Assessment of the Impact of RNase in Patients With Severe Fatigue Related to Post-Acute Sequelae of SARS-CoV-2 Infection (PASC): A Randomized Phase 2 Trial of RSLV-132.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and RNA debris persist in viral reservoirs for weeks to months following infection, potentially triggering interferon production and chronic inflammation. RSLV-132 is a biologic drug composed of catalytically active human RNase1 fused to human IgG1 Fc and is designed to remain in circulation and digest extracellular RNA. We hypothesized that removal of SARS-CoV-2 viral RNA from latent reservoirs may improve inflammation, neuroinflammation, and fatigue associated with post-acute sequelae of SARS-CoV-2 infection (PASC). METHODS: This was a phase 2, double-blind, placebo-controlled randomized clinical trial in participants with a 24-week history of PASC and severe fatigue. The primary endpoint of the trial assessed the impact of 6 intravenous doses of RSLV-132 on the mean change from baseline at day 71 in the Patient-Reported Outcomes Measurement Information System Fatigue Short Form 7a (PROMIS Fatigue SF 7a). RESULTS: A statistically significant difference on day 71 was not observed with respect to the primary or secondary endpoints. This was likely due to a placebo response that increased during the trial. Statistically significant improvement in fatigue as measured by the PROMIS Fatigue SF 7a, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and Physicians Global Assessment (PGA) instruments were observed earlier in the trial, with women demonstrating greater responses to RSLV-132 than men. CONCLUSION: While fatigue was not statistically significantly improved at Day 71, earlier timepoints revealed statistically significant improvement in fatigue and physician global assessment. The data suggest eliminating latent viral RNA by increasing serum RNase activity may improve fatigue in PASC patients. Women may respond better to this approach than men. Future studies will aim to confirm these findings.

Frailty and Risk of Serious Infections in Patients With Rheumatoid Arthritis Treated With Biologic or Targeted-Synthetic Disease-Modifying Antirheumatic Drugs.

OBJECTIVE: It remains unknown whether frailty status portends an increased risk of adverse outcomes in patients with rheumatoid arthritis (RA) initiating biologic or targeted-synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The objective of our study was to evaluate the association between frailty and serious infections in a younger population of patients (<65 years old) with RA who initiated b/tsDMARDs. METHODS: Using MarketScan data, we identified new users of tumor necrosis factor inhibitors (TNFi), non-TNFi biologic DMARDs, or Janus kinase inhibitors (JAKi) between 2008 and 2019 among those with RA. Patients' baseline frailty risk score was calculated using a Claims-Based Frailty Index (≥0.2 defined as frail) 12 months prior to drug initiation. The primary outcome was time to serious infection; secondarily, we examined time-to-any infection and all-cause hospitalizations. We used Cox proportional hazards to estimate adjusted hazard ratios and 95% confidence intervals (95% CIs) and assessed the significance of interaction terms between frailty status and drug class. RESULTS: A total of 57,980 patients, mean (±SD) age 48.1 ± 10.1 were included; 48,139 (83%) started TNFi, 8,111 (14%) non-TNFi biologics, and 1,730 (3%) JAKi. Among these, 3,560 (6%) were categorized as frail. Frailty was associated with a 50% increased risk of serious infections (adjusted hazard ratio [95% CI] 1.5, 1.2-1.9) and 40% higher risk of inpatient admissions (1.4 [1.3-1.6]) compared with nonfrail patients among those who initiated TNFi. Frailty was also associated with a higher risk of any infection relative to nonfrail patients among those on TNFi (1.2 [1.1-1.3]) or non-TNFi (1.2 [1.0-1.4]) or JAKi (1.4 [1.0-2.0]). CONCLUSION: Frailty is an important predictor for the risk of adverse outcomes among patients with RA treated with biologic or targeted-synthetic DMARDs.

Exploring risk factors for persistent neurocognitive sequelae after hospitalization for COVID-19.

OBJECTIVE: In this study of patients hospitalized during acute SARS-CoV2 infection with 6-months of follow-up data, we identified risk factors associated with the development of neuro-PASC. METHODS: We conducted an exploratory, observational single-center cohort study of patients hospitalized for COVID-19 from November 2020 to March 2022. Our primary outcome was persistent neurocognitive symptoms, defined as fatigue, headache, loss of taste/smell, brain fog, confusion, concentration/memory/word finding difficulty, and/or change in speech present at 1-month and persisting for 6-months following acute SARS-CoV2 infection. Secondary outcomes included persistent impairment scores on PROMIS cognitive function and abilities scales. Multivariate logistic regression analyses identified potential risk factors for neuro-PASC. RESULTS: Of 89 participants, 60% reported persistent neurocognitive symptoms at 6-months; fatigue was the most prevalent, occurring in 53% of participants, followed by brain fog in 34% of participants. Lower self-reported socioeconomic status and increased pre-COVID-19 anxiety scores on the Hospital Anxiety and Depression Scale were associated with increased odds of developing persistent neurocognitive symptoms. Being female and of Hispanic descent were associated with increased odds of persistent cognitive function and ability impairment. INTERPRETATION: Sociodemographic factors and pre-COVID-19 anxiety symptoms may be important risk factors for neuro-PASC. These findings underscore the need to assess various sociodemographic factors in research on PASC. Our study also highlights premorbid mental health symptoms as a potential predictor of persistent neurocognitive symptoms following hospitalization with SARS-CoV2 infection.

Appendicular Lean Mass, Grip Strength, and the Incidence of Dementia Among Older Adults in the Health ABC Study.

BACKGROUND: Identification of novel risk factors for dementia in older adults could facilitate development of methods to identify patients most at risk and improve their cognitive outcomes. We aimed to determine whether lower appendicular lean mass (ALM), assessed by dual-energy x-ray absorptiometry (DXA), and lower grip strength are associated with a greater likelihood of incident dementia among older adults in the Health Aging and Body Composition Study (Health ABC). METHODS: Health ABC data from 1997 to 2008 were analyzed (n = 2 704). Baseline ALM to body mass index (BMI) ratio (ALMBMI) was assessed by DXA. Baseline grip strength was assessed by hand-held dynamometry. Incident dementia diagnosis was defined as either (i) dementia-related hospitalization plus a Modified Mini-Mental State Examination (3MS) score of ≤ 90; or (ii) record of prescription for anti-dementia medication; or (iii) decline of at least 1.5 SDs on the 3MS score compared to baseline. Cox proportional hazard models estimated associations of ALMBMI and grip strength with incident dementia over follow-up with and without adjusting for covariates, stratified by sex. RESULTS: Among older men, each standard deviation decrement in ALMBMI (adjusted hazard ratio [aHR]: 1.33; 95% confidence interval [CI]: 1.07, 1.65) or grip strength (aHR 1.22; 95% CI: 1.06, 1.41) was associated with increased likelihood of incident dementia. CONCLUSIONS: Lower ALMBMI and grip strength may be important risk factors for the development of dementia among older men. How these factors may belong to a causal pathway of dementia must be elucidated in future work.

Physical function and fatigue recovery at 6 months after hospitalization for COVID-19.

INTRODUCTION: There are an increasing number of individuals with long-term symptoms of coronavirus-19 disease (COVID-19); however, the prognosis for recovery of physical function and fatigue after COVID-19 is uncertain. OBJECTIVE: To report the changes in functional recovery between 1 and 6 months after hospitalization of adults hospitalized for COVID-19 and explore the baseline factors associated with physical function recovery. DESIGN: A prospective cohort study. SETTING: Tertiary care hospital. PARTICIPANTS: U.S. adult COVID-19 survivors. INTERVENTION: N/A. MAIN OUTCOME MEASURES: Telephone interviews assessed three outcome domains: basic and instrumental activities of daily living (ADLs) performance, fatigue, and general physical function (Health Assessment Questionnaire [HAQ]). RESULTS: The age of participants (n = 92) ranged from 22 to 95 years (54.3 ± 17.2). Across outcome domains, a majority (63%-67%) of participants developed new ADL impairment, fatigue, or worsening HAQ severity by 1 month. Of those, 50%-79% partially or fully recovered by 6 months, but 21%-50% did not recover at least partially. Fifteen to 30% developed new impairment between 1 and 6 months. For those without any improvement in ADL impairments at 6 months, lower socioeconomic status was significantly more common (p = .01) and age ≥ 65 (p = .06), trending toward being more common. CONCLUSION: In this cohort, a substantial proportion of the participants who developed new ADL impairment, worsening fatigue, or HAQ severity after hospitalization for COVID-19 did not recover at least partially by 6 months after discharge. Evaluating functional status 1 month after discharge may be important in understanding functional prognosis and recovery after hospitalization for COVID-19.

Low cumulative disease activity is associated with higher bone mineral density in a majority Latinx and Asian US rheumatoid arthritis cohort.

OBJECTIVE: Prior studies have found conflicting results when evaluating the association between rheumatoid arthritis (RA) disease activity and bone mineral density (BMD). Whether or not cumulative RA disease activity is associated with BMD remains unanswered. METHODS: Data were from the University of California San Francisco RA Cohort from years 2006-2018. Those with BMD measures and at least two study visits prior to BMD measure were included in the study. The association between low cumulative disease activity, as measured by DAS28ESR, with the primary outcome of femoral neck BMD was assessed using multivariable linear regression. Sensitivity analyses were performed substituting CDAI for the disease activity measure as well as total hip and lumbar spine BMD as outcomes. RESULTS: 161 participants with RA were studied. The cohort was 62.4 ± 10.2 years old and 88% female. Hispanic/Latino (N = 73, 45%) and Asian (N = 59, 37%) were the most common racial/ethnic groups in our cohort. Mean RA duration was 10.5 ± 7.3 years and 83% were ACPA positive. Low disease activity was independently associated with higher femoral neck BMD compared to the moderate/high disease activity group (ß= 0.071 [95%CI: 0.021 to 0.122], p = 0.020). The relationship between low cumulative disease activity was similar when CDAI and other BMD sites were substituted in the multivariable models. CONCLUSION: Low cumulative disease activity as measured by DAS28ESR was associated with higher femoral neck BMD, independent of traditional osteoporosis risk factors (e.g., age, sex, BMI) in a unique RA cohort. Results were similar when evaluating cumulative low CDAI and other BMD sites.

Lean mass, grip strength, and hospital-associated disability among older adults in Health ABC.

INTRODUCTION: Older adults with cognitive impairment, including those with Alzheimer's disease and related dementias, are particularly at risk for hospitalization and hospital-associated disability. Understanding of key risk factors for hospital-associated disability is limited. Sarcopenia, age-related declines in muscle mass and strength, is common in older adults with cognitive impairment and may be an important risk factor for hospital-associated disability. METHODS: Using data from the Health ABC Study, we examined associations of pre-hospitalization appendicular lean mass (ALM) and grip strength with the development of a new activity of daily living (ADL) disability at the next annual assessment after hospitalization. RESULTS: Grip strength, but not ALM, was negatively associated with increased risk of hospital-associated ADL disability, and this association was greater among those with cognitive impairment compared to those without. DISCUSSION: Lower grip strength may be an important risk factor for hospital-associated ADL disability in older adults, particularly those with cognitive impairment.

Appendicular Lean Mass, Grip Strength, and the Development of Hospital-Associated Activities of Daily Living Disability Among Older Adults in the Health ABC Study.

BACKGROUND: Half of all physical disability, including activity of daily living (ADL) disability, among older adults occurs in the setting of hospitalization. This study examines whether appendicular lean mass (ALM) and grip strength, which are commonly included in various definitions of sarcopenia, are associated with the development of hospital-associated ADL disability in older adults in the Health ABC Study. METHODS: Individuals hospitalized during the first 5 years of follow-up (n = 1 724) were analyzed. ALM to body mass index (BMI) ratio (ALMBMI), by dual-energy x-ray absorptiometry (DXA), and grip strength, by hand-held dynamometery, were assessed annually. Development of new ADL disability was assessed at the time of the next annual assessment after hospitalization. Separate regression analyses modeled the association of prehospitalization ALMBMI or grip strength with death before the next scheduled annual assessment. Next, among those who survived to the next annual assessment, separate regression analyses modeled the association of ALMBMI or grip strength with development of ADL disability. RESULTS: Each standard deviation decrement in prehospitalization grip strength was associated with an adjusted 1.80 odds of new ADL disability at follow-up (95% CI: 1.18, 2.74). Low, compared with not low, grip strength (per FNIH definition) was associated with an adjusted 2.36 odds of ADL disability at follow-up (95% CI: 1.12, 4.97). ALM measures were not associated with the development of hospital-associated ADL disability. ALM and grip strength measures were not associated with death. CONCLUSIONS: Prehospitalization lower grip strength may be an important risk factor for ADL disability among older adult survivors of hospitalization.

Patient-reported functional outcomes 30 days after hospitalization for COVID-19.

BACKGROUND: Many coronavirus disease 2019 (COVID-19) survivors experience persistent symptoms, such as fatigue, dyspnea, and musculoskeletal pain. However, less is known about the impact of COVID-19 on longer term functional outcomes. OBJECTIVE: To evaluate patient-reported activity of daily living (ADL) function and fatigue symptoms 30 days after hospitalization for COVID-19. DESIGN: Cross-sectional study. SETTING: Tertiary care university hospital. PARTICIPANTS: Adults 18 years or older hospitalized for COVID-19 and survived to 30 days after discharge. METHODS: A standardized telephone questionnaire was administered 30 days after hospital discharge. MAIN OUTCOME MEASURES: Ability to perform basic and instrumental ADLs and fatigue symptoms severity (Patient-Reported Outcome Measurement Information System [PROMIS] Fatigue Short Form 7a) were assessed by self-report. RESULTS: Participants (n = 55) were 22-95 years old. Compared to pre-COVID hospitalization, 52% developed new difficulty and 6% new dependence with performing basic ADLs (bADLs), 48% developed new difficulty and 11% new dependence with instrumental ADLs (iADLs), and 69% experienced a clinically significant worsening in their fatigue symptom severity. The average fatigue symptom severity T-score before hospitalization was 44.2 ± 7.4 and after hospitalization was 54.5 ± 9.8. In exploratory multivariate analyses, each additional COVID symptom at presentation was associated with a predicted increase of 1.43 units (95% confidence interval [CI], 0.45-2.42) in the 30-day fatigue symptom severity T-score, each additional day of hospitalization was associated with an 1.2 times increased odds of worsening fatigue (95% CI, 0.98-1.5; p = .08), and each unit increase in baseline body mass index was associated with 0.8 times decreased odds of new bADL or iADL dependence at 30 days (95% CI, 0.65-0.99). CONCLUSIONS: New functional impairments are common at 30 days after discharge among survivors of hospitalization for COVID-19. Early rehabilitation, advance care planning, and referrals to appropriate therapies should be considered in postacute COVID-19 care to maximize patients' functional outcomes. However, ongoing research is still needed regarding management of these patients.

Appendicular Lean Mass, Grip Strength, and the Development of Knee Osteoarthritis and Knee Pain Among Older Adults.

OBJECTIVE: The association of sarcopenia with development of knee osteoarthritis (OA) or knee pain in older adults is uncertain. We examined the relationship of grip strength and appendicular lean mass (ALM) with the likelihood of developing knee OA and knee pain in older adults in the Health ABC (Health, Aging, and Body Composition) Study. METHODS: ALM and grip strength were assessed at baseline by dual-energy x-ray absorptiometry and handheld dynamometry, respectively. Incident clinically diagnosed, symptomatic knee OA, defined as new participant report of physician-diagnosed knee OA and concurrent frequent knee pain, and incident frequent knee pain over 5 years of follow-up were examined. Separate regression analyses, stratified by sex, modeled associations of baseline ALM and grip strength with the likelihood of incident clinically diagnosed, symptomatic knee OA and incident knee pain over follow-up, adjusting for covariates. RESULTS: Among the 2779 subjects without OA at baseline, 95 men (6.9%) and 158 women (11.3%) developed clinically diagnosed, symptomatic knee OA, and, among the 2182 subjects without knee pain at baseline, 315 men (28.3%) and 385 women (36.1%) developed knee pain over follow-up. Among men only, each SD decrement of ALM was associated with decreasing likelihood of incident knee OA (odds ratio [OR] per SD decrement: 0.68; 95% confidence interval [CI]: 0.47-0.97), and each SD decrement of grip strength was associated with increasing likelihood of incident knee pain (OR per SD decrement: 1.20; 95% CI: 1.01-1.42). CONCLUSION: In older men, ALM and grip strength may be associated with the development of knee OA and knee pain, respectively.

Sex differences in frailty and its association with low bone mineral density in rheumatoid arthritis.

OBJECTIVES: Frailty in the general population is associated with poor health outcomes including low bone mass and osteoporotic fracture. The relationship between frailty and low bone mineral density (BMD) in rheumatoid arthritis (RA) is unknown. This study examined associations between frailty and BMD in RA, controlling for established osteoporosis risk factors. METHODS: We performed a cross-sectional analysis of a longitudinal RA cohort (n = 138; 117 female, 21 male). Participants fulfilled ACR RA classification criteria. Frailty was evaluated using the Fried Index, categorizing each participant as robust, pre-frail or frail. To identify independent predictors of BMD, we performed a multivariable linear regression analysis. Because risk factors for low BMD differ between sexes, we performed additional sex-stratified multivariable analyses. RESULTS: Mean age and disease duration were 58.0 ± 10.8 and 19 ± 10.9 years, respectively. The majority of participants were categorized as pre-frail (70%) or frail (10%). Females had higher rates of frailty than males. In the whole cohort, both pre-frail and frail had independent negative associations with BMD (ß = -0.074 and -0.092 respectively, p < 0.05). In sex-stratified analyses, frailty did not have a significant association with BMD in females, but had a strong independent negative association in males (ß = -0.247, p = 0.001). CONCLUSION: Frailty was associated with BMD in patients with RA. Females had higher rates of frailty than males, yet frailty was independently associated with BMD in males but not in females. Frailty appears to be an important factor associated with low BMD; sex may influence this relationship in RA.

The Impact of Frailty on Changes in Physical Function and Disease Activity Among Adults With Rheumatoid Arthritis.

OBJECTIVE: Reduced physical function and frailty are common in rheumatoid arthritis (RA). However, relationships between frailty and changes in physical function and disease activity over time in RA are unknown. We tested whether frailty is a risk factor for worsening patient-reported physical function and disease activity in RA. METHODS: Adults from a longitudinal RA cohort (N = 124) participated. By using an established frailty definition, individuals with three or more of the following deficits were considered frail: 1) body mass index less than or equal to 18.5, 2) low grip strength, 3) severe fatigue, 4) slow 4-m walking speed, and 5) low physical activity. Individuals with one to two or zero deficits were considered "pre-frail" or "robust," respectively. Physical function and RA disease activity were assessed by the Health Assessment Questionnaire (HAQ) and Rheumatoid Arthritis Disease Activity Index (RADAI), respectively, at baseline and follow-up 2 years later. Regression analyses modeled associations of frailty status with change in HAQ and RADAI scores between baseline and follow-up with and without controlling for covariates. Associations of individual frailty components with change in HAQ and RADAI scores were also examined. RESULTS: Among adults with RA, baseline frailty status predicted significant increases, or worsening, in HAQ (ß: 0.4; 95% confidence interval: 0.1-0.8; P < 0.01) but not RADAI scores (ß: 0.5; 95% confidence interval: -0.4 to 1.5; P > 0.05) between baseline and follow-up in fully adjusted models. Fatigue was an important contributor to this effect. CONCLUSION: Frailty may be an important risk factor for reduced physical function over time in RA. Future studies should address whether interventions to reduce frailty improve physical function in RA.

Frailty and reduced physical function go hand in hand in adults with rheumatoid arthritis: a US observational cohort study.

Reduced physical function and health-related quality of life are common in rheumatoid arthritis (RA), and further studies are needed that examine novel determinates of reduced physical function in RA. This study examines whether frailty, a state of increased vulnerability to stressors, is associated with differences in self-reported physical function among adults with RA. Adults from a longitudinal RA cohort (n = 124) participated in the study. Using an established definition of frailty, individuals with three or more of the following physical deficits were classified as frail: (1) body mass index ≤18.5, (2) low grip strength (adjusted for sex and body mass index (BMI), measured by handheld dynamometer), (3) severe fatigue (measured by the Multidimensional Assessment of Fatigue), (4) slow 4-m walking speed (adjusted for sex and height), and (5) low physical activity (measured by the International Physical Activity Questionnaire). Individuals with one or two deficits were classified as "pre-frail" and those with no deficits as "robust." Self-reported physical function was assessed by the Health Assessment Questionnaire (HAQ) and the Valued Life Activities Difficulty scale. Regression analyses modeled associations of frailty category with HAQ and Valued Life Activities (VLA) Difficulty scores with and without controlling for age, sex, disease duration, C-reactive protein, use of oral steroids, and pain. Among adults with RA, being frail compared to being robust was associated with a 0.44 worse VLA score (p < 0.01) when the effects of covariates are held constant. Being frail, compared to being robust, is associated with clinically meaningful differences in self-reported physical function among adults with RA.

Serum biomarkers of inflammation and muscle strength among women with systemic lupus erythematosus.

OBJECTIVES: Muscle strength is an important determinant of physical function in women with systemic lupus erythematosus (SLE). Serum biomarkers of inflammation, including interleukin-6 (IL-6) and C-Reactive Protein (CRP), are associated with differences in muscle strength among individuals without rheumatologic disease. We examined whether serum levels of IL-6 and CRP are associated with upper and lower extremity muscle strength among adult women with SLE. METHODS: One hundred thirty-six women with SLE participated in this cross-sectional study. High-sensitivity CRP was analyzed by nephelometry. IL-6 serum levels were analyzed by high sensitivity enzyme-linked immunosorbent assay. Upper and lower extremity muscle strength were assessed by grip strength and peak torque of knee extension and flexion, respectively. Regression analyses modeled associations of CRP and IL-6 with upper and lower extremity muscle strength controlling for age, SLE duration, physical activity, prednisone use, BMI, plaquenil use, and pain. RESULTS: Higher serum levels of IL-6 and CRP were associated with significantly weaker upper and lower extremity muscle strength even when controlling for covariates. CONCLUSIONS: Increased serum IL-6 and CRP are associated with clinically significant differences in upper and lower extremity muscle strength and may be useful in identifying those at risk for weakness and decreased physical function.

Muscle Strength and Changes in Physical Function in Women With Systemic Lupus Erythematosus.

OBJECTIVE: Cross-sectional studies have observed that muscle weakness is associated with worse physical function among women with systemic lupus erythematosus (SLE). The present study examines whether reduced upper and lower extremity muscle strength predict declines in function over time among adult women with SLE. METHODS: One hundred forty-six women from a longitudinal SLE cohort participated in the study. All measures were collected during in-person research visits approximately 2 years apart. Upper extremity muscle strength was assessed by grip strength. Lower extremity muscle strength was assessed by peak knee torque of extension and flexion. Physical function was assessed using the Short Physical Performance Battery (SPPB). Regression analyses modeled associations of baseline upper and lower extremity muscle strength with followup SPPB scores controlling for baseline SPPB, age, SLE duration, SLE disease activity (Systemic Lupus Activity Questionnaire), physical activity level, prednisone use, body composition, and depression. Secondary analyses tested whether associations of baseline muscle strength with followup in SPPB scores differed between intervals of varying baseline muscle strength. RESULTS: Lower extremity muscle strength strongly predicted changes over 2 years in physical function even when controlling for covariates. The association of reduced lower extremity muscle strength with reduced physical function in the future was greatest among the weakest women. CONCLUSION: Reduced lower extremity muscle strength predicted clinically significant declines in physical function, especially among the weakest women. Future studies should test whether therapies that promote preservation of lower extremity muscle strength may prevent declines in function among women with SLE.

Muscle strength, muscle mass, and physical disability in women with systemic lupus erythematosus.

OBJECTIVE: Data describing relationships between muscle strength, muscle mass, and physical disability among individuals with systemic lupus erythematosus (SLE) are limited. The present study examines the relationship of muscle strength and muscle mass with physical disability among adult women with SLE. METHODS: A total of 146 women from a longitudinal SLE cohort participated in the study. All measures were collected during an in-person research visit. Lower extremity muscle strength was assessed by peak knee torque of extension and flexion and by chair-stand time. Total lean body mass, appendicular lean mass, and fat mass (kg/m(2) ) were measured by whole-body dual x-ray absorptiometry. Self-reported physical disability was assessed using the Short Form 36 health survey (SF-36) physical functioning subscale, and the Valued Life Activities (VLA) disability scale. Spearman's rank correlation coefficients tested the correlations between muscle strength, muscle mass, and disability scores. Regression analyses modeled the effect of lower extremity muscle strength and mass on SF-36 and VLA disability scores controlling for age, SLE duration, SLE disease activity measured with the Systemic Lupus Activity Questionnaire, physical activity level, prednisone use, body composition, and depression. RESULTS: On all measures, reduced lower extremity muscle strength was associated with poorer SF-36 and VLA disability scores. Trends persisted after adjustment for covariates. Muscle mass was moderately correlated with muscle strength, but did not contribute significantly to adjusted regression models. CONCLUSION: Lower extremity muscle strength, but not muscle mass, was strongly associated with physical disability scores. While further studies are needed, these findings suggest that improving muscle strength may reduce physical disability among women with SLE.

Pain as a risk factor for disability or death.

OBJECTIVES: To determine whether pain predicts future activity of daily living (ADL) disability or death in individuals aged 60 and older. DESIGN: Prospective cohort study. SETTING: The 1998 to 2008 Health and Retirement Study (HRS), a nationally representative study of older community-living individuals. PARTICIPANTS: Twelve thousand six hundred thirty-one participants in the 1998 HRS aged 60 and older who did not need help in any ADL. MEASUREMENTS: Participants reporting that they had moderate or severe pain most of the time were defined as having significant pain. The primary outcome was time to development of ADL disability or death over 10 yrs, assessed at five successive 2-year intervals. ADL disability was defined as needing help performing any ADL: bathing, dressing, transferring, toileting, eating, or walking across a room. A discrete hazards survival model was used to examine the relationship between pain and incident disability over each 2-year interval using only participants who started the interval with no ADL disability. Several potential confounders were adjusted for at the start of each interval: demographic factors, seven chronic health conditions, and functional limitations (ADL difficulty and difficulty with five measures of mobility). RESULTS: At baseline, 2,283 (18%) participants had significant pain. Participants with pain were more likely (all P < .001) to be female (65% vs 54%), have ADL difficulty (e.g., transferring 12% vs 2%, toileting 11% vs 2%), have difficulty walking several blocks (60% vs 21%), and have difficulty climbing one flight of stairs (40% vs 12%). Over 10 years, participants with pain were more likely to develop ADL disability or death (58% vs 43%, unadjusted hazard ratio (HR) = 1.67, 95% confidence interval (CI) = 1.57-1.79), although after adjustment for confounders, participants with pain were not at greater risk for ADL disability or death (HR = 0.98, 95% CI = 0.91-1.07). Adjustment for functional status almost entirely explained the difference between the unadjusted and adjusted results. CONCLUSION: Although there are strong cross-sectional relationships between pain and functional limitations, individuals with pain are not at higher risk of subsequent disability or death after accounting for functional limitations. Like many geriatric syndromes, pain and disability may represent interrelated phenomena that occur simultaneously and require unified treatment paradigms.

Reading performance correlates with white-matter properties in preterm and term children.

AIM: We used diffusion tensor imaging to investigate the association between white-matter integrity and reading ability in a cohort of 28 children. Nineteen preterm children (14 males, five females; mean age 11 y 11 mo [SD 1 y 10 mo], mean gestational age 30.5 wks (SD 3.2), mean birthweight was 1455 g [SD 625]); and nine term children (five males, four females; mean age 12 y 8 mo [SD 2 y 5 mo], mean gestational age 39.6 wks (SD 1.2), and mean birthweight 3877 g [SD 473]). METHOD: We tested whether fractional anisotropy in a left hemisphere temporoparietal region and in the corpus callosum correlates with birthweight and scores on the following three subtests of the Woodcock-Johnson III Tests of Achievement: word identification, word attack, and passage comprehension. RESULTS: Preterm children had lower reading scores than a comparison group for all reading subtests (p<0.05). We found significant correlations between birthweight and fractional anisotropy in the whole corpus callosum (p=0.001), and between fractional anisotropy and reading skill in the genu (p=0.001) and body (p=0.001) of the corpus callosum. The correlation between reading skill and fractional anisotropy in a left temporoparietal region previously associated with reading disability was not significant (p=0.095). INTERPRETATION: We conclude that perinatal white-matter injury of the central corpus callosum may have long-term developmental implications for reading performance.