than those with high positive affect; participants with high negative affect had 50% greater risk of incident participation restriction compared to those with low negative affect. Participants with both low positive and high negative affect had 80% greater risk of incident participation restriction compared to other combinations of positive and negative affect.Conclusion: Low positive and high negative affect, both alone and in combination, increase the risk of participation restriction among adults with knee OA. Efforts aimed at preventing participation restriction in this population should consider these mood states. [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]

Objective: Obesity is strongly associated with incident gout risk, but its association with the risk of recurrent gout attacks has been null or weak, constituting an obesity paradox. We sought to demonstrate and overcome the methodologic issues associated with the obesity paradox for risk of recurrent gout attacks.Methods: Using the Multiple Risk Factor Intervention Trial database, we decomposed the total effect of obesity into its direct and indirect (i.e., mediated) effects using marginal structural models. We also estimated the total effect of body mass index (BMI) change from baseline among incident gout patients.Results: Of 11,816 gout-free subjects at baseline, we documented 408 incident gout cases, with 132 developing recurrent gout attacks over a 7-year followup period. The adjusted odds ratio (OR) for incident gout among obese individuals was 2.6, whereas that for recurrent gout attacks among gout patients was 0.98 (i.e., the obesity paradox). These ORs correlated well with the ORs for the indirect and direct effects of obesity on the risk of recurrent gout attacks (2.83 and 0.98, respectively). Compared with no BMI change, the OR of increasing versus decreasing >5% of baseline BMI was 0.61 and 1.60 for recurrent gout attacks, respectively (P for trend < 0.01), suggesting a dose-response association.Conclusion: The obesity paradox for the risk of recurrent gout attacks is explained by the absence of the direct effect, which is often measured in conventional analyses and misinterpreted as the intended total effect of interest. In contrast, the BMI change analysis correctly estimated the intended total effect of BMI, and revealed a dose-response relationship. [ABSTRACT FROM AUTHOR]

Objective: To systematically rate the evidence on the measurement properties of work functioning instruments for people with arthritis and other rheumatologic conditions.Methods: A systematic review was conducted through a structured search to identify the quality of articles describing studies of assessment development and studies of their psychometric properties. The Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist was used to appraise the included studies. Finally, an evidence synthesis was performed to combine findings.Results: Nine arthritis-specific work outcome assessments were identified; 17 articles examining the psychometric properties of these instruments were identified and their quality was reviewed. Quality of studies was highly variable. The evidence synthesis showed that the Work Limitations Questionnaire had the strongest quality evidence of internal consistency and content validity (including structural validity and hypothesis testing), followed by the Work Instability Scale. None of the instruments had strong quality evidence of criterion validity or responsiveness.Conclusion: Considering the high variability and the low quality of the literature, we recommend that instrument developers integrate a full psychometric assessment of their instruments, including responsiveness and criterion validity, and consult guidelines (i.e., COSMIN) in reporting their findings. [ABSTRACT FROM AUTHOR]

Objective: The relationship between central and total fat measured by anthropometry, dual energy X-ray absorptiometry, and magnetic resonance imaging (MRI) with each other and systolic blood pressure (SBP) was examined. Design and Methods: Participants of the Avon Longitudinal Study of Parents and Children were examined at ages 9, 11, 13, and 15 years ( n = 3,796-6,567). MRI was available on a subset of children at 11 ( n = 156) and 13 ( n = 95). Results: Body mass index (BMI) and waist circumference (WC) were highly correlated ( r = 0.84-0.91, across ages), and total body fat mass (TBFM) and trunk fat mass (TFM) were very strongly correlated ( r ≥ 0.98). Among boys, BMI vs. WC explained a similar degree of variation in TBFM and TFM (41-71% vs. 43-76%, across age and overweight groups); in girls, BMI accounted for 62-73% variance and WC 47-69%. Adiposity measures were generally similarly correlated with SBP within age groups. Further, the relationship between intra-abdominal adipose tissue (IAAT) volume and adiposity measures did not vary greatly at 11 (0.65-0.67) and 13 (0.64-0.67). Conclusions: BMI and WC contain a large amount of overlapping information as evidenced by their high correlation and similarly sized associations with fat mass, SBP, and IAAT. This suggests that WC may be an inadequate marker of central adiposity during childhood. [ABSTRACT FROM AUTHOR]

The article examines the item selection and weighting in the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG). The BVAS/WG data from the Wegener's Granulomatosis Etanercept Trial and linear regression with generalized estimating equations were used. Calculated in the study were the scoring frequencies of the 34 predefined items an other items that were added by the clinicians. It suggests possibilities to improve the item selection and weighting of the BVAS/WG.

The article reports on a study on the association of contemporary prevalence and incidence of work disability with rheumatoid arthritis (RA) in the U.S. The study was done on 5,384 patients with average age of 52 years, 82 percent of which were female and all had arthritis for an average of 14 years. It was found that work disability affected 35 percent of the patients averaging 10 years of having the disease.

The article presents a study which evaluated the efficacy and safety of adjunctive low-dose methotrexate (MTX) in giant cell arteritis (GCA). The study performed an individual patient data meta-analysis of 3 randomized placebo-controlled trials in patients with newly diagnosed GCA. Results showed that use of MTX resulted in a reduction in the corticosteroid cumulative dose by 842 mg within 48 weeks.

The article identifies factors that explain heterogeneity in trials of glucosamine. The study found that heterogeneity among trials of glucosamine is larger than would be expected by chance. It also found that effect sizes were consistently higher among trials with industry involvement. Explanations for the difference include different glucosamine preparations, inadequate allocation concealment, and industry bias.

A letter to the editor is presented in response to the article "Glucosamine for Pain in Osteoarthritis: Why Do Trial Results Differ?," by S. C. Vlad SC et al in the 2007 issue.

Objective: Although bone marrow lesions (BMLs) are powerful predictors of joint space loss as visualized on radiographs, the natural history of these lesions, their relationship to cartilage loss, and the association between change in these lesions and cartilage loss are unknown. These questions were tested using longitudinal magnetic resonance imaging (MRI) data in a natural history study of symptomatic knee osteoarthritis (OA)., Methods: MRI of the knee was performed at baseline, 15 months, and 30 months in 217 patients with primary knee OA (122 men, 95 women; mean +/- SD age 66.4 +/- 9.4 years). To assess mechanical alignment, long-limb films were obtained at 15 months. Subchondral bone marrow abnormalities, graded in the medial and lateral tibiofemoral joints, were defined as poorly marginated areas of increased signal intensity in the marrow on fat-suppressed, T2-weighted images. Cartilage morphologic features in the medial and lateral tibiofemoral joints were scored at all time points using a semiquantitative scale. For each of the medial and lateral compartments, generalized estimating equations were used to evaluate the longitudinal relationship of tibiofemoral BMLs to the tibiofemoral cartilage score, with adjustment for malalignment., Results: Fifty-seven percent of knees had BMLs at baseline, of which 99% remained the same or increased in size at followup. Knee compartments with a higher baseline BML score had greater cartilage loss. An increase in BMLs was strongly associated with further worsening of the cartilage score. Enlarging or new BMLs occurred mostly in malaligned limbs, on the side of the malalignment (e.g., new medial BMLs in varus-aligned knees). The association of BML change with medial tibiofemoral cartilage loss was not significant after adjusting for alignment., Conclusion: Lesions of the bone marrow are unlikely to resolve and often get larger over time. Compared with BMLs that stay the same, enlarging BMLs are strongly associated with more cartilage loss. Furthermore, any change in BML is mediated by limb alignment.

Objective: To evaluate the reliability, validity, and sensitivity to change of tibiofemoral (TF) narrowing on lateral radiographic views., Methods: In a natural history study of symptomatic knee osteoarthritis (OA), both lateral view and fluoroscopically positioned posteroanterior (PA) semiflexed view radiographs of the knee in 30 degrees of flexion and with weight bearing were obtained at baseline and at 30 months. Test-retest reliability was evaluated using repeat radiographs, with joint space width measured using electronic calipers. All radiographs were scored on a 0-3 scale, and progression of joint space loss was defined as narrowing of the joint space by 1 grade. We evaluated sensitivity to change compared with the PA view. We evaluated validity by examining whether knees with progression showed expected malalignment on full-limb films., Results: Test-retest reliability of the TF joint space using the lateral view had a root mean square error of 0.303 mm, with 92.5% of repeats within 1 mm. More knees showed progression on the lateral view alone (n = 41) than on the PA view alone (n = 27). Compared with knees without joint space loss, knees with medial compartment loss on the lateral view only were more varus malaligned (P < 0.001), while those with lateral compartment loss were more valgus malaligned (P = 0.008)., Conclusion: In the assessment of TF joint space loss, lateral view radiographs are reliable, valid, and more sensitive to change than fluoroscopically positioned PA radiographs.

Objective: To determine the relationship between radiographic progression of joint space narrowing and cartilage loss on magnetic resonance imaging (MRI) in patients with symptomatic knee osteoarthritis (OA), and to investigate the location of MRI-based cartilage loss in the knee and its relation to radiographic progression., Methods: Two hundred twenty-four men and women (mean age 66 years) were studied. Radiographs and MRI of the more symptomatic knee were obtained at baseline and at 15- and 30-month followup. Radiographs of the knee (with weight-bearing) were read for joint space narrowing (scale 0-3), with progression defined as any worsening in score. We used a semiquantitative method to score cartilage morphology in all 5 regions of the tibiofemoral joint, and defined cartilage loss as an increase in score (scale 0-4) at any region. We examined the relationship between progression of joint space narrowing on radiographic images and cartilage loss on MRI, using a generalized estimating equation proportional odds logistic regression, adjusted for baseline cartilage score, age, body mass index, and sex. The medial and lateral compartments were analyzed separately., Results: In the medial compartment, 104 knees (46%) had cartilage loss detected by MRI. The adjusted odds ratio was 3.7 (95% confidence interval 2.2-6.3) for radiographic progression being predictive of cartilage loss on MRI. However, there was still a substantial proportion of knees (80 of 189 [42%]) with cartilage loss visible on MRI when no radiographic progression was apparent. Cartilage loss occurred frequently in the central regions of the femur and tibia as well as the posterior femur region, but radiographic progression was less likely to be observed when posterior femur regions showed cartilage loss. Radiographic progression appeared specific (91%) but not sensitive (23%) for cartilage loss. Overall findings were similar for the lateral compartment., Conclusion: While our results provide longitudinal evidence that radiographic progression of joint space narrowing is predictive of cartilage loss assessed on MRI, radiography is not a sensitive measure, and if used alone, will miss a substantial proportion of knees with cartilage loss.

Objective: Bone marrow lesions are associated with pain and compartment-specific progression of joint space narrowing in patients with knee osteoarthritis (OA). Bone marrow lesions occur in regions under increased loading, and excess loading produces increased bone mineral density (BMD). The ratio of BMD in the medial tibial plateau compared with that in the lateral tibial plateau (M:L BMD ratio) reflects loading in the knee. Therefore, we hypothesized that a higher M:L BMD ratio would be associated with medial bone marrow lesions, and that lower ratios would be associated with lateral bone marrow lesions., Methods: Participants in the Framingham Osteoarthritis Study underwent magnetic resonance imaging (MRI), measurement of bone mineral density (BMD), and knee radiography between 2002 and 2004. MRI was used to define medial and lateral bone marrow lesions in the medial and lateral tibiofemoral compartments, respectively. We performed a logistic regression analysis with medial bone marrow lesions as the outcome, testing M:L BMD ratio groups as predictor variables. We adjusted for age, sex, body mass index, and systemic BMD, using generalized estimating equations to adjust for correlations between knees. An identical analysis evaluating lateral bone marrow lesions was performed., Results: Medial bone marrow lesions were strongly associated with a high M:L BMD ratio. The odds ratios (ORs) for prevalent medial bone marrow lesions, for the lowest to the highest quartile of M:L BMD ratios, were 1.0 (referent), 1.3, 5.0, and infinity (P for trend < 0.0001). Lateral bone marrow lesions were strongly associated with low M:L BMD ratios (the ORs for prevalent lateral bone marrow lesions, for the highest to the lowest quartile, were 1.0 [referent], 3.0, 26.8, and 54.0 [P for trend < 0.0001])., Conclusion: Medial bone marrow lesions occur in knees with relatively higher local medial tibial bone density, and lateral bone marrow lesions occur in knees with relatively higher lateral tibial bone density, supporting the hypothesis that local BMD reflects loading within the knee. Our findings emphasize the importance of loading in the pathophysiology of OA.

Objective: Job loss is a major consequence of rheumatic diseases, and clinicians may refer patients to vocational rehabilitation for help. When provided after job loss, the impact of vocational rehabilitation is short term. This randomized controlled trial with 48 months of followup was undertaken to determine the efficacy of vocational rehabilitation provided to persons with rheumatic diseases while they are still employed, but at risk for job loss., Methods: A total of 242 patients with rheumatic diseases residing in Massachusetts were recruited through their rheumatologists for study. Participants were randomly assigned to the experimental group (n = 122) or the control group (n = 120). Subjects in the experimental group received two 1.5-hour sessions of vocational rehabilitation; those in the control group received print materials about disability employment issues and resources by mail. The main outcome assessed was the time to first job loss. Job losses were defined as permanent disability, premature retirement, or a period of unemployment. All analyses were conducted on an intent-to-treat basis., Results: Job loss was delayed in the experimental group compared with the control group (P = 0.03 by log rank test). After adjustment for confounders, participation in the experimental group was found to be protective against job loss (odds ratio 0.58 [95% confidence interval 0.34-0.99], P = 0.05 by pooled logistic regression)., Conclusion: Vocational rehabilitation delivered to patients at risk for job loss, but while they were still employed, delayed job loss. Such an intervention has the potential to reduce the high indirect costs, as well as the personal impact, of rheumatic diseases.