Association between knee inflammation and knee pain in patients with knee osteoarthritis: a systematic review.

OBJECTIVE: To systematically review the literature on the relationship between markers of inflammation and pain in patients with knee osteoarthritis (OA). METHODS: We searched MEDLINE, Web of Science and EMBASE databases from inception until June 2021. Eligible articles had to report on the association between inflammation (as measured by effusion, synovitis, baker's cysts, cytokines and C-reactive protein) and pain in patients with radiographic knee OA. Two reviewers independently performed a screening on title and abstracts, data extraction and risk of bias assessment using the Newcastle-Ottawa Scale (NOS). A best evidence synthesis was conducted for each inflammatory sign included in this review. RESULTS: 37 studies were included. Articles reported on the following measures: effusion or synovitis assessed via ultrasound (n = 9) or magnetic resonance imaging (MRI) (n = 17); baker's cyst (n = 3); cytokine concentrations (n = 11); and C-reactive protein levels (n = 4). The strength of the association between inflammation and pain does not exceed the moderate level (i.e., correlation coefficient values ranging from 0.19 to 0.61). Moderate levels of evidence were found for the association between synovitis (measured with ultrasound or contrast enhanced MRI) and pain. The levels of evidence between effusion (assessed via ultrasound), effusion/synovitis (assessed via non-contrast enhanced MRI), Baker's cyst, cytokines, C-reactive protein and pain were conflicting. CONCLUSIONS: Different inflammatory markers are associated with pain but the correlation ranges from weak to moderate, and the quality of evidence from conflicting to moderate. Further research is needed to strengthen the level of evidence and to establish mechanisms.

Natural disease progression in finger osteoarthritis: results from a 10 year follow-up cohort.

Objective: Limited evidence is available about long-term natural disease progression in hand osteoarthritis (HOA). The objective is to study natural radiographic and clinical disease progression in HOA after longer follow-up (i.e. 10 years) and to identify predictors for progression. Method: At baseline (T0), 270 patients with HOA were included in the Belgian HOA register. The majority (84.8%) was female and the mean age was 62.9 years. In total, 154 (57%) and 106 (39.3%) patients consented to follow-up after approximately 5 (T1) and 10 years (T2), respectively. Clinical and functional outcome measures were collected. Hand radiographs were taken and scored according to the anatomical phase scoring system. Results: At T2, most of the patients (73.3%) showed any radiographic progression compared to T0. Remodelling was most frequently seen and new erosive joints rather rarely. Functional Index for Hand Osteoarthritis (0-30) and Australian/Canadian Osteoarthritis Hand Index function (0-90) increased over time, from 8.8 to 9.9 (p = 0.017) and 39.3 to 41.9 (p = 0.035), respectively, after T2. Visual analogue scale pain (0-100) did not change (40.2 to 38.6 from T0 to T2, p = 0.656). Univariate and multivariate logistic regression retained baseline soft-tissue swelling [odds ratio (OR) 8.20 and 8.76, respectively], higher levels of pain (OR 4.08 and 4.30), and number of baseline erosive joints (OR 31.82 and 30.02) as significant predictors for radiographic progression. Conclusions: Significant radiographic progression is seen over time in HOA. While pain remains similar after 10 years, functional status declines. Patients with soft-tissue swelling, high levels of pain, and already erosive disease at baseline are prone to progression over time.

Correction to: Prevalence of musculoskeletal complaints in urban communities in multi-ethnic Suriname: a cross-sectional study with the COPCORD methodology (stage 1, phase 1 and 2).

The footnote of Fig. 2 in the published original version of the above article went missing and the correct figure is presented in this article.].

Prevalence of musculoskeletal complaints in urban communities in multi-ethnic Suriname: a cross-sectional study with the COPCORD methodology (stage 1, phase 1 and 2).

INTRODUCTION/OBJECTIVES: Musculoskeletal complaints (MSCs) are a major burden worldwide. In Suriname, a South American developing country, the epidemiology of MSCs and its related disorders is still unknown. Therefore, a cross-sectional survey was carried out to determine prevalence and risk factors of MSCs in urban areas of Suriname. METHODS: This is the first Community Oriented Program for the Control of Rheumatic Diseases survey in a Caribbean Community. Trained interviewers collecting self-reported data conducted this house-to-house community-based survey. Data was analyzed using SPSS version 23 and Stata version 14.1. RESULTS: The prevalence of MSCs was 62.1% with a higher prevalence rate among women compared with men (resp. 64.3% vs. 58.6%) (Odds ratio = 1.185; p ≤ 0.05). The most decisive self-reported variables associated with MSCs were older age (defined as ≥ 45 years) and moderate to heavy physical workload. The prevalence of MSCs was also associated with women, low educational level, smoking, alcohol use, high-intensity physical activity level, and body mass index (≥ 25 kg/m2). The highest prevalence of MSCs was found among African descendants (Maroons (68.8%) and Creoles (68.0%)), followed by the Indigenous (65.0%) and Asian descendants (Hindustani (64.3%) and Javanese (49.5%)). Most persons with MSCs (75.7%) reported multisite complaints with lower back, knee, and shoulder being the most frequently reported sites. In our study population, MSCs were not considered disabling (mean Health Assessment Questionnaire Disability Index score of 0.23). CONCLUSIONS: The prevalence of MSCs in this urban multi-ethnic Surinamese community is high; therefore, future research is needed to further explore the burden of MSCs in Suriname.Key Points• Musculoskeletal complaints are highly prevalent in different ethnic groups in an urban Surinamese community; almost two-thirds of the population reported MSCs with the highest prevalence rate among women and African descendants.• The most decisive self-reported variables associated with MSCs were older age (defined as ≥ 45 years) and moderate to heavy physical workload. Gender, educational level, smoking, alcohol use, high-intensity physical activity, and body mass index were also significantly associated with musculoskeletal complaints.

Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: a double-blind multicenter randomized placebo controlled three-arm study.

OBJECTIVES: Comparison of two doses of bio-optimized Curcuma longa extract (BCL) in the management of symptomatic knee osteoarthritis (OA). METHODS: A prospective, randomized, 3-month, double-blind, multicenter, three-group, placebo-controlled trial assessing Patient Global Assessment of Disease Activity (PGADA) and serum sColl2-1, a biomarker of cartilage degradation, as co-primary endpoints. Pain on visual analog scale (VAS), Knee injury and Osteoarthritis Outcome Score (KOOS), and paracetamol/non-steroidal anti-inflammatory drug (NSAID) consumption were used as secondary endpoints. RESULTS: One hundred fifty patients with knee OA were followed for 90 days. Low and high doses of BCL showed a greater decrease of PGADA than placebo. Analysis of sColl2-1 showed in the placebo and BCL low-dose groups, but not in the BCL high-dose group, a transient but non-significant increase of sColl2-1 between T0 and T1. Thereafter, in all groups, sColl2-1 decreased between T1 and T3 (all p < 0.01), but no difference between the groups was found. Pain reduction at day 90 in the low- and high-dose BCL groups (- 29.5 mm and - 36.5 mm) was higher than that in the placebo (- 8 mm; p = 0.018). The global KOOS significantly decreased overtime, but changes were comparable across treatment arms. The ratio of patients with adverse events (AE) related to the product was similar in the placebo and treatment groups, but the number of AE linked to the product was higher in the high-dose BCL group compared to the placebo (p = 0.012). CONCLUSIONS: BCL appeared safe and well-tolerated with no evidence of severe adverse effects. Efficacy analysis suggested positive trends for measurements of PGADA and serum levels of an OA biomarker and showed a rapid and significant decrease of pain in knee OA (Trial registration: ISRCTN, ISRCTN12345678. Registered 21 September 2016-retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02909621?term=osteoarthritis+curcumin&rank=5-Evaluation of FLEXOFYTOL® Versus PLACEBO (COPRA) NCT02909621).

Clinical and radiological factors associated with erosive radiographic progression in hand osteoarthritis.

OBJECTIVE: To identify prognostic factors of erosive progression in hand osteoarthritis (OA). METHOD: One hundred and fifty-four patients with hand OA were selected from an earlier cohort. X-rays, clinical and demographic data at baseline were present. All patients were seen for a follow-up between January and March 2014. Interphalangeal (IP) finger joints were scored on both radiographs using the anatomical scoring system. Radiographic progression was defined as a joint progressing from at least one anatomical phase, excluding the progression from a 'Normal' to 'Stationary' phase. Odds ratios (OR) and 95% confidence intervals (95% CI) of potential clinical and radiographic prognostic factors were calculated on joint, hand and patient level with a generalized estimating equation (GEE) model. RESULTS: Radiographic progression, including progression from 'N' to 'S' phase, was present in 1014 of 2750 joints (36.9%) after a mean follow-up of 5.8 years. On joint level, the following clinical factors were associated with radiographic progression (OR [95% CI]): presence of pain (1.48 [1.01-2.15]), tenderness (2.18 [1.56-3.05]), and soft tissue swelling (2.56 [1.54-4.24]). The following radiographic variables were significantly associated with erosive progression: presence of 'J' (16.74 [9.09-30.83]) and 'E' phase (76.34 [42.17-138.23]). On hand and patient level, soft tissue swelling, 'J' and 'E' phase were retained as prognostic factors. CONCLUSION: Pain, tenderness, soft tissue swelling, 'J' and 'E' phase were significantly associated with erosive progression in hand OA. These prognostic factors should be confirmed in further studies and considered when selecting patients for therapeutic trials with potential disease-modifying osteoarthritis drugs (DMODs).

A challenging case of septic sacroiliitis with psoas involvement.

OBJECTIVE AND IMPORTANCE: We report on a rare case of septic arthritis of the sacroiliac joint in a young patient without apparent predisposing factors. CLINICAL PRESENTATION: A 22-year-old female presented with severe right pelvic and gluteal pain and systemic illness. She had a recent diagnosis of bilateral sacroiliitis. INTERVENTION: Systemic illness quickly subsided after initiation of intravenous antibiotic treatment. Subsequently, gluteal pain gradually diminished. CONCLUSION: Pyogenic sacroiliitis should be taken into account in patients with sacroiliitis and fever onset. Magnetic resonance imaging shows signal anomalies well beyond disappearance of symptoms, which may or may not require prolonged antibiotic therapy.

3 T DCE-MRI assessment of synovitis of the interphalangeal joints in patients with erosive osteoarthritis for treatment response monitoring.

OBJECTIVE: To study the value of 3 T dynamic contrast-enhanced (DCE)-MRI for assessment of synovitis of the interphalangeal joints in patients with erosive osteoarthritis (EOA) for treatment response monitoring. MATERIALS AND METHODS: The interphalangeal joints of fingers two to five were examined at 3 T MRI in nine patients with EOA. Two musculoskeletal radiologists recorded erosions, bone marrow oedema (BME), synovitis and osteophytes. Interobserver reliability was calculated using κ statistics. In six patients, DCE-MRI time intensity curves of synovitis in two affected joints were analysed. The maximum upslope, absolute and relative enhancement of synovitis were compared with MRI after 12 months of anti-tumour necrosis factor treatment. Intraobserver reproducibility was calculated using intra-class correlation coefficient. RESULTS: Interobserver reliability was 'good' for detection of erosions (κ = 0.70), BME (κ = 0.77) and synovitis (κ = 0.77), but 'poor' for osteophytes (κ = 0.12). Post-treatment DCE-MRI showed decreasing maximum upslope (p = 0.002) and absolute (p = 0.002) and relative (p = 0.01) enhancement compared to the initial scan. Intraobserver reproducibility of DCE-MRI was 'almost perfect' or 'strong' for all parameters. CONCLUSIONS: 3 T DCE-MRI demonstrates changes in time intensity curves of synovitis in EOA of the interphalangeal joints in a longitudinal study, indicating this technique is promising for monitoring therapy response.

Classification models for disease: the effect of associations between markers on calculating the risk for disease by likelihood ratio products.

OBJECTIVES: The risk for disease or a bad prognosis can be calculated by means of prediction or classification models that take into account multiple variables. Different methods exist to construct such models. Some of those methods, including the likelihood ratio (LR) product method neglect dependency between variables. We aimed to evaluate the effect of neglecting dependency between variables in prediction or classification models. PATIENTS AND METHODS: Population I consisted of 1003 consecutive patients with a new diagnostic problem for which RA was included in the differential diagnosis and final diagnoses (RA or non-RA) were established after 1 year. The baseline variables included in the model are rheumatoid factor, anti-citrullinated protein/peptide antibodies and the HLA-shared epitope. Population II consisted of 847 patients with definite ankylosing spondylitis (AS). Six variables (psoriasis, inflammatory bowel disease, uveitis, HLA-B27 status and latest available CRP) were evaluated. Here, specificities of the features were derived from literature and different scenarios of association between variables in controls and diseased are estimated. RESULTS: When two features are similarly associated in cases and controls, risks for disease will be overestimated by neglecting dependency between variables. In the presented datasets, this resulted in a up to 12% overestimation of the risk. CONCLUSIONS: We showed how the height of over- or underestimation of risks can be evaluated when dependencies between two variables are neglected. This is important to evaluate the predictive value of combinations of features in cases where no data are available on associations in controls.

Cross-cultural adaptation of the Dutch version of the Functional Index for Hand Osteoarthritis (FIHOA) and a study on its construct validity.

OBJECTIVE: To validate a cross-culturally translated and adapted Dutch version of the Functional Index for Hand Osteoarthritis (FIHOA) in patients with osteoarthritis (OA) of the hands and to evaluate its construct validity by comparing with the Australian/Canadian Osteoarthritis Hand Index (AUSCAN). METHODS: The FIHOA was translated into Dutch and cross-culturally adapted. The questionnaire was administered to 72 patients with hand OA (female/male ratio: 64/8, handedness: right: 62/left: 7/both: 3). A visual analogue scale (VAS) pain scale (100mm) and the AUSCAN questionnaire were also recorded. An item-item analysis was performed. Test-retest reliability (time interval: 5 days) was assessed in 21 patients with intraclass correlation coefficient (ICC) and Bland and Altman graphical method. Construct validity was assessed by Spearman rank correlation coefficient between the FIHOA and AUSCAN. RESULTS: Internal consistency was high (Cronbach's alpha=0.89). All items, except for one ('Are you able to clench the fist?'), and the mean total FIHOA scores were statistically different between the subgroups based on the VAS (mean total score=7.46 and 14.19, in a-/mild symptomatic and symptomatic group, respectively (P<0.001)). The Spearman's correlation between all subscales of the AUSCAN (pain, stiffness, functionality) and the FIHOA was good, especially with the subscale functionality (r=0.81, P<0.01). Test-retest reliability was excellent with an ICC of 0.96 for the total score and the Bland and Altman plot showing a homogeneous distribution of the differences. CONCLUSION: The psychometric properties of the Dutch version of the FIHOA are excellent. There is a good correlation between the FIHOA and all subscales of the AUSCAN, especially the subscale functionality.