Identifying Knee Osteoarthritis: Classification, early recognition and imaging

Osteoarthritis (OA) is one of the most frequently occurring health problems in middle aged and older people. Treatment of OA is focused on treating symptoms while it might be more effective to start treatment before symptoms are present. Early predictive signs for evident knee OA need to be identified, so it will be possible to define people that will get OA in the future. This thesis describes the evaluation of different classification criteria and the identification of radiographic and MRI features that are related to different aspects of clinical symptoms and risk factors of (early) knee O

Opioid prescriptions in patients with osteoarthritis: a population-based cohort study

OBJECTIVES: To examine the incidence, prevalence and trends for opioid prescriptions in patients with OA. Furthermore, types of opioids prescribed and long-term prescription rates were examined. Finally, the patient characteristics associated with the prescription of opioids wer

10-Year natural course of early hip osteoarthritis in middle-aged persons with hip pain: A CHECK study

Objective: To explore the natural course of hip osteoarthritis (OA) in a population of first-time presenters with hip complaints. Methods: Data were collected at baseline and after 2, 5, 8 and 10 years on participants from the Cohort Hip and Cohort Knee study with early symptomatic hip OA. Descriptive statistics were used to analyse the natural course of the hip complaints with respect to clinical signs and symptoms, physical functioning and radiographic osteoarthritis (ROA) features. Results: In total, 588 participants were included with hip complaints and 86% completed the 10-year follow-up. The 10-year follow-up showed that 12% (69 participants) underwent hip replacement (HR), an increase of ROA of the hip (Kellgren and Lawrence score≥2) from 19% to 49%, and an increase in clinical hip OA according to the American College of Rheumatology criteria from 27% to 43%. All Western Ontario and McMaster Osteoarthritis Index subscales and physical activity remained on average constant during the 10-year follow-up for those who did not undergo an HR. The use of pain medication increased from 43% at baseline to 50% after 10 years. Conclusion: One out of nine participants with early hip problems received an HR during the 10-year follow-up. Prevalence of clinical hip OA and hip ROA increased steadily during the 10-year follow-up. Overall, we observed more hip OA, but fewer or stable complaints with respect to clinical signs and symptoms, and physical functioning. So it could be cautiously concluded that after 10 years, first-time presenters with hip complaints either received an HR or their symptoms remained stable

Intestinal microbiome composition and its relation to joint pain and inflammation

Macrophage-mediated inflammation is thought to have a causal role in osteoarthritis-related pain and severity, and has been suggested to be triggered by endotoxins produced by the gastrointestinal microbiome. Here we investigate the relationship between joint pain and the gastrointestinal microbiome composition, and osteoarthritis-related knee pain in the Rotterdam Study; a large population based cohort study. We show that abundance of Streptococcus species is associated with increased knee pain, which we validate by absolute quantification of Streptococcus species. In addition, we replicate these results in 867 Caucasian adults of the Lifelines-DEEP study. Finally we show evidence that this association is driven by local inflammation in the knee joint. Our results indicate the microbiome is a possible therapeutic target for osteoarthritis-related knee pain

A machine learning approach to distinguish between knees without and with osteoarthritis using MRI-based radiomic features from tibial bone

Objectives: Our aim was to assess the ability of semi-automatically extracted magnetic resonance imaging (MRI)–based radiomic features from tibial subchondral bone to distinguish between knees without and with osteoarthritis. Methods: The right knees of 665 females from the population-based Rotterdam Study scanned with 1.5T MRI were analyzed. A fast imaging employing steady-s

Effectiveness and cost-effectiveness of duloxetine added to usual care for patients with chronic pain due to hip or knee osteoarthritis

__Introduction__ Osteoarthritis (OA) is a highly prevalent painful condition of the musculoskeletal system. The effectiveness of current analgesic options has proven to be limited and improved analgesic treatment is needed. Several randomised placebo-controlled trials have now demonstrated the efficacy of duloxetine, an antidepressant with a centrally acting effect, in the treatment of OA pain. The aim of the current study is to investigate if duloxetine is effective and cost-effective as a third-choice analgesic added to usual care for treating chronic pain compared with usual care alone in general practice. __Methods and analysis__ A pragmatic open, cluster randomised trial is conducted. Patients with pain due to hip or knee OA on most days of the past 3 months with insufficient benefit of non-steroidal anti-inflammatory drugs or contraindications or intolerable side effects are included. General practices are randomised to either (1) duloxetine and usual care or (2) usual care only. Primary outcome is pain at 3 months measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcomes at 3 months and 1 year are pain (WOMAC, at 1 year), function (WOMAC), adverse reactions, quality of life and modification of the response to treatment by the presence of centrally sensitised pain (modified PainDETECT). At 1 year, medical and productivity costs will be assessed. Analyses will be performed following the intention-to-treat principle taking the cluster design into account. __Ethics and dissemination__ The study is approved by the local Medical Ethics Committee (2015-293). Results will be published in a scientific peer-reviewed journal and will be communicated at conferences. _Trial registration number_ Dutch Trial Registry(ntr4798); Pre-results

Evaluation of intermediate care for knee and hip osteoarthritis

Background: To evaluate intermediate care for knee and hip osteoarthritis (KHOA) in the general practice that incorporate specialist services into general practice to prevent unnecessary referrals to hospitals. Methods: We used a mixed methods approach including semi-structured interviews, patient experience questionnaires and data from medical records from three intermediate care projects. Semi-structured interviews were conducted with patients, general practitioners (GPs), orthopaedists and a healthcare manager in intermediate care. Satisfaction of patients who received intermediate care (n = 100) was collected using questionnaires. Referral data and healthcare consumption from medical records were collected retrospectively from KHOA patients before (n = 96) and after (n = 208) the implementation of intermediate care. Results: GPs and orthopaedists in intermediate care experienced more intensive collaboration compared to regular care. This led to a perceived increase in GPs’ knowledge enabling better selection of referrals to orthopaedics and less healthcare consumption. Orthopaedists felt a higher workload and limited access to diagnostic facilities. Patients were satisfied and experienced better access to specialists’ knowledge in a trusted environment compared to regular care. Referrals to physiotherapy increased significantly after the implementation of intermediate care (absolute difference = 15%; 95% CI = 7.19 to 22.8), but not significantly to orthopaedics (absolute difference = 5.9%; 95% CI = -6.18 to 17.9). Conclusions: Orthopaedists and GPs perceived the benefits of an intensified collaboration in intermediate care. Intermediate care may contribute to high quality of care through more physiotherapy referrals. Further research with longer follow-up is needed to confirm these findings and give more insight in referrals and healthcare consumption.</p

Patients', healthcare providers', and insurance company employees' preferences for knee and hip osteoarthritis care: a discrete choice experiment

Objective: To determine patients', healthcare providers', and insurance company employees' preferences for knee and hip osteoarthritis (KHOA) care. Design: In a discrete choice experiment, patients with KHOA or a joint replacement, healthcare providers, and insurance company employees were repetitively asked to choose between KHOA care alternatives that differed in six attributes: waiting times, out of pocket costs, travel distance, involved healthcare providers, duration of consultation, and access to specialist equipment. A (panel latent class) conditional logit model was used to determine preference heterogeneity and relative importance of the attributes. Results: Patients (n = 648) and healthcare providers (n = 76) valued low out of pocket costs most, while insurance company employees (n = 150) found a joint consultation by general practitioner (GP) and orthopaedist most important. Patients found the duration of consultation less important than healthcare providers and insurance company employees did. Patients without a joint replacement were likely to prefer healthcare with low out of pocket costs. Patients with a joint replacement and/or low disease-specific quality of life were likely to prefer healthcare from an orthopaedist. Patients who already received healthcare for knee/hip problems were likely to prefer a joint consultation by GP and orthopaedist, and direct access to specialist equipment. Conclusions: Patients, healthcare providers, and insurance company employees highly prefer a joint consultation by GP and orthopaedist with low out of pocket costs. Within patients, there is substantial preference heterogeneity. These results can be used by policy makers and healthcare providers to choose the most optimal combination of KHOA care aligned to patients' preferences

Associations between joint effusion in the knee and gene expression levels in the circulation: A meta-analysis

Objective: To identify molecular biomarkers for early knee osteoarthritis (OA), we examined whether joint effusion in the knee associated with different gene expression levels in the circulation. Materials and Methods: Joint effusion grades measured with magnetic resonance (MR) imaging and gene expression levels in blood were determined in women of the Rotterdam Study (N=135) and GARP (N=98). Associations were examined using linear regression analyses, adjusted for age, fasting status, RNA quality, technical batch effects, blood cell counts, and BMI. To investigate enriched pathways and protein-protein interactions, we used the DAVID and STRING webtools. Results: In a meta-analysis, we identified 257 probes mapping to 189 unique genes in blood that were nominally significantly associated with joint effusion grades in the knee. Several compelling genes were identified such as C1orf38 and NFATC1. Significantly enriched biological pathways were: response to stress, gene expression, negative regulation of intracellular signal transduction, and antigen processing and presentation of exogenous pathways. Conclusion: Meta-analyses and subsequent enriched biological pathways resulted in interesting candidate genes associated with joint effusion that require further characterization. Associations were not transcriptome-wide significant most likely due to limited power. Additional studies are required to replicate our findings in more samples, which will greatly help in understanding the pathophysiology of OA and its relation to inflammation, and may result in biomarkers urgently needed to diagnose OA at an early stage