The association of comorbidities with sleep quality among Australians with multiple sclerosis: Insights from the Australian Multiple Sclerosis Longitudinal Study.

BACKGROUND: Comorbidities and poor sleep quality are prevalent among individuals with multiple sclerosis (MS). Our understanding of the effects of comorbidities on sleep quality in MS remains limited. OBJECTIVES: The objectives were to investigate whether the number and presence of specific comorbidities have associations with sleep quality and to assess the relative contribution of comorbidity groups to sleep quality. METHODS: We collected data on sleep quality (using Pittsburgh Sleep Quality Index (PSQI)) and presence of comorbidities in people with MS (n = 1597). Associations between comorbidities and sleep quality were examined using linear regression and dominance analysis. RESULTS: Having more comorbidities was associated with poorer sleep quality (p for trend < 0.001). All 13 groups of comorbidities explained 12.9% of the variance in PSQI from which half of the variance was contributed by mental health disorders. In total, 16 of the 28 comorbidities were associated with significantly worse sleep quality, with the strongest associations seen for 'other autoimmune diseases' (ß = 1.98), depression (ß = 1.76), anxiety (ß = 1.72) and rheumatoid arthritis (ß = 1.62). CONCLUSIONS: Many individual comorbidities are associated with poorer sleep quality, with mental health disorders making the largest relative contribution. Optimal management of comorbidities that make the greatest contributions could have the largest benefit for improving sleep in MS.

Experiences of participants in the co-design of a community-based health service for people with high healthcare service use.

BACKGROUND: Incorporating perspectives of health consumers, healthcare workers, policy makers and stakeholders through co-design is essential to design services that are fit for purpose. However, the experiences of co-design participants are poorly understood. The aim of this study is to explore the experiences and perceptions of people involved in the co-design of a new service for people with high healthcare service utilisation. METHODS: A methodology informed by the principles of grounded theory was used in this qualitative study to evaluate the experiences and perceptions of co-design participants. Participants were healthcare professionals, health managers and leaders and health consumers involved in the co-design of the new service in Tasmania, Australia. Semi-structured interviews were conducted, and data were iteratively and concurrently collected and analysed using constant comparative analysis. Audio/audio-visual recordings of interviews were transcribed verbatim. Transcripts, memos, and an audit trail were coded for experiences and perspectives of participants. RESULTS: There were thirteen participants (5 health professionals, 6 health managers and leaders, and 2 health consumers). Codes were collapsed into six sub-themes and six themes. Themes were bureaucracy hinders co-design, importance of consumers and diversity, importance of a common purpose, relationships are integral, participants expectations inform their co-design experience and learning from co-design. CONCLUSION: Most participants reported positive aspects such as having a common purpose, valuing relationships, and having a personal motivation for participating in co-design. However, there were factors which hindered the adaptation of co-design principles and the co-design process. Our research highlights that bureaucracy can hinder co-design, that including people with lived experience is essential and the need to consider various types of diversity when assembling co-design teams. Future co-design projects could use these findings to improve the co-design experience for participants, and ultimately the outcome for communities.

Calcium and vitamin D for increasing bone mineral density in premenopausal women.

BACKGROUND: Osteoporosis is a condition where bones become fragile due to low bone density and impaired bone quality. This results in fractures that lead to higher morbidity and reduced quality of life. Osteoporosis is considered a major public health concern worldwide. For this reason, preventive measurements need to be addressed throughout the life course. Exercise and a healthy diet are among the lifestyle factors that can help prevent the disease, the latter including intake of key micronutrients for bone, such as calcium and vitamin D. The evidence on whether supplementation with calcium and vitamin D improves bone mineral density (BMD) in premenopausal women is still inconclusive. In this age group, bone accrual is considered to be the goal of supplementation, so BMD is relevant for the future stages of life. OBJECTIVES: To evaluate the benefits and harms of calcium and vitamin D supplementation, alone or in combination, to increase the BMD, reduce fractures, and report the potential adverse events in healthy premenopausal women compared to placebo. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was 12 April 2022. SELECTION CRITERIA: We included randomised controlled trials in healthy premenopausal women (with or without calcium or vitamin D deficiency) comparing supplementation of calcium or vitamin D (or both) at any dose and by any route of administration versus placebo for at least three months. Vitamin D could have been administered as cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Outcomes included total hip bone mineral density (BMD), lumbar spine BMD, quality of life, new symptomatic vertebral fractures, new symptomatic non-vertebral fractures, withdrawals due to adverse events, serious adverse events, all reported adverse events and additional withdrawals for any reason. MAIN RESULTS: We included seven RCTs with 941 participants, of whom 138 were randomised to calcium supplementation, 110 to vitamin D supplementation, 271 to vitamin D plus calcium supplementation, and 422 to placebo. Mean age ranged from 18.1 to 42.1 years. Studies reported results for total hip or lumbar spine BMD (or both) and withdrawals for various reasons, but none reported fractures or withdrawals for adverse events or serious adverse events. Results for the reported outcomes are presented for the three comparisons: calcium versus placebo, vitamin D versus placebo, and calcium plus vitamin D versus placebo. In all comparisons, there was no clinical difference in outcomes, and the certainty of the evidence was moderate to low. Most studies were at risk of selection, performance, detection, and reporting biases. Calcium versus placebo Four studies compared calcium versus placebo (138 participants in the calcium group and 123 in the placebo group) with mean ages from 18.0 to 47.3 years. Calcium supplementation may have little to no effect on total hip or lumbar spine BMD after 12 months in three studies and after six months in one study (total hip BMD: mean difference (MD) -0.04 g/cm2, 95% confidence interval (CI) -0.11 to 0.03; I2 = 71%; 3 studies, 174 participants; low-certainty evidence; lumbar spine BMD: MD 0 g/cm2, 95% CI -0.06 to 0.06; I2 = 71%; 4 studies, 202 participants; low-certainty evidence). Calcium alone supplementation does not reduce or increase the withdrawals in the trials (risk ratio (RR) 0.78, 95% CI 0.52 to 1.16; I2 = 0%; 4 studies, 261 participants: moderate-certainty evidence). Vitamin D versus placebo Two studies compared vitamin D versus placebo (110 participants in the vitamin D group and 79 in the placebo group), with mean ages from 18.0 to 32.7 years. These studies reported lumbar spine BMD as a mixture of MDs and percent of change and we were unable to pool the results. In the original studies, there were no differences in lumbar BMD between groups. Vitamin D alone supplementation does not reduce or increase withdrawals for any reason between groups (RR 0.74, 95% CI 0.46 to 1.19; moderate-certainty evidence). Calcium plus vitamin D versus placebo Two studies compared calcium plus vitamin D versus placebo (271 participants in the calcium plus vitamin D group and 270 in the placebo group; 220 participants from Woo 2007 and 50 participants from Islam 2010). The mean age range was 18.0 to 36 years. These studies measured different anatomic areas, one study reported total hip BMD and the other study reported lumbar spine BMD; therefore, data were not pooled for this outcome. The individual studies found no difference between groups in percent of change on total hip BMD (-0.03, 95% CI -0.06 to 0; moderate-certainty evidence), and lumbar spine BMD (MD 0.01, 95% CI -0.01 to 0.03; moderate-certainty evidence). Calcium plus vitamin D supplementation may not reduce or increase withdrawals for any reason (RR 0.82, 95% CI 0.29 to 2.35; I2 = 72%; 2 studies, 541 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Our results do not support the isolated or combined use of calcium and vitamin D supplementation in healthy premenopausal women as a public health intervention to improve BMD in the total hip or lumbar spine, and therefore it is unlikely to have a benefit for the prevention of fractures (vertebral and non-vertebral). The evidence found suggests that there is no need for future studies in the general population of premenopausal women; however, studies focused on populations with a predisposition to diseases related to bone metabolism, or with low bone mass or osteoporosis diagnosed BMD would be useful.

Association of serum levels of inflammatory markers and adipokines with joint symptoms and structures in participants with knee osteoarthritis.

OBJECTIVE: To investigate the longitudinal associations of serum inflammatory markers and adipokines with joint symptoms and structures in participants with knee OA. METHODS: Two hundred participants (46.5% female, mean age 63.1 years, mean BMI 29.5 kg/m2) from Tasmania, part of the VIDEO (Vitamin D Effect on OA) study, were randomly selected in the current study. Serum levels of 19 biomarkers, scores of WOMAC and MRI-assessed knee structures were evaluated at baseline and month 24. The patterns of biomarkers were derived from principal component analysis and their association with knee symptoms and structures were examined using adjusted generalized estimating equations. RESULTS: Five components explained 78% of the total variance. IL-1ß, -2, -4, -6, -8, -17 A, -17 F, -21, -22 and -23 loaded the highest on the first component, which was associated with increased bone marrow lesions (BMLs) and WOMAC dysfunction score. IL-10, -12 and GM-CSF loaded on the second component, which was associated with increased cartilage volume, and decreased effusion synovitis and WOMAC scores. Leptin, adipsin and CRP loaded on the third component, which was positively associated with WOMAC scores. Resistin loaded on the fourth component, which was associated with increased BMLs and cartilage defects. Apelin-36 and adiponectin loaded on the fifth component, which was associated with increased BMLs. CONCLUSION: Various inflammatory and metabolic components were associated differently with joint symptoms and structural changes in knee OA, suggesting a complex inflammatory and metabolic interrelationship in the pathogenesis of knee OA.

Cross-sectional and temporal differences in health-related quality of life of people with and without osteoarthritis: a 10-year prospective study.

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

The impact of comorbidities on health-related quality of life of people with osteoarthritis over 10 years.

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

Associations of blood pressure and arterial stiffness with knee cartilage volume in patients with knee osteoarthritis.

OBJECTIVE: To describe the associations of blood pressure and arterial stiffness with knee cartilage volume in patients with knee OA. METHODS: A secondary analysis was performed on the data from participants in a randomized controlled trial that identified the effects of vitamin D supplementation on knee structures and symptoms among patients with symptomatic knee OA. Brachial and central blood pressure, arterial stiffness indicators and knee cartilage volume were measured at baseline and the 2 year follow-up. Associations were assessed using generalized estimating equations. RESULTS: Among 231 participants (average age 63.2 years), 48.9% were females. Higher supine systolic and diastolic pressures were significantly associated with lower tibial cartilage volume (systolic: lateral ß -6.23, medial ß -5.14, total ß -11.35 mm3/mmHg; diastolic: lateral ß -10.25, medial ß -11.29, total ß -21.50 mm3/mmHg). Higher supine systolic pressure was associated with lower femoral cartilage volume (lateral ß -17.35, total ß -28.31 mm3/mmHg). Central systolic pressure and arterial stiffness indicators (including pulse wave velocity, central pulse pressure and peripheral pulse pressure) were largely not associated with knee cartilage volume; however, higher augmentation index was associated with lower tibial and femoral cartilage volume (tibial: medial ß -8.24, total ß -19.13 mm3/%; femoral: lateral ß -23.70, medial ß -26.42, total ß -50.12 mm3/%). CONCLUSIONS: Blood pressure and arterial stiffness are associated with knee cartilage volume at several sites in knee OA patients. This supports that blood pressure and arterial stiffness may involve in the progression of knee OA.

Comorbidity patterns in people with multiple sclerosis: A latent class analysis of the Australian Multiple Sclerosis Longitudinal Study.

BACKGROUND AND PURPOSE: This study was undertaken to identify clinically meaningful comorbidity patterns and their associations with the demographic/clinical characteristics of people with multiple sclerosis (MS). METHODS: We conducted latent class analysis to identify clinically distinct comorbidity patterns in MS using the 15 most common comorbidities among 1518 Australian Multiple Sclerosis Longitudinal Study participants. The associations between demographic/clinical characteristics and comorbidity patterns were examined using log-binomial and multinomial logistic regression. RESULTS: Five distinct comorbidity patterns were identified: "minimally diseased class" (30.8%), consisting of participants with no or one comorbidity; "metabolic class" (22.7%); "mental health-allergy class" (21.7%); "nonmetabolic class" (7.6%); and "severely diseased class" (7.0%), consisting of participants with higher prevalence of these comorbidities. The relative probabilities of being assigned to comorbidity classes compared to the minimally diseased class were significantly increased for participants who were older (metabolic: relative risk ratio [RRR] = 1.09, 95% confidence interval [CI] = 1.06-1.11; nonmetabolic: RRR = 1.07, 95% CI = 1.04-1.11; severely diseased: RRR = 1.04, 95% CI = 1.01-1.08), female (nonmetabolic: RRR = 5.35, 95% CI = 1.98-14.42; severely diseased: RRR = 2.21, 95% CI = 1.02-4.77), and obese (metabolic: RRR = 4.06, 95% CI = 2.45-6.72; mental health-allergy: RRR = 1.57, 95% CI = 1.00-2.46; severely diseased: RRR = 4.53, 95% CI = 2.21-9.29) and who had moderate disability (mental health-allergy: RRR = 2.32, 95% CI = 1.47-3.64; severely diseased: RRR = 2.65, 95% CI = 1.16-6.04). CONCLUSIONS: Comorbidity patterns exist in MS. Women, people who were older, people who were obese, and people who had higher disability levels were more likely to be in classes with higher levels of comorbidity. These findings may offer opportunities for designing more personalised approaches to comorbidity prevention and treatment.

Efficacy and Safety of Turmeric Extracts for the Treatment of Knee Osteoarthritis: a Systematic Review and Meta-analysis of Randomised Controlled Trials.

PURPOSE OF THE REVIEW: Finding appropriate pharmacological options to treat osteoarthritis (OA) remain challenging. We aimed to determine the efficacy and safety of all types of turmeric extracts for the management of knee OA. RECENT FINDINGS: Sixteen RCTs of up to 16 weeks duration including 1810 adults with knee OA were included. Eleven RCTs compared the efficacy of turmeric extracts with placebo and five with active comparators (NSAIDs). The overall risk bias of included RCTs was moderate. Turmeric extracts significantly reduced knee pain (SMD - 0.82, 95% CI - 1.17 to - 0.47, I2 = 86.23%) and improved physical function (SMD - 0.75, 95% CI - 1.18 to - 0.33, I2 = 90.05%) compared to placebo but had similar effects compared to NSAIDs. BMI was the major contributor to heterogeneity in the placebo-controlled studies (explained 37.68% and 67.24%, respectively, in the models) and modified the effects of the turmeric on pain and physical function with less improvement with higher BMI (SMD 0.26 95% CI 0.04 to 0.48; SMD 0.48 95% CI 0.21 to 0.74). No significant between-group differences were reported for either biochemical markers or imaging outcomes. Turmeric extracts had 12% fewer adverse events than NSAIDs and similar rates to placebo. Turmeric extract is a safe and effective option for the symptomatic management of knee OA, compared to placebo or NSAIDs. However, current evidence from short-term studies is heterogeneous and has moderate risk of bias leading to some uncertainty about the true effect.

Bone Microarchitecture, Volumetric or Areal Bone Mineral Density for Discrimination of Vertebral Deformity in Adults: A Cross-sectional Study.

INTRODUCTION/BACKGROUND: Both areal bone mineral density (aBMD) and bone microarchitecture have been associated with vertebral deformity (VD), but there are limited data on the utility of bone microarchitecture measures in combination with aBMD in discriminating VD. This study aimed to describe whether radial bone microarchitecture measures alone or in combinations with radial volumetric bone mineral density (vBMD) or spine aBMD can improve discrimination of VD in adults. METHODS: Data on 196 subjects (mean age (standard deviation, SD) = 72 (7) years, female 46%) were utilized. VD of T4-L4 and spine aBMD were measured using dual-energy X-ray absorptiometry. VD was defined if anterior to posterior height ratio was more than 3-SD, 4-SD below, or >25% decrease compared with the sex-matched normal means. Bone microarchitecture parameters at distal radius were collected using high-resolution peripheral quantitative computed tomography and analyzed using StrAx. RESULTS: The strongest associations were seen for the cortical thickness (odds ratios (ORs): 2.63/SD decrease for 25% and 2.38/SD decrease for 3-SD criterion) and compact cortical area (OR: 3.33/SD decrease for 4-SD criterion). The area under the receiver operating characteristic curve (AUC) for spine aBMD for VD was 0.594, 0.597, and 0.634 for 25%, 3-SD and 4-SD criteria, respectively (all p < 0.05). Compact cortical area, cortical thickness and compact cortical thickness alone had the largest AUCs for VD (0.680-0.685 for 25% criterion, 0.659-0.674 for 3-SD criterion, and 0.699-0.707 for 4-SD criterion). Adding spine aBMD or radial vBMD to each cortical measure did not improve VD discrimination (∆ AUC 0.8%-2.1%). CONCLUSIONS: Cortical measures had the best utility for discriminating VD when used alone. Adding either spine aBMD or radial vBMD did not improve the utility of cortical measures.

Depression in patients with knee osteoarthritis: risk factors and associations with joint symptoms.

BACKGROUND: To describe demographic and clinical factors associated with the presence and incidence of depression and explore the temporal relationship between depression and joint symptoms in patients with symptomatic knee osteoarthritis (OA). METHODS: Three hundred ninety-seven participants were selected from a randomized controlled trial in people with symptomatic knee OA and vitamin D deficiency (age 63.3 ± 7.1 year, 48.6% female). Depression severity and knee joint symptoms were assessed using the patient health questionnaire (PHQ-9) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively, at baseline and 24 months. RESULTS: The presence and incidence of depression was 25.4 and 11.2%, respectively. At baseline, having younger age, a higher body mass index (BMI), greater scores of WOMAC pain (PR: 1.05, 95%CI:1.03, 1.07), dysfunction (PR: 1.02, 95%CI:1.01, 1.02) and stiffness (PR: 1.05, 95%CI: 1.02, 1.09), lower education level, having more than one comorbidity and having two or more painful body sites were significantly associated with a higher presence of depression. Over 24 months, being female, having a higher WOMAC pain (RR: 1.05, 95%CI: 1.02, 1.09) and dysfunction score (RR: 1.02, 95%CI: 1.01, 1.03) at baseline and having two or more painful sites were significantly associated with a higher incidence of depression. In contrast, baseline depression was not associated with changes in knee joint symptoms over 24 months. CONCLUSION: Knee OA risk factors and joint symptoms, along with co-existing multi-site pain are associated with the presence and development of depression. This suggests that managing common OA risk factors and joint symptoms may be important for prevention and treatment depression in patients with knee OA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01176344 . Anzctr.org.au identifier: ACTRN12610000495022 .

Effectiveness of Curcuma longa Extract for the Treatment of Symptoms and Effusion-Synovitis of Knee Osteoarthritis : A Randomized Trial.

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.

Comorbidities are prevalent and detrimental for employment outcomes in people of working age with multiple sclerosis.

BACKGROUND: More work is needed to understand the burden of comorbidities in people with multiple sclerosis (MS). OBJECTIVE: To assess prevalence of 30 comorbidities and impacts of comorbidities on employment outcomes in a working-aged MS cohort. METHODS: Participants were from the Australian MS Longitudinal Study (n = 929). Information on specific comorbidity was obtained (whether or not each was present, doctor-diagnosed, limited their activities and being treated). RESULTS: Comorbidities most frequently reported to limit activities were osteoarthritis (51%), migraines (40%), anxiety (33%), depression (29%) and allergies (18%). Mean MS-related work productivity loss in past 4 weeks was 1.3 days for those without comorbidities and 2.5 days for those with any comorbidity. The annual population costs of work productivity loss were highest for people with depression, allergies, anxiety, migraines and osteoarthritis. Higher number of comorbidities was associated with more work productivity loss and a higher likelihood of not working. These associations were substantially reduced after adjustment for MS symptom severity. CONCLUSIONS: Comorbidities substantially impact employment outcomes and these effects were mainly mediated through MS symptom severity. This suggests that optimal and simultaneous management of comorbidities may be a viable strategy to reduce MS symptom severity, which in turn could improve employment outcomes.

Effect of Intravenous Zoledronic Acid on Tibiofemoral Cartilage Volume Among Patients With Knee Osteoarthritis With Bone Marrow Lesions: A Randomized Clinical Trial.

Importance: A proof-of-principle study suggested that intravenous zoledronic acid may reduce knee pain and the size of bone marrow lesions in people with knee osteoarthritis, but data from large trials are lacking. Objective: To determine the effects of intravenous zoledronic acid on knee cartilage volume loss in patients with symptomatic knee osteoarthritis and bone marrow lesions. Design, Setting, and Participants: A 24-month multicenter, double-blind placebo-controlled randomized clinical trial conducted at 4 sites in Australia (1 research center and 3 hospitals). Adults aged 50 years or older with symptomatic knee osteoarthritis and subchondral bone marrow lesions detected by magnetic resonance imaging (MRI) were enrolled from November 2013 through September 2015. The final date of follow-up was October 9, 2017. Interventions: Intravenous infusion with either 5 mg of zoledronic acid in a 100-mL saline solution (n = 113) or a placebo saline solution (n = 110) at baseline and 12 months. Main Outcomes and Measures: The primary outcome was absolute change in tibiofemoral cartilage volume assessed using MRI over 24 months (the minimum clinically important difference [MCID] has not been established). Three prespecified secondary outcomes were change in knee pain assessed by a visual analog scale (0 [no pain] to 100 [unbearable pain]; MCID, 15) and the Western Ontario and McMaster Universities Osteoarthritis Index (0 [no pain] to 500 [unbearable pain]; MCID, 75) over 3, 6, 12, 18, and 24 months and change in bone marrow lesion size over 6 and 24 months (the MCID has not been established). Results: Of 223 participants enrolled (mean age, 62.0 years [SD, 8.0 years]; 52% were female), 190 (85%) completed the trial. Change in tibiofemoral cartilage volume was not significantly different between the zoledronic acid group and the placebo group over 24 months (-878 mm3 vs -919 mm3; between-group difference, 41 mm3 [95% CI, -79 to 161 mm3]; P = .50). No significant between-group differences were found for any of the prespecified secondary outcomes, including changes in knee pain assessed by a visual analog scale (-11.5 in the zoledronic acid group vs -16.8 in the placebo group; between-group difference, 5.2 [95% CI, -2.3 to 12.8]; P = .17), changes in knee pain assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (-37.5 vs -58.0, respectively; between-group difference, 20.5 [95% CI, -11.2 to 52.2]; P = .21), and changes in bone marrow lesion size (-33 mm2 vs -6 mm2; between-group difference, -27 mm2 [95% CI, -127 to 73 mm2]; P = .60) over 24 months. Adverse events were more common with zoledronic acid than with placebo (96% vs 83%, respectively) and consisted mainly of acute reactions (defined as symptoms within 3 days of administration of infusion; 87% vs 56%). Conclusions and Relevance: Among patients with symptomatic knee osteoarthritis and bone marrow lesions, yearly zoledronic acid infusions, compared with placebo, did not significantly reduce cartilage volume loss over 24 months. These findings do not support the use of zoledronic acid in the treatment of knee osteoarthritis. Trial Registration: anzctr.org.au Identifier: ACTRN12613000039785.

The Association between First Fractures Sustained during Childhood and Adulthood and Bone Measures in Young Adulthood.

OBJECTIVE: To describe the association between fractures sustained at different stages of growth and bone measures in early adulthood. STUDY DESIGN: Participants (n = 201) in southern Tasmania were at birth at a higher risk of sudden infant death syndrome; they were followed to age 25. Outcomes were areal bone mineral density at the spine, hip, and total body (by dual-energy x-ray absorptiometry) and trabecular and cortical bone measures at the radius and tibia (by high-resolution peripheral quantitative computed tomography). Fractures were self-reported and confirmed by radiographs at 8, 16, and 25 years of age. Multivariable linear regression was used to analyze the association of the occurrence of prepubertal (<9 years of age), pubertal (9-16 years of age), and postpubertal (17-25 years of age) fractures with all bone measures. RESULTS: Over 25 years, 99 participants had at least 1 fracture. For high-resolution peripheral quantitative computed tomography measures at age 25, prepubertal fractures were negatively associated with cortical and trabecular volumetric bone mineral density and most microarchitecture measures at both the tibia and radius. Prepubertal fractures had a significant association with smaller increase of areal bone mineral density from age 8 to 16 years and at 25 years of age compared with participants with no fractures. Pubertal fractures had no association with any bone measures and postpubertal fractures were only associated with a lower trabecular number at the tibia. CONCLUSIONS: Prepubertal fractures are negatively associated with areal bone mineral density increases during growth and high-resolution peripheral quantitative computed tomography bone measures in young adulthood. There is little evidence that fractures occurring from age 8 years onward with bone measures in young adulthood, implying that prepubertal fractures may be associated with bone deficits later in life.

The Association of Vitamin D in Youth and Early Adulthood with Bone Mineral Density and Microarchitecture in Early Adulthood.

This study aimed to describe the association of vitamin D status at different stages of growth with bone measures in adolescence and early adulthood. There were 415 participants followed from age 8 to 16, and 201 further followed to age 25. Areal bone mineral density (BMD) at the spine, hip and total body was measured by dual-energy X-ray absorptiometry at ages 16 and 25, and tibial and radial trabecular and cortical bone microarchitecture by high resolution peripheral quantitative computerised tomography at age 25. Serum 25-hydroxyvitamin D (25OHD) concentrations were measured at ages 8, 16 and 25. Multivariable linear regression was used to analyse the association of 25OHD concentrations at three timepoints with bone measures at ages 16 and 25. The proportion of participants with vitamin D deficiency (< 50 nmol/L) was 11%, 43% and 41% at three timepoints, respectively. Serum 25OHD concentrations at age 8 were not significantly associated with any bone measures at age 16 or 25. Serum 25OHD concentrations at age 16 had a significant association with higher BMD at nearly all sites at ages 16 and 25 as well as lower radial porosity and more compact trabecular microarchitecture (higher density, increased number and reduced separation) at both the radius and tibia at age 25. Serum 25OHD concentrations at age 25 were only associated with hip BMD. Higher vitamin D concentrations in adolescence, to a lesser extent at age 25, have beneficial associations with BMD and bone microarchitecture in early adulthood. Optimising vitamin D status particularly during adolescence should be a priority.

Vitamin D supplementation and inflammatory and metabolic biomarkers in patients with knee osteoarthritis: post hoc analysis of a randomised controlled trial.

The aim of this study was to determine whether vitamin D supplementation and maintaining vitamin D sufficiency are associated with changes in inflammatory and metabolic biomarkers in patients with knee osteoarthritis (OA) and vitamin D deficiency. A total of 413 participants with symptomatic knee OA and vitamin D deficiency were enrolled in a randomised, placebo-controlled trial and received 1·25 mg vitamin D3 or placebo monthly for 24 months across two sites. In this post hoc analysis, 200 participants from one site (ninety-four from the placebo group and 106 from the vitamin D group; mean age 63·1 (sd 7·3) years, 53·3 % women) were randomly selected for measurement of serum levels of inflammatory and metabolic biomarkers at baseline and 24 months using immunoassays. In addition, participants were classified into two groups according to serum 25-hydroxyvitamin D (25(OH)D) levels at months 3 and 24: (1) not consistently sufficient (25(OH)D≤50 nmol/l at either month 3 or 24, n 61), and (2) consistently sufficient (25(OH)D>50 nmol/l at both months 3 and 24, n 139). Compared with placebo, vitamin D supplementation had no significant effect on change in serum high-sensitive C-reactive protein, IL-6, IL-8, IL-10, leptin, adiponectin, resistin, adipsin and apelin. Being consistently vitamin D sufficient over 2 years was also not associated with changes in these biomarkers compared with not being consistently sufficient. Vitamin D supplementation and maintaining vitamin D sufficiency did not alter serum levels of inflammatory and metabolic biomarkers over 2 years in knee OA patients who were vitamin D insufficient, suggesting that they may not affect systemic inflammation in knee OA patients.

Barriers to Optimal Pain Management in Aged Care Facilities: An Australian Qualitative Study.

Up to 80% of residents in aged care facilities (ACFs) experience pain, which is often suboptimally managed. The purpose of this study was to characterize pain management in ACFs and identify the barriers to optimal pain management. This exploratory descriptive qualitative study used semistructured interviews in five Southern Tasmania, Australian ACFs. Interviewees included 23 staff members (18 nurses and 5 facility managers) and were conducted from September to November 2015. Interviews included questions about how pain was measured or assessed, what happened if pain was identified, barriers to pain management, and potential ways to overcome these barriers. Interviewees noted that there were no formal requirements regarding pain assessment at the ACFs reviewed; however, pain was often informally assessed. Staff noted the importance of adequate pain management for the residents' quality of life and employed both nonpharmacologic and pharmacologic techniques to reduce pain when identified. The barriers to optimal pain management included difficulty identifying and assessing pain, residents' resistance to reporting pain and/or taking medications, and communication barriers between the nursing staff and GPs. Staff interviewed were dedicated to managing residents' pain effectively; however, actions in a number of areas could improve resident outcomes. These include a more consistent approach to documenting pain in residents' progress notes and improving nurse-GP communications to ensure that new or escalating pain is identified and expedient changes can be made to the resident's management. Additionally, resident, family, nurse, and carer education, conducted within the facilities on a regular basis, could help improve the pain management of residents.

Associations of dietary patterns with bone mass, muscle strength and balance in a cohort of Australian middle-aged women.

Influences of dietary patterns on musculoskeletal health are poorly understood in middle-aged women. This cross-sectional analysis from a cohort of 347 women (aged 36-57 years) aimed to examine associations between dietary patterns and musculoskeletal health outcomes in middle-aged women. Diet was measured by the Cancer Council of Victoria FFQ. Total body bone mineral content (TB BMC), femoral neck and lumbar spine bone density (dual-energy X-ray absorptiometry), lower limbs muscle strength (LMS) and balance tests (timed up and go test, step test, functional reach test (FRT) and lateral reach test) were also measured. Exploratory factor analysis was used to identify dietary patterns and scores for each pattern generated using factor loadings with absolute values ≥0·20. Associations between food pattern scores and musculoskeletal outcomes were assessed using multivariable linear regression. Three dietary patterns were identified: 'Healthy' (high consumption of a plant-based diet - vegetables, legumes, fruit, tomatoes, nuts, snacks, garlic, whole grains and low intake of high-fat dairy products), 'high protein, high fat' (red meats, poultry, processed meats, potatoes, cruciferous and dark-yellow vegetables, fish, chips, spirits and high-fat dairy products) and 'Processed foods' (high intakes of meat pies, hamburgers, beer, sweets, fruit juice, processed meats, snacks, spirits, pizza and low intake of cruciferous vegetables). After adjustment for confounders, Healthy pattern was positively associated with LMS, whereas Processed foods pattern was inversely associated with TB BMC and FRT. The associations were not significant after accounting for multiple comparisons. There were no associations with any other outcomes. These results suggest that maintaining a healthy diet could contribute to bone acquisition, muscle strength and balance in adult life. However, while they provide some support for further investigating dietary strategies for prevention of age-related loss of muscle and deterioration in balance, the exploratory nature of the analyses means that confirmation in longitudinal studies and/or trials with pre-specified hypotheses is needed.

Growing and retaining general practice research leaders in Australia: How can we do better?

BACKGROUND: The aim of this study was to explore the experiences of Australian general practitioners (GPs) with a Doctor of Philosophy (PhD) about their choice to abandon or pursue an academic career. METHODS: A qualitative study of 18 GPs (PhD obtained between 2006 and 2016) was conducted. Semi-structured telephone interviews were transcribed and analysed using concurrent thematic analysis. RESULTS: General practice researchers faced insecure career pathways. They often work in isolation, there is a lack of critical mass, and research was often described as a hobby (ie unfunded, done from home). Solutions included expanding academic general practice registrar positions to include advanced research training, building professional networks, mentoring, and better marketing of general practice research. DISCUSSION: Focused investment in developing clear and sustainable career pathways is essential to nurture and retain general practice researchers and research leaders. The research culture and professional standing of general practice researchers also need to improve. Support from professional bodies and colleagues, and enabling research collaborations, are key.