ObjectiveOur objective was to evaluate the diagnostic performance of the EULAR, American College of Rheumatology (ACR), and National Institute for Health and Care Excellence (NICE) criteria by... Show moreObjectiveOur objective was to evaluate the diagnostic performance of the EULAR, American College of Rheumatology (ACR), and National Institute for Health and Care Excellence (NICE) criteria by using clinical experts' diagnosis of clinically relevant knee osteoarthritis (OA) as the outcome of interest.MethodsIn a previous study, we recruited clinical experts to evaluate longitudinal (5-, 8-, and 10-year follow-up) clinical and radiographic data of symptomatic knees from the Cohort Hip and Cohort Knee (CHECK) study for the presence or absence of clinically relevant OA. In the current study, ACR, EULAR, and NICE criteria were applied to the same 5-, 8-, and 10-year follow-up data; then a knee was diagnosed with OA if fulfilling the criteria at one of the three time points (F1), two of the time points (F2), or at all three time points (F3). Using clinically relevant OA as the reference standard, the sensitivity, specificity, and positive and negative predictive values for the three criteria were assessed.ResultsA total of 539 participants for a total of 833 examined knees were included. Thirty-six percent of knees were diagnosed with clinically relevant OA by experts. Sixty-seven percent to 74% of the knees received the same diagnosis (OA or non-OA) by the three criteria sets for the different definitions (F1 to F3). EULAR consistently (F1 through F3) had the highest specificity, and NICE consistently had the highest sensitivity.ConclusionThe diagnoses only moderately overlapped among the three criteria sets. The EULAR criteria seemed to be more suitable for study enrollment (when aimed at recruiting clinically relevant OA knees), given the highest specificities. The NICE criteria, given the highest sensitivities, could be more useful for an initial diagnosis in clinical practice. Show less
Meulen, C. van der; Stadt, L.A. van de; Rosendaal, F.R.; Runhaar, J.; Kloppenburg, M. 2023
Objectives: To investigate pain, pain trajectories and their determinants in hand osteoarthritis (OA). Methods: Data from the HOSTAS (Hand OSTeoArthritis in Secondary care) consisting of... Show moreObjectives: To investigate pain, pain trajectories and their determinants in hand osteoarthritis (OA). Methods: Data from the HOSTAS (Hand OSTeoArthritis in Secondary care) consisting of consecutive hand OA patients were used. Australian Canadian Osteoarthritis Hand Index (AUSCAN) pain was measured yearly for four years. Patients with complete AUSCAN at >= 2 time points were eligible for longitudinal analysis. Associations between variables of interest and baseline AUSCAN pain were investigated with linear regression. Development of pain over time was modelled using latent class growth analysis (LCGA). Associations of LCGA classes with variables of interest were analysed using multinomial logistic regression adjusted for baseline pain. Results: A total of 484/538 patients [mean (s.d.) age 60.8 (8.5) years, 86% women, mean (s.d.) AUSCAN pain 9.3 (4.3)] were eligible for longitudinal analysis. Sex, marital and working status, education, disease duration and severity, anxiety and depression scores, lower health-related quality of life (HR-QoL), specific illness perceptions and coping styles were associated with baseline pain. LCGA yielded three classes, characterized by average pain levels at baseline; average pain remained stable over time within classes. Classes with more pain were positively associated with BMI, tender joint count, symptom duration, hand function scores and depression scores, negatively with physical HR-QoL, and education level. Conclusion: Baseline pain was associated with patient and disease characteristics, and psychosocial factors. LCGA showed three pain trajectories in hand OA patients, with different baseline pain levels and stable pain over time. Classes were distinguished by BMI, education level, disease severity, depression and HR-QoL. Show less
Wang, Q.K.; Runhaar, J.; Kloppenburg, M.; Boers, M.; Bijlsma, J.W.J.; Bacardit, J.; ... ; CREDO Experts Grp 2022
Objectives To identify highly ranked features related to clinicians' diagnosis of clinically relevant knee OA. Methods General practitioners (GPs) and secondary care physicians (SPs) were recruited... Show moreObjectives To identify highly ranked features related to clinicians' diagnosis of clinically relevant knee OA. Methods General practitioners (GPs) and secondary care physicians (SPs) were recruited to evaluate 5-10 years follow-up clinical and radiographic data of knees from the CHECK cohort for the presence of clinically relevant OA. GPs and SPs were gathered in pairs; each pair consisted of one GP and one SP, and the paired clinicians independently evaluated the same subset of knees. A diagnosis was made for each knee by the GP and SP before and after viewing radiographic data. Nested 5-fold cross-validation enhanced random forest models were built to identify the top 10 features related to the diagnosis. Results Seventeen clinician pairs evaluated 1106 knees with 139 clinical and 36 radiographic features. GPs diagnosed clinically relevant OA in 42% and 43% knees, before and after viewing radiographic data, respectively. SPs diagnosed in 43% and 51% knees, respectively. Models containing top 10 features had good performance for explaining clinicians' diagnosis with area under the curve ranging from 0.76-0.83. Before viewing radiographic data, quantitative symptomatic features (i.e. WOMAC scores) were the most important ones related to the diagnosis of both GPs and SPs; after viewing radiographic data, radiographic features appeared in the top lists for both, but seemed to be more important for SPs than GPs. Conclusions Random forest models presented good performance in explaining clinicians' diagnosis, which helped to reveal typical features of patients recognized as clinically relevant knee OA by clinicians from two different care settings. Show less
Wang, Q.K.; Runhaar, J.; Kloppenburg, M.; Boers, M.; Bijlsma, J.W.J.; Bierma-Zeinstra, S.M.A.; CREDO Expert Grp 2022
Objective: To internally and externally validate our diagnostic criteria of early stage knee osteoarthritis (OA) in the CHECK and OAI cohorts. Design: We applied two previously developed diagnostic... Show moreObjective: To internally and externally validate our diagnostic criteria of early stage knee osteoarthritis (OA) in the CHECK and OAI cohorts. Design: We applied two previously developed diagnostic models to all knees in CHECK and OAI cohorts to calculate probabilities of early stage knee OA at baseline. Knees were categorized into three groups based on probability: 'no OA' (probability <= 30%), 'uncertain' (probability between 30% and 70%) and 'early stage OA' (probability >= 70%). To validate the diagnosis, we obtained OA related outcome measures at 10-year follow-up in the CHECK cohort, and at 8-9-year follow-up in the OAI cohort. We compared outcome measures between 'no OA' and 'early stage OA' knees, and between 'no OA' and 'uncertain' knees using generalized estimating equations. Results: In CHECK (n = 1042 knees) both models showed 'early stage OA' knees presented with significant and clinically relevant higher WOMAC scores, higher Kellgren & Lawrence (KL) grade, and higher rates of joint space narrowing (JSN) progression after 10 years, compared to 'no OA' knees. In OAI (n = 2937 knees) both models showed 'early stage OA' knees presented with significant and clinically relevant higher WOMAC scores, higher KL grade, and higher rates of KL and JSN progression after 8-9 years, compared to 'no OA' knees. Smaller, but still significant differences between 'uncertain' and 'no OA' knees were observed in both cohorts. Conclusions: These results support internal and external validity of the two sets of diagnostic criteria for early stage knee OA. (C) 2022 The Author(s). Published by Elsevier Inc. Show less
IMPORTANCE Intra-articular (IA) glucocorticoid injection is widely used in patients with knee osteoarthritis (OA), but the safety of this technique is in question among physicians. Intramuscular ... Show moreIMPORTANCE Intra-articular (IA) glucocorticoid injection is widely used in patients with knee osteoarthritis (OA), but the safety of this technique is in question among physicians. Intramuscular (IM) glucocorticoid injection could be an alternative approach.OBJECTIVE To investigate whether an IM glucocorticoid injection is noninferior to an IA glucocorticoid injection in reducing knee pain for patients with knee OA in primary care.DESIGN, SETTING, AND PARTICIPANTS The KIS trial, a multicenter, open-label, randomized clinical noninferiority trial including patients with symptomatic knee OA, was conducted in 80 primary care general practices in the southwest of the Netherlands. The study was conducted from March 1, 2018, to July 28, 2020.INTERVENTIONS Patients were randomly allocated to receive an injection of triamcinolone acetonide, 40 mg, either IM in the ipsilateral ventrogluteal region or IA in the knee joint. All patients were followed up for 24 weeks.MAIN OUTCOMES AND MEASURES The pain score at 4 weeks measured with Knee Injury and Osteoarthritis Outcome Score (range, 0-100; 0 indicates extreme pain), with a noninferiority margin of -7 (IM minus IA). A per-protocol analysis was prespecified as the primary analysis.RESULTS A total of 145 patients (94 women [65%]; mean [SD] age, 67 [10] years) were included; of these, 138 patients (IM, 72; IA, 66) were included in the per-protocol analysis. Clinically relevant improvements in knee pain were reached up to 12 weeks after the injection in both groups. At 4 weeks, the estimated mean difference in the Knee Injury and Osteoarthritis Outcome Score between the 2 groups was -3.4 (95% CI, -10.1to 3.3). Noninferiority could not be declared because the lower limit exceeded the noninferiority margin. Intramuscular injection was noninferior to IA injection at 8 (mean difference, 0.7; 95% CI, -6.5 to 7.8) and 24 (mean difference, 1.6; 95% CI, -5.7 to 9.0) weeks. No significant difference was found among all the secondary outcomes. These results were similar for the sensitivity analysis in an intention-to-treat population. The most frequently reported adverse events were hot flush (IM, 7 [10%] vs IA, 14 [21%]) and headache (IM, 10 [14%] vs IA, 12 [18%]), and all events were classified as nonserious.CONCLUSIONS AND RELEVANCE Based on the findings of this trial, among patients with knee OA in primary care, IM glucocorticoid injection could present an inferior effect in reducing pain at 4 weeks compared with IA injection. Noninferiority of an IM injection was observed at 8 and 24 weeks after injection. This trial provides data for shared decision-making, taking into account the advantages and disadvantages of both types of injections. Show less
Hall, M.; Esch, M. van der; Hinman, R.S.; Peat, G.; Zwart, A. de; Quicke, J.G.; ... ; Bennell, K.L. 2022
Hip and knee osteoarthritis (OA) are leading causes of global disability. Most research to date has focused on the knee, with results often extrapolated to the hip, and this extends to treatment... Show moreHip and knee osteoarthritis (OA) are leading causes of global disability. Most research to date has focused on the knee, with results often extrapolated to the hip, and this extends to treatment recommendations in clinical guidelines. Extrapolating results from research on knee OA may limit our understanding of disease characteristics specific to hip OA, thereby constraining development and implementation of effective treatments. This review highlights differences between hip and knee OA with respect to prevalence, prognosis, epigenetics, pathophysiology, anatomical and biomechanical factors, clinical presentation, pain and non-surgical treatment recommendations and management. (c) 2021 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Show less
Runhaar, J.; Ozbulut, O.; Kloppenburg, M.; Boers, M.; Bijlsma, J.W.J.; Bierma-Zeinstra, S.M.A.; CREDO Expert Grp 2021
Objectives. Although there is a general focus on early diagnosis and treatment of hip OA, there are no validated diagnostic criteria for early-stage hip OA. The current study aimed to take the... Show moreObjectives. Although there is a general focus on early diagnosis and treatment of hip OA, there are no validated diagnostic criteria for early-stage hip OA. The current study aimed to take the first steps in developing diagnostic criteria for early-stage hip OA, using factors obtained through history taking, physical examination, radiography and blood testing at the first consultation in individuals presenting with hip pain, suspicious for hip OA, in primary care.Methods. Data of the 543 individuals with 735 symptomatic hips at baseline who had any follow-up data available from the prospective CHECK cohort study were used. A group of 26 clinical experts [general practitioners (GPs), rheumatologists and orthopaedic surgeons] evaluated standardized clinical assessment forms of all subjects on the presence of clinically relevant hip OA 5-10 years after baseline. Using the expert-based diagnoses as reference standard, a backward selection method was used to create predictive models based on pre-defined baseline factors from history taking, physical examination, radiography and blood testing.Results. Prevalence of clinically relevant hip OA during follow-up was 22%. Created models contained four to eight baseline factors (mainly WOMAC pain items, painful/restricted movements and radiographic features) and obtained area under the curve between 0.62 (0.002) and 0.71 (0.002).Conclusion. Based on clinical and radiographic features of hip OA obtained at first consultation at a GP for pain/stiffness of the hip, the prediction of clinically relevant hip OA within 5-10 years was 'poor' to /fair'. Show less
Wang, Q.K.; Runhaar, J.; Kloppenburg, M.; Boers, M.; Bijlsma, J.W.J.; Bierma-Zeinstra, S.M.A.; CREDO Expert Grp 2021
Background Early diagnosis of knee osteoarthritis (OA) is important in managing this disease, but such an early diagnostic tool is still lacking in clinical practice. The purpose of this study was... Show moreBackground Early diagnosis of knee osteoarthritis (OA) is important in managing this disease, but such an early diagnostic tool is still lacking in clinical practice. The purpose of this study was to develop diagnostic models for early stage knee OA based on the first 2-year clinical course after the patient's initial presentation in primary care and to identify whether these course factors had additive discriminative value over baseline factors. Methods We extracted eligible patients' clinical and radiographic data from the CHECK cohort and formed the first 2-year course factors according to the factors' changes over the 2 years. Clinical expert consensus-based diagnosis, which was made via evaluating patients' 5- to 10-year follow-up data, was used as the outcome factor. Four models were developed: model 1, included clinical course factors only; model 2, included clinical and radiographic course factors; model 3, clinical baseline factors + clinical course factors; and model 4, clinical and radiographic baseline factors + clinical and radiographic course factors. All the models were built by a generalized estimating equation with a backward selection method. Area under the receiver operating characteristic curve (AUC) and its 95% confidence interval (CI) were calculated for assessing model discrimination. Delong's method compared AUCs. Results Seven hundred sixty-one patients with 1185 symptomatic knees were included in this study. Thirty-seven percent knees were diagnosed as OA at follow-up. Model 1 contained 6 clinical course factors; model 2: 6 clinical and 3 radiographic course factors; model 3: 6 baseline clinical factors combined with 5 clinical course factors; and model 4: 4 clinical and 1 radiographic baseline factors combined with 5 clinical and 3 radiographic course factors. Model discriminations are as follows: model 1, AUC 0.70 (95% CI 0.67-0.74); model 2, 0.74 (95% CI 0.71-0.77); model 3, 0.77 (95% CI 0.74-0.80); and model 4, 0.80 (95% CI 0.77-0.82). AUCs of model 3 and model 4 were slightly but significantly higher than corresponding baseline-factor models (model 3 0.77 vs 0.75, p = 0.031; model 4 0.80 vs 0.76, p = 0.003). Conclusions Four diagnostic models were developed with "fair" to "good" discriminations. First 2-year course factors had additive discriminative value over baseline factors. Show less
Runhaar, J.; Kloppenburg, M.; Boers, M.; Bijlsma, J.W.J.; Bierma-Zeinstra, S.M.A.; CREDO Expert Grp 2021
Objectives. There is a general consensus that a shift in focus towards early diagnosis and treatment of knee OA is warranted. However, there are no validated and widely accepted diagnostic criteria... Show moreObjectives. There is a general consensus that a shift in focus towards early diagnosis and treatment of knee OA is warranted. However, there are no validated and widely accepted diagnostic criteria for early knee OA available. The current study aimed to take the first steps towards developing diagnostic criteria for early knee OA.Methods. Data of 761 individuals with 1185 symptomatic knees at baseline were selected from the CHECK study. For CHECK, individuals with pain/stiffness of the knee, aged 45-65 years, who had no prior consultation or a first consultation with the general practitioner for these symptoms in the past 6 months were recruited and followed for 10 years. A group of 36 experts (17 general practitioners and 19 secondary care physicians) evaluated the medical records in pairs to diagnose the presence of clinically relevant knee OA 5-10 years after enrolment. A backward selection methods was used to create predictive models based on pre-defined baseline factors from history taking, physical examination, radiography and blood testing, using the experts' diagnoses as gold standard outcome.Results. Prevalence of clinically relevant knee OA during follow-up was 37%. Created models contained 7-11 baseline factors and obtained an area under the curve between 0.746(0.002) and 0.764(0.002).Conclusion. The obtained diagnostic models for early knee OA had 'fair' predictive ability in individuals presenting with knee pain in primary care. Further modelling and validation of the identified predictive factors is required to obtain clinically feasible and relevant diagnostic criteria for early knee OA. Show less
Wang, Q.K.; Runhaar, J.; Kloppenburg, M.; Boers, M.; Bijlsma, J.W.J.; Bierma-Zeinstra, S.M.A.; CREDO Expert Grp 2020
Objective: The purpose of this study was to evaluate the added value of radiographs for diagnosing knee osteoarthritis (KOA) by general practitioners (GPs) and secondary care physicians (SPs).... Show moreObjective: The purpose of this study was to evaluate the added value of radiographs for diagnosing knee osteoarthritis (KOA) by general practitioners (GPs) and secondary care physicians (SPs). Methods: Seventeen GPs and nineteen SPs were recruited to evaluate 1185 knees from the CHECK cohort (presenters with knee pain in primary care) for the presence of clinically relevant osteoarthritis (OA) during follow-up. Experts were required to make diagnoses independently, first based on clinical data only and then on clinical plus radiographic data, and to provide certainty scores (ranging from 1 to 100, where 1 was "certainly no OA" and 100 was "certainly OA"). Next, experts held consensus meetings to agree on the final diagnosis. With the final diagnosis as gold standard, diagnostic indicators were calculated (sensitivity, specificity, positive/negative predictive value, accuracy and positive/negative likelihood ratio) for all knees, as well as for clinically "certain" and "uncertain" knees, respectively. Student paired t-tests compared certainty scores. Results: Most diagnoses of GPs (86%) and SPs (82%) were "consistent" after assessment of radiographic data. Diagnostic indicators improved similarly for GPs and SPs after evaluating the radiographic data, but only improved relevantly in clinically "uncertain" knees. Radiographs added some certainty to "consistent" OA knees (GP 69 vs. 72, p < 0.001; SP 70 vs. 77, p < 0.001), but not to the consistent no OA knees (GP 21 vs. 22, p = 0.16; SP 20 vs. 21, p = 0.04). Conclusions: The added value of radiographs is similar for GP and SP, in terms of diagnostic accuracy and certainty. Radiographs appear to be redundant when clinicians are certain of their clinical diagnosis. Show less
Background The knee is symptomatically the most frequent affected joint in osteoarthritis and, in the Netherlands and other Western countries, is mainly managed by general practitioners (GPs). An... Show moreBackground The knee is symptomatically the most frequent affected joint in osteoarthritis and, in the Netherlands and other Western countries, is mainly managed by general practitioners (GPs). An intra-articular glucocorticoid injection is recommended in (inter) national guidelines for patients with knee osteoarthritis as an option for a flare of knee pain and/or for those who are not responding well to pain medication. An innovative approach that could replace the intra-articular injection is an intramuscular gluteal glucocorticoid injection. An intramuscular injection is easier to perform than an intra-articular injection with lesser risk of severe local adverse reactions. We hypothesize that intramuscular gluteal glucocorticoid injection is non-inferior in reducing knee pain compared to intra-articular glucocorticoid injection, with potentially a longer lasting effect than intra-articular injection. Methods/design The study will be a pragmatic randomized controlled non-inferiority trial with two parallel groups. A total of 140 patients aged 45 years and older with knee osteoarthritis who contacted their general practitioner and have persistent knee pain (score >= 3 on 0-10 numerical rating scale; 0 = no knee pain) will be included. Patients will be randomly allocated (1:1) to an injection of 40 mg triamcinolone acetonide intra-articular in the knee joint or intramuscular in the ipsilateral ventrogluteal area. The effect of treatment will be evaluated by questionnaires at 2, 4, 8, 12, and 24 weeks after injection. The primary outcome is patients' reported severity of knee pain measured with the pain subscale of the Knee injury and Osteoarthritis Outcome Score 4 weeks after injection. Statistical analysis will be based on both the per-protocol and the intention-to-treat principle. Discussion This study will evaluate non-inferiority of intramuscular glucocorticoid injection compared to intra-articular glucocorticoid injection for knee osteoarthritis symptoms. Trial sponsor Erasmus MC University Medical Center Rotterdam. PO-box 2040. 3000 CA Rotterdam. The Netherlands. Show less
Damen, J.; Runhaar, J.; Kloppenburg, M.; Meijer, R.; Bierma-Zeinstra, S.; Oei, E. 2016
