Population-based user-perceived experience of Rheumatic?: a novel digital symptom-checker in rheumatology

Objective: Digital symptom-checkers (SCs) have potential to improve rheumatology triage and reduce diagnostic delays. In addition to being accurate, SCs should be user friendly and meet patient's needs. Here, we examined usability and acceptance of Rheumatic?-a new and freely available online SC (currently with >44 000 users)-in a real-world setting. Methods: Study participants were recruited from an ongoing prospective study, and included people >= 18 years with musculoskeletal complaints completing Rheumatic? online. The user experience survey comprised five usability and acceptability questions (11-point rating scale), and an open-ended question regarding improvement of Rheumatic? Data were analysed in R using t-test or Wilcoxon rank test (group comparisons), or linear regression (continuous variables). Results: A total of 12 712 people completed the user experience survey. The study population had a normal age distribution, with a peak at 50-59 years, and 78% women. A majority found Rheumatic? useful (78%), thought the questionnaire gave them an opportunity to describe their complaints well (76%), and would recommend Rheumatic? to friends and other patients (74%). Main shortcoming was that 36% thought there were too many questions. Still, 39% suggested more detailed questions, and only 2% suggested a reduction of questions.Conclusion: Based on real-world data from the largest user evaluation study of a digital SC in rheumatology, we conclude that Rheumatic? is well accepted by women and men with rheumatic complaints, in all investigated age groups. Wide-scale adoption of Rheumatic?, therefore, seems feasible, with promising scientific and clinical implications on the horizon.Pathophysiology and treatment of rheumatic disease

Efficacy of bisphosphonates in specific knee osteoarthritis subpopulations: protocol for an OA Trial Bank systematic review and individual patient data meta-analysis

INTRODUCTION: Randomised clinical trials to date investigating the efficacy of bisphosphonates in knee osteoarthritis (OA) have found divergent results, with a recent meta-analysis finding no superiority of these drugs over placebo. Whether particular patient subgroups are more likely to benefit from this therapy than others is still unclear. We aim to investigate the effects of bisphosphonates compared with a control group (placebo, no treatment, another active treatment) on clinical and structural outcomes in specific knee OA subpopulations with possible distinct rates of subchondral bone turnover. METHODS AND ANALYSIS: Medline, Embase, Scopus, Web of Sciences and Cochrane Central Register of Controlled Trials will be searched from inception to February 2018. Randomised clinical trials will be eligible if they reported at least one potential treatment effect modifier at baseline: gender, menopausal status, age, body mass index, radiographic stage, knee pain severity, presence of bone marrow lesions, levels of biochemical markers of bone turnover (serum and/or urinary) and systemic bone mineral density status. Authors of original trials will be contacted to obtain individual patient data from each study. Risk of bias will be assessed using the Cochrane Collaboration's tool. The primary o

An automated workflow based on hip shape improves personalized risk prediction for hip osteoarthritis in the CHECK study

Objective: To design an automated workflow for hip radiographs focused on joint shape and tests its prognostic value for future hip osteoarthritis. Design: We used baseline and 8-year follow-up data from 1,002 participants of the CHECK-study. The primary outcome was definite radiographic hip osteoarthritis (rHOA) (Kellgren–Lawrence grade ≥2 or joint replacement) at 8-year follow-up. We designed a method to automatically segment the hip joint from radiographs. Subsequently, we applied machine learning algorithms (elastic net with automated parameter optimization) to provide the Shape-Score, a single value describing the risk for future rHOA based solely on joint shape. We built and internally validated prediction models using baseline demographics, physical examination, and radiologists scores and tested the added prognostic value of the Shape-Score using Area-Under-the-Curve (AUC). Missing data was imputed by multiple imputation by chained equations. Only hips with pain in the corresponding leg were included. Results: 84% were female, mean age was 56 (±5.1) years, mean BMI 26.3 (±4.2). Of 1,044 hips with pain at baseline and complete follow-up, 143 showed radiographic osteoarthritis and 42 were replaced. 91.5% of the hips had follow-up data available. The Shape-Score was a significant predictor of rHOA (odds ratio per decimal increase 5.21, 95%-CI (3.74–7.24)). The prediction model using demographics, physical examination, and radiologists scores demonstrated an AUC of 0.795, 95%-CI (0.757–0.834). After addition of the Shape-Score the AUC rose to 0.864, 95%-CI (0.833–0.895). Conclusions: Our Shape-Score, automatically derived from radiographs using a novel machine learning workflow, may strongly improve risk prediction in hip osteoarthritis

Serum fatty acid chain length associates with prevalent symptomatic end-stage osteoarthritis, independent of BMI

Higher body mass index (BMI) is associated with osteoarthritis (OA) in both weight-bearing and non-weight-bearing joints, suggesting a link between OA and poor metabolic health beyond mechanical loading. This risk may be influenced by systemic factors accompanying BMI. Fluctuations in concentrations of metabolites may mark or even contribute to development of OA. This study explores the association of metabolites with radiographic knee/hip OA prevalence and progression. A 1H-NMR-metabolomics assay was performed on plasma samples of 1564 cases for prevalent OA and 2,125 controls collected from the Rotterdam Study, CHECK, GARP/NORREF and LUMC-arthroplasty cohorts. OA prevalence and 5 to 10 year progression was assessed by means of Kellgren-Lawrence (KL) score and the OARSI-atlas. End-stage knee/hip OA (TJA) was defined as indication for arthroplasty surgery. Controls did not have OA at baseline or follow-up. Principal component analysis of 227 metabolites demonstrated 23 factors, of which 19 remained interpretable after quality-control. Associations of factor scores with OA definitions were investigated with logistic regression. Fatty acids chain length (FALen), which was included in two factors which associated with TJA, was individually associated with both overall OA as well as TJA. Increased Fatty Acid chain Length is associated with OA

Effect of a Mediterranean type diet on inflammatory and cartilage degradation biomarkers in patients with osteoarthritis

Objectives: To investigate the effects of a Mediterranean type diet on patients with osteoarthritis (OA). Participants: Ninety-nine volunteers with OA (aged 31 - 90 years) completed the study (83% female). Setting: Southeast of England, UK. Design: Participants were randomly allocated to the dietary intervention (DIET, n = 50) or control (CON, n = 49). The DIET group were asked to follow a Mediterranean type diet for 16 weeks whereas the CON group were asked to follow their normal diet. Measurements: All participants completed an Arthritis Impact Measurement Scale (AIMS2) pre-, mid- and post- study period. A subset of participants attended a clinic at the start and end of the study for assessment of joint range of motion, ROM (DIET = 33, CON = 28), and to provide blood samples (DIET = 29, CON = 25) for biomarker analysis (including serum cartilage oligomeric matrix protein (sCOMP) (a marker of cartilage degradation) and a panel of other relevant biomarkers including pro- and anti-inflammatory cytokines). Results: There were no differences between groups in the response of any AIMS2 components and most biomarkers (p > 0.05), except the pro-inflammatory cytokine IL-1?, which decreased in the DIET group (~47%, p = 0.010). sCOMP decreased in the DIET group by 1 U/L (~8%, p = 0.014). There was a significant improvement in knee flexion and hip rotation ROM in the DIET group (p < 0.05). Conclusions: The average reduction in sCOMP in the DIET group (1 U/L) represents a meaningful change, but the longer term effects require further study

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and

CHECKing biochemical markers in early-stage knee and hip osteoarthritis, a critical appraisal

Osteoarthritis (OA) is the most common joint disease and poses a large social and financial burden for societies worldwide. OA is characterized by symptoms of pain, stiffness, and incidental soft tissue swelling of synovial joints. Synovial joints, such as knees and hips, unite bone ends covered by thin layers of articular cartilage in a joint capsule with synovial tissue on its inner surface. Structural signs of OA include articular cartilage loss, growth of bone spurs along the joint margins (osteophytes), and inflammation of synovial tissue (synovitis). These structural signs follow or precede changes in matrix turnover (i.e. degradation and synthesis) of cartilage, bone, and/or synovial tissue and, presumably, are reflected in an altered release of matrix molecules (e.g. synthesis and degradation products of the matrices). In this thesis serum and urinary levels of such molecules were related to radiographic signs and pain of early-stage knee and hip OA in subjects of CHECK (Cohort Hip and Cohort Knee). CHECK is a nationwide cohort that is unique worldwide and is initiated and funded by the Dutch Arthritis Association. Using biochemical markers, especially cartilage degradation and synovitis could be identified as processes underlying the development of radiographic signs and early-stage knee and hip OA. Interestingly, degradation of collagen fibrils in articular cartilage especially appeared to be a risk factor for progression of radiographic knee OA when collagen synthesis was low (i.e. dissociation of degradation and synthesis). Also bone turnover (and with that maybe bone mineral density) could be a relevant factor in the development of radiographic OA, but its effect may be different between knee and hip. Among the metabolic processes monitored, synovitis and osteophyte development appeared important in causing joint pain in knee OA. Finally, also products of adipose tissue, so-called adipokines, could play a role in the pathogenesis of knee OA. Among them, especially leptin could act as a mediator in the effects of obesity (more fat) and female gender (other fat distribution) on knee OA. Notably, the putative cartilage (collagen type II) degradation marker, CTX-II, showed striking similarities with markers of bone metabolism and associations with bone density distant from joints. These data question cartilage specificity of this marker and suggest that CTX-II may also originate from bone. Furthermore, the marker COMP (cartilage oligomeric matrix protein) that is most frequently interpreted as a marker of cartilage degradation might in early-stage OA mainly originate from (inflamed) synovial tissue instead. Although the associations between marker levels and radiographic knee and hip OA were very informative on the pathogenic mechanism behind early-stage OA, they were too weak to be of direct use for clinical research and practice. Further research is needed for increasing the specificity of markers for joints and/or joint compartments, decreasing interference from systemic distribution and metabolism of markers, and better understanding of the pathogenesis of OA. This way, we may succeed in developing markers for detecting critical events in the pathogenesis of OA in relevant OA (sub)populations