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The relationship between high plasma high-density lipoprotein cholesterol (HDL-C) and cause and mortality are not well established in healthy older people. This study examined the associations between HDL-C levels and mortality in initially healthy older men and women. This analysis included participants from the Aspirin in Reducing Events in the Elderly (ASPREE; n=18,668) trial and a matched cohort from the UK Biobank (UKB; n=62,849 ≥65 years). Cox regression was used to examine hazard ratios between HDL-C categories <1.03 mmol/L, 1.03–1.55 mmol/L (referent category), 1.55–2.07 mmol/L, and >2.07 mmol/L and all-cause, cancer, cardiovascular disease (CVD), and "non-cancer non-CVD" mortality. Genetic contributions were assessed using a polygenic score for HDL-C. Among ASPREE participants (aged 75±5 years), 1836 deaths occurred over a mean follow-up of 6.3±1.8 years. In men, the highest category of HDL-C levels was associated with increased risk of all-cause (HR 1.60, 95% CI 1.26–2.03), cancer (HR 1.37, 95% CI 0.96–2.00), and "non-cancer non-CVD" mortality (HR 2.35, 95% CI 1.41–3.42) but not CVD mortality (HR 1.08, 95% CI 0.60–1.94). The associations were replicated among UKB participants (aged 66.9±1.5 years), including 8739 deaths over a mean follow-up of 12.7±0.8 years. There was a non-linear association between HDL-C levels and all-cause and cause-specific mortality. The association between HDL-C levels and mortality was unrelated to variations in the HDL-C polygenic score. No significant association was found between HDL-C levels and mortality in women. Higher HDL-C levels are associated with increased risk from cancer and "non-cancer non-CVD" mortality in healthy older men but no such relationship was observed in women. [ABSTRACT FROM AUTHOR]

Background Blood concentrations of testosterone and estrone tend to increase in women aged ≥70 years, whereas concentrations of their precursor hormone dehydroepiandrosterone decline. It is unknown whether these changes influence physical function. We investigated whether concentrations of these hormones were associated with grip strength and self-reported physical function in community-dwelling older women. Methods A total of 9 179 Australian women, aged ≥70 years, were recruited to the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Sex hormones were measured in Sex Hormones in Older Women, an ASPREE substudy, by liquid chromatography–tandem mass spectrometry in 6 358 women. The associations between hormone concentrations and physical function (handgrip strength and self-reported physical function assessed by SF-12v2 physical component summary [PCS]) were examined using multiple linear regression. Results The median age of the 5,447 participants was 74.0 (interquartile range 71.7–77.6) years. Testosterone concentrations above the lowest quartile were associated with less decline in grip strength (mean –1.39 [95% CI –1.54 to –1.24] vs –1.75 [–2.00 to –1.50] kg, p  = .02), and dehydroepiandrosterone concentrations above the lowest quartile were associated with less decline in grip strength (–1.39 [–1.54 to –1.25] vs –1.82 [–2.11 to –1.55] kg, p  = .007) and PCS scores (–1.49 [–1.80 to –1.17] vs –2.33 [–2.93 to –1.72], p  = .02) over 4 years, compared with those in the respective lowest quartile. Conclusions Low endogenous concentrations of testosterone and dehydroepiandrosterone were associated the greatest likelihood of physical function decline in community-based women aged ≥70 years. Further studies are warranted to determine whether testosterone and dehydroepiandrosterone therapy prevent functional decline in this at-risk group using sensitive measures of muscle strength and performance. [ABSTRACT FROM AUTHOR]

Objective: Both grip strength and gait speed can be used as markers of muscle function, however, no previous study has examined them in the same population with respect to risk of falls. Methods: In this prospective cohort study, utilising data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and ASPREE-Fracture substudy, we analysed the association of grip strength and gait speed and serious falls in healthy older adults. Grip strength was measured using a handheld dynamometer and gait speed from 3-metre timed walks. Serious falls were confined to those involving hospital presentation. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for associations with falls. Results: Over an average of 4.0±1.3 years, amongst 16,445 participants, 1,533 had at least one serious fall. After adjustment for age, sex, physical activity, body mass index, Short Form 12 (state of health), chronic kidney disease, polypharmacy and aspirin, each standard deviation (SD) lower grip strength was associated with 27% (HR 1.27, 95% CI 1.17–1.38) higher risk of falls. The results remained the same for males and females. There was a dose-response relationship in the association between grip strength and falls risk. The higher risk of falls was observed in males in all body mass index (BMI) categories, but only in obese females. The association between gait speed and falls risk was weaker than the association between grip strength and falls risk. Conclusions: All males and only obese females with low grip strength appear to be at the greatest risk of serious falls. These findings may assist in early identification of falls. [ABSTRACT FROM AUTHOR]

Objective There is increasing evidence for the involvement of vascular disease in the pathogenesis of knee OA. Popliteal artery wall thickness can be used as a surrogate marker of atherosclerosis. We examined the association between popliteal artery wall thickness and knee cartilage volume in individuals with symptomatic knee OA. Methods This prospective cohort study analysed 176 participants from a randomized placebo-controlled trial examining the effect of atorvastatin on structural progression in knee OA. The participants underwent MRI of the study knee at baseline and 2-year follow-up. Popliteal artery wall thickness and tibial cartilage volume were measured from MRI using validated methods. The top quartile of the rate of tibial cartilage volume loss was defined as rapid progression. Results At baseline, every 10% increase in popliteal artery wall thickness was associated with 120.8 mm3 (95% CI 5.4, 236.2, P  = 0.04) lower of medial tibial cartilage volume and 151.9 mm3 (95% CI 12.1, 291.7, P  = 0.03) lower of lateral tibial cartilage volume. Longitudinally, for every 10% increase in popliteal artery wall thickness, the annual rate of medial tibial cartilage volume loss was increased by 1.14% (95% CI 0.09%, 2.20%, P  = 0.03), and there was a 2.28-fold (95% CI 1.07, 4.83, P  = 0.03) risk of rapid progression of medial tibial cartilage loss, adjusted for age, sex, BMI, tibial bone area, smoking, vigorous physical activity, and intervention group allocation. Conclusion The findings support a role for vascular pathology in the progression of knee OA. Targeting atherosclerosis has the potential to improve outcomes in knee OA. [ABSTRACT FROM AUTHOR]

Background: Few studies have explored the impact of low back or lower limb pain severity on recurrent (≥2) falls in older adults.Objectives: Investigate the association between the severity of low back or lower limb pain, and ≥2 falls or falls-related injuries.Methods: Community-dwelling Australian males and females in the ASPREE Longitudinal Study of Older Persons (ALSOP), aged ≥70 years. Self-reported, cross-sectional questionnaire data regarding number of falls and falls-related injuries in the last 12 months; and sites and severity of pain experienced on most days. Adjusted relative risks (RR) were estimated from multivariable Poisson regression models, for males and females separately.Results: Of 14,892 ALSOP participants, 13% (n = 1983) reported ≥2 falls ('recurrent fallers') in the last 12 months. Males and females who reported severe low back, or severe lower limb pain on most days were more likely to report ≥2 falls in the last 12 months compared to those with mild pain (lower back: males RR = 1.70 and females RR = 1.5, p = 0.001; lower limb: males RR = 2.0, p < 0.001 and females RR = 1.4, p = 0.003). Female recurrent fallers who reported severe low back (RR = 1.3, p = 0.029) or lower limb (RR = 1.2, p = 0.024) pain on most days were more likely to report a falls-related injury in the last 12 months compared to females with mild pain.Conclusion: Severe low back or lower limb pain was associated with an increased likelihood of recurrent falls (males/females) or falls-related injuries (females only). Assessment of severe low back and lower limb pain should be considered as a priority when undertaking falls-risk evaluation.Significance: Severe low back pain, or severe lower limb pain is associated with an increased likelihood of recurrent falls in older males and females, and an increased likelihood of falls-related injuries in older female recurrent fallers. Assessment and management of severe low back and lower limb pain should be prioritized when undertaking falls-risk assessment. Future longitudinal research is required to further interrogate this relationship and its underlying mechanisms. [ABSTRACT FROM AUTHOR]

We examined the effect of person‐related factors on capacity to obtain needed healthcare for non‐COVID‐19 health conditions/disabilities under COVID‐19 restrictions. This was an anonymous online survey of Australian residents ≥18 years (3rd April to 2nd May 2020). We determined the ability to obtain care needed for non‐COVID‐19 health conditions/disabilities, experience of COVID‐19, COVID‐19 restrictions and sociodemographic characteristics using study‐specific questions; and clinically significant depressive and anxiety symptoms using Patient Health Questionnaire 9 and Generalised Anxiety Disorder Scale 7 respectively. We calculated the population attributable fraction (PAF) to determine the proportion of worse access to non‐COVID‐19 health/disability care attributable to independent risk factors. 13,829 (91.5%) participants had complete data. 6,712 (46.4%) identified a need for healthcare/disability services (<45 years 42.1%, ≥45 years 50.3%). 31.6% aged <45 years and 24.3% aged ≥45 years reported worse access to health/disability care than experienced prior to the pandemic. In those aged <45 years the PAF was highest for depressive symptoms (21.4%; 95% CI 12.6%–29.3%) and anxiety (PAF 19.9%, 12.3%–26.9%). with a PAF of 49.6% (40.1%–57.6%) if any one of the following was being experienced: doing unpaid work; being a student; depressive symptoms; symptoms of anxiety; experiencing high adverse impact of COVID‐19 restrictions. In those ≥45 years, PAF was highest for having depressive symptoms (PAF 20.9%, 16.6–24.8) with a PAF of 44.1% (36.0%–51.2%) if any one of the following was being experienced: depressive symptoms; symptoms of anxiety; doing unpaid work; living alone; being in lowest socioeconomic quintile; main source of income from government benefits; any personal experience of COVID‐19. The identified risk factors, which include many that characterise those with worse health outcomes generally, explained 44%–50% of worse access to necessary health/disability care. These data have the potential to inform targeted strategies aimed at reducing a post‐pandemic escalation of poor health outcomes, especially in vulnerable populations. [ABSTRACT FROM AUTHOR]

Background: There is some evidence that corticosteroids may have a beneficial effect in hand osteoarthritis. We examined the efficacy of corticosteroids on symptoms and structural outcomes in hand osteoarthritis.Methods: Ovid MEDLINE, Embase and Cochrane Central Register of Controlled Trials were searched from inception to October 2021 for randomized controlled trials investigating the efficacy of corticosteroids in hand osteoarthritis. Two authors independently screened records, extracted data, and assessed risk of bias using the RoB 2 tool. Standardized mean difference (SMD) or mean difference (MD) was calculated, and random-effects meta-analyses were performed.Results: Of 13 included trials, 3 examined oral corticosteroids and clinical outcomes in any hand joints, 9 examined intra-articular injection of corticosteroids and clinical outcomes at the first carpometacarpal joint and one in the interphalangeal joints. In meta-analysis, oral corticosteroids reduced pain (SMD -0.53, 95% CI -0.79 to -0.28) and improved stiffness (MD -5.03, 95% CI -9.91 to -0.15; Australian Canadian Osteoarthritis Hand Index stiffness subscale) and function (SMD -0.37, 95% CI -0.63 to -0.12) at 4-6 weeks. However, there was no significant persistent effect on pain and function at 3 months which was 6-8 weeks after study medication was stopped. There was no significant effect of intra-articular corticosteroids on pain or function at 4-6 weeks or over 3-12 months in first carpometacarpal osteoarthritis. Two trials evaluated joint structure at 4-6 weeks: one study showed oral corticosteroids reduced synovial thickening, neither showed an effect on synovitis.Conclusions: There was low-certainty evidence for a medium effect of oral corticosteroids on pain relief and stiffness improvement and small-to-medium effect on functional improvement at 4-6 weeks, with no significant effect for intra-articular corticosteroids. Corticosteroids had no significant effect on any outcomes over longer term (3-12 months) off treatment. No trials examined the effect of corticosteroids on disease progression. The role of corticosteroids in hand osteoarthritis is limited. [ABSTRACT FROM AUTHOR]

Background: Undertreated risk factors are major contributors to the burden of cardiovascular disease (CVD). Those with arthritis have an increased prevalence of CVD risk factors. CVD risk factors are often asymptomatic, which may be a barrier their treatment. Arthritis causes pain and immobility, and is a common reason for individuals to seek healthcare. Our aims were to (1) examine the relationship between arthritis and CVD risk factors in Australian adults, and (2) calculate the proportion of CVD risk factors that could be reduced if individuals with arthritis were targeted.Methods: This cross-sectional study uses data from the 2017-18 Australian National Health Survey which included 13,776 participants, categorised into young (18-39 years), middle aged (40-64 years) and older (≥ 65 years) adults. Hypertension, height and weight were measured. Arthritis, dyslipidemia and diabetes were self-reported. The associations between arthritis and CVD risk factors were examined using logistic regression, and the population attributable fraction (PAF) of arthritis for each CVD risk factor was calculated.Results: Arthritis was reported by 4.0% of young adults, 28.8% of middle-aged adults and 54.5% of older adults. Those with arthritis were at increased odds of obesity (2.07 fold in young, 1.75 fold in middle-aged and 1.89 fold in older adults), increased odds of diabetes (5.70 fold in young, 1.64 fold in middle-aged and 1.37 fold in older adults), increased odds of hypertension (2.72 fold in young, 1.78 fold in middle-aged and 1.48 fold in older adults) and an increased odds of dyslipidaemia (4.64 fold in young, 2.14 fold in middle-aged and 1.22 fold in older adults) compared to those without arthritis. This elevated chance remained significant even after adjusting for obesity, with the exception of diabetes in the older population. This elevated chance remained significant even after adjusting for obesity, with the exception of diabetes in the older population. The PAF of the presence of arthritis for having at least one CVD risk factor was 30.7% in middle-aged adults and 70.4% in older adults.Conclusion: Australian adults of all ages with arthritis are at increased odds of having CVD risk factors. For young and middle-aged adults, this increased odds remains significant even when adjusted for obesity. Presentation to healthcare practitioners with arthritis is an opportunity to screen for asymptomatic CVD risk factors with the potential of improving outcomes for both diseases. By adopting an approach of managing arthritis and CVD risk factors in parallel, rather than in silos, we could reduce the burden of CVD risk factors by 20-30%. [ABSTRACT FROM AUTHOR]

Background: Pain sensitisation plays a major role in musculoskeletal pain. However, effective treatments are limited, and although there is growing evidence that exercise may improve pain sensitisation, the amount and type of exercise remains unclear. This systematic review examines the evidence for an effect of aerobic exercise on pain sensitisation in musculoskeletal conditions.Methods: Systematic searches of six electronic databases were conducted. Studies were included if they examined the relationship between aerobic physical activity and pain sensitisation in individuals with chronic musculoskeletal pain, but excluding specific patient subgroups such as fibromyalgia. Risk of bias was assessed using Cochrane methods and a qualitative analysis was conducted.Results: Eleven studies (seven repeated measures studies and four clinical trials) of 590 participants were included. Eight studies had low to moderate risk of bias. All 11 studies found that aerobic exercise increased pressure pain thresholds or decreased pain ratings in those with musculoskeletal pain [median (minimum, maximum) improvement in pain sensitisation: 10.6% (2.2%, 24.1%)]. In these studies, the aerobic exercise involved walking or cycling, performed at a submaximal intensity but with incremental increases, for a 4-60 min duration. Improvement in pain sensitisation occurred after one session in the observational studies and after 2-12 weeks in the clinical trials.Conclusions: These findings provide evidence that aerobic exercise reduces pain sensitisation in individuals with musculoskeletal pain. Further work is needed to determine whether this translates to improved patient outcomes, including reduced disability and greater quality of life. [ABSTRACT FROM AUTHOR]

Background: Hand osteoarthritis is a common and disabling chronic joint disease with a lack of effective therapies. Emerging evidence suggests the role of local inflammation in causing pain in hand osteoarthritis. Corticosteroids are potent anti-inflammatory drugs used in many rheumatic diseases. The aim of this randomised, double-blind, placebo-controlled trial is to determine whether topical corticosteroid reduces pain over 6 weeks in patients with hand osteoarthritis.Methods: One hundred participants with hand osteoarthritis will be recruited from the community in Melbourne, Australia, and randomly allocated in a 1:1 ratio to receive either topical Diprosone OV or placebo ointment administered 3 times daily on the painful hand joints for 6 weeks. The primary outcome is pain reduction (assessed by 100 mm visual analogue scale) at 6 weeks. The secondary outcomes include changes in pain and function assessed using Functional Index for Hand Osteoarthritis, Australian Canadian Osteoarthritis Hand Index, Michigan Hand Outcomes Questionnaire, and tender and swollen joint count at 6 weeks. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups.Discussion: This study will provide high-quality evidence to determine whether topical corticosteroid reduces pain over 6 weeks in patients with hand osteoarthritis, with major clinical and public health importance by informing clinical practice guidelines for the management of hand osteoarthritis and reducing the burden of the disabling disease.Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12620000599976 . Registered 22 May 2020. [ABSTRACT FROM AUTHOR]

Objective: To determine whether atorvastatin slows tibial cartilage volume loss in patients with symptomatic knee osteoarthritis (OA) in a multicenter, randomized, double‐blind, placebo‐controlled trial. Methods: Participants ages 40–70 years were randomized to receive oral atorvastatin (40 mg once daily) (n = 151) or matching placebo (n = 153). The primary end point was annual percentage change in tibial cartilage volume over 2 years, assessed using magnetic resonance imaging (MRI). The prespecified secondary end points were progression of cartilage defects and bone marrow lesions over 2 years, which were assessed using MRI and change in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index pain, stiffness, and function scores. Results: A total of 248 of 304 participants (81.6%) completed the trial (mean age 55.7 years; 55.6% women). The annual change in tibial cartilage volume differed minimally between the atorvastatin and placebo groups (mean change –1.66% versus –2.17%, between‐group difference 0.50% [95% confidence interval (95% CI) –0.17%, 1.17%]). There were no significant differences in the progression of cartilage defects (odds ratio [OR] 0.86 [95% CI 0.52, 1.41]) or progression of bone marrow lesions (OR 1.00 [95% CI 0.62, 1.63]). Moreover, there were no significant differences in change in WOMAC pain, stiffness, or function scores over 2 years between the atorvastatin and placebo groups (mean change in pain score –36.0 versus –29.5, adjusted difference –2.7 [95% CI –27.1, 21.7]; mean change in stiffness score –14.2 versus –11.8, adjusted difference –0.2 [95% CI –12.2, 11.8]; mean change in function score –89.4 versus –87.5, adjusted difference 0.3 [95% CI –83.1, 83.6]). The incidence of adverse events (AEs) was similar between the atorvastatin and placebo groups (57 [37.7%] versus 52 [34.0%] experiencing AEs). Conclusion: Treatment with oral atorvastatin (40 mg once daily), compared to placebo, did not significantly reduce cartilage volume loss over 2 years in patients with symptomatic knee OA. These findings do not support the use of atorvastatin for the treatment of knee OA. [ABSTRACT FROM AUTHOR]

Background: To examine the association between circulating 25(OH)D concentrations and incidence of total hip replacement for osteoarthritis in a prospective cohort study.Methods: This study examined a random sample of 2651 participants in the Melbourne Collaborative Cohort Study who had 25(OH)D concentrations measured from dried blood spots collected in 1990-1994. Participants who underwent total hip replacement for osteoarthritis between January 2001 and December 2018 were identified by linking the cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of total hip replacement for osteoarthritis in relation to 25(OH)D concentrations, adjusted for confounders.Results: Eighty-six men and eighty-seven women had a total hip replacement for osteoarthritis. Compared with men in the lowest (1st) quartile of 25(OH)D concentration, the HR for total hip replacement was 2.32 (95% CI 1.05, 5.13) for those in the 2nd quartile, 2.77 (95% CI 1.28, 6.00) for those in the 3rd quartile, and 1.73 (95% CI 0.75, 4.02) for those in the highest quartile of 25(OH)D concentrations (p for trend 0.02). There was little evidence of an association in women.Conclusions: Higher circulating 25(OH)D concentrations were associated with an increased risk of total hip replacement for osteoarthritis in men but not in women. Although the underlying mechanism warrants further investigation, our findings highlight the need to determine the optimal levels of circulating 25(OH)D to reduce the risk of hip osteoarthritis. [ABSTRACT FROM AUTHOR]

Background: To determine the relationship between clusters of back pain and joint pain and prescription opioid dispensing.Methods: Of 11,221 middle-aged participants from the Australian Longitudinal Study of Women's Health, clusters of back pain and joint pain from 2001 to 2013 were identified using group-based trajectory modelling. Prescription opioid dispensing from 2003 to 2015 was identified by linking the cohort to Pharmaceutical Benefit Scheme dispensing data. Multinomial logistic regression was used to examine the association between back pain and joint pain clusters and dispensing of prescription opioids. The proportion of opioids dispensed in the population attributable to back and join pain was calculated.Results: Over 12 years, 68.5 and 72.0% women reported frequent or persistent back pain and joint pain, respectively. There were three clusters ('none or infrequent', 'frequent' and 'persistent') for both back pain and joint pain. Those in the persistent back pain cluster had a 6.33 (95%CI 4.38-9.16) times increased risk of having > 50 opioid prescriptions and those in persistent joint pain cluster had a 6.19 (95%CI 4.18-9.16) times increased risk of having > 50 opioid prescriptions. Frequent and persistent back and joint pain clusters together explained 41.7% (95%CI 34.9-47.8%) of prescription opioid dispensing. Women in the frequent and persistent back pain and joint pain clusters were less educated and reported more depression and physical inactivity.Conclusion: Back pain and joint pain are major contributors to opioid prescription dispensing in community-based middle-aged women. Additional approaches to reduce opioid use, targeted at those with frequent and persistent back pain and joint pain, will be important in order to reduce the use of opioids and their consequent harm in this population. [ABSTRACT FROM AUTHOR]

Background: Knee osteoarthritis is a major cause of pain and disability. Pain control is poor, with most patients remaining in moderate to severe pain. This may be because central causes of pain, a common contributor to knee pain, are not affected by current treatment strategies. Antidepressants, such as amitriptyline, have been used to treat chronic pain in other conditions. The aim of this randomised, double blind, controlled trial, is to determine whether low dose amitriptyline reduces pain in people with painful knee osteoarthritis over 3 months compared to benztropine, an active placebo.Methods/design: One hundred and sixty people with painful radiographic knee osteoarthritis will be recruited via clinicians, local and social media advertising. Participants will be randomly allocated in a 1:1 ratio to receive either low dose amitriptyline (25 mg) or active placebo (benztropine mesylate, 1 mg) for 3 months. The primary outcome is change from baseline in knee pain (WOMAC pain subscale) at 12 weeks. Secondary outcomes include change in function (total WOMAC) and the proportion of individuals achieving a substantial response (≥ 50% reduction in pain intensity, measured by Visual Analog Scale, VAS, from no pain to worst pain imaginable, 0-100 mm) and moderate response (≥ 30% reduction in pain intensity, measured by VAS) at 12 weeks. Intention to treat analyses will be performed. Subgroup analyses will be done.Discussion: This study will provide high level evidence regarding the effectiveness of low dose amitriptyline compared to benztropine in reducing pain and improving function in knee OA. This trial has the potential to provide an effective new therapeutic approach for pain management in knee osteoarthritis, with the potential of ready translation into clinical practice, as it is repurposing an old drug, which is familiar to clinicians and with a well described safety record.Trial Registration: Australian New Zealand Clinical Trials Registry prior to recruitment commencing ( ACTRN12615000301561 , March 31, 2015, amended 14 December 2018, February 2021). Additional amendment requested 18 July 2021. [ABSTRACT FROM AUTHOR]

Background: Back and lower limb pain have a major impact on physical function and quality of life. While obesity is a modifiable risk factor for musculoskeletal pain, the role of adiposity is less clear. This systematic review aimed to examine the relationship between both adiposity and its distribution and back and lower limb pain. Methods: A systematic search of electronic databases was conducted to identify studies that examined the association between anthropometric and/or direct measures of adiposity and site specific musculoskeletal pain. Risk of bias was assessed and a best evidence synthesis was performed. Results: A total of 56 studies were identified which examined 4 pain regions, including the lower back (36 studies), hip (two studies), knee (13 studies) and foot (eight studies). 31(55%) studies were assessed as having low to moderate risk of bias. 17(30%) studies were cohort in design. The best evidence synthesis provided evidence of a relationship between central adiposity and low back and knee pain, but not hip or foot pain. There was also evidence of a longitudinal relationship between adiposity and the presence of back, knee and foot pain, as well as incident and increasing foot pain. Conclusions: This systematic review provides evidence of an association between both body fat and its central distribution and low back and knee pain, and a longitudinal relationship between adiposity and back, knee and foot pain. These results highlight the potential for targeting adiposity in the development of novel treatments at these sites. [ABSTRACT FROM AUTHOR]

Objective: To systematically review the evidence for the efficacy of mesenchymal stem cell (MSC) injections in improving osteoarthritis (OA)-related structural outcomes.Methods: Ovid Medline and EMBASE were searched from their inceptions to April 2020 using MeSH terms and key words. Independent reviewers extracted data and assessed methodological quality. Qualitative evidence synthesis was performed due to the heterogeneity of interventions and outcome measures.Results: Thirteen randomized controlled trials (phase I or II) were identified: 10 in OA populations and 3 in populations at risk of OA, with low (n = 9), moderate (n = 3), or high (n = 1) risk of bias. Seven studies used allogeneic MSCs (4 bone marrow, 1 umbilical cord, 1 placenta, 1 adipose tissue), 6 studies used autologous MSCs (3 adipose tissue, 2 bone marrow, 1 peripheral blood). Among the 11 studies examining cartilage outcomes, 10 found a benefit of MSCs on cartilage volume, morphology, quality, regeneration, and repair, assessed by magnetic resonance imaging, arthroscopy, or histology. The evidence for subchondral bone was consistent in all 3 studies in populations at risk of OA, showing beneficial effects. Sixteen unpublished, eligible trials were identified by searching trial registries, including 8 with actual or estimated completion dates before 2016.Conclusion: Our systematic review of early-phase clinical trials demonstrated consistent evidence of a beneficial effect of intraarticular MSC injections on articular cartilage and subchondral bone. Due to the heterogeneity of MSCs, modest sample sizes, methodological limitations, and potential for publication bias, further work is needed before this therapy is recommended in the management of OA. [ABSTRACT FROM AUTHOR]

Objective: To examine the risk of total knee arthroplasty (TKA) due to osteoarthritis associated with obesity defined by body mass index (BMI) or waist circumference (WC) and whether there is discordance between these measures in assessing this risk. Methods: 36,784 participants from the Melbourne Collaborative Cohort Study with BMI and WC measured at 1990–1994 were included. Obesity was defined by BMI (≥30 kg/m2) or WC (men ≥102cm, women ≥88cm). The incidence of TKA between January 2001 and December 2018 was determined by linking participant records to the National Joint Replacement Registry. Results: Over 15.4±4.8 years, 2,683 participants underwent TKA. There were 20.4% participants with BMI-defined obesity, 20.8% with WC-defined obesity, and 73.6% without obesity defined by either BMI or WC. Obesity was classified as non-obese (misclassified obesity) in 11.7% of participants if BMI or WC alone was used to define obesity. BMI-defined obesity (HR 2.69, 95%CI 2.48–2.92), WC-defined obesity (HR 2.28, 95%CI 2.10–2.48), and obesity defined by either BMI or WC (HR 2.53, 95%CI 2.33–2.74) were associated with an increased risk of TKA. Compared with those without obesity, participants with misclassified obesity had an increased risk of TKA (HR 2.06, 95%CI 1.85–2.30). 22.7% of TKA in the community can be attributable to BMI-defined obesity, and a further 3.3% of TKA can be identified if WC was also used to define obesity. Conclusions: Both BMI and WC should be used to identify obese individuals who are at risk of TKA for osteoarthritis and should be targeted for prevention and treatment. [ABSTRACT FROM AUTHOR]

Objective: There are concerns that lumbar spine imaging represents low value care. Our aim was to examine the use of lumbar spine imaging [radiography, computed tomography (CT), magnetic resonance imaging (MRI)] over 20 years, and costs and person-level characteristics of imaging in a large cohort of Australian women. Methods: The Australian Longitudinal Study on Women's Health (ALSWH) is a longitudinal population-based survey of women randomly selected from national health insurance scheme (Medicare) database. This study examined 13458 women born in 1973–1978 who consented to link their ALSWH and Medical Benefits Scheme records. Self-reported data on demographics, body mass index, depression, physical and mental health, and back pain were collected in each survey performed in 1996, 2000, 2003, 2006, 2009, 2012, and 2015. Data on lumbar spine imaging from 1996 to 2015 were obtained from the Medical Benefits Scheme database. Results: 38.9% of women underwent some form of lumbar spine imaging over 20 years. While radiography increased from 1996 to 2011 and decreased thereafter, CT and MRI continued to increase from 1996 to 2015. In women with self-reported back pain, depression and poorer physical health were associated with imaging, with no significant differences in types of imaging. Based on imaging rates in ALSWH, the estimated costs for Australian women aged 30–39 years were AU$51,735,649 over 2011–2015. Conclusions: Lumbar spine imaging was common in population-based Australian women, with rates increasing over 20 years. Depression and poor physical health were associated with lumbar spine imaging. Raising awareness of this in clinicians is likely to result in significant cost savings if clinical guidelines are followed, with the potential of freeing resources for high value care and health outcomes. [ABSTRACT FROM AUTHOR]

Objective To examine whether the presence of bulge sign or patellar tap was associated with frequent knee pain, progression of radiographic OA (ROA) and total knee replacement (TKR). Methods This study included 4344 Osteoarthritis Initiative participants examined at baseline for bulge sign and/or patellar tap. The clinical signs were categorized as no (none at baseline and 2 years), resolved (present at baseline only), developed (present at 2 years only) and persistent (present at both time points). Frequent knee pain and progression of ROA over 4 years and TKR over 6 years were assessed. Binary logistic regression was used to examine the associations. Results A total of 12.7% of participants had bulge sign only, 2.0% had patellar tap only and 3.3% had both. A positive baseline bulge sign was associated with an increased risk of frequent knee pain [OR 1.31 (95% CI 1.04, 1.64), P = 0.02] and TKR [OR 1.47 (95% CI 1.06, 2.05), P = 0.02]. Developed bulge sign was associated with an increased risk of frequent knee pain [OR 1.75 (95% CI 1.34, 2.29), P < 0.001] and progressive ROA [OR 1.67 (95% CI 1.11, 2.51), P = 0.01]. Persistent bulge sign was associated with an increased risk of frequent knee pain [OR 1.60 (95% CI 1.09, 2.35), P = 0.02], progressive ROA [OR 1.84 (95% CI 1.01, 3.33), P = 0.045] and TKR [OR 2.13 (95% CI 1.23, 3.68), P = 0.007]. Patellar tap was not examined for its association with joint outcomes due to its low prevalence. Conclusion The presence of bulge sign identifies individuals at increased risk of frequent knee pain, progression of ROA and TKR. This provides clinicians with a quick, simple, inexpensive method for identifying those at higher risk of progressive knee OA who should be targeted for therapy. [ABSTRACT FROM AUTHOR]

Background: To examine the associations between hip muscle cross-sectional area and hip pain and function in community-based individuals with mild-to-moderate hip osteoarthritis.Methods: This study included 27 participants with mild-to-moderate hip osteoarthritis. Cross-sectional area of hip muscles, including psoas major, rectus femoris, gluteus maximus, gluteus medius and minimus, adductor longus and magnus, obturator internus, and obturator externus, were measured from magnetic resonance images. Hip pain and function were evaluated using the Hip Disability and Osteoarthritis Outcome Score (HOOS) categorised into 5 subscales: pain, symptoms, activity of daily living, sport and recreation function, and hip-related quality of life (for each subscale 0 representing extreme problems and 100 representing no problems).Results: Mean age of the 27 participants was 63.2 (SD 7.6) years and 66.7% (n = 18) were female. After adjusting for age and gender, greater cross-sectional area of adductor longus and magnus was associated with a higher HOOS score in quality of life (regression coefficient 1.4, 95% confidence interval (CI) 0.2-2.7, p = 0.02), activity of daily living (regression coefficient 1.3, 95% CI 0.1-2.6, p = 0.04) and sport and recreation function (regression coefficient 1.6, 95% CI 0.1-3.0, p = 0.04). There was a trend towards an association between greater cross-sectional area of psoas major and a higher quality of life score (regression coefficient 3.6, 95% CI - 0.5 to 7.7, p = 0.08). The cross-sectional area of hip muscles was not significantly associated with HOOS pain or symptom score.Conclusion: Greater cross-sectional area of hip adductors was associated with better function and quality of life in individuals with mild-to-moderate hip osteoarthritis. Greater cross-sectional area of hip flexors might be associated with better quality of life. These findings, while need to be confirmed in longitudinal studies, suggest that targeting the hip adductor and flexor muscles may improve function and quality of life in those with mild-to-moderate hip osteoarthritis. [ABSTRACT FROM AUTHOR]

Objective: Vascular pathology (changes in blood vessels) and osteoarthritis (OA) are both common chronic conditions associated with aging and obesity, but whether vascular pathology is a risk factor for OA is unclear. The aim of this study was to systematically review the evidence for an association between vascular pathology and risk of joint-specific OA.Methods: Scopus, Ovid Medline, and EMBASE were searched from inception to February 2019. MeSH terms and keywords were used to identify studies examining the association between vascular pathology and OA. Two reviewers independently extracted the data and assessed the methodological quality. Qualitative evidence synthesis was performed.Results: Fifteen studies with high (n = 3), fair (n = 3), or low (n = 9) quality were included. Features of vascular pathology included atherosclerosis, vascular stiffness, and endothelial dysfunction in different vascular beds. There was evidence for an association between vascular pathology and risk of hand OA in women but not men, and between vascular pathology and risk of knee OA in both men and women. Only 2 studies examined hip OA showing no association between vascular pathology and risk of hip OA.Conclusion: There is evidence suggesting an association between vascular pathology and risk of hand and knee OA, with a potential causal relationship for knee OA. Based on the limited evidence, it is hard to conclude an association for hip OA. Further stronger evidence is needed to determine whether there is a causal relationship. [ABSTRACT FROM AUTHOR]

Objective To examine whether baseline knee joint effusion volume and the change in effusion volume over 1 year are associated with cartilage volume loss, progression of radiographic OA (ROA) over 4 years and risk of total knee replacement over 6 years. Methods This study included 4115 Osteoarthritis Initiative participants with knee joint effusion volume quantified by MRI at baseline. The change in effusion volume over 1 year was assessed. Cartilage volume loss and progression of ROA over 4 years were assessed using MRI and X-ray and total knee replacement over 6 years was assessed. Multiple linear regression and binary logistic regression were used for data analyses. Results Baseline knee effusion volume (per 5 ml) was positively associated with a loss of medial and lateral cartilage volume [regression coefficient 0.13%/year (95% CI 0.10, 0.17) and 0.13%/year (95% CI 0.10, 0.16), respectively, both P < 0.001], progression of ROA [odds ratio (OR) 1.28 (95% CI 1.20, 1.37), P < 0.001], and risk of knee replacement [OR 1.12 (95% CI 1.05, 1.20), P = 0.001]. A 5 ml increase in knee effusion volume over 1 year was positively associated with medial cartilage volume loss [regression coefficient 0.09%/year (95% CI 0.04, 0.15), P = 0.001], progression of ROA [OR 1.21 (95% CI 1.11, 1.33), P < 0.001] and risk of knee replacement [OR 1.24 (95% CI 1.12, 1.37), P < 0.001]. Conclusions Knee joint effusion volume assessed from MRI provides a continuous and sensitive measure that was associated with cartilage volume loss, progression of ROA and risk of total knee replacement. It may provide a method to identify individuals with an inflammatory OA phenotype who are at higher risk of disease progression. [ABSTRACT FROM AUTHOR]

Objective: To examine the associations of female reproductive and hormonal factors with incidence of total knee arthroplasty (TKA) for osteoarthritis (OA), and to determine whether the associations differ according to overweight/obesity status. Methods: This study included 22,289 women in the Melbourne Collaborative Cohort Study. Data on age at menarche, pregnancy, parity, years of menstruation, oral contraceptive (OC) use, menopausal status, and hormone replacement therapy (HRT) were collected in 1990–1994. Incidence of TKA during 2001–2013 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. All analyses were adjusted for age, body mass index (BMI) at midlife, change in BMI (from early reproductive age to midlife), country of birth, physical activity, smoking, and education level. Results: Over the course of 12.7 years, 1,208 TKAs for OA were identified. Ever being pregnant was associated with increased risk of TKA (hazard ratio [HR] 1.32 [95% confidence interval (95% CI) 1.06–1.63]). Parity was positively associated with risk of TKA (P for trend = 0.003). OC users had increased risk of TKA compared with non‐users (for OC use of <5 years, HR 1.25 [95% CI 1.08–1.45]; for OC use of ≥5 years, HR 1.17 [95% CI 1.00–1.37]). A 1‐year increase in menstruation was associated with a 1% decrease in risk of TKA (HR 0.99 [95% CI 0.97–0.99]). These associations remained significant only in women of normal weight at early reproductive age. Current HRT users had increased risk of TKA compared with non‐users (HR 1.37 [95% CI 1.14–1.64]); the association was significant only in non‐obese women at midlife. Conclusion: Reproductive and hormonal factors were associated with risk of knee OA. These associations remained significant in women of normal weight at early reproductive age and in non‐obese women at midlife. Further work is needed to understand the complex effect of these factors on knee OA. [ABSTRACT FROM AUTHOR]

The aim of this systematic review is to assess patient-related factors affecting glycaemic control among people with type 2 diabetes in the Arabian Gulf Council countries. MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL databases were searched from their date of inception to May 2016. Two researchers independently identified eligible studies and assessed the risk of bias. A total of 13 studies met the inclusion criteria. One study was population based, six recruited participants from multiple centres, and the remaining were single centred. The majority of the studies were of low to moderate quality. Factors associated with poor glycaemic control include longer duration of diabetes, low level of education, poor compliance to diet and medication, poor attitude towards the disease, poor self-management behaviour, anxiety, depression, renal impairment, hypertension, and dyslipidaemia. Healthcare providers should be aware of these factors and provide appropriate education and care especially for those who have poor glycaemic control. Innovative educational programs should be implemented in the healthcare systems to improve patient compliance and practices. A variation in the results of the included studies was observed, and some potentially important risk factors such as dietary habits, physical activity, family support, and cognitive function were not adequately addressed. Further research is needed in this area. [ABSTRACT FROM AUTHOR]

Objective We hypothesized that preterm birth and being born SGA would be associated with changes in retinal microvascular architecture and that these changes would be more marked among those born preterm. We further hypothesized that these microvascular changes would correlate with early markers of CVD in mid-adulthood. Methods The Cardiovascular Risk in Young Finns Study included randomly selected children from 5 Finnish University cities. Retinal microvascular architecture of participants born preterm, born at term and SGA and a control group born at term and AGA were compared (aged 34-49 years). Results In participants born preterm, arteriolar tortuosity (×102) was higher-means (standard error), 0.06 (0.01) versus 0.04 (0.01), p = 0.001, arteriolar length (pixels) were greater-644.9 (35.9) versus 591.7 (33.5), p = 0.007 and arteriolar diameters (pixels) were narrower-19.9 (0.4) versus 20.3 (0.3), p = 0.034 compared to participants born AGA, after adjustment. In participants born SGA, only arteriolar tortuosity was higher-0.05 (0.01) versus 0.04 (0.01), p = 0.074 compared to participants born AGA. Conclusion This study demonstrated that being born SGA and in particular preterm birth are associated with changes in retinal microvascular architecture. The prenatal and immediate postnatal environment may contribute to the mechanisms. [ABSTRACT FROM AUTHOR]

Background: Recently, there has been both immense interest and controversy regarding a randomised, controlled trial which showed antibiotics to be effective in the treatment of chronic low back pain (disc herniation with Modic Type 1 change). While this research has the potential to result in a paradigm shift in the treatment of low back pain, several questions remain unanswered. This systematic review aims to address these questions by examining the role of bacteria in low back pain and the relationship between bacteria and Modic change. Methods: We conducted electronic searches of MEDLINE and EMBASE and included studies that examined the relationship between bacteria and back pain or Modic change. Studies were rated based on their methodological quality, a best-evidence synthesis was used to summarise the results, and Bradford Hill's criteria were used to assess the evidence for causation. Results: Eleven studies were identified. The median (range) age and percentage of female participants was 44.7 (41-46.4) years and 41.5% (27-59%), respectively, and in 7 of the 11 studies participants were diagnosed with disc herniation. Nine studies examined the presence of bacteria in spinal disc material and all identified bacteria, with the pooled estimate of the proportion with positive samples being 34%. Propionibacterium acnes was the most prevalent bacteria, being present in 7 of the 9 studies, with median (minimum, maximum) 45.0% (0-86.0) of samples positive. The best evidence synthesis found moderate evidence for a relationship between the presence of bacteria and both low back pain with disc herniation and Modic Type 1 change with disc herniation. There was modest evidence for a cause-effect relationship. Conclusions: We found that bacteria were common in the spinal disc material of people undergoing spinal surgery. There was moderate evidence for a relationship between the presence of bacteria and both low back pain with disc herniation and Modic Type 1 change associated with disc herniation and modest evidence for causation. However, further work is needed to determine whether these organisms are a result of contamination or represent low grade infection of the spine which contributes to chronic low back pain. [ABSTRACT FROM AUTHOR]

Background Recently, there has been both immense interest and controversy regarding a randomised, controlled trial which showed antibiotics to be effective in the treatment of chronic low back pain (disc herniation with Modic Type 1 change). While this research has the potential to result in a paradigm shift in the treatment of low back pain, several questions remain unanswered. This systematic review aims to address these questions by examining the role of bacteria in low back pain and the relationship between bacteria and Modic change. Methods We conducted electronic searches of MEDLINE and EMBASE and included studies that examined the relationship between bacteria and back pain or Modic change. Studies were rated based on their methodological quality, a best-evidence synthesis was used to summarise the results, and Bradford Hill's criteria were used to assess the evidence for causation. Results Eleven studies were identified. The median (range) age and percentage of female participants was 44.7 (41-46.4) years and 41.5% (27-59%), respectively, and in 7 of the 11 studies participants were diagnosed with disc herniation. Nine studies examined the presence of bacteria in spinal disc material and all identified bacteria, with the pooled estimate of the proportion with positive samples being 34%. Propionibacterium acnes was the most prevalent bacteria, being present in 7 of the 9 studies, with median (minimum, maximum) 45.0% (0-86.0) of samples positive. The best evidence synthesis found moderate evidence for a relationship between the presence of bacteria and both low back pain with disc herniation and Modic Type 1 change with disc herniation. There was modest evidence for a cause-effect relationship. Conclusions We found that bacteria were common in the spinal disc material of people undergoing spinal surgery. There was moderate evidence for a relationship between the presence of bacteria and both low back pain with disc herniation and Modic Type 1 change associated with disc herniation and modest evidence for causation. However, further work is needed to determine whether these organisms are a result of contamination or represent low grade infection of the spine which contributes to chronic low back pain. [ABSTRACT FROM AUTHOR]

Objective The increased prevalence of osteoarthritis (OA) in postmenopausal women suggests that changes in either circulating sex steroid concentrations or the tissue response to sex steroids may have a role in the pathogenesis of OA. The aim of this study was to examine whether circulating sex steroid concentrations are associated with the incidence of total knee and total hip replacement for OA. Methods Study subjects (n = 2,621; all women) were recruited in 1990-1994 from the Melbourne Collaborative Cohort Study (MCCS). Circulating sex steroid concentrations were measured in blood samples obtained from the women at the time of recruitment. The incidence of total knee and total hip replacement for OA during 2001-2011 was determined by linking the MCCS records to the Australian Orthopaedic Association National Joint Replacement Registry. Results During the followup period, 115 women had undergone total knee replacement and 99 had undergone total hip replacement for OA. Greater log-transformed concentrations of estradiol were associated with a lower incidence of knee replacement (hazard ratio [HR] 0.70, 95% confidence interval [95% CI] 0.50-0.96), and greater log-transformed concentrations of androstenedione were associated with a lower incidence of hip replacement (HR 0.70, 95% CI 0.52-0.93). In contrast, greater log-transformed concentrations of sex hormone binding globulin (SHBG) were associated with a higher incidence of hip replacement (HR 1.70, 95% CI 1.05-2.77). Conclusion A lower estradiol concentration is a risk factor for knee OA, while a lower androstenedione concentration and higher SHBG concentration are risk factors for hip OA in women. These findings suggest that circulating sex steroids have a role in the pathogenesis of OA, and that modifying these steroid concentrations may provide a potential strategy for the prevention and treatment of knee and hip OA. [ABSTRACT FROM AUTHOR]

Objective. The data are conflicting for the association between the index-to-ring finger length ratio (2D:4D) and the risk of OA. The aim of this cohort study was to examine the relationship between 2D:4D and the risk of severe knee and hip OA requiring total joint replacement.Methods. A total of 14 511 participants in the Melbourne Collaborative Cohort Study had 2D:4D assessed from hand photocopies. The incidence of total knee replacement and total hip replacement between 2001 and 2011 was determined by linking the cohort records to the Australian Orthopaedic Association National Joint Replacement Registry.Results. Over an average 10.5 years of follow-up, 580 participants had total knee replacement and 499 had total hip replacement. Greater right 2D:4D [hazard ratio (HR) 0.91 for a s.d. increase in 2D:4D, 95% CI 0.84, 0.99, P = 0.03] and average right and left 2D:4D (HR 0.91 for a s.d. increase in 2D:4D, 95% CI 0.84, 0.99, P = 0.02) were associated with a reduced incidence of total knee replacement. These associations persisted when participants whose fingers had any features that might have affected the validity of 2D:4D measurements were excluded. No significant associations were observed between 2D:4D and the incidence of total hip replacement.Conclusion. A lower 2D:4D is associated with an increased risk of severe knee OA requiring total knee replacement, but not the risk of severe hip OA. The underlying mechanisms for the association warrant further investigation. [ABSTRACT FROM PUBLISHER]

Background: Histological and epidemiological data suggest that increased signal intensity at the proximal patellar tendon on magnetic resonance imaging is a response to tendon loading. As patellofemoral geometry is a mediator of loading, we examined the association between patellofemoral geometry and the prevalence of increased signal intensity at the patellar tendon in community-based middle-aged adults.Methods: Two hundred-one adults aged 25-60 years in a study of obesity and musculoskeletal health had the patellar tendon assessed from magnetic resonance imaging. Increased signal intensity at the proximal patellar tendon was defined as hyper-intense regions of characteristic pattern, size and distribution on both T1- and T2-weighted sequences. Indices of patellofemoral geometry, including Insall-Salvati ratio, patellofemoral congruence angle, sulcus angle, and lateral condyle-patella angle, were measured from magnetic resonance imaging using validated methods. Binary logistic regression was used to examine the association between patellofemoral geometrical indices and the prevalence of increased signal intensity at the patellar tendon.Results: The prevalence of increased signal intensity at the patellar tendon was 37.3%. A greater Insall-Salvati ratio (odds ratio 0.80, 95% confidence interval 0.66-0.97 per 0.1 change in the ratio, p = 0.02), indicative of a higher-riding patella, and a larger patellofemoral congruence angle (odds ratio 0.91, 95% confidence interval 0.85-0.98 per 5 degree change in the angle, p = 0.01), indicating a more laterally placed patella, were associated with reduced odds of increased signal intensity at the patellar tendon. Sulcus angle and lateral condyle-patella angle were not significantly associated with the odds of increased signal intensity at the patellar tendon.Conclusions: In community-based asymptomatic middle-aged adults, increased signal intensity at the patellar tendon was common and associated with Insall-Salvati ratio and patellofemoral congruence angle, suggesting a biomechanical mechanism. Such work is likely to inform tissue engineering and cell regeneration approaches to improving outcomes in those with tendon pathology. [ABSTRACT FROM AUTHOR]