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  • Impact of Diet and/or Exercise Intervention on Infrapatellar Fat Pad Morphology: Secondary Analysis from the Intensive Diet and Exercise for Arthritis (IDEA) Trial.

    9 November 2018

    OBJECTIVES: The infrapatellar fat pad (IPFP) represents intra-articular adipose tissue that may contribute to intra-articular inflammation and pain by secretion of proinflammatory cytokines. Here we examined the impact of weight loss by diet and/or exercise interventions on the IPFP volume. METHODS: Intensive Diet and Exercise for Arthritis (IDEA) was a single-blinded, single-center, 18-month, prospective, randomized controlled trial that enrolled 454 overweight and obese older adults with knee pain and radiographic osteoarthritis. Participants were randomized to 1 of 3 groups: exercise-only control (E), diet-induced weight loss (D), and diet-induced weight loss + exercise (D+E). In a subsample (n = 106; E: n = 36, D: n = 35, and D+E: n = 35), magnetic resonance images were acquired at baseline and at the 18-month follow-up, from which we analyzed IPFP volume, surface areas, and thickness in this secondary analysis. RESULTS: The average weight loss amounted to 1.0% in the E group, 10.5% in the D group, and 13.0% in the D+E group. A significant (p < 0.01) reduction in IPFP volume was observed in the E (2.1%), D (4.0%), and D+E (5.2%) groups. The IPFP volume loss in the D+E group was significantly greater than that in the E group (p < 0.05) when not adjusting for parallel comparisons. Across intervention groups, there were significant correlations between IPFP volume change, individual weight loss (r = 0.40), and change in total body fat mass (dual-energy X-ray absorptiometry; r = 0.44, n = 88) and in subcutaneous thigh fat area (computed tomography; r = 0.32, n = 82). CONCLUSIONS: As a potential link between obesity and knee osteoarthritis, the IPFP was sensitive to intervention by diet and/or exercise, and its reduction was correlated with changes in weight and body fat.

  • No abatement of steroid injections for tennis elbow in Australian General Practice: A 15-year observational study with random general practitioner sampling.

    9 November 2018

    OBJECTIVE: Evaluate general practitioner (GP) management of tennis elbow (TE) in Australia. METHODS: Data about the management of TE by GPs from 2000 to 2015 were extracted from the Bettering the Evaluation of Care of Health program database. Patient and GP characteristics and encounter management data were classified by the International Classification of Primary Care, version 2, and reported using descriptive statistics with point estimates and 95% confidence intervals. RESULTS: TE was managed by GPs 242,000 times per year on average. Patients were mainly female (52.3%), aged between 35 and 64 years (mean: 49.3 yrs), had higher relative risks of concomitant disorders (e.g. carpal tunnel syndrome and other tendonitis) and their TE was 10 times more likely to be work related than problems managed for patients who did not have TE. Use of diagnostic tests was low, implying a clinical examination based diagnosis of TE. Management was by procedural treatments (36 per 100 TE problems), advice, education or counselling (25 per 100), and referral to other health care providers (14 per 100, mainly to physiotherapy). The rate of local injection did not change over the 15 years and was performed at similar rates as physiotherapy referral. CONCLUSION: The high risk of comorbidities and work relatedness and no abatement in the reasonably high rate of local injections (which is contrary to the evidence from clinical trials) provides support for the development and dissemination of TE clinical guidelines for GPs.

  • Investigational drugs for the treatment of osteoarthritis.

    9 November 2018

    INTRODUCTION: Osteoarthritis (OA) is a common joint disease with multiple pathophysiological processes, affecting the whole joint. Current therapeutic options such as NSAIDs can provide a palliative effect on symptoms but have limited effect on disease progression. New drugs targeting OA structures may retard disease progression at an earlier stage and delay the need for joint replacement. AREAS COVERED: Some drugs have entered into clinical trials and a few, such as strontium ranelate, do have improvements in both pain and structure changes. However, most of them have failed in clinical trials largely due to increased side effects or the failure to identify the right OA phenotype for the right drug in clinical design. This review describes various investigational drugs developed for the treatment of OA covering those at stages from preclinical experiments to early phase clinical trials. They include drugs for slowing cartilage degradation, regulating cartilage metabolism, targeting subchondral bone, controlling inflammation and relieving pain. EXPERT OPINION: Treatment options for OA remain limited. However, with the emergence of sensitive tools to detect early disease progression and identification of different OA phenotypes, disease-modifying anti-OA drugs with increased benefit and reduced risks will become available for OA treatment in the near future.

  • Developing an Online Decision Aid for Osteoarthritis.

    9 November 2018

    A decision aid for osteoarthritis was developed using the best available evidence on effect size, potential harms and self-rated performance for other attributes. The aid was developed using a multi-criteria decision analytic tool capable of combing evidence and an individual's preferences for the attributes related to treatment.

  • Evaluation of bone marrow lesion volume as a knee osteoarthritis biomarker--longitudinal relationships with pain and structural changes: data from the Osteoarthritis Initiative.

    9 November 2018

    INTRODUCTION: Bone marrow lesion (BML) size may be an important imaging biomarker for osteoarthritis-related clinical trials and reducing BML size may be an important therapeutic goal. However, data on the interrelationships between BML size, pain, and structural progression are inconsistent and rarely examined in the same cohort. Therefore, we evaluated the cross-sectional and longitudinal associations of BML volume with knee pain and joint space narrowing (JSN). METHODS: A BML volume assessment was performed on magnetic resonance images of the knee collected at the 24- and 48-month Osteoarthritis Initiative visits from a convenience sample of 404 participants in the progression cohort. During the same visits, knee pain was assessed with WOMAC pain scores and knee radiographs were acquired and scored for JSN. BML volume was summed to generate a total knee volume and an index tibiofemoral compartment volume (compartment with greater baseline JSN). Primary analyses included multiple linear regressions (outcome = pain, predictor = total knee BML volume) and logistic regressions (outcome = JSN, predictor = index tibiofemoral compartment BML volume). RESULTS: This sample was 49% female with a mean age of 63 (9.2 standard deviation (SD)) years, and 71% had radiographic osteoarthritis in the study knee. Larger baseline BMLs were associated with greater baseline knee pain (P = 0.01), the presence of JSN at baseline (odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.23 to 1.83), and JSN progression (OR = 1.27, 95%CI = 1.11 to 1.46). Changes in total knee BML volume had a positive association with changes in knee pain severity (P = 0.004) and this association may be driven by knees that were progressing from no or small baseline BMLs to larger BMLs. In contrast, we found no linear positive relationship between BML volume change and JSN progression. Instead, regression of medial tibiofemoral BML volume was associated with JSN progression compared to knees with no or minimal changes in BML volume (OR = 3.36, 95%CI = 1.55 to 7.28). However, follow-up analyses indicated that the association between JSN progression and BML volume change may primarily be influenced by baseline BML volume. CONCLUSION: Large baseline BMLs are associated with greater baseline knee pain, the presence of JSN at baseline, and disease progression. Additionally, BML regression is associated with decreased knee pain but not a reduced risk of concurrent JSN progression.

  • Bone marrow lesion volume reduction is not associated with improvement of other periarticular bone measures: data from the Osteoarthritis Initiative.

    9 November 2018

    INTRODUCTION: We evaluated the associations between bone marrow lesion (BML) volume change and changes in periarticular bone mineral density (paBMD) as well as subchondral sclerosis to determine whether BML change is associated with other local bone changes. METHODS: The convenience sample comprised participants in the Osteoarthritis Initiative (OAI) with weight-bearing posterior-anterior knee radiographs and magnetic resonance images (MRIs) at the 24- and 48-month visits and dual-energy x-ray absorptiometry (DXA) at the 30-/36-month and 48-month visits. The right knee was assessed unless contraindicated for MRI. We used knee DXA scans to measure medial tibia paBMD and medial/lateral paBMD ratio (M:L paBMD). Knee radiographs were scored for sclerosis (grades 0 to 3) in the medial tibia. Two raters determined BML volume on sagittal fat-suppressed MRI by using a semiautomated segmentation method. To focus on knees with only medial tibia BML changes, knees with lateral tibial BMLs were excluded. Medial tibial BML volume change was classified into three groups: BML regression (lowest quartile of medial tibial BML volume change), no-to-minimal change (middle two quartiles), and BML progression (highest quartile). We used proportional odds logistic regression models to evaluate the association between quartiles of changes in medial paBMD or M:L paBMD ratio, as outcomes, and BML volume change. RESULTS: The sample (n = 308) included 163 (53%) female subjects, 212 (69%) knees with radiographic osteoarthritis, and participants with a mean age of 63.8 ± 9.3 years and mean body mass index of 29.8 ± 4.7 kg/m(2). We found an association between greater increases in medial tibia paBMD and BML regression (OR = 1.7 (95% confidence interval (CI) = 1.1 to 2.8)) and a similar trend for BML progression (OR = 1.6 (95% CI = 1.0 to 2.6]). We also detected associations between greater increase in M:L paBMD and BML regression (OR = 1.6 (95% CI = 1.0 to 2.7]) and BML progression (OR = 1.8 (95% CI = 1.1 to 3.0)), although BML regression had borderline statistical significance. The frequency of sclerosis progression in the medial tibia (n = 14) was greater among knees with BML progression or regression compared with knees without BML change (P = 0.01 and P = 0.04, respectively). CONCLUSION: BML regression and BML progression are characterized by concurrent increases in paBMD and sclerosis, which are characteristic of increased radiographic osteoarthritis severity. At least during 24 months, BML regression is not representative of improvement in other periarticular bone measures.

  • Informed conditioning on clinical covariates increases power in case-control association studies.

    9 November 2018

    Genetic case-control association studies often include data on clinical covariates, such as body mass index (BMI), smoking status, or age, that may modify the underlying genetic risk of case or control samples. For example, in type 2 diabetes, odds ratios for established variants estimated from low-BMI cases are larger than those estimated from high-BMI cases. An unanswered question is how to use this information to maximize statistical power in case-control studies that ascertain individuals on the basis of phenotype (case-control ascertainment) or phenotype and clinical covariates (case-control-covariate ascertainment). While current approaches improve power in studies with random ascertainment, they often lose power under case-control ascertainment and fail to capture available power increases under case-control-covariate ascertainment. We show that an informed conditioning approach, based on the liability threshold model with parameters informed by external epidemiological information, fully accounts for disease prevalence and non-random ascertainment of phenotype as well as covariates and provides a substantial increase in power while maintaining a properly controlled false-positive rate. Our method outperforms standard case-control association tests with or without covariates, tests of gene x covariate interaction, and previously proposed tests for dealing with covariates in ascertained data, with especially large improvements in the case of case-control-covariate ascertainment. We investigate empirical case-control studies of type 2 diabetes, prostate cancer, lung cancer, breast cancer, rheumatoid arthritis, age-related macular degeneration, and end-stage kidney disease over a total of 89,726 samples. In these datasets, informed conditioning outperforms logistic regression for 115 of the 157 known associated variants investigated (P-value = 1 × 10(-9)). The improvement varied across diseases with a 16% median increase in χ(2) test statistics and a commensurate increase in power. This suggests that applying our method to existing and future association studies of these diseases may identify novel disease loci.

  • Advanced imaging in osteoarthritis.

    9 November 2018

    Historically plain radiography has been the primary investigative tool by which structure in osteoarthritis is measured. Magnetic resonance imaging (MRI) is widely used in medical diagnosis for its various advantageous features, such as high-resolution capability, the ability to produce an arbitrary anatomic cross-sectional image, and wide range of available tissue contrast. Its ability to image features such as the subchondral bone, cartilage and soft tissue structures means that its application in knee osteoarthritis (OA) raises hope of improving our understanding of structural associations of pain and function in OA joints, previously based on conventional radiography. Additionally, MRI has the potential for assessing the effect of risk factors for epidemiologic investigation and the effectiveness of therapeutic interventions in OA clinical trials.

  • Aspirin and other Anti-Platelet Drugs

    7 June 2018

    Aspirin can block the aggregation of blood platelets and in the early 1980s several randomised trials assessed whether it might be able to prevent heart attacks and strokes in people at high risk of such an event. These trials were too small to provide a definitive answer, so we established the Anti-Platelet Trialists’ (APT) Collaboration to conduct a meta-analysis of all such trials.

  • Big Data

    7 June 2018

    The emergence of new digital technologies is allowing huge quantities of information on health exposures and outcomes to be captured, stored, and analysed using advanced statistical techniques. ‘Big data’ will provide new ways to conduct research and offers the potential of a dramatic increase in the scale and efficiency of clinical studies.

  • Cancer

    7 June 2018

    Despite improvements in survival in recent decades, cancer remains a major cause of death. The most common types of cancer in males are lung cancer, prostate cancer, colorectal cancer, and stomach cancer, and in females, are breast cancer, colorectal cancer, lung cancer, and cervical cancer.

  • Cardiovascular Disease

    7 June 2018

    Cardiovascular disease (CVD) includes all the diseases of the heart and circulation such as coronary heart disease, angina, heart attack, congenital heart disease and stroke. Despite improvements in the prevention and treatment of CVD, it remains the leading cause of death worldwide particularly in developed countries.

  • Cholesterol

    7 June 2018

    Blood lipids are a major cause of cardiovascular disease. It has been known for some time that higher levels of LDL ("bad") cholesterol and lower levels of HDL cholesterol are associated with higher heart disease risk, but effective treatments to substantially lower LDL cholesterol have only become available in recent decades.

  • Dementia and other Neurodegenerative Diseases

    7 June 2018

    Degenerative diseases of the brain and nervous system such as dementia, Parkinson’s disease and motor neuron disease, are common and serious health problems of middle and old age.

  • Diet, Nutrition and Obesity

    7 June 2018

    Obesity is a major factor influencing the burden of disease globally. We investigate the impact of obesity on health and on the healthcare system across a range of diseases. Our research into diet and nutrition assesses the environmental determinants of dietary behaviour and models and evaluates population based interventions, such as food labelling and so-called junk food taxes, which aim to promote healthier eating.

  • Healthcare Economics

    7 June 2018

    Health Economics research explores the economic aspects of health and disease including the determinants of health, the economic consequences of ill health, the costs and benefits of prevention and treatment, and the financing, design and evaluation of health systems.

  • Health Ethics and Law

    7 June 2018

    The translation of medical research into health care practice can present a range of ethical challenges. If ethical and social issues are not identified, analysed and appropriately addressed as research progresses, they have the potential to block the successful completion of the research and its translation into health benefits. In a time of rapid scientific advances and emerging technologies in healthcare, the exploration of the relationships between law, ethics and practice can identify how new technologies may be accommodated within existing legal frameworks and whether these frameworks need to change.

  • Kidney Disease and Diabetes

    7 June 2018

    More than half a million people worldwide have a kidney transplant and many more are waiting for one. People with kidney disease have a much higher risk of developing a number of diseases, particularly cardiovascular disease. In Diabetes Mellitus blood sugar levels are raised over a prolonged period. People with diabetes are at increased risk of cardiovascular disease, kidney disease and damage to the eyes. Rates of type-2 diabetes have increased rapidly in recent decades due to changes in diet and other lifestyle factors.