Gait Alterations and Association With Worsening Knee Pain and Physical Function: A Machine Learning Approach With Wearable Sensors in the Multicenter Osteoarthritis Study.

OBJECTIVE: The objective of this study was to identify gait alterations related to worsening knee pain and worsening physical function, using machine learning approaches applied to wearable sensor-derived data from a large observational cohort. METHODS: Participants in the Multicenter Osteoarthritis Study (MOST) completed a 20-m walk test wearing inertial sensors on their lower back and ankles. Parameters describing spatiotemporal features of gait were extracted from these data. We used an ensemble machine learning technique ("super learning") to optimally discriminate between those with and without worsening physical function and, separately, those with and without worsening pain over two years. We then used log-binomial regression to evaluate associations of the top 10 influential variables selected with super learning with each outcome. We also assessed whether the relation of altered gait with worsening function was mediated by changes in pain. RESULTS: Of 2,324 participants, 29% and 24% had worsening knee pain and function over two years, respectively. From the super learner, several gait parameters were found to be influential for worsening pain and for worsening function. After adjusting for confounders, greater gait asymmetry, longer average step length, and lower dominant frequency were associated with worsening pain, and lower cadence was associated with worsening function. Worsening pain partially mediated the association of cadence with function. CONCLUSION: We identified gait alterations associated with worsening knee pain and those associated with worsening physical function. These alterations could be assessed with wearable sensors in clinical settings. Further research should determine whether they might be therapeutic targets to prevent worsening pain and worsening function.

Relation of gait measures with mild unilateral knee pain during walking using machine learning.

Gait alterations in those with mild unilateral knee pain during walking may provide clues to modifiable alterations that affect progression of knee pain and osteoarthritis (OA). To examine this, we applied machine learning (ML) approaches to gait data from wearable sensors in a large observational knee OA cohort, the Multicenter Osteoarthritis (MOST) study. Participants completed a 20-m walk test wearing sensors on their trunk and ankles. Parameters describing spatiotemporal features of gait and symmetry, variability and complexity were extracted. We used an ensemble ML technique ("super learning") to identify gait variables in our cross-sectional data associated with the presence/absence of unilateral knee pain. We then used logistic regression to determine the association of selected gait variables with odds of mild knee pain. Of 2066 participants (mean age 63.6 [SD: 10.4] years, 56% female), 21.3% had mild unilateral pain while walking. Gait parameters selected in the ML process as influential included step regularity, sample entropy, gait speed, and amplitude dominant frequency, among others. In adjusted cross-sectional analyses, lower levels of step regularity (i.e., greater gait variability) and lower sample entropy(i.e., lower gait complexity) were associated with increased likelihood of unilateral mild pain while walking [aOR 0.80 (0.64-1.00) and aOR 0.79 (0.66-0.95), respectively].

Thresholds in the Relationship of Quadriceps Strength With Functional Limitations in Women With Knee Osteoarthritis.

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.

Concurrent Change in Quadriceps Strength and Physical Function Over Five Years in the Multicenter Osteoarthritis Study.

OBJECTIVE: Quadriceps weakness, associated with functional limitations, is a target of treatment of knee osteoarthritis (OA). Limited data exist on the relationship between modest strength increases and improvements in function. The aim of this study was to evaluate concurrent change in strength and physical function over 5 years. METHODS: Among subjects from the Multicenter Osteoarthritis (MOST) study, we excluded those with knee replacement after baseline. A 3-category variable defined whether, at 5 years, knee extensor strength increased, decreased, or remained within 15% of baseline, a clinically important cut-off. The outcomes were the 5-times sit-to-stand test, 20-meter walk test, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) physical function score, and 3 individual physical functions from WOMAC: arising from a chair, going up stairs, and getting on/off toilet. Linear and logistic models, stratified by sex, evaluated associations between change in strength and change in physical function over 5 years. To compare weaker versus stronger women, we stratified analyses at 56 Nm baseline strength. RESULTS: Among 1,534 participants (60.6% women), 22% of men and 30% of women increased strength by at least 15% at 5 years. Compared with women whose strength did not change, women whose strength increased had improved chair stand performance (odds ratio 2.27 [95% confidence interval 1.56, 3.30]) but no improvement in other functions. In men, an increase in strength was not associated with significant improvement in physical function. Similar results were observed for a 20% or 30% increase. CONCLUSION: Modest improvement in quadriceps strength was associated with improved chair stand performance in women but not in men. Most functions did not improve with an increase in strength, and targeted interventions may be required to improve functional status.

Perceived racism and incident diabetes in the Black Women's Health Study.

AIMS/HYPOTHESIS: Our aim was to assess the association of perceived racism with type 2 diabetes, and the possible mediating influence of diet and BMI. METHODS: The Black Women's Health Study, a follow-up of 59,000 African-American women, began in 1995. Over 16 years 5344 incident cases of diabetes occurred during 576,577 person-years. Cox proportional hazards models were used to estimated HRs and 95% CIs for categories of 'everyday racism' (interpersonal racism in daily life) and 'lifetime racism' (reporting ever treated unfairly due to race with respect to police, housing or work) and incident type 2 diabetes. Models were adjusted for age, questionnaire cycle, marital status, socioeconomic status, education, family history of diabetes, physical activity, alcohol use and smoking status, with and without inclusion of terms for dietary patterns and adult BMI. RESULTS: Compared with women in the lowest quartile of exposure, women in the highest quartile of exposure to everyday racism had a 31% increased risk of diabetes (HR 1.31; 95% CI 1.20, 1.42) and women with the highest exposure to lifetime racism had a 16% increased risk (HR 1.16; 95% CI 1.05, 1.27). Mediation analysis estimated that BMI accounted for half of the association between either the everyday or lifetime racism measure and incident diabetes. CONCLUSIONS/INTERPRETATION: Perceived everyday and lifetime racism were associated with increased risk of type 2 diabetes in this cohort of African-American women and appear to be at least partly mediated by BMI.

Photothermal therapy mediated by gum Arabic-conjugated gold nanoparticles suppresses liver preneoplastic lesions in mice.

This study validates the utility of Gum Arabic-conjugated gold nanoparticles (GA-AuNPs) and laser to induce photothermal inhibition of hepatocarcinogenesis, via employing a diethylnitrosamine (DEN)-mediated hepatocellular carcinoma model. This work included both of in vitro and in vivo studies; to investigate the GA-AuNPs cytotoxicity and phototoxicity in hepatic cell line; to delineate the GA-AuNPs therapeutic efficiency in DEN-induced preneoplastic lesions (PNLs) in the liver of Balb-C mice. The therapeutic effects of GA-AuNPs on the mediators of apoptosis, inflammation, and tumor initiation, as well as the histopathological changes in preneoplastic liver have been investigated. Our results infer that GA-AuNPs in combination with laser irradiation led to a significant reduction in the cell viability and in histone deacetylase activity in hepatocarcinoma HepG2 cells. In chemically-induced PNLs mice model our results have demonstrated that GA-AuNPs, with or without laser irradiation, induced cancer cell apoptosis through the activation of death receptors DR5 and caspase-3 and inhibited both of the PNLs incidence and the initiation marker (placental glutathione S-transferase; GST-P). The laser-stimulated GA-AuNPs significantly reduced the tumor necrosis factor-α levels. In summary, GA-AuNPs with laser treatment inhibited liver PNLs via the induction of the extrinsic apoptosis pathway and the inhibition of inflammation.

Longitudinal and Reciprocal Relationships Between Depression and Disability in Older Women Caregivers and Noncaregivers.

PURPOSE OF THE STUDY: Depressive symptoms and disability each increase the risk of the other, yet few studies have examined reciprocal associations between these conditions in a single study, or over periods longer than 3 years. These associations may differ in older caregivers due to chronic stress, health characteristics, or factors related to caregiving. DESIGN AND METHODS: Structural equation models were used to investigate relationships between depressive symptoms and disability over 3 interviews spanning 6 years among 956 older women (M = 81.5 years) from the Caregiver Study of Osteoporotic Fractures. Results were evaluated separately for 611 noncaregivers and 345 caregivers to a relative or friend. RESULTS: In noncaregivers, more depressive symptoms significantly predicted greater disability, whereas greater disability predicted increased depressive symptoms at the next interview in age-adjusted models. In contrast, there was not a significant relationship between depression and disability in either direction for caregivers. Further adjustment for body mass index and medical condition variables did not change these relationships. IMPLICATIONS: Caregivers did not exhibit longitudinal or reciprocal relationships between depressive symptoms and disability observed in noncaregivers. It is possible that older women caregivers are buffered by better physical condition or social interactions related to caregiving activities.