Search

This observational study evaluated the impact of a sponsor company-provided Patient Support Program (PSP) on discontinuation of adalimumab in adult Australian patients eligible for Pharmaceutical Benefit Scheme (PBS)-reimbursed adalimumab for Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), Psoriatic Arthritis (PsA), Crohn's Disease (CD), Ulcerative Colitis (UC), or Hidradenitis Suppurativa (HS). Patients initiating adalimumab between May 2018 and September 2019 were enrolled into two prospective cohorts based on their decision to opt for or decline the PSP (PSP or non-PSP cohorts). In addition, a historical, retrospective Non-PSP cohort was established from the Services Australia 10% PBS dataset by extracting data of patients initiating adalimumab prior to the introduction of adalimumab PSPs and based on adalimumab PBS listing dates (AS: April 2007 to March 2009; PsA/RA: January 2007 to December 2008; CD: January 2009 to December 2010; HS and UC indications not included). Follow-up for all cohorts was 12 months. The primary endpoint was the time to discontinuation, compared between the prospective PSP cohort and the prospective or retrospective Non-PSP cohort. Inverse probability of treatment weighting was used to balance the cohorts. A Cox proportional hazards model indicated no difference in time to discontinuation between the prospective PSP (n = 162) and non-PSP (n = 65) cohorts (HR [95% CI] = 1.256 [0.616–2.563], p = 0.5304). The 12-month adalimumab persistence rates (95% CI) were 78% (69%, 84%) and 82% (67%, 90%), respectively. In contrast, discontinuation was less likely in the prospective PSP (n = 151) compared with the retrospective non-PSP (n = 297) cohort (HR [95% CI] = 0.44 [0.28–0.68], p<0.001). The 12-month persistence rates (95% CI) were 81% (76%, 90%) and 61% (56%, 67%), respectively. Overall, this study suggests that optimal adalimumab persistence can be achieved with either a structured PSP or healthcare support from other sources, but this was not the case more than a decade ago. [ABSTRACT FROM AUTHOR]

Hand osteoarthritis is a disabling condition with few effective therapies. Hand osteoarthritis with synovitis is a common inflammatory phenotype associated with pain. We aimed to examine the efficacy and safety of methotrexate at 6 months in participants with hand osteoarthritis and synovitis. In this multisite, parallel-group, double-blind, randomised, placebo-controlled trial, participants (aged 40–75 years) with hand osteoarthritis (Kellgren and Lawrence grade ≥2 in at least one joint) and MRI-detected synovitis of grade 1 or more were recruited from the community in Melbourne, Hobart, Adelaide, and Perth, Australia. Participants were randomly assigned (1:1) using block randomisation, stratified by study site and self-reported sex, to receive methotrexate 20 mg or identical placebo orally once weekly for 6 months. The primary outcome was pain reduction (measured with a 100 mm visual analogue scale; VAS) in the study hand at 6 months assessed in the intention-to-treat population. Safety outcomes were assessed in all randomly assigned participants. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000877381). Between Nov 22, 2017, and Nov 8, 2021, of 202 participants who were assessed for eligibility, 97 (48%) were randomly assigned to receive methotrexate (n=50) or placebo (n=47). 68 (70%) of 97 participants were female and 29 (30%) were male. 42 (84%) of 50 participants in the methotrexate group and 40 (85%) of 47 in the placebo group provided primary outcome data. The mean change in VAS pain at 6 months was –15·2 mm (SD 24·0) in the methotrexate group and –7·7 mm (25·3) in the placebo group, with a mean between-group difference of –9·9 (95% CI –19·3 to –0·6; p=0·037) and an effect size (standardised mean difference) of 0·45 (0·03 to 0·87). Adverse events occurred in 31 (62%) of 50 participants in the methotrexate group and 28 (60%) of 47 participants in the placebo group. Treatment of hand osteoarthritis and synovitis with 20 mg methotrexate for 6 months had a moderate but potentially clinically meaningful effect on reducing pain, providing proof of concept that methotrexate might have a role in the management of hand osteoarthritis with an inflammatory phenotype. National Health and Medical Research Council of Australia. [ABSTRACT FROM AUTHOR]

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]

Background: Chronic musculoskeletal pain has been linked to dementia; however, chronic pain typically occurs in multiple sites; therefore, this study was to investigate whether greater number of chronic pain sites is associated with a higher risk of dementia and its subtypes. Methods: Participants (N = 356,383) in the UK Biobank who were dementia-free at baseline were included. Pain in the hip, knee, back, and neck/shoulder or 'all over the body' and its duration were assessed. Participants were categorised into six groups: no chronic pain; chronic pain in 1, 2, 3, and 4 sites, and 'all over the body'. All-cause dementia and its subtypes were ascertained using hospital inpatient and death registry records. Cox regression was used to investigate the associations between the number of chronic pain sites and the incidence of all-cause dementia and its subtypes. Results: Over a median follow-up of 13 years, 4959 participants developed dementia. After adjustment for sociodemographic, lifestyle, comorbidities, pain medications, psychological problems, and sleep factors, greater number of chronic pain sites was associated with an increased risk of incident all-cause dementia (hazard ratio [HR] = 1.08 per 1 site increase, 95% CI 1.05–1.11) and Alzheimer's disease (AD) (HR = 1.09 per 1-site increase, 95% CI 1.04–1.13) in a dose–response manner but not vascular and frontotemporal dementia. No significant association was found between the number of chronic pain sites and the risk of incident all-cause dementia among a subsample that underwent a fluid intelligence test. Conclusions: Greater number of chronic pain sites was associated with an increased risk of incident all-cause dementia and AD, suggesting that chronic pain in multiple sites may contribute to individuals' dementia risk and is an underestimated risk factor for dementia. [ABSTRACT FROM AUTHOR]

Background: There is an unmet need for treatments for knee osteoarthritis (OA). Effusion-synovitis is a common inflammatory phenotype of knee OA and predicts knee pain and structural degradation. Anti-inflammatory therapies, such as diacerein, may be effective for this phenotype. While diacerein is recommended for alleviating pain in OA patients, evidence for its effectiveness is inconsistent, possibly because studies have not targeted patients with an inflammatory phenotype. Therefore, we will conduct a multi-centre, randomised, placebo-controlled double-blind trial to determine the effect of diacerein on changes in knee pain and effusion-synovitis over 24 weeks in patients with knee OA and magnetic resonance imaging (MRI)-defined effusion-synovitis.Methods: We will recruit 260 patients with clinical knee OA, significant knee pain, and MRI-detected effusion-synovitis in Hobart, Melbourne, Adelaide, and Perth, Australia. They will be randomly allocated to receive either diacerein (50mg twice daily) or identical placebo for 24 weeks. MRI of the study knee will be performed at screening and after 24 weeks of intervention. The primary outcome is improvement in knee pain at 24 weeks as assessed by a 100-mm visual analogue scale (VAS). Secondary outcomes include improvement in volumetric (ml) and semi-quantitative (Whole-Organ Magnetic Resonance Imaging Score, 0-3) measurements of effusion-synovitis using MRI over 24 weeks, and improvement in knee pain (VAS) at 4, 8, 12, 16, and 20 weeks. Intention-to-treat analyses of primary and secondary outcomes will be performed as the primary analyses. Per protocol analyses will be performed as the secondary analyses.Discussion: This study will provide high-quality evidence to determine whether diacerein improves pain, changes disease trajectory, and slows disease progression in OA patients with effusion-synovitis. If diacerein proves effective, this has the potential to significantly benefit the substantial proportion (up to 60%) of knee OA patients with an inflammatory phenotype.Trial Registration: Australian and New Zealand Clinical Trial Registry ACTRN12618001656224 . Registered on 08 October 2018. [ABSTRACT FROM AUTHOR]

Chronic plantar heel pain (CPHP) is associated with calcaneal bone spurs, but its associations with other calcaneal bone features are unknown. This study therefore aimed to determine associations between having CPHP and bone density and microarchitecture of the calcaneus. We assessed 220 participants with CPHP and 100 age- and sex-matched population-based controls. Trabecular bone density, thickness, separation and number, BV/TV, and cortical density, thickness and area were measured using a Scanco Xtreme1 HR-pQCT scanner at a plantar and mid-calcaneal site. Clinical, physical activity and disease history data were also collected. Associations with bone outcomes were assessed using multivariable linear regression adjusting for age, sex, physical activity, BMI and ankle plantarflexor strength. We assessed for potential effect modification of CPHP on these covariates using interaction terms. There were univariable associations at the plantar calcaneus where higher trabecular bone density, BV/TV and thickness and lower trabecular separation were associated with CPHP. In multivariable models, having CPHP was not independently associated with any bone outcome, but modified associations of BMI and ankle plantarflexor strength with mid-calcaneal and plantar bone outcomes respectively. Beneficial associations of BMI with mid-calcaneal trabecular density (BMI-case interaction standardised X/unstandardised Y beta -10.8(mgHA/cm3) (se 4.6), thickness -0.002(mm) (se 0.001) and BV/TV -0.009(%) (se 0.004) were reduced in people with CPHP. Beneficial associations of ankle plantarflexor strength with plantar trabecular density (ankle plantarflexor strength -case interaction -11.9(mgHA/cm3) (se 4.4)), thickness -0.003(mm) (se 0.001), separation -0.003(mm) (se 0.001) and BV/TV -0.010(%) (se 0.004) were also reduced. CPHP may have consequences for calcaneal bone density and microarchitecture by modifying associations of BMI and ankle plantarflexor strength with calcaneal bone outcomes. The reasons for these case-control differences are uncertain but could include a bone response to entheseal stress, altered loading habits and/or pain mechanisms. Confirmation with longitudinal study is required. [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: Current pharmacologic therapies for patients with osteoarthritis are suboptimal.Objective: To determine the efficacy of Curcuma longa extract (CL) for reducing knee symptoms and effusion-synovitis in patients with symptomatic knee osteoarthritis and knee effusion-synovitis.Design: Randomized, double-blind, placebo-controlled trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000080224).Setting: Single-center study with patients from southern Tasmania, Australia.Participants: 70 participants with symptomatic knee osteoarthritis and ultrasonography-defined effusion-synovitis.Intervention: 2 capsules of CL (n = 36) or matched placebo (n = 34) per day for 12 weeks.Measurements: The 2 primary outcomes were changes in knee pain on a visual analogue scale (VAS) and effusion-synovitis volume on magnetic resonance imaging (MRI). The key secondary outcomes were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and cartilage composition values. Outcomes were assessed over 12 weeks.Results: CL improved VAS pain compared with placebo by -9.1 mm (95% CI, -17.8 to -0.4 mm [P = 0.039]) but did not change effusion-synovitis volume (3.2 mL [CI, -0.3 to 6.8 mL]). CL also improved WOMAC knee pain (-47.2 mm [CI, -81.2 to -13.2 mm]; P = 0.006) but not lateral femoral cartilage T2 relaxation time (-0.4 ms [CI, -1.1 to 0.3 ms]). The incidence of adverse events was similar in the CL (n = 14 [39%]) and placebo (n = 18 [53%]) groups (P = 0.16); 2 events in the CL group and 5 in the placebo group may have been treatment related.Limitation: Modest sample size and short duration.Conclusion: CL was more effective than placebo for knee pain but did not affect knee effusion-synovitis or cartilage composition. Multicenter trials with larger sample sizes are needed to assess the clinical significance of these findings.Primary Funding Source: University of Tasmania and Natural Remedies Private Limited. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To describe the persistence of biologic disease modifying anti‐rheumatic drugs (bDMARDs) in Australian rheumatoid arthritis (RA) patients, and assess the influence of methotrexate and other conventional DMARD (cDMARD) concomitant medications, and treatment line on bDMARD persistence and glucocorticoids usage. Method: RA patients, from the 10% Australian Medicare random sample, aged ≥18 for whom bDMARDs were dispensed were included. Individual sub‐cutaneous (SC) anti‐tumor necrosis factor‐α (anti‐TNFα) agents were combined as they were equivalent. Results: Data from 1230 patients were analyzed. For all patients the 12‐month persistence rates (based on Kaplan–Meier estimates) were 76% for intravenous (IV) tocilizumab, 63% abatacept (SC/IV), 61% SC‐anti‐TNFs and 36% IV‐infliximab. Persistence rates on first‐line bDMARDs were 79% (tocilizumab and abatacept), 64% (SC‐anti‐TNFs) and 13% (infliximab); rates were sustained for tocilizumab but dropped to 49% for abatacept and 51% for SC‐anti‐TNFs in the second‐line setting. Median treatment persistence was 40 months tocilizumab (95% CI: 30‐ND), 33 months abatacept (95% CI: 20‐ND); 22 months SC‐anti‐TNF (95% Cl: 18–27), and 4 months infliximab (95% CI: 2–13). Longer persistence was observed for SC‐anti‐TNFs and abatacept combined with methotrexate or other cDMARDs. For tocilizumab, persistence was robust with or without concomitant medications. The median oral glucocorticoid doses decreased from 4.1 mg/day (min 0, max 21) to 2.0 mg/day (min 0, max 17.3) over 2 years. Conclusions: Treatment persistence was longer on tocilizumab followed by abatacept then SC‐anti‐TNF therapy and was influenced by co‐therapy. Glucocorticoid dosage decreased with bDMARD use. This real‐world data highlights that persistence on bDMARDs differs according to biologics mode of action and co‐therapy. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy and safety of lesinurad in combination with febuxostat in a 12-month phase III trial in patients with tophaceous gout. Methods Patients with serum urate (UA) ≥8.0 mg/dl (≥6.0 mg/dl with urate-lowering therapy) and ≥1 measurable target tophus were given febuxostat 80 mg/day for 3 weeks before randomization to receive lesinurad (200 or 400 mg daily) or placebo in addition to the febuxostat. The primary end point was the proportion of patients achieving a serum UA level of <5.0 mg/dl (month 6). The key secondary end point was the proportion of patients with complete resolution of ≥1 target tophus (month 12). Other end points included the percentage change in total target tophi area. Safety assessments included adverse events and laboratory data. Results Patients (n = 324) were predominantly male, with a mean age of 54.1 years. Significantly more patients achieved the serum UA target by month 6 with the addition of lesinurad 400 mg (76.1%; P < 0.0001), but not 200 mg (56.6%; P = 0.13), to the febuxostat therapy as compared with febuxostat alone (46.8%). At all other time points, significantly more patients in the lesinurad 200 mg group achieved the serum UA target. The number of patients with complete tophus resolution was not different between groups. Treatment with lesinurad (200 mg and 400 mg) plus febuxostat reduced the total target tophi area as compared with febuxostat alone (50.1% and 52.9% versus 28.3%, respectively; P < 0.05). Safety was generally comparable with that of febuxostat alone, except for higher rates of predominantly reversible elevations in the serum creatinine level, particularly with lesinurad 400 mg. Conclusion Treatment with lesinurad in combination with febuxostat demonstrated superior lowering of serum UA levels as compared with febuxostat alone, with clinically relevant added effects on tophi and an acceptable safety profile with lesinurad 200 mg in patients with tophaceous gout warranting additional therapy. [ABSTRACT FROM AUTHOR]

Importance: Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis, but current trial evidence is contradictory.Objective: To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels.Design, Setting, and Participants: A multicenter randomized, double-blind, placebo-controlled clinical trial in Tasmania and Victoria, Australia. Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D (12.5-60 nmol/L) were enrolled from June 2010 to December 2011. The trial was completed in December 2013.Interventions: Participants were randomly assigned to receive monthly treatment with oral vitamin D3 (50,000 IU; n = 209) or an identical placebo (n = 204) for 2 years.Main Outcomes and Measures: Primary outcomes were change in tibial cartilage volume (assessed using magnetic resonance imaging [MRI]) and change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score (0 [no pain] to 500 [worst pain]) from baseline to month 24. Secondary outcomes were cartilage defects and bone marrow lesions (assessed using MRI).Results: Of 413 enrolled participants (mean age, 63.2 years; 50% women), 340 (82.3%) completed the study. The level of 25-hydroxyvitamin D increased more in the vitamin D group (40.6 nmol/L) than in the placebo group (6.7 nmol/L) (P < .001) over 2 years. There were no significant differences in annual change of tibial cartilage volume or WOMAC pain score. There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions. Adverse events (≥ 1 per patient) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group (P = .04). [table: see text].Conclusions and Relevance: Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels, vitamin D supplementation, compared with placebo, did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years. These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis.Trial Registration: clinicaltrials.gov Identifier: NCT01176344; anzctr.org.au Identifier: ACTRN12610000495022. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the leading musculoskeletal cause of disability. Despite this, there is no consensus on the precise definition of OA and what is the best treatment to improve symptoms and slow disease progression. Current pharmacological treatments include analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX) inhibitors. None of those treatments are disease-modifying agents that target the core pathological processes in OA. Diacerein, a semi-synthetic anthraquinone derivative, inhibits the interleukin-1-beta (IL-1β) cytokine which, according to animal studies, plays a key role in the pathogenesis of OA. Diacerein was synthesized in 1980 and licensed in some European Union and Asian countries for up to 20 years. It has shown modest efficacy and acceptable tolerability in a number of trials of low to moderate quality. Early this year, the European Medicines Agency (EMA) conducted a review and restricted the use of diacerein-containing medicines. This was because of major concerns about the frequency and severity of diarrhoea and liver disorders in OA patients. In addition, the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) questioned the limited clinical benefits of diacerein, which, in their view, did not outweigh its risks. The aim of this review is to provide a benefit-risk assessment of diacerein in the treatment of OA, based on asystematic evaluation of the published efficacy and safety data. Overall, there is evidence that diacerein is modestly effective for symptoms and possibly for radiographic changes, but this needs to be balanced against higher rates of gastrointestinal toxicity. [ABSTRACT FROM AUTHOR]

University Hospitals Southampton NHS Foundation Trust aspires to be a national leader in the reduction of healthcare associated infections (HCAIs). The need to further improve patient safety requires continual improvements in infection control practice in order to sustain high quality and safe patient care. To help achieve this, an infection prevention ward accreditation scheme was introduced across the trust in 2009. The accreditation scheme was initially based on the results of clinical wards'/areas' infection prevention audits, aiming to motivate wards to achieve success and support areas to identify and address gaps in compliance. The ward accreditation scheme acts as a certification of best practice and policy compliance related to reducing HCAIs. Since its introduction four years ago, the ward accreditation programme has been expanded and developed to incorporate other elements of infection prevention policy and practice and continues to be developed in order to drive the trust forward as leaders in infection prevention. The introduction and ongoing development of the accreditation scheme has encouraged healthy competition, aiding local ownership and driving forward improvements, and with this, the trust has significantly reduced infection rates over the last four years. [ABSTRACT FROM AUTHOR]

Objective Obesity is characterized by hyperleptinaemia, which is associated with diabetes, hypertension and coronary heart disease. The aim of this study was to determine if body fat and muscle measures predict the natural increase in leptin over 2·6 years in older adults. Methods A total of 190 subjects (50% females) aged between 50 and 79 years were selected to perform the serum measurements for leptin. Height and weight were measured and body mass index ( BMI) was calculated. Fat and lean mass of the whole body and the trunk were acquired through dual-energy X-ray absorptiometry ( DXA). Leg muscle strength and handgrip strength were measured using dynamometry. Results In multivariable analyses, leg muscle strength was negatively associated with both baseline leptin (β: −0·05 μg/l per kg, 95% CI: −0·08, −0·02) and follow-up leptin (β: −0·04 μg/l per kg, 95% CI: −0·07, −0·01). BMI, and percentage total fat and trunk fat and their respective change per annum (cpa) were significantly and positively associated with leptin. Lean mass was negatively associated with baseline leptin. Gender-specific analyses produced similar associations between leg muscle strength, fat measures and follow-up leptin in males and females. Conclusion Besides positive associations between body fat, trunk fat and leptin, we found that leg muscle strength was negatively associated with leptin after 2·6 years in a sample of older population. This suggests that interventions to maintain or increase muscle strength may have a protective effect on hyperleptinaemia. [ABSTRACT FROM AUTHOR]

Pain in osteoarthritis is multifactorial, but a disconnect between radiographic features and symptoms hampers our understanding of pain. New imaging data suggest that pain arises from virtually all structures in the joint and that cartilage loss is only a minor contributor to pain symptoms but is important for disease progression. [ABSTRACT FROM AUTHOR]

Objectives. There have been no reported studies of the association between parity and cartilage in young individuals. The aim of this study was to describe the association between parity, cartilage volume and cartilage defects in women aged 31–41 years.Methods. Cross-sectional study of 144 women, mean age 36 years and BMI 25 kg/m2, who were participants in an established prospective study. Parity was assessed using a questionnaire. Knee (medial tibial, lateral tibial and patellar) cartilage volume, cartilage defects (grade 0–4 depending on the severity of cartilage thickness loss at tibial and patellar sites) and tibial bone area were assessed using T1-weighted fat-suppressed MRI.Results. The prevalence of cartilage defects (grade &geq;2) in this population was 13%. Parity was associated with a higher risk of cartilage defects at the patellar [prevalence ratio (PR) per birth 1.52, 95% CI 1.05, 2.21; PR parous vs nulliparous 1.93, 95% CI 0.66, 5.65], but not tibial sites, after adjustment for confounders including age, BMI, smoking, physical activity, knee injury and tibial bone area. This association between parity and patellar cartilage defects was stronger for those women who had three or more births (vs nulliparous, PR 5.27, 95% CI 1.39, 20.01). There were no significant associations between parity and cartilage volume.Conclusion. Parity was associated with knee cartilage defects primarily at the patellar site in this sample of young women. This association was more apparent with increasing number of live births, suggesting a possible adverse effect of parity on knee cartilage. [ABSTRACT FROM PUBLISHER]

Background: Osteoarthritis (OA) is a common health issue worldwide in the aging population who are also commonly deficient in vitamin D. Our previous study suggested that higher serum 25-(OH)D levels were associated with reduced knee cartilage loss, implying that vitamin D supplementation may prevent the progression of knee OA. The aim of the VItamin D Effects on OA (VIDEO) study is to compare, over a 2- year period, the effects of vitamin D supplementation versus placebo on knee structural changes, knee pain, and lower limb muscle strength in patients with symptomatic knee OA. Methods/design: Randomised, placebo-controlled, and double-blind clinical trial aiming to recruit 400 subjects( 200 from Tasmania and 200 from Victoria) with both symptomatic knee OA and vitamin D deficiency (serum [25-(OH)D] level of >12.5 nmol/liter and <60 nmol/liter). Participants will be randomly allocated to vitamin D supplementation (50,000 IU compounded vitamin D3 capsule monthly) or identical inert placebo group for 2 years. The primary endpoint is loss of knee cartilage volume measured by magnetic resonance imaging (MRI) and Western Ontario and McMaster Universities Index of OA (WOMAC) knee pain score. The secondary endpoints will be other knee structural changes, and lower limb muscle strength. Several other outcome measures including core muscle images and central blood pressure will be recorded. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modeling analyses. Both intention to treat and per protocol analyses will be utilized. Discussion: The trial is designed to test if vitamin D supplementation will reduce loss of knee cartilage volume, prevent the progression of other knee structural abnormalities, reduce knee pain and strengthen lower limb muscle strength, thus modify disease progression in knee OA. [ABSTRACT FROM AUTHOR]

The assessment of bone in children is more difficult than in adults mainly due to the effect of growth and/or puberty. Despite this, there is an increasing body of evidence showing that measurement of different components of bone is of clinical relevance. Fracture incidence peaks during the early teenage years, and dual energy X-ray absorptiometry (DXA) has been shown to predict fractures in children, especially those of the upper limb, in four prospective studies. Case control and cross-sectional studies have also shown similar associations for peripheral quantitative computed tomography (pQCT), heel ultrasound, metacarpal index, and skeletal age deviation. In some cases, these latter results are additive to DXA suggesting a multifaceted approach to bone assessment in children will lead to greater information. Size or age adjusted Z scores are mandatory for the interpretation of DXA in children. However, other modalities such as heel ultrasound are less affected by growth. Lastly, children have very high bone turnover in comparison to adults but markers of bone turnover also have clinical utility for linear growth, assessment of the impact of vitamin D deficiency and assessment of short term influences on bone such as diet. [ABSTRACT FROM AUTHOR]

Recent years have seen many exciting developments in the treatment of rheumatoid arthritis. Tocilizumab (TCZ) is a monoclonal antibody which inhibits the interleukin-6 receptor. After initial studies in Japan, it has been extensively studied in five multicentre clinical trials. This report summarises the key efficacy and toxicity findings from the major clinical trials. TCZ works quickly and effectively in rheumatoid arthritis either as monotherapy or in combination with other agents in early disease, DMARD inadequate responders, seronegative disease and after anti-TNF failure. The toxicity profile is manageable but includes infections (most notably skin and soft tissue), increases in serum cholesterol, transient decreases in neutrophil count and abnormal liver function tests (especially in combination with methotrexate). In summary, there is sufficient evidence to make TCZ a first line biologic therapy for rheumatoid arthritis especially for those who are unable to take methotrexate or who fail anti-TNF therapy. [ABSTRACT FROM AUTHOR]

Background: There have been few studies examining the associations between menstrual irregularity, androgens and bone mass in population-based samples of premenopausal women. This study aimed to describe the associations between menstrual pattern, testosterone, sex hormone binding globulin (SHBG) and bone mass in a population-based sample of premenopausal women. Methods: Cross-sectional study (N = 382, mean age 31.5 years). Menstrual pattern was assessed by questionnaire, bone mass measured by quantitative ultrasound (QUS) and androgen status was assessed by levels of serum testosterone, SHBG and the free androgen index (FAI). Results: Women with irregular cycles (n = 41, 11%) had higher free androgen index (FAI, P = 0.01) and higher QUS measurements including speed of sound (SOS, 1%, P < 0.05), quantitative ultrasound index (QUI, 7%, p < 0.05), and broadband ultrasound attenuation (BUA, 7%, p = 0.10). These associations persisted after adjustment for age and body mass index (BMI). After further adjustment for hormonal factors (either testosterone, SHBG or FAI), the strength of the associations was moderately attenuated, however, women with irregular cycles still had a 6% increase in mean QUS. Total testosterone, FAI and SHBG were also associated with QUS measures (testosterone and FAI, r +0.11 to +0.21, all p < 0.05; SHBG r -0.14 to -0.16, all p < 0.05) and the associations remained significant after adjustment. Conclusion: Irregular menstrual cycles were associated with higher bone mass in this population-based sample of premenopausal women suggesting menstrual disturbance should continue to be evaluated but may be less harmful for bone mass. The association between menstrual irregularity and bone mass was partially mediated by markers of androgen status especially free testosterone. [ABSTRACT FROM AUTHOR]

During this time, the understanding of the pathophysiology of osteoarthritis has markedly increased; however, this increased understanding has not yet translated into improved treatment.[1] In fact, there are still few available treatments for osteoarthritis, the most prevalent joint disease worldwide. In The Lancet, Féline Kroon and colleagues[10] report the results of their double-blind, randomised, placebo-controlled trial of daily 10 mg prednisolone in patients with hand osteoarthritis. 10 FPB Kroon, MC Kortekaas, A Boonen, Results of a 6-week treatment with 10 mg prednisolone in patients with hand osteoarthritis (HOPE): a double-blind, randomised, placebo-controlled trial. [Extracted from the article]

Effective therapies for the treatment of osteoporosis and fracture have been available for a number of years. Despite this, there are numerous reports indicating very low uptake rates in those admitted to hospital with fracture. The aim of this retrospective audit was to assess the impact of a fracture protocol on inpatient prescriptions of osteoporosis therapy. A fracture protocol was arrived at by consensus and was based on recommendations from the Australian Fracture Prevention Summit, which included specific advice on the commencement in hospital of calcium, vitamin D, synthetic estrogen receptor modulators (SERMs) and bisphosphonates. We studied subjects who were treated for fractured neck of the femur at Royal Hobart Hospital from March 2002 to March 2004 and included 161 prior to the start of the protocol and 93 after. As compared to the baseline period, subjects after the introduction of the protocol had higher rates of in-hospital prescription for any treatment (58 vs. 36%, P <0.01), calcium (51 vs. 26%, P <0.01), vitamin D (48 vs. 29%, P <0.01) and oral bisphosphonates (24 vs. 5%, P <0.01), but not SERMs as expected (1 vs. 1%, P =0.70). Additional factors affecting the decision to start any treatment included in-hospital death (OR 0.16, 95% CI 0.05–0.49), dementia (OR 0.39, 95% CI 0.21–0.74), a trend for female sex (OR 1.79, 95%CI 0.96–3.36), but not age. In conclusion, a structural approach to changing hospital policy from the top down is effective at substantially increasing the usage of effective therapy after fractured neck of the femur. [ABSTRACT FROM AUTHOR]

Objective: To understand and address students’ concerns about attending one of the new Commonwealth-funded Rural Clinical Schools. Design: Analysis of students’ reported reasons for clinical school selection from 2003 to 2004. Setting: The School of Medicine and the Rural Clinical School, University of Melbourne. Participants: Data were obtained from de-identified preference documents submitted by the medical student cohort assigned to the University of Melbourne clinical schools to begin in July, 2004. Results: Thirteen categories of student concerns (social) were identified from written student preference documents. Conclusions: Evaluation of the students’ concerns about social dislocation if they were assigned to a rural clinical school has provided important information about perceived barriers to rural training. These issues must be systematically addressed at the school, university and community level. [ABSTRACT FROM AUTHOR]

In social insects, recognition of nestmates from aliens is based on olfactory cues, and many studies have demonstrated that such cues are contained within the lipid layer covering the insect cuticle. These lipids are usually a complex mixture of tens of compounds in which aliphatic hydrocarbons are generally the major components. The experiments described here tested whether artificial changes in the cuticular profile through supplementation of naturally occurring alkanes and alkenes in honeybees affect the behaviour of nestmate guards. Compounds were applied to live foragers in microgram quantities and the bees returned to their hive entrance where the behaviour of the guard bees was observed. In this fashion we compared the effect of single alkenes with that of single alkanes; the effect of mixtures of alkenes versus that of mixtures of alkanes and the whole alkane fraction separated from the cuticular lipids versus the alkene fraction. With only one exception (the comparison between n-C19 and (Z)9-C19), in all the experiments bees treated with alkenes were attacked more intensively than bees treated with alkanes. This leads us to conclude that modification of the natural chemical profile with the two different classes of compounds has a different effect on acceptance and suggests that this may correspond to a differential importance in the recognition signature. [ABSTRACT FROM AUTHOR]

There are limited data on vitamin D insufficiency in healthy children. The aim of this study was to describe the prevalence and determinants of vitamin D insufficiency and its association with bone turnover in adolescent boys (N=136, mean age 16 years). Sun exposure and physical activity were assessed by questionnaire. Vitamin D stores were assessed by serum 25-hydroxyvitamin D3 (25[OH]D3). Bone turnover was assessed by bone-specific alkaline phosphatase (BAP) and urinary pyridinoline (PYR) to creatinine (Cr) ratio (mmol PYR/µmol Cr). The mean 25(OH)D3 level was low (44 nmol/l; 68%<50 nmol/l; range, 16-87) and was associated with self-reported sun exposure on winter weekends (r=0.23,p=0.01), school holidays (r=0.22,p=0.01), and weekdays (r=0.17,p=0.05). It was also associated with number of sports (r=0.34,p<0.001) and vigorous activity (r=0.22,p=0.01) but not television, computer, and video watching (r=-0.04,p=0.68). In multivariate analysis, number of sports but not total sun exposure remained significantly associated with 25(OH)D3. Furthermore, 25(OH)D3 was significantly associated with BAP in cutpoint analysis (cutpoint 55 nmol/l,p=0.03) but not continuous analysis (r=-0.12,p=0.16) and PYR in both forms (r=-0.23,p=0.01, cutpoint 43 nmol/l,p=0.01). In conclusion, vitamin D insufficiency is common in healthy adolescent boys in winter in our setting, is primarily derived from sports-related sun exposure, and is associated with bone turnover markers. These data suggest that a 25(OH)D3 level of at least 43-55 nmol/l is required for optimal bone health in children. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this population-based case-control study was to describe the association among skeletal age deviation (SAD), bone density, and upper limb fracture risk in male and female children aged 9–16 years. A total of 321 fracture cases and 321 randomly selected individually matched controls were studied. Skeletal age was assessed by standard atlas. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) and metacarpal index (MI). There were no significant differences in mean skeletal age or chronological age between fracture cases and controls. However, SAD was associated with total, hand, and female fracture risk (all P &#60; 0.05). The fracture associations became nonsignificant after adjustment for BMD and MI in all subgroups with the exception of hand fractures (OR, 0.67/year; 95% CI, 0.47–0.96). SAD was also positively associated with BMD at all sites (r = 0.33–0.35, all P &#60; 0.05) and MI (r = 0.20, P &#60; 0.05). The strength of association reduced but remained significant at most sites after adjustment for body size, maturity, age, and sex. In conclusion, SAD is positively associated with measures of bone strength and negatively associated with upper limb fracture risk (especially those of the hand) in children. SAD is simple to measure and gives additional information regarding bone health and fracture risk in children. [Copyright &y& Elsevier]

Despite worker-laid and queen-laid honeybee eggs having significantly different hydrocarbon profiles, bioassays and chemical supplementation studies show that changing the hydrocarbon profile does not affect egg identity. Furthermore, full-sized eggs that are tested just before being laid or just after being laid have similar hydrocarbon patterns but are treated differently in egg-discrimination bioassays with only the laid eggs surviving. This suggests that hydrocarbons play no role in the egg-recognition system in honeybees. [ABSTRACT FROM AUTHOR]

To assess the extent of undergraduate health student placements in regional hospitals in northern Victoria in 1999, prior to substantial changes in rural undergraduate medical education in Australia. Cross sectional postal survey with telephone follow-up in north-east Victoria. Subjects were all 17 regional and rural hospitals involved in health student teaching in North-east Victoria. Main outcome measures were the numbers, duration and discipline of health students placements and reported barriers to such placements. Large regional hospitals accounted for two-thirds of all undergraduate health student placements. Smaller sites placed few allied health students. Barriers to a larger, more sustainable system of rural placements and rotations included accommodation shortages and funding constraints, particularly in smaller rural hospitals. Adequate resourcing of placements of a meaningful duration, stronger institutional support, and improved resourcing of regional accommodation is required to facilitate a larger, more systematic and sustainable system of medical and health student placements in rural areas. The extent of training of health professionals in rural Australia is increasing rapidly. Fears have been expressed that the capacity to deliver quality experience in rural practice may be limited. This cross sectional survey of rural Victorian hospitals shows that there is a major untapped potential in rural hospitals of all sizes to assist with training in rural practice, but that a number of barriers to such training need to be removed to reach full capacity. [ABSTRACT FROM AUTHOR]

Studies the association between individual meningococcal antigens and the development of protective immunity to both serogroup C and B meningococci before and during an outbreak of serogroup C infection among university students. Levels of bactericidal activity against the outbreak strain; Development of bactericidal activity among patients who survived infection.

Determines the prevalence of vertebral deformity in patients receiving long-term corticosteroid therapy. Risk factors; Comparison of the chance of vertebral deformity among young and older patients; Comparison of lumbar spine and femoral neck deformity in steroid versus non-steroid group.

Registration of remote imagery underpins a number of important applications in 'remote sensing' including mosaicing, sensor fusion, temporal change detection and integration with GIS databases. Accurate and automatic methods of establishing dense correspondences between images are vital given the increasing volume of high resolution imagery available. An explicit 'structural matching' framework is presented derived from the experience in the wider computer vision community of matching in a variety of domains including stereopsis, motion and object recognition. Match constraints can be combined within an optimization framework enabling the exploitation of a variety of minimization techniques. In this work, a multi-resolution representation of coastline contours is used to enable matching to handle very large scale difference between images, and to reduce the dimensionality of the match problem. Nonetheless, the resultant optimization problem remains huge and highly non-convex necessitating the use of 'genetic algorithms' to recover accurate correspondences. [ABSTRACT FROM AUTHOR]

Studies the lack of immunity in university students before an outbreak of serogroup C meningococcal infection. Natural immunity to meningococcal infection prior to an outbreak; Lack of bactericidal activity against the outbreak strain; Factors that predict higher rates of meningococcal carriage.

Objective: To determine the effect of zoledronic acid (ZA) on the risk of total knee replacement (TKR) in patients with symptomatic knee osteoarthritis and without severe joint space narrowing (JSN). Methods: We included 222 participants (mean age 62 years, 52% female) from the two‐year Zoledronic Acid for Osteoarthritis Knee Pain trial (113 received 5 mg of ZA annually and 109 received placebo) conducted between November 2013 and October 2017. Primary TKR were identified until February 22, 2022. The effect of ZA on TKR risk was evaluated using Cox proportional hazard regression models. Because the treatment effect failed the proportional hazards assumption, a time‐varying coefficients analysis for treatment was conducted by splitting the study into two periods (ie, within and after two years of randomization). Results: Over a mean follow‐up of seven years, 39% and 30% of participants had any TKR in the ZA and placebo groups, and 28% and 18% had TKR in the study knee, respectively. Use of ZA was associated with a higher risk of TKR in any knee (hazard ratio [HR] 4.2, 95% confidence interval [CI] 1.2–14.7) and showed a trend in the study knee (HR 6.8, 95%CI 0.9–53.9) during the trial. In the posttrial period, the risk of TKR was similar in the ZA and the placebo groups for any knee (HR 1.2, 95%CI 0.5–1.8) and the study knee (HR 1.4, 95%CI 0.5–2.2). Conclusion: These results suggest that ZA is not protective against TKR in patients with symptomatic knee osteoarthritis and without severe JSN. [ABSTRACT FROM AUTHOR]

Key Points: Question: In people with knee osteoarthritis who have significant knee pain and effusion-synovitis present on magnetic resonance imaging, does krill oil supplementation, compared with placebo, improve knee pain? Findings: In this randomized clinical trial that included 262 adults, compared with placebo, 2 g/d of krill oil supplementation did not improve knee pain as measured on a visual analog scale (range, 0-100, with 0 indicating least pain) (mean difference, 0.30; 95% CI, −6.9 to 6.4; P =.94) over 24 weeks. Meaning: This study does not support 2 g/d of krill oil supplementation for improving knee pain in people with knee osteoarthritis who have significant knee pain and effusion-synovitis. Importance: Knee osteoarthritis is disabling, with few effective treatments. Preliminary evidence suggested that krill oil supplementation improved knee pain, but effects on knee osteoarthritis remain unclear. Objective: To evaluate efficacy of krill oil supplementation, compared with placebo, on knee pain in people with knee osteoarthritis who have significant knee pain and effusion-synovitis. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled clinical trial in 5 Australian cities. Participants with clinical knee osteoarthritis, significant knee pain, and effusion-synovitis on magnetic resonance imaging were enrolled from December 2016 to June 2019; final follow-up occurred on February 7, 2020. Interventions: Participants were randomized to 2 g/d of krill oil (n = 130) or matching placebo (n = 132) for 24 weeks. Main Outcomes and Measures: The primary outcome was change in knee pain as assessed by visual analog scale (range, 0-100; 0 indicating least pain; minimum clinically important improvement = 15) over 24 weeks. Results: Of 262 participants randomized (mean age, 61.6 [SD, 9.6] years; 53% women), 222 (85%) completed the trial. Krill oil did not improve knee pain compared with placebo (mean change in VAS score, −19.9 [krill oil] vs −20.2 [placebo]; between-group mean difference, −0.3; 95% CI, −6.9 to 6.4) over 24 weeks. One or more adverse events was reported by 51% in the krill oil group (67/130) and by 54% in the placebo group (71/132). The most common adverse events were musculoskeletal and connective tissue disorders, which occurred 32 times in the krill oil group and 42 times in the placebo group, including knee pain (n = 10 with krill oil; n = 9 with placebo), lower extremity pain (n = 1 with krill oil; n = 5 with placebo), and hip pain (n = 3 with krill oil; n = 2 with placebo). Conclusions and Relevance: Among people with knee osteoarthritis who have significant knee pain and effusion-synovitis on magnetic resonance imaging, 2 g/d of daily krill oil supplementation did not improve knee pain over 24 weeks compared with placebo. These findings do not support krill oil for treating knee pain in this population. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12616000726459; Universal Trial Number: U1111-1181-7087 This randomized clinical trial assesses the effect of krill oil supplementation vs placebo on knee pain improvement in patients with knee osteoarthritis, significant knee pain, and effusion-synovitis. [ABSTRACT FROM AUTHOR]

Explains how signal representation of 1-D signals in the time-frequency plane may be interpreted. Instantaneous parameters and their application to non-stationary signal analysis; Generalized instantaneous parameters in time-frequency distributions; Concepts of window matching in the time-frequency plane; Algorithm to generate an Adaptive Energy Distribution (AED); Application of AED to synthetic and real signals; Conclusions.

Presents an article from the `Physical Therapy' periodical, which reviews and analyzes the role of vision and spatial orientation in maintaining posture and balance. Factors in the development of posture; Relationship between posture and voluntary movement; Importance of spatial orientation.

Objective To summarize effects of intravenous bisphosphonates (IVBP) in patients with symptomatic knee OA and bone marrow lesions (BMLs), using a meta-analysis of randomized controlled trials (RCTs). Methods Literature databases were searched for placebo-controlled RCTs of IVBPs for knee OA from inception, and included validated pain and function scales, BML size and incidence of adverse events. Efficacy was compared using standardized mean differences (SMD) and risk ratios (RR) with fixed-effect or random-effects models. Methodological quality was assessed using the Cochrane risk of bias tool, heterogeneity was assessed by I 2 statistics. Results We included 428 patients in four RCTs of 2–24 months duration; most patients (84%) received zoledronic acid (ZA). Risk of bias was low-moderate. IVBP had large effect sizes on pain within 3 months [SMD = − 2.33 (95% CI: − 3.02, − 1.65)] mainly driven by neridronate (resulting in substantial heterogeneity, I 2 = 92%) with no effect for ZA alone. Differences in knee function were statistically significant at 3 months [SMD = − 0.22 (− 0.43, − 0.01), I 2 = 0.2%]. Effect sizes for pain did not reach statistical significance at any other time point. IVBPs improved a semi-quantitative measure of BML size within 6 months [SMD = − 0.52 (− 0.89, − 0.14), I 2 = 0%] but not at 12 months or two years. Adverse events [RR = 1.19 (1.00, 1.41) I 2 = 52%], occurred more frequently with IVBP. Conclusion ZA has no effect on knee pain, possibly a short-term effect on BML size and higher rates of adverse events. Neridronate may improve pain in the short term, but this is based on a single trial. [ABSTRACT FROM AUTHOR]

Background: Hand osteoarthritis is a common and disabling problem without effective therapies. Accumulating evidence suggests the role of local inflammation in causing pain and structural progression in hand osteoarthritis, and hand osteoarthritis with synovitis is a commonly encountered clinical phenotype. Methotrexate is a well-established, low-cost, and effective treatment for inflammatory arthritis with a well-described safety profile. The aim of this multicentre, randomised, double-blind, placebo-controlled trial is to determine whether methotrexate reduces pain over 6 months in patients with hand osteoarthritis and synovitis.Methods: Ninety-six participants with hand osteoarthritis and synovitis will be recruited through the Osteoarthritis Clinical Trial Network (Melbourne, Hobart, Adelaide, and Perth), and randomly allocated in a 1:1 ratio to receive either methotrexate 20 mg or identical placebo once weekly for 6 months. The primary outcome is pain reduction (assessed by 100 mm visual analogue scale) at 6 months. The secondary outcomes include changes in physical function and quality of life assessed using Functional Index for Hand Osteoarthritis, Australian Canadian Osteoarthritis Hand Index, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, Short-Form-36, tender and swollen joint count, and grip strength, and structural progression assessed using progression of synovitis and bone marrow lesions from magnetic resonance imaging and radiographic progression at 6 months. 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 address whether methotrexate has an effect on reducing pain over 6 months in patients with hand osteoarthritis and synovitis, with major clinical and public health importance. While a positive trial will inform international clinical practice guidelines for the management of hand osteoarthritis, a negative trial would be highly topical and change current trends in clinical practice.Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000877381. Registered 15 June 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373124. [ABSTRACT FROM AUTHOR]

Objectives To describe associations between MRI markers with knee symptoms in young adults. Methods Knee symptoms were assessed using the WOMAC scale during the Childhood Determinants of Adult Health Knee Cartilage study (CDAH-knee; 2008–2010) and at the 6- to 9-year follow-up (CDAH-3; 2014–2019). Knee MRI scans obtained at baseline were assessed for morphological markers (cartilage volume, cartilage thickness, subchondral bone area) and structural abnormalities [cartilage defects and bone marrow lesions (BMLs)]. Univariable and multivariable (age, sex, BMI adjusted) zero-inflated Poisson (ZIP) regression models were used for analysis. Results The participants' mean age in CDAH-knee and CDAH-3 were 34.95 (s. d. 2.72) and 43.27 (s. d. 3.28) years, with 49% and 48% females, respectively. Cross-sectionally, there was a weak but significant negative association between medial femorotibial compartment (MFTC) [ratio of the mean (RoM) 0.99971084 (95% CI 0.9995525, 0.99986921), P  < 0.001], lateral femorotibial compartment (LFTC) [RoM 0.99982602 (95% CI 0.99969915, 0.9999529), P  = 0.007] and patellar cartilage volume [RoM 0.99981722 (95% CI 0.99965326, 0.9999811), P  = 0.029] with knee symptoms. Similarly, there was a negative association between patellar cartilage volume [RoM 0.99975523 (95% CI 0.99961427, 0.99989621), P  = 0.014], MFTC cartilage thickness [RoM 0.72090775 (95% CI 0.59481806, 0.87372596), P  = 0.001] and knee symptoms assessed after 6–9 years. The total bone area was negatively associated with knee symptoms at baseline [RoM 0.9210485 (95% CI 0.8939677, 0.9489496), P  < 0.001] and 6–9 years [RoM 0.9588811 (95% CI 0.9313379, 0.9872388), P  = 0.005]. The cartilage defects and BMLs were associated with greater knee symptoms at baseline and 6–9 years. Conclusion BMLs and cartilage defects were positively associated with knee symptoms, whereas cartilage volume and thickness at MFTC and total bone area were weakly and negatively associated with knee symptoms. These results suggest that the quantitative and semiquantitative MRI markers can be explored as a marker of clinical progression of OA in young adults. [ABSTRACT FROM AUTHOR]

Background Recent operational definitions of sarcopenia have not been replicated and compared in Australia and New Zealand (ANZ) populations. We aimed to identify sarcopenia measures that discriminate ANZ adults with slow walking speed (<0.8 m/s) and determine the agreement between the Sarcopenia Definitions and Outcomes Consortium (SDOC) and revised European Working Group for Sarcopenia in Older People (EWGSOP2) operational definitions of sarcopenia. Methods Eight studies comprising 8 100 ANZ community-dwelling adults (mean age ± standard deviation, 62.0 ± 14.4 years) with walking speed, grip strength (GR), and lean mass data were combined. Replicating the SDOC methodology, 15 candidate variables were included in sex-stratified classification and regression tree models and receiver operating characteristic curves on a pooled cohort with complete data to identify variables and cut points discriminating slow walking speed (<0.8 m/s). Agreement and prevalence estimates were compared using Cohen's Kappa (CK). Results Receiver operating characteristic curves identified GR as the strongest variable for discriminating slow from normal walking speed in women (GR <20.50 kg, area under curve [AUC] = 0.68) and men (GR <31.05 kg, AUC = 0.64). Near-perfect agreement was found between the derived ANZ cut points and SDOC cut points (CK 0.8–1.0). Sarcopenia prevalence ranged from 1.5% (EWGSOP2) to 37.2% (SDOC) in women and 1.0% (EWGSOP2) to 9.1% (SDOC) in men, with no agreement (CK <0.2) between EWGSOP2 and SDOC. Conclusions Grip strength is the primary discriminating characteristic for slow walking speed in ANZ women and men, consistent with findings from the SDOC. Sarcopenia Definitions and Outcomes Consortium and EWGSOP2 definitions showed no agreement suggesting these proposed definitions measure different characteristics and identify people with sarcopenia differently. [ABSTRACT FROM AUTHOR]

We examined the longitudinal associations of accelerometer-measured physical activity and sedentary time with leg muscle strength (LMS), balance, and falls in middle-aged women. This was a 5-year cohort study among 308 women aged 36–56 years. We used linear mixed-effects models to examine associations of baseline and change in accelerometer-measured sedentary time, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) with baseline and 5-year change in LMS and balance (timed up and go test [TUG], functional reach test [FRT], lateral reach test [LRT], and step test [ST]), and negative binomial/Poisson and log-binomial regression as appropriate to assess associations with falls after 5-year follow-up. Greater baseline MVPA was associated with better baseline LMS (β = 4.65 kg/SD, 95% CI: 1.37, 7.93) and TUG (β = −0.09 s/SD, 95% CI: –0.18, –0.01) but not with change in them over 5 years. Baseline MVPA was not associated with FRT at baseline but associated with a greater decrease in FRT (β = −0.87 cm/SD, 95% CI: –1.57, –0.17). Increased MVPA over 5 years was associated with less deterioration in FRT (β = 0.88 cm/SD, 95% CI: 0.14, 1.61). Increased sedentary time over 5 years was associated with a larger decrease in FRT (β = −0.82 cm/SD, 95% CI: –1.58, –0.07). Higher baseline LPA was associated with higher falls risk (IRR = 1.27, 95% CI: 1.02, 1.57). Higher baseline MVPA may benefit LMS and balance, while increasing MVPA in the medium term has little effect on change in these outcomes in mid-life. Detrimental association of LPA with falls may be due to greater exposures to environmental hazards. Highlights Our study for the first time examined the longitudinal associations of objectively measured physical activity and sedentary time with leg muscle strength, balance and falls in middle-aged women. Higher baseline moderate-to-vigorous physical activity (MVPA) may be beneficial for muscle strength and balance at baseline but increasing MVPA in the medium term has little effect on change in LMS or balance outcomes in middle-aged women. Higher baseline light physical activity (LPA) was associated with an increased risk of falls. The detrimental association of LPA with falls may be due to a greater exposure to environmental hazards in midlife, which needs to be clarified in future research. [ABSTRACT FROM AUTHOR]

The author reflects on the role of vitamin D in calcium metabolism and bone health in children, wherein he thinks can also be postulated to contribute to non-bone conditions like respiratory illnesses, atopy, and schizophrenia.

Introduction: Diabetes UK launched its online risk score www.diabetes.org.uk/riskscore - to test your risk of developing Type 2 diabetes - on 1 July 2010. Answering seven questions gives a score from 1-47, in one of four risk levels: Low, Increased, Moderate, High. If you score Moderate or High we recommend a GP blood test. The original online tool used photo testimonies of real people, representing the four risk levels, in pop-ups after answering each question, and with the result. Aims and objectives: We planned a major outdoor and online advertising campaign in autumn 2013 to encourage people to see their GP or take the test online. To optimise the test, we commissioned 1-1 user research, focusing on the most at-risk C2DE socio-economic groups. This told us we had to improve the online test. Some changes were technology-based (eg advent of touchscreens, responsive mobile) but most were from learning how people used the tool. Our redesign addressed the following issues. - Users did not measure their weight or waist size. Exacerbated on mobile devices, without access to tape measure or scales - so needing a reminder for mobile users to re-take the test at home. - Usability issues - eg unable to operate 'slider' controls on touchscreens. - Some just used sliders to estimate a position on a general 'low to high' scale. This under-reporting meant many users would be scoring too low and being placed in the wrong risk band. - Users were in 'test mode' while taking the test, expecting to work their way through questions quickly without distraction - not in 'learning mode', and tended to ignore or resent pop-ups. - Disappointed by brevity of promised 'full report', expecting fuller, personalised information and more compelling, practical information about next steps. - Thought email/social sharing meant results would be shared, not simply the test. - Would friends/family find it offensive - suggesting they were unhealthy/overweight? Results: We saw immediate improvement in usage and referral figures following the redesign. The risk score records every completed test, displaying this on a homepage counter. More detailed reporting was introduced in May 2011, so we only have a breakdown from year two onwards. The relaunched test saw more uses (29,500) in the two weeks of the ad campaign, than it saw in the previous three months (25,000). But even without advertising to support it, we have seen more uses (105,500) in less than six months since the end of the campaign than we saw in the whole first year (100,000). Conclusions: In the six months since relaunch, from 135,000 tests, the online risk score has referred 35,282 people at the highest risk of Type 2 diabetes to their GPs. This compares with 28,833 people referred after 175,000 tests in the previous 27 months, and shows the benefits of the user-centred redesign, supported by focused audience research, and a boost from advertising. Significantly, the proportion of people being referred increased from 16.5% to 26%, which suggests that the redesign reduced the amount of under-reporting. [ABSTRACT FROM AUTHOR]

Background: Previous studies have been inconsistent concerning the association between smoking and risk of osteoarthritis (OA). This study aimed to explore the associations of smoking status and change in cartilage volume of OA in two longitudinal cohorts. Methods: Subjects from the Osteoarthritis Initiative cohort (OAI, n = 593) and the Tasmanian Older Adult Cohort (TASOAC, n = 394) were included in this study. For both cohorts, participants were classified into three groups based on their smoking status, namely 'never', 'former', and 'current' smokers. The outcome measures were the annual rate of change of tibiofemoral cartilage volume over 2 years in OAI and of tibial cartilage volume over 2.6 years in TASOAC. Potential confounders were balanced using the inverse probability of treatment weighting (IPTW) method. Results: Overall, 42.3% and 37.4% of participants were former smokers, and 5.7% and 9.3% were current smokers in the OAI and TASOAC cohorts, respectively. Compared to never smokers, neither former nor current smoking was associated with risk of the annual rate of change of tibiofemoral cartilage volume in OAI (former smoker: β=-0.068%/year, 95% confidence interval [CI] -0.824 to 0.688, p = 0.860; current smoker: β=-0.222%/year, 95% CI -0.565 to 0.120, p = 0.204) and tibial cartilage volume in TASOAC (former smoker: β = 0.001%/year, 95% CI -0.986 to 0.989, p = 0.998; current smoker: β=-0.839%/year, 95% CI -2.520 to 0.844, p = 0.329). Conclusions: Our findings from two independent cohorts consistently showed that smoking was not associated with knee cartilage loss in older adults. [ABSTRACT FROM AUTHOR]

The authors reflect on the cardiovascular risks of calcium supplementation in older women and on research which has examined the use of calcium supplements in older women. They suggest that the increased risk of myocardial infarction associated with calcium supplementation outweighs a proven reduction in fracture that has been associated with calcium supplementation. They argue that based on available evidence it seems prudent to only use calcium supplementation in patients who are also being given treatment for osteoporosis with drugs including bisphopsphonates.

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]