Racial/Ethnic, Socioeconomic, and Geographic Disparities in the Epidemiology of Knee and Hip Osteoarthritis

It is estimated that 32.5 million US adults have clinical osteoarthritis (OA), with the most common sites being knee and hip. OA is associated with substantial individual and societal costs. Race/ethnicity, socioeconomic status (SES), and geographic variations in the prevalence of knee and hip OA are well established around the world. In addition, clinical outcomes associated with hip and knee OA differ according to race/ethnicity, SES, and geography. This variation is likely multifactorial and may also reflect country-specific differences in health care systems. The interplay between different factors, such as geography, SES, and race/ethnicity, is difficult to study

FOXO1a acts as a selective tumor suppressor in alveolar rhabdomyosarcoma

Rhabdomyosarcoma (RMS), the most common pediatric soft-tissue sarcoma, has two major histological subtypes: embryonal RMS (ERMS), which has a favorable prognosis, and alveolar RMS (ARMS), which has a poor outcome. Although both forms of RMS express muscle cell–specific markers, only ARMS cells express PAX3-FOXO1a or PAX7-FOXO1a chimeric proteins. In mice, Pax3 and Pax7 play key roles in muscle cell development and differentiation, and FoxO1a regulates myoblast differentiation and fusion; thus, the aberrant regulation of these proteins may contribute to the development of ARMS. In this paper, we report that FOXO1a is not expressed in primary ARMS tumors or ARMS-derived tumor cell lines and that restoration of FOXO1a expression in ARMS cells is sufficient to induce cell cycle arrest and apoptosis. Strikingly, the effects of FOXO1a are selective, as enforced expression of FOXO1a in ERMS-derived tumor cell lines had no effect. Furthermore, FOXO1a induced apoptosis in ARMS by directly activating the transcription of caspase-3. We conclude that FOXO1a is a potent and specific tumor suppressor in ARMS, suggesting that agents that restore or augment FOXO1a activity may be effective as ARMS therapeutics

Accelerometer-Based Physical Activity Patterns and Associations with Outcomes among Individuals with Osteoarthritis

Background This study examined patterns of physical activity and associations with pain, function, fatigue, and sleep disturbance among individuals with knee or hip osteoarthritis. Methods Participants (n = 54) were enrolled in a telephone-based physical activity coaching intervention trial; all data were collected at baseline. Self-reported measures of pain and function (WOMAC [Western Ontario and McMaster Universities Osteoarthritis Index] subscales), fatigue (10-point numeric rating scale), and PROMIS (Patient-Reported Outcomes Information System) Sleep Disturbance were collected via telephone. Accelerometers were mailed to participants and were worn for at least 3 days. Proportion of time participants spent in sedentary behavior during the morning (from wake until 12:00 pm), afternoon (12:00 pm until 5:59 pm) and evening (6:00 pm until sleep) each day was averaged across all days of wear. Pearson correlations assessed associations between activity and self-reported measures. Results Participants spent a large proportion of time in sedentary behavior: 65.6% of mornings, 70.0% of afternoons, and 76.6% of evenings. Associations between proportion of time spent in sedentary behavior and reported outcomes were generally strongest in the afternoon, strongest for WOMAC function, and lowest for PROMIS Sleep Disturbance. In the evening hours, sedentary time was most strongly associated with fatigue. Conclusions Overall, findings stress the importance of reducing sedentary behavior among adults with osteoarthritis and suggest behavioral interventions may be strengthened by considering patients' within-day variation in symptoms and activity

Defining multiple joint osteoarthritis, its frequency and impact in a community-based cohort

Background/purpose: To update definitions of multiple joint osteoarthritis (MJOA), and to determine the frequency and impact of MJOA in a community-based cohort. Methods: Following PRISMA guidelines and with the help of a professional research librarian, we performed a systematic review in Medline using the terms osteoarthritis, generalized, polyarticular, multiple joint, and multi-joint among others, to obtain articles related to MJOA. A total of 42 articles were included for data extraction based on multiple criteria including the requirement for a clearly stated definition of OA assessed at more than one body site. We assessed frequency of these definitions in the Johnston County OA Project (JoCo OA)cohort as well as outcomes related to general health and physical function. Results: A total of 6 clearly stated definitions for MJOA were identified. These definitions were integrated with a list of 24 definitions from our previous systematic review and distilled down to produce 10 literature-derived, operationalized MJOA definitions. Based on these definitions, high frequencies of radiographic (4–74%)and symptomatic (2–52%)MJOA were found in the JoCo OA. Significant detrimental effects were seen on general health and physical function for most definitions. Conclusions: We constructed a list of 10 summary MJOA definitions based in the literature that are frequent and associated with important clinical outcomes. These definitions capture some of the variability of MJOA phenotypes and provide a starting point for future analyses of both existing and newly initiated studies

The calibration of the Sudbury Neutrino Observatory using uniformly distributed radioactive sources

The production and analysis of distributed sources of 24Na and 222Rn in the Sudbury Neutrino Observatory (SNO) are described. These unique sources provided accurate calibrations of the response to neutrons, produced through photodisintegration of the deuterons in the heavy water target, and to low energy betas and gammas. The application of these sources in determining the neutron detection efficiency and response of the 3He proportional counter array, and the characteristics of background Cherenkov light from trace amounts of natural radioactivity is described.Comment: 24 pages, 13 figure

Comorbid conditions and the transition among states of hip osteoarthritis and symptoms in a community-based study: A multi-state time-to-event model approach

Background: We examined the association of three common chronic conditions (obesity, diabetes mellitus [DM], and cardiovascular disease [CVD]) with transitions among states of hip osteoarthritis (HOA). Methods: This longitudinal analysis used data from the Johnston County Osteoarthritis Project (JoCo OA, n = 3857), a community-based study in North Carolina, USA, with 18.4 ± 1.5 years of follow-up. Transitions across the following states were modeled: development of radiographic HOA (rHOA; Kellgren-Lawrence grade [KLG] of< 2); development of hip symptoms (self-reported hip pain, aching, or stiffness on most days) or symptomatic HOA (sxHOA; rHOA and symptoms in the same hip), and resolution of symptoms. Obesity (body mass index ≥ 30 kg/m2) and self-reported DM and CVD were the time-dependent comorbid conditions of interest. Markov multi-state models were used to estimate adjusted hazard ratios and 95% confidence intervals to describe the associations between the conditions and HOA states. Results: The sample included 33% African Americans, 39% men, with a mean (SD) age of 62.2 (9.8) years; the frequencies of the comorbidities increased substantially over time. When considered individually, obesity was associated with incident hip symptoms, while CVD and DM were associated with reduced symptom resolution. For those with > 1 comorbidity, the likelihood of incident sxHOA increased, while that of symptom resolution significantly decreased. When stratified by sex, the association between obesity and incident symptoms was only seen in women; among men with DM versus men without, there was a significant (~ 75%) reduction in symptom resolution in those with rHOA. When stratified by race, African Americans with DM, versus those without, were much more likely to develop sxHOA. Conclusions: Comorbid chronic conditions are common in individuals with OA, and these conditions have a significant impact on the persistence and progression of HOA. OA management decisions, both pharmacologic and non-pharmacologic, should include considerations of the inter-relationships between OA and common comorbidities such as DM and CVD

Genetic polymorphisms of diabetes-related genes, their interaction with diabetes status, and breast cancer incidence and mortality: The Long Island Breast Cancer Study Project

To examine 143 diabetes risk single nucleotide polymorphisms (SNPs), identified from genome-wide association studies, in association with breast cancer (BC) incidence and subsequent mortality. A population-based sample of Caucasian women with first primary invasive BC (n = 817) and controls (n = 1021) were interviewed to assess diabetes status. Using the National Death Index, women with BC were followed for >18 years during which 340 deaths occurred (139 BC deaths). Genotyping was done using DNA extracted from blood samples. We used unconditional logistic regression to estimate age-adjusted odds ratios and 95% confidence intervals (CIs) for BC incidence, and Cox regression to estimate age-adjusted hazard ratios and CIs for all-cause and BC-specific mortality. Twelve SNPs were associated with BC risk in additive genotype models, at α = 0.05. The top three significant SNPs included SLC30A8-rs4876369 (P = 0.0034), HHEX-rs11187146 (P = 0.0086), and CDKN2A/CDKN2B-rs1333049 (P = 0.0094). Diabetes status modified the associations between rs4876369 and rs2241745 and BC incidence, on the multiplicative interaction scale. Six SNPs were associated with all-cause (CDKAL1-rs981042, P = 0.0032; HHEX-rs1111875, P = 0.0361; and INSR-rs919275, P = 0.0488) or BC-specific (CDKN2A/CDKN2B-rs3218020, P = 0.0225; CDKAL1-rs981042, P = 0.0246; and TCF2/HNF1B-rs3094508, P = 0.0344) mortality in additive genotype models, at α = 0.05. Genetic polymorphisms that increase the risk of developing diabetes may also increase the risk of developing and dying from BC

Associations of Comorbid Conditions and Transitions Across States of Knee Osteoarthritis in a Community-Based Cohort

Objective: To examine relationships between knee osteoarthritis (KOA) and obesity, diabetes mellitus (DM), and cardiovascular disease (CVD). Methods: Associations of time-dependent obesity, DM, and CVD with KOA transition states over approximately 18 years were examined among 4093 participants from a community-based cohort. Transition states were 1) no knee symptoms and no radiographic KOA (rKOA; Kellgren-Lawrence grade ≥2 in at least one knee), 2) asymptomatic rKOA, 3) knee symptoms only, 4) symptomatic rKOA (sxKOA; rKOA and symptoms in same knee). Markov multistate models estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for associations between comorbid conditions and transitions across states, adjusting for baseline age, sex, race, education, enrollment cohort, birth year, and time-dependent knee injury history. Results: At baseline, 40% of participants had obesity, 13% had DM, and 22% had CVD (mean age = 61 years; 34% Black; 37% male). Compared with those without obesity, those with obesity had a higher hazard of worsening from no rKOA/no symptoms to asymptomatic rKOA (aHR = 1.7; 95% CI = 1.3-2.2) and from knee symptoms to sxKOA (aHR = 1.7; 95% CI = 1.3-2.3), as well as a lower hazard of symptom resolution from sxKOA to asymptomatic rKOA (aHR = 0.5 [95% = CI 0.4-0.7]). Compared with those without CVD, those with CVD had a higher hazard of worsening from no rKOA/symptoms to knee symptoms (aHR = 1.5; 95% CI = 1.1-2.1). DM was not associated with transitions of rKOA. Conclusion: Prevention of obesity and CVD may limit the development or worsening of rKOA and symptoms