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Obesity is a global pandemic, but there is yet no effective measure to control it. Recent metabolomics studies have identified a signature of altered amino acid profiles to be associated with obesity, but it is unclear whether these findings have actionable clinical potential. The aims of this study were to reveal the metabolic alterations of obesity and to explore potential strategies to mitigate obesity. We performed targeted metabolomic profiling of the plasma/serum samples collected from six independent cohorts and conducted an individual data meta-analysis of metabolomics for body mass index (BMI) and obesity. Based on the findings, we hypothesized that restriction of branched-chain amino acids (BCAAs), phenylalanine, or tryptophan may prevent obesity and tested our hypothesis in a dietary restriction trial with eight groups of 4-week-old male C57BL/6J mice (n = 5/group) on eight different types of diets, respectively, for 16 weeks. A total of 3397 individuals were included in the meta-analysis. The mean BMI was 30.7 ± 6.1 kg/m2, and 49% of participants were obese. Fifty-eight metabolites were associated with BMI and obesity (all p ≤ 2.58 × 10-4), linked to alterations of the BCAA, phenylalanine, tryptophan, and phospholipid metabolic pathways. The restriction of BCAAs within a high-fat diet (HFD) maintained the mice's weight, fat and lean volume, subcutaneous and visceral adipose tissue weight, and serum glucose and insulin at levels similar to those in the standard chow group, and prevented obesity, adipocyte hypertrophy, adipose inflammation, and insulin resistance induced by HFD. Our data suggest that four metabolic pathways, BCAA, phenylalanine, tryptophan, and phospholipid metabolic pathways, are altered in obesity and restriction of BCAAs within a HFD can prevent the development of obesity and insulin resistance in mice, providing a promising strategy to potentially mitigate diet-induced obesity.

Background: There is increasing use of complementary and alternative medicines (CAMs) alone or as an adjuvant therapy to conventional medicines in osteoarthritis (OA) patients. Objectives: This study aimed to describe the prevalence and correlates of the use of CAMs among community‐dwelling older adults. Methods: Data from the Tasmania Older Adult Cohort Study (TASOAC, n = 1099) were used to describe the prevalence of CAM use. Correlates of CAM use were assessed by comparing CAM users and non‐users. To further assess correlates of CAM use, participants with at least one joint with pain were classified into four categories: CAM‐only, analgesics‐only, co‐therapy, and "neither CAMs nor analgesics" (NCNA). Results: In all, 385 (35.0%) of our participants reported use of CAMs, among which vitamins/minerals were used most (22.6%, n = 232). Compared with CAM non‐users, CAM users were more likely to be female, were less likely to be overweight, were better educated, had more joints with OA, had fewer WOMAC scores, and did more steps per day. Among participants with any joint pain, the CAM‐only group were less likely to be overweight, consumed more alcohol, had higher quality of life, had more steps per day, and had fewer pain‐related symptoms compared with the analgesic‐only group. Conclusion: Complementary and alternative medicines were commonly used among Tasmanian older adults, with 35% of the population using CAMs either alone or in combination with conventional analgesics. CAM users were more likely to be female, be better educated, have more joints with OA, and had healthier lifestyles, including lower body mass index and higher number of steps per day. [ABSTRACT FROM AUTHOR]

Objective: Using a qualitative design this study aimed to (1) explore the experience of people living with osteoarthritis (OA), (2) gain an understanding of their navigation of the health system and, (3) explore their opinions on the role of exercise and joint replacement surgery for the management of OA. Methods: Purposive sampling was used to recruit 26 participants with knee OA, aged 45 years and over, from Tasmania, Australia. Semi‐structured interviews were audio‐recorded, transcribed, coded, and thematically analysed to document participant understanding and experience of OA and their opinions on the role of exercise and surgery in managing OA. Results: Of the 26 participants, 80% (n = 21) were female with a mean age of 66 years. The main theme identified was that individuals with knee OA were navigating a maze of OA treatments. Three related subthemes were that participants: (i) perceived their general practitioner did not have an ongoing role in their OA care, (ii) self‐directed their management and, (iii) sampled from a 'smorgasbord' of treatment options, including low‐value care options. Two other major themes were: the role of exercise for OA management, and surgery as a last resort. Conclusion: Our findings suggest that OA patients may not be choosing consistent, high‐value care for their OA. This highlights the importance of an evidence‐based multi‐disciplinary approach to guide patients to self‐manage their OA and support their navigation of the health system. Reducing emphasis on the pathway to surgery and streamlining access to conservative management strategies may assist people to receive high‐value care. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common joint disorder for which there is no cure. Current treatments are suboptimal. Exercise is a core treatment for knee OA, with muscle strengthening exercise commonly recommended. Yoga is a mind-body exercise intervention that can improve flexibility, muscle strength, balance, and fitness and potentially reduce symptoms of OA. However, there is a scarcity of robust, high-quality conclusive evidence on the efficacy of yoga in knee OA. We are currently conducting the first randomised comparative effectiveness and cost-effectiveness trial of a yoga program compared with a strengthening exercise program in patients with symptomatic knee OA. This study protocol describes the design and conduct of this trial. The YOGA study is a phase III, single-centre, parallel, superiority, randomised, active-controlled trial which will be conducted in Hobart, Australia. One hundred and twenty-six participants (63 in each arm) aged over 40 years with symptomatic knee OA will be recruited from the community and randomly allocated to receive either a 24-week yoga program (3×/week) or a strengthening exercise program (3×/week). The primary outcome will be change in knee pain over 12 weeks, assessed using a 100 mm visual analogue scale (VAS). The secondary outcomes include change in knee pain, patient global assessment, physical function, quality of life, gait speed, biomarkers, and others over 12 and 24 weeks. We will also assess whether the presence of neuropathic pain moderates the effects of yoga compared to strengthening exercise. Additional data, such as cost and resource utilization, will be collected for the cost-effectiveness analysis. The primary analysis will be conducted using an intention-to-treat approach. Adverse events will be monitored throughout the study. Once completed, this trial will contribute to the knowledge of whether yoga can be used as a simple, effective, low-cost option for the management of knee OA, thus saving economic costs in the healthcare system. [ABSTRACT FROM AUTHOR]

Background: A socioeconomic gradient exists in the utilisation of total hip replacements (THR) and total knee replacements (TKR) for osteoarthritis. However, the relations between socioeconomic status (SES) and time to THR or TKR is unknown. Aim: To describe the association between SES and time to THR and TKR. Methods: One thousand and seventy‐two older adults residing in Tasmania, Australia, were studied. Incident primary THR and TKR were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. At baseline, each participant's area‐level SES was determined using the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) from the Australian Bureau of Statistics' 2001 census data. The IRSAD was analysed in two ways: (i) categorised into quartiles, whereby quartile 1 represented the most socioeconomically disadvantaged group; and (ii) the cohort dichotomised at the quartile 1 cut‐point. Results: The mean age was 63.0 (±7.5) years and 51% were women. Over the median follow up of 12.9 (interquartile range: 12.2–13.9) years, 56 (5%) participants had a THR and 79 (7%) had a TKR. Compared with the most disadvantaged quartile, less disadvantaged participants were less likely to have a THR (i.e. less disadvantaged participants had a longer time to THR; hazard ratio (HR): 0.56; 95% confidence interval (CI) 0.32, 1.00) but not TKR (HR: 0.90; 95% CI 0.53, 1.54). However, the former became non‐significant after adjustment for pain and radiographic osteoarthritis, suggesting that the associations may be mediated by these factors. Conclusions: The present study suggests that time to joint replacement was determined according to the symptoms/need of the participants rather than their SES. [ABSTRACT FROM AUTHOR]

Objective To investigate the impact of total number and patterns of comorbidities on health-related quality of life (HRQoL) and identify the most prevalent and influential comorbidity patterns in people with OA over 10 years. Methods Participants from the Tasmanian Older Adult Cohort aged 50–80 years, with self-reported OA and data on comorbidities and HRQoL were included. Participants were interviewed at baseline (n  = 398), 2.5 (n  = 304), 5 (n  = 269) and 10 years (n  = 191). Data on the self-reported presence of 10 chronic comorbidities were collected at baseline. HRQoL was assessed using the Assessment of Quality of Life-4-Dimensions. The long-term impacts of the number and of the nine most prevalent combinations of cardiovascular (CVD), non-OA musculoskeletal (Ms), metabolic and respiratory comorbidities on HRQoL over 10 years were analysed using linear mixed regressions. Results Compared with comorbidity-free OA participants, the health state utility (HSU) of those with 2 or ≥3 comorbidities was respectively −0.07 and −0.13 units lower over 10 years, largely driven by reduced scores for independent living, social relationships and psychological wellness. Comorbidity patterns including 'CVD+Ms' were most influential, and associated with up to 0.13 units lower HSU, mostly through negative impacts on independent living (up to −0.12), psychological wellness (up to −0.08) and social relationship (up to −0.06). Conclusion Having more comorbidities negatively impacted OA patients' long-term HRQoL. OA patients with CVD and non-OA musculoskeletal conditions had the largest HSU impairment, and therefore optimal management and prevention of these conditions may yield improvements in OA patients' HRQoL. [ABSTRACT FROM AUTHOR]

Background: This study aims to describe the relationships between physical activity (PA), body composition, and multimorbidity over 10 years.Method: Participants (N = 373; 49% women; average age 61.3 ± 6.7 years) were followed for 10 years. Multimorbidity was defined by self-report as the presence of 2 or more of 12 listed chronic conditions. PA (steps per day) at baseline was assessed by pedometer, handgrip strength (HGS) by dynamometer, and appendicular lean mass (ALM) and total body fat mass by dual-energy x-ray absorptiometry. Relative HGS and ALM were calculated by dividing each body mass index (BMI). Regression cubic splines were used to assess evidence for a nonlinear relationship.Results: After 10 years, 45% participants had multimorbidity. There was a nonlinear relationship between PA and multimorbidity-PA was associated with lower multimorbidity risk among individuals who engaged in <10 000 steps/d (relative risk [RR] = 0.91, 95% CI: 0.85, 0.97, per 1 000 steps/d), but not among those who participated in ≥10 000 steps/d (RR = 1.04, 95% CI: 0.93, 1.09, per 1 000 steps/d). Higher BMI (RR = 1.05, 95% CI: 1.02, 1.08, per kg/m2) and fat mass (RR = 1.03, 95% CI: 1.01, 1.04, per kg), and lower relative HGS (RR = 0.85, 95% CI: 0.77, 0.94, per 0.1 psi/kg/m2) and ALM (RR = 0.93, 95% CI: 0.88, 0.98, per 0.1 kg/kg/m2) were linearly associated with a higher risk of multimorbidity. Absolute HGS and ALM were not significantly associated with multimorbidity.Discussion: These findings highlight the potential clinical importance of maintaining adequate levels of PA and of reducing adiposity and maintaining muscle function for minimizing the risk of multimorbidity in older adults. [ABSTRACT FROM AUTHOR]

Objective: To comprehensively synthesize the evolution of health‐economic evaluation models (HEEMs) of all osteoarthritis (OA) interventions, including preventions, core treatments, adjunct nonpharmacologic interventions, pharmacologic interventions, and surgical treatments. Methods: The literature was searched within health‐economic/biomedical databases. Data extracted included OA type, population characteristics, model setting/type/events, study perspective, and comparators; the reporting quality of the studies was also assessed. The review protocol was registered at the International Prospective Register of Systematic Reviews (CRD42018092937). Results: Eighty‐eight studies were included. Pharmacologic and surgical interventions were the focus in 51% and 44% of studies, respectively. Twenty‐four studies adopted a societal perspective (with increasing popularity after 2013), but most (63%) did not include indirect costs. Quality‐adjusted life years was the most popular outcome measure since 2008. Markov models were used by 62% of studies, with increasing popularity since 2008. Until 2010, most studies used short‐to‐medium time horizons; subsequently, a lifetime horizon became popular. A total of 86% of studies reported discount rates (predominantly between 3% and 5%). Studies published after 2002 had a better coverage of OA‐related adverse events (AEs). Reporting quality significantly improved after 2001. Conclusion: OA HEEMs have evolved and improved substantially over time, with the focus shifting from short‐to‐medium‐term pharmacologic decision‐tree models to surgical‐focused lifetime Markov models. Indirect costs of OA are frequently not considered, despite using a societal perspective. There was a lack of reporting sensitivity of model outcome to input parameters, including discount rate, OA definition, and population parameters. While the coverage of OA‐related AEs has improved over time, it is still not comprehensive. [ABSTRACT FROM AUTHOR]

Context: Vitamin D deficiency is a common, modifiable determinant of musculoskeletal health.Objective: There are limited data that examine the longitudinal change in population 25-hydroxyvitamin D (25[OH]D) and none that evaluate the long-term skeletal outcomes of longitudinal vitamin D status.Methods: A prospective cohort analysis was conducted of community-dwelling adults aged 50 to 80 years who had 25(OH)D assessed by radioimmunoassay and bone mineral density (BMD) by dual-energy x-ray absorptiometry at baseline (n = 1096), 2.5 (n = 870), and 10 (n = 565) years. Sun exposure was quantified by questionnaire and supplement use at clinic review. 25(OH)D less than 50 nmol/L was considered deficient. Participants were provided with their 25(OH)D results.Results: Over 10 years 25(OH)D increased (52.2 ± 17.0 to 63.5 ± 23.6 nmol/L, P < .001). Participants with baseline deficiency had larger 25(OH)D increases than baseline sufficient participants (19.2 ± 25.3 vs 1.6 ± 23.3 nmol/L, P < .001). Longitudinal change in 25(OH)D was associated with baseline summer (β = 1.46, P < .001) and winter (β = 1.29, P = .003) sun exposure, change in summer (β = 1.27, P = .002) and winter (β = 1.47, P < .001) sun exposure, and vitamin D supplement use (β = 25.0-33.0, P < .001). Persistent vitamin D sufficiency was associated with less BMD loss at the femoral neck (β = 0.020, P = .027), lumbar spine (β = 0.033, P = .003), and total hip (β = 0.023, P = .021) compared to persistent vitamin D deficiency. Achieving vitamin D sufficiency was associated with less BMD loss at the lumbar spine (β = 0.045, P < .001) compared to persistent vitamin D deficiency.Conclusions: Population 25(OH)D concentration increased because of a combination of increased sun exposure and supplement use. Maintaining or achieving vitamin D sufficiency was associated with less BMD loss over 10 years. [ABSTRACT FROM AUTHOR]

Objective To describe the impact of OA on health-related quality of life (HRQoL) in the forms of health state utilities (HSUs) and health-dimension scores, and to compare the longitudinal changes in HRQoL for people with and without OA, using an Australian population-based longitudinal cohort. Methods Participants of the Tasmanian Older Adult Cohort with data on OA diagnosis and HRQoL were included [interviewed at baseline (n  = 1093), 2.5 years (n  = 871), 5 years (n  = 760) and 10 years (n  = 562)]. HRQoL was assessed using the Assessment of Quality of Life four-dimensions and analysed using multivariable linear mixed regressions. Results Compared with participants without OA, HSUs for those with OA were 0.07 (95% confidence interval: 0.09, 0.05) units lower on average over 10 years. HSUs for participants with knee and/or hip OA were similar to those with other types of OA at the 2.5 year follow-up and then diverged, with HSUs of the former being up to 0.09 units lower than the latter. Those with OA had lower scores for psychological wellness, independent living and social relationships compared with those without OA. Independent living and social relationships were mainly impacted by knee and/or hip OA, with the effect on the former increasing over time. Conclusion Interventions to improve HRQoL should be tailored to specific OA types, health dimensions, and times. Support for maintaining psychological wellness should be provided, irrespective of OA type and duration. However, support for maintaining independent living could be more relevant to knee and/or hip OA patients living with the disease for longer. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of total number and patterns of comorbidities on health-related quality of life (HRQoL) and identify the most prevalent and influential comorbidity patterns in people with OA over 10 years., Methods: Participants from the Tasmanian Older Adult Cohort aged 50-80 years, with self-reported OA and data on comorbidities and HRQoL were included. Participants were interviewed at baseline (n = 398), 2.5 (n = 304), 5 (n = 269) and 10 years (n = 191). Data on the self-reported presence of 10 chronic comorbidities were collected at baseline. HRQoL was assessed using the Assessment of Quality of Life-4-Dimensions. The long-term impacts of the number and of the nine most prevalent combinations of cardiovascular (CVD), non-OA musculoskeletal (Ms), metabolic and respiratory comorbidities on HRQoL over 10 years were analysed using linear mixed regressions., Results: Compared with comorbidity-free OA participants, the health state utility (HSU) of those with 2 or ≥3 comorbidities was respectively -0.07 and -0.13 units lower over 10 years, largely driven by reduced scores for independent living, social relationships and psychological wellness. Comorbidity patterns including 'CVD+Ms' were most influential, and associated with up to 0.13 units lower HSU, mostly through negative impacts on independent living (up to -0.12), psychological wellness (up to -0.08) and social relationship (up to -0.06)., Conclusion: Having more comorbidities negatively impacted OA patients' long-term HRQoL. OA patients with CVD and non-OA musculoskeletal conditions had the largest HSU impairment, and therefore optimal management and prevention of these conditions may yield improvements in OA patients' HRQoL., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)