Comparison of weight loss interventions in overweight and obese adults with knee osteoarthritis: A systematic review and network meta-analysis of randomized trials.

OBJECTIVE: To ascertain the comparative effectiveness of weight-loss strategies for osteoarthritis (OA) to develop rational treatment algorithms aimed at improving OA-related symptoms in overweight/obese individuals. DESIGN: Medline, Embase, CINAHL, Scopus, and Web of Science were searched from inception to June 2023 for observational studies and randomized trials. Network meta-analyses were performed using a frequentist approach. Effect sizes for pain and function were computed as standardized mean differences, while change in body weight was computed as mean differences. RESULTS: 13 RCTs on knee OA (KOA) (2800 participants) with 7 interventions: diet (D); exercise (E); diet and exercise (DE); pharmacological (L); psychological (P); psychological, diet, and exercise (PDE); and Mediterranean diets (M) were networked. For weight change (kg), all interventions significantly outperformed control comparators, with effect sizes ranging from -11.2 (95% CI, -16.0, -6.5 kg) for the most effective approach (PDE) to -4.7 (95% CI, -6.7, -2.7 kg) for the least effective approach (DE). In terms of pain (0-20 scale), only DE outperformed control comparators (-2.2, 95% CI: -4.1, -0.21), whereas PDE was not superior to control comparators (-3.9, 95% CI: -8.4, 0.5) in improving the pain. Regardless of the chosen intervention, prediction intervals from meta-regression analysis indicate that significant pain relief may be anticipated when patients achieve at least a weight reduction of 7%. CONCLUSIONS: PDE and DE interventions may offer the most effective approach for weight loss, potentially leading to improvements in pain and physical function among overweight/obese individuals with KOA if they achieve more than 7% weight loss.

Appraisal of quality and analysis of the similarities and differences between osteoarthritis Clinical Practice Guideline recommendations: A systematic review.

OBJECTIVE: Clinical Practice Guidelines (CPGs) aim to support management of hip and knee osteoarthritis (OA), but recommendations are often conflicting and implementation is poor, contributing to evidence-to-practice gaps. This systematic review investigated the contextual and methodological factors contributing to conflicting recommendations for hip and knee OA. METHOD: Our systematic review appraised CPGs for managing hip and knee OA in adults ≥18 years (PROSPERO CRD42021276635). We used AGREE-II and AGREE-REX to assess quality and extracted data on treatment gaps, conflicts, biases, and consensus. Heterogeneity of recommendations was determined using Weighted Fleiss Kappa (K). The relationship between (K) and AGREE-II/AGREE-REX scores was explored. RESULTS: We identified 25 CPGs across eight countries and four international organisations. The ACR, EULAR, NICE, OARSI and RACGP guidelines scored highest for overall AGREE-II quality (83%). The highest overall AGREE-REX scores were for BMJ Arthroscopy (80%), RACGP (78%) and NICE (76%). CPGs with the least agreement for pharmacological recommendations were ESCEO and NICE (-0.14), ACR (-0.08), and RACGP (-0.01). The highest agreements were between RACGP and NICE (0.53), RACGP and ACR (0.61), and NICE and ACR (0.91). Decreased internal validity determined by low-quality AGREE scores(<60%) in editorial independence were associated with less agreement for pharmacological recommendations. CONCLUSION: There were associations between guideline quality and agreement scores. Future guideline development should be informed by robust evidence, editorial independence and methodological rigour to ensure a harmonisation of recommendations. End-users of CPGs must recognise the contextual factors associated with the development of OA CPGs and balance these factors with available evidence.

Psychosocial factors in knee osteoarthritis: Scoping review of evidence and future opportunities.

OBJECTIVE: Identify, describe and produce an evidence map of studies investigating psychosocial factors association with, or effect on, clinical outcomes for people with knee osteoarthritis. METHODS: Scoping review of interventional and observational studies was performed. Medline (Ovid), Embase (Ovid), Cumulated Index in Nursing and Allied Health Literature, PsycInfo and Web of Science were searched on the 15th May 2023. Screening, data extraction and analysis was performed by two independent researchers. Extracted information included characteristics of studies plus which psychosocial factors were used to investigate association with, or effect on, clinical outcome(s). Descriptive statistics summarized the study design, temporal trend, geographic distribution, frequency of each psychosocial factor and whether associations/effects were observed. RESULTS: 23,065 records were screened, with 108 studies selected. Eighty-two percent of studies (n = 89/108) were cross-sectional in design. Number of studies increased over time and spanned 28 countries. Most research originated from the Americas region (55 %, 59/108). Twenty-four psychosocial factors (11 psychological, 13 social) were identified. Depression (47 %, n = 48/102) and education (28 %, n = 29/102) were the most frequently reported psychological and social factors, respectively. Psychological factors were often reported to have an association with/effect on pain (81 %, n = 71/88) and physical function (75 %, n = 56/74). Social factors were less frequently reported to have an association with or effect on pain (57 %, n = 46/81) and physical function (50 %, n = 18/36). CONCLUSION: Psychosocial factors are often associated with clinical outcomes for people with knee osteoarthritis. High-quality longitudinal studies examining a wide range of psychosocial factors across diverse cultural and geographical settings are key to continue informing the development of biopsychosocial models of care.

Priorities for the effective implementation of osteoarthritis management programs: an OARSI international consensus exercise.

OBJECTIVE: The Joint Effort Initiative was endorsed by Osteoarthritis Research Society International (OARSI) in 2018 as a collaboration between international researchers and clinicians with an interest in the implementation of osteoarthritis management programs (OAMPs). This study aimed to identify and prioritise activities for future work of the Joint Effort Initiative. DESIGN: A survey was emailed to delegates of the 2018 OARSI World Congress attending a pre-conference workshop or with a known interest in OAMPs (n = 115). Delegates were asked about the most important issues regarding OAMP implementation. The top 20 issues were synthesised into 17 action statements, and respondents were invited to participate in a priority ranking exercise to determine the order of importance of the statements. RESULTS: Survey respondents (n = 51, 44%) were most commonly female (71%), with an allied health background (57%), affiliated with universities (73%) from Oceania (37%), and Europe/UK (45%). The five highest ranked action statements were: CONCLUSION: Prioritising statements will bring focus to the future work of the Joint Effort Initiative in the future and provide a basis for longer-term actions.

Effectiveness of a new model of primary care management on knee pain and function in patients with knee osteoarthritis: Protocol for THE PARTNER STUDY.

BACKGROUND: To increase the uptake of key clinical recommendations for non-surgical management of knee osteoarthritis (OA) and improve patient outcomes, we developed a new model of service delivery (PARTNER model) and an intervention to implement the model in the Australian primary care setting. We will evaluate the effectiveness and cost-effectiveness of this model compared to usual general practice care. METHODS: We will conduct a mixed-methods study, including a two-arm, cluster randomised controlled trial, with quantitative, qualitative and economic evaluations. We will recruit 44 general practices and 572 patients with knee OA in urban and regional practices in Victoria and New South Wales. The interventions will target both general practitioners (GPs) and their patients at the practice level. Practices will be randomised at a 1:1 ratio. Patients will be recruited if they are aged ≥45 years and have experienced knee pain ≥4/10 on a numerical rating scale for more than three months. Outcomes are self-reported, patient-level validated measures with the primary outcomes being change in pain and function at 12 months. Secondary outcomes will be assessed at 6 and 12 months. The implementation intervention will support and provide education to intervention group GPs to deliver effective management for patients with knee OA using tailored online training and electronic medical record support. Participants with knee OA will have an initial GP visit to confirm their diagnosis and receive management according to GP intervention or control group allocation. As part of the intervention group GP management, participants with knee OA will be referred to a centralised multidisciplinary service: the PARTNER Care Support Team (CST). The CST will be trained in behaviour change support and evidence-based knee OA management. They will work with patients to develop a collaborative action plan focussed on key self-management behaviours, and communicate with the patients' GPs. Patients receiving care by intervention group GPs will receive tailored OA educational materials, a leg muscle strengthening program, and access to a weight-loss program as appropriate and agreed. GPs in the control group will receive no additional training and their patients will receive usual care. DISCUSSION: This project aims to address a major evidence-to-practice gap in primary care management of OA by evaluating a new service delivery model implemented with an intervention targeting GP practice behaviours to improve the health of people with knee OA. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12617001595303 , date of registration 1/12/2017.

The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium.

Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9-11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9-13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47-0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61-78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.

Does neighbourhood deprivation influence low back pain and arthritis: An empirical study using multilevel twin design.

OBJECTIVE: Neighbourhood deprivation has been found to be associated with many health conditions, but its association with low back pain (LBP) and arthritis is unclear. This study aimed to examine the association between neighbourhood deprivation with LBP and arthritis, and its potential interaction with individual socioeconomic status (SES) on these outcomes. METHODS: Monozygotic (MZ) twins from the Washington State Twin Registry were used to control for genetic and common environmental factors that could otherwise confound the purported relationship. Multilevel models were employed to examine the association between neighbourhood deprivation as well as individual-level SES with LBP/arthritis, adjusting for age, sex, body mass index (BMI) and residence rurality. RESULTS: There were 6,380 individuals in the LBP sample and 2,030 individuals in the arthritis sample. Neighbourhood deprivation was not associated with LBP (P = 0.26) or arthritis (P = 0.61), and neither was its interaction with individual-level SES. People without a bachelor's degree were more likely to report LBP (OR 1.44, 95% CI 1.26-1.65) or both LBP and arthritis (OR 1.67, 95% CI 1.14-2.45) than those with a bachelor's degree, but not for arthritis alone (P = 0.17). Household income was not significantly associated with LBP (P = 0.16) or arthritis (p = 0.23) independent of age, sex, and BMI. CONCLUSION: Our study did not find significant associations between neighbourhood deprivation and the presence of LBP or arthritis. More research using multilevel modelling to investigate neighbourhood effects on LBP and arthritis is recommended.

Efficacy and safety of an oral complementary medicine combination in people with symptomatic knee osteoarthritis: Protocol for the double-blind, randomized, placebo-controlled ATLAS trial.

Objective: To investigate the efficacy and safety of an oral complementary medicine combination formulation relative to placebo, on changes in pain intensity from baseline to week 12, in people with knee osteoarthritis (OA). Design: A placebo-controlled, double-blind, two-arm, superiority, phase II, Randomized Controlled Trial (RCT) (ACTRN12623000380695). We will recruit 82 participants (∼41 per arm), aged ≥40 years, with a clinical diagnosis of symptomatic knee OA and radiographic change on x-ray (Kellgren-Lawrence Grade ≥2). Participants will be randomly allocated to receive either a complementary medicine formulation containing a daily dose of Boswellia serrata extract (Boswellin® Super, 250 â€‹mg/day), pine bark extract (Fenoprolic™ 70 Organic 100 â€‹mg/day), curcumin (500 â€‹mg/day), piperine (5 â€‹mg/day), and methylsulfonylmethane (MSM, 1500 â€‹mg/day), or placebo, for 12-weeks. The primary endpoint will be change from baseline in average knee pain intensity at 12-weeks (visual analogue scale). Secondary endpoints will include change in knee pain from baseline to 12-weeks in the Knee Injury and Osteoarthritis Outcome Score (KOOS), global assessment of disease activity, global rating of change, and health-related quality of life (AQoL-8D). Ethics and dissemination: This protocol has been approved by the University of Sydney Human Research Ethics Committee (#2021/877). Dissemination will occur through lay summaries, infographics, conference abstracts, oral presentations, theses, and scientific publications. Conclusion: This RCT will provide credible evidence about the efficacy and safety of this complementary medicine combination and inform updates to international clinical practice standards on the use of complementary medicines in the management of symptomatic knee OA.

The contribution of twins to the study of cognitive ageing and dementia: the Older Australian Twins Study.

The Older Australian Twins Study (OATS) is a major longitudinal study of twins, aged ≥ 65 years, to investigate genetic and environmental factors and their interactions in healthy brain ageing and neurocognitive disorders. The study collects psychiatric, neuropsychological, cardiovascular, metabolic, biochemical, neuroimaging, genomic and proteomic data, with two-yearly assessments, and is currently in its third wave. The initial cohort comprises 623 individuals (161 monozygotic and 124 dizygotic twin pairs; 1 MZ triplets; 27 single twins and 23 non-twin siblings), of whom 426 have had wave 2 assessment. A number of salient findings have emerged thus far which assist in the understanding of genetic contributions to cognitive functions such as processing speed, executive ability and episodic memory, and which support the brain reserve hypothesis. The heritability of brain structures, both cortical and subcortical, brain spectroscopic metabolites and markers of small vessel disease, such as lacunar infarction and white matter hyperintensities, have been examined and can inform future genetic investigations. Work on amyloid imaging and functional magnetic resonance imaging is proceeding and epigenetic studies are progressing. This internationally important study has the potential to inform research into cognitive ageing in the future, and offers an excellent resource for collaborative work.