Corrigendum to "Study protocol for the follow-up examination of the Nor-Hand study: A hospital-based observational cohort study exploring pain and biomarkers in people with hand osteoarthritis" [Osteoarthr. Cartil. Open 3 (2021) 100198].

[This corrects the article DOI: 10.1016/j.ocarto.2021.100198.].

Associations between fluorescence optical imaging and magnetic resonance imaging and symptoms in hand osteoarthritis.

OBJECTIVES: To investigate whether Fluorescence Optical Imaging (FOI) enhancement and MRI-defined synovitis are associated with pain and physical function in hand OA patients. METHODS: Bilateral FOI scans and MRI of the dominant hand were available for 221 patients. Finger joints were examined for tenderness on palpation. Pain in individual finger joints during the last 24 h and last 6 weeks and hand pain intensity by the Australian/Canadian hand index and Numeric Rating Scale were self-reported. On joint level, we applied logistic regression with generalized estimating equations to examine whether FOI enhancement and MRI-defined synovitis were associated with pain in the same joint. On subject level, we applied linear regression to assess whether FOI and MRI sum scores were associated with pain intensity and physical function. RESULTS: Metacarpophalangeal and thumb base joints were excluded from analyses due to little/no FOI enhancement. Finger joints with FOI enhancement on the composite image had higher odds (95% CI) of pain during the last 6 weeks [grade 1: 1.4 (1.2-1.6); grade 2-3: 2.1 (1.7-2.6)]. Similar results were found for joint pain during the last 24 h and joint tenderness in fingers. Numerically stronger associations were found between MRI-defined synovitis and finger joint pain/tenderness. FOI and MRI sum scores demonstrated no/weak associations with hand pain and physical function. CONCLUSION: FOI enhancement and MRI-defined synovitis were associated with pain in the same finger joint. None of the imaging modalities demonstrated consistent associations with pain, stiffness and physical function on subject level.

Comparison of 2 Postoperative Therapy Regimens After Trapeziectomy Due to Osteoarthritis: A Randomized, Controlled Trial.

PURPOSE: The main aim of the present study was to evaluate whether early mobilization after trapeziectomy in the first carpometacarpal joint is noninferior to a postoperative regimen comprising the use of a rigid orthosis and mobilization after 6 weeks, with regards to patient-reported activity performance and the effect of surgery in patients with first carpometacarpal osteoarthritis. METHODS: In this prospective, randomized, controlled noninferiority trial, participants were assessed at baseline (before group allocation) and at 3, 6, and 12 months after surgery. The primary outcomes were activity performance, measured using the Canadian Occupational Performance Measure (1-10, where 1 = unable to perform), and the patient-reported effect of surgery on a 6-point scale ranging from "much worse" to "completely recovered." A change of 2.0 points in the Canadian Occupational Performance Measure was used as a noninferiority margin. Secondary outcomes included hand function (patient-reported in the Measure of Activity Performance of the Hand questionnaire), pain on a numeric rating scale, grip and pinch strengths, and joint mobility. We performed both intention-to-treat and per-protocol analyses. RESULTS: Of the 59 participants (88% women) with a mean age of 65 years, 55 (93%) completed all assessments. We found no differences between the groups in primary or secondary outcomes at any time point, except for more decreased pain at rest in the intervention group (n = 28) compared with the control group (n = 27) after 12 months. The per-protocol analyses did not change these results. Fifteen participants experienced 1 or more adverse events during the first 3 months, but the types and frequencies of adverse events were similar between the 2 groups. CONCLUSIONS: A postoperative regimen with early mobilization after trapeziectomy is as safe and effective as a postoperative regimen with longer immobilization in patients with first carpometacarpal osteoarthritis. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Study protocol for the follow-up examination of the Nor-Hand study: A hospital-based observational cohort study exploring pain and biomarkers in people with hand osteoarthritis.

Objective: This study aims to increase the understanding of pain mechanisms in hand OA and explore potential risk factors for pain development or worsening in a biopsychosocial framework. Another important aim is to validate potential soluble and imaging OA biomarkers. Design: The follow-up examination of the Nor-Hand hospital-based observational cohort study started in October 2019 and was completed in May 2021. In total, 212 of the 300 participants with hand OA who were examined at baseline attended the follow-up study. The participants underwent clinical joint examinations, medical and functional assessments, quantitative sensory testing, fluorescence optical imaging, ultrasound of the hands, acromioclavicular joints, feet, knees and hips, conventional radiographs of the hands and feet and magnetic resonance imaging of the dominant hand. Blood and urine samples were collected, and all participants answered questions about demographic factors and OA-related questionnaires. Associations between disease variables and symptoms will be examined in cross-sectional and longitudinal analyses. Longitudinal analyses will be performed to assess the predictive value of baseline variables on hand OA outcomes. Conclusion: Current knowledge about predictors for disease progression in hand OA is limited, but with longitudinal data we will be able to explore the predictive value of baseline variables on hand OA outcomes, such as changes in patient-reported outcomes or changes in soluble and imaging biomarkers. This provides a unique opportunity to gain more knowledge about the natural disease course of hand OA.

Validity and diagnostic performance of fluorescence optical imaging measuring synovitis in hand osteoarthritis: baseline results from the Nor-Hand cohort.

OBJECTIVE: Fluorescence optical imaging (FOI) demonstrates enhanced microcirculation in finger joints as a sign of inflammation. We wanted to assess the validity and diagnostic performance of FOI measuring synovitis in persons with hand OA, comparing it with magnetic resonance imaging (MRI)- and ultrasound-detected synovitis. METHODS: Two hundred and twenty-one participants with hand OA underwent FOI and ultrasound (gray-scale synovitis and power Doppler activity) of the bilateral hands and contrast-enhanced MRI examination of the dominant hand. Fifteen joints in each hand were scored on semi-quantitative scales (grade 0-3) for all modalities. Four FOI images were evaluated: one composite image (Prima Vista Mode (PVM)) and three images representing phases of fluorescent dye distribution. Spearman's correlation coefficients were calculated between sum scores of FOI, MRI, and ultrasound. Sensitivity, specificity, and area under the curve (AUC) were calculated for FOI using MRI or ultrasound as reference. RESULTS: FOI did not demonstrate enhancement in the thumb base, and the joint was excluded from further analyses. FOI sum scores showed poor to fair correlations with MRI (rho 0.01-0.24) and GS synovitis sum scores (rho 0.12-0.25). None of the FOI images demonstrated both good sensitivity and specificity, and the AUC ranged from 0.50-0.61 and 0.51-0.63 with MRI and GS synovitis as reference, respectively. FOI demonstrated similar diagnostic performance with PD activity and GS synovitis as reference. CONCLUSION: FOI enhancement correlated poorly with synovitis assessed by more established imaging modalities, questioning the value of FOI for the evaluation of synovitis in hand OA.

Fluorescence optical imaging for treatment monitoring in patients with early and active rheumatoid arthritis in a 1-year follow-up period.

BACKGROUND: Fluorescence optical imaging (FOI) enables visualization of inflammation in the hands in rheumatic joint diseases with currently a lack of long-term follow-up studies. OBJECTIVE: To investigate FOI for treatment monitoring in a homogenous cohort of patients with early (disease duration < 2 years) and active (DAS28 > 3.2) RA over a period of 12 months. METHODS: Thirty-five RA patients (24 (68.6%) females, mean age 53.3 years (SD 13.6)) were investigated clinically by DAS28, tender joint count (TJC) and swollen joint count (SJC) and by FOI in phases 1-3 and PrimaVistaMode (PVM) before therapy change and after 12 months. The FOI activity score (FOIAS) was calculated based on individual joint scores from 0 to 3 in 30 joints per patient, adding up to a sum score (0-90). RESULTS: We found a statistically significant reduction of FOIAS in phase 1 from baseline (median 5.0, IQR 24.96) to follow-up (median 1.0, IQR 4.0) in all patients (p = 0.0045), both in responders and non-responders according to EULAR response criteria by DAS28. Statistically significant reductions over 12 months were found for median DAS28(ESR) 5.61 to 3.31, TJC 7.0 to 1.0, and SJC 5.0 to 1.0 (each p <  0.001). No statistically significant correlations were detected between the FOIAS change in phase 1 and DAS28(ESR), TJC, or SJC. Correlations between the other phases and clinical outcomes were weak to moderate. CONCLUSION: Reduced early enhancement in FOI phase 1 can be observed in clinically responding and non-responding early RA patients under treatment. Regarding potential marker performance, FOI probably shows a reduction of inflammation more objectively.

Non-pharmacological treatment gap preceding surgical consultation in thumb carpometacarpal osteoarthritis - a cross-sectional study.

BACKGROUND: Osteoarthritis (OA) in the thumb carpometacarpal joint (CMCJ) is a prevalent disease which may lead to structural damage, severe pain and functional limitations. Evidence-based treatment recommendations state that all patients with hand OA should be offered non-pharmacological treatment. Surgery should be considered only when other treatment has proven insufficient in relieving pain. The purpose of this study was to investigate prior treatment and characteristics of patients referred to specialist health care surgical consultation due to CMCJ OA. The study includes exploring differences in pain and function between referred and non-referred hand, between men and women, and between patients with and without OA affection of other finger joints than CMCJ. METHODS: Patients in this cross-sectional study reported prior non-pharmacological treatment for CMCJ OA. Patient demographics, disease and functional variables were assessed based on hand radiographs, patient-reported and observer-based outcome measures. Differences in pain and function between referred and non-referred hand, men and women, and between patients with and without additional affection of finger joints other than CMCJ, were analysed using Paired-samples T-tests, Wilcoxon Signed Rank, or Chi-Square tests. RESULTS: One hundred and eighty patients were included. The mean age was 63 years and 79% were women. Only 21% reported having received non-pharmacological treatment before referral to surgical consultation. The results show a statistically significant worse function for referred hands, women and involvement of additional interphalangeal joints. Most patients reported no pain or mild pain in their referred hand. CONCLUSIONS: The results of this study show a non-pharmacological treatment gap in OA care. Most patients report no pain or mild pain, and that they had not received non-pharmacological treatment prior to being referred to CMCJ OA surgical consultation. The results furthermore show that CMCJ OA negatively affects all aspects of function. Strategies need to be developed to improve OA care, including educating general practitioners in evidence-based treatment recommendations and in the assessment of hand pain, and encourage the routine referral of patients with symptomatic hand OA to occupational therapy before considering surgery.

A hospital-based observational cohort study exploring pain and biomarkers in patients with hand osteoarthritis in Norway: The Nor-Hand protocol.

INTRODUCTION: We have limited knowledge about the underlying disease mechanisms and causes of pain in hand osteoarthritis (OA). Consequently, no disease-modifying drug exists, and more knowledge about the pathogenesis of hand OA is needed, as well as a validation of different outcome measures. Our first aim of this study is to explore the validity of various imaging modalities for the assessment of hand OA. Second, we want to gain a better understanding of the disease processes, with a special focus on pain mechanisms. METHODS AND ANALYSIS: The Nor-Hand study is a hospital-based observational study including 300 patients with evidence of hand OA by ultrasound and/or clinical examination. The baseline examination consists of functional tests and joint assessment of the hands, medical assessment, pain sensitisation tests, ultrasound (hands, acromioclavicular joint, hips, knees and feet), CT and MRI of the dominant hand, conventional radiographs of the hands and feet, fluorescence optical imaging of the hands, collection of blood and urine samples as well as self-reported demographic factors and OA-related questionnaires. Two follow-up examinations are planned. Cross-sectional analyses will be used to investigate agreements and associations between different relevant measures at the baseline examination, whereas the longitudinal data will be used for evaluation of predictors for clinical outcomes. ETHICS AND DISSEMINATION: The protocol is approved by the Norwegian Regional Committee for Medical and Health Research Ethics (Ref. no: 2014/2057). The participants receive oral and written information about the project and sign a consent form before participation. They can, whenever they want, withdraw from the study, and all de-identified data will be safely stored on the research server at Diakonhjemmet Hospital. Results will be presented at international and national congresses and in peer-reviewed rheumatology journals. TRIAL REGISTRATION NUMBER: NCT03083548; Pre-results.

Long term type 1 diabetes is associated with hand pain, disability and stiffness but not with structural hand osteoarthritis features - The Dialong hand study.

OBJECTIVE: To explore whether having long-term type 1 diabetes (>45 years) is associated with a higher prevalence of radiographic hand OA, erosive hand OA and increased hand pain, disability and stiffness. METHODS: In total N = 96 persons with type 1 diabetes diagnosed before 1970 were included (mean [SD] age: 62.2 [7.4], mean [SD] HbA1c: 7.43 [0.80] and N = 49 [51%] men). Regular measurements of their HbA1c were obtained till 2015. We included N = 69 healthy controls without any diabetes (mean [SD] age: 63.0 [7.0], mean [SD] HbA1c: 5.41 [0.32], N = 29 [42%] men). The groups were compared for radiographic hand OA (Kellgren-Lawrence grade ≥2 in ≥1 joint) and erosive hand OA (central erosions in ≥1 joint), Australian/Canadian index (AUSCAN) for hand pain, disability and stiffness using regression analyses adjusted for age, sex, educational level and waist circumference. RESULTS: We found no associations between having long term type 1 diabetes and more prevalent radiographic hand OA (OR = 0.83, 95% CI = 0.38-1.81). We found a trend towards higher prevalence of erosive hand OA in diabetes patients (OR = 2.96, 95% CI = 0.82-10.64). Strong and consistent associations were observed between long term type 1 diabetes and increased hand pain (B = 2.78, 95% CI = 1.65-3.91), disability (B = 5.30, 95% CI = 3.48-7.12) and stiffness (B = 2.00, 95% CI = 1.33-2.67). These associations were particularly strong for women and participants below the median age of 61 years. CONCLUSION: Long-term type 1 diabetes was not associated with radiographic hand OA, but was strongly associated with hand pain, disability and stiffness. The association between diabetes and erosive hand OA warrants further investigation.

The comparison of magnetic resonance imaging and radiographs to assess structural progression over 5 years in hand osteoarthritis.

Objective: . The aim was to explore the agreement between 1.0 T MRI and conventional radiography (CR) to detect progression of hand OA over 5 years and the associations between structural progression and incident joint tenderness. Methods: Paired radiographs and paired MRIs of the second-fifth IP joints of the dominant hand from 69 hand OA patients were read for osteophytes, joint space narrowing and erosions. Patients with two or more joints demonstrating progression of any structural feature(s) were classified as progressors per imaging modality. Agreement between methods to detect progressors was evaluated with κ and intraclass correlation coefficients. At the joint level, the associations between methods to detect progression were explored with generalized estimating equations. Likewise, we analysed the associations between progression per imaging modality and incident pain. Results: MRI (58.0%) and CR (62.3%) detected similar numbers of progressors. The agreement between methods to detect progressors was good (κ = 0.61). We found good agreement between methods regarding the number of progressive joints (intraclass correlation coefficient = 0.61, 95% CI: 0.43, 0.76). At the joint level, MRI progression was associated with radiographic progression (P < 0.001). Incident joint tenderness was more common in joints with progression by MRI and CR, but statistically significance was not reached. Conclusion: Both 1.0 T MRI and CR detect a similar amount of progression over 5 years in patients with hand OA, although not in exactly the same joints. As CR assesses more joints for a lower cost, CR should be the imaging modality of choice rather than 1.0 T MRI in observational studies with a long period of follow-up.

Imaging of osteoarthritis (OA): What is new?

In daily clinical practice, conventional radiography is still the most applied imaging technique to supplement clinical examination of patients with suspected osteoarthritis (OA); it may not always be needed for diagnosis. Modern imaging modalities can visualize multiple aspects of the joint, and depending on the diagnostic need, radiography may no longer be the modality of choice. Magnetic resonance imaging (MRI) provides a complete assessment of the joint and has a pivotal role in OA research. Computed tomography (CT) and nuclear medicine offer alternatives in research scenarios, while ultrasound can visualize bony and soft-tissue pathologies and is highly feasible in the clinic. In this chapter, we overview the recent literature on established and newer imaging modalities, summarizing their ability to detect and quantify the range of OA pathologies and determining how they may contribute to early OA diagnosis. This accurate imaging-based detection of pathologies will underpin true understanding of much needed structure-modifying therapies.

Effects of a soft prefabricated thumb orthosis in carpometacarpal osteoarthritis.

AIMS: To explore the feasibility and assess the effect of a prefabricated soft thumb-base orthosis on pain, hand strength, and activity performance in persons with osteoarthritis of the CMC joint. METHODS: In this randomized controlled trial, 29 patients received hand exercises only (control group) and 30 patients received hand exercises and an orthosis (orthosis group). The primary outcome was pain, while secondary outcomes included grip and pinch strength, and self-reported symptoms and activity performance. Outcome assessments, and measures of grip strength and pain with and without orthosis in the orthosis group, were made after two months. RESULTS: 55 participants (mean age 70.5 years) completed all assessments. There were no significant differences between the groups in primary or secondary outcomes after two months. However, in the orthosis group, pain was significantly less when wearing the orthosis than when not wearing it. Participants reported that the orthosis felt uncomfortable during activities involving water and one-third wanted more support of the CMC joint. CONCLUSIONS: A soft prefabricated orthosis seems to have an immediate pain-relieving effect during use, but no effects in terms of less hand pain, or improved strength or activity performance when not worn.

Role of modern imaging techniques in hand osteoarthritis research and clinical practice.

Hand osteoarthritis (OA) is a frequent disease, which may lead to considerable pain and physical limitations. However, limited research has been performed in hand OA. Lately, modern imaging techniques, such as ultrasonography (US) and magnetic resonance imaging (MRI), have gained increasing attention in hand OA clinical research. Both modalities may provide important knowledge about the natural history and pathogenesis of the disease, in addition to serving as potential outcome measures in clinical trials. In clinical practice, the diagnosis of hand OA should be based on clinical examination and conventional radiography, if necessary. However, US and MRI can provide information about the degree of inflammation and exclude potential differential diagnoses.

Ultrasonographic assessment of osteophytes in 127 patients with hand osteoarthritis: exploring reliability and associations with MRI, radiographs and clinical joint findings.

OBJECTIVE: To investigate the reliability of ultrasonographic assessment of osteophytes and explore the concordance of osteophytes detected by ultrasound, MRI, conventional radiography (CR) and clinical joint examination in patients with hand osteoarthritis (HOA). METHODS: The study included 127 HOA patients (116 women, mean age 68.6 years (SD 5.8)) with ultrasound, CR and clinical examination of both hands and MRI of dominant hand. Osteophytes were assessed by all imaging modalities on 0-3 scales, whereas clinical bony enlargement was assessed as absent/present. An ultrasound atlas of ostephytes was developed, and the intra and inter-reader reliability of scoring ultrasound osteophytes on still images using the atlas as reference was examined. The reliability for ultrasound readings was examined with κ and percentage exact agreement (PEA) and percentage close agreement (PCA), and the sensitivity, specificity and PEA/PCA of ultrasound was calculated in comparison with MRI, CR and clinical examination. RESULTS: Ultrasound had high sensitivity (0.83) and specificity (0.75) in detecting osteophytes compared with MRI, with excellent PCA (96.1%). Moderate/large osteophytes (grade 2-3) were demonstrated more often by ultrasound (n=401) than by MRI (n=288) in 851 interphalangeal joints. Ultrasound detected more osteophytes (53.2%) than CR (30.0%) and clinical examination (36.9%). Intra and inter-reader reliability of ultrasound was excellent (PEA >88%, PCA 100% and weighted kappa >0.91). CONCLUSION: Ultrasound can reliably assess osteophytes in patients with HOA. Good agreement was found between osteophytes detected by ultrasound and MRI, while ultrasound was more sensitive than CR and clinical examination, which could be due to a multiplanar joint demonstration by ultrasound.

The association between erosive hand osteoarthritis and subchondral bone attrition of the knee: the Framingham Osteoarthritis Study.

OBJECTIVE: To examine whether erosive hand osteoarthritis (OA) is associated with knee subchondral bone attrition (SBA) and systemic bone mineral density (BMD). METHODS: Associations of MRI-defined knee SBA with radiographic erosive hand OA were evaluated in 1253 Framingham participants using logistic regression with generalised estimating equations. We also examined the association between the number of erosive OA finger joints and SBA adjusted for the number of non-erosive OA finger joints. Associations between erosive hand OA and femoral neck BMD were explored in 2236 participants with linear regression. Analyses were adjusted for age, sex and body mass index. RESULTS: Participants with erosive hand OA had increased odds of knee SBA (OR=1.60, 95% CI 1.07 to 2.38). The relation between the number of erosive OA finger joints and SBA became non-significant when adjusted for the number of non-erosive OA joints as a proxy for the burden of disease. There was a non-significant trend towards higher BMD in erosive hand OA compared with participants without hand OA. CONCLUSIONS: Erosive hand OA was associated with knee SBA, but the relation might be best explained by a heightened burden of disease. No significant relation of erosive hand OA with BMD was found.

Associations between MRI-defined synovitis, bone marrow lesions and structural features and measures of pain and physical function in hand osteoarthritis.

OBJECTIVES: To explore associations between MRI features and measures of pain and physical function in hand osteoarthritis (OA). METHODS: Eighty-five patients (77 women) with mean (SD) age of 68.8 (5.6) years underwent contrast-enhanced MRI of the interphalangeal joints (dominant hand) and clinical joint assessment. One investigator read the MRIs for presence/severity of osteophytes, joint space narrowing, erosions, bone attrition, cysts, malalignment, synovitis, flexor tenosynovitis, bone marrow lesions (BMLs) and ligament discontinuity according to the proposed Oslo hand OA MRI score. Pain and physical function were assessed by joint palpation (tenderness yes/no), self-reported questionnaires (Australian/Canadian (AUSCAN) hand index, Functional Index of hand osteoarthritis (FIHOA), Arthritis Impact Measurement Scale-2 (AIMS-2) hand/finger) and grip strength. Logistic regression with generalised estimating equations was used to explore associations between the presence of MRI features and joint tenderness, and linear regression for associations between the burden of MRI abnormalities and patient-reported outcomes and grip strength (adjusted for age and sex). MRI features with p<0.25 were introduced into a multivariate model. The final model included features with p≤0.10 (backward selection). RESULTS: MRI-defined moderate/severe synovitis (OR=2.4; p<0.001), BMLs (OR=1.5; p=0.06), erosions (OR=1.4; p=0.05), attrition (OR=2.5; p<0.001) and osteophytes (OR=1.4; p=0.10) were associated with joint tenderness independently of each other (final model adjusted for age and sex). The sum score of MRI-defined attrition was associated with FIHOA (B=0.58; p=0.005), while the sum score of osteophytes was associated with grip strength (B=-0.39; p<0.001). No significant associations were found with AUSCAN pain/physical function or AIMS-2 hand/finger subscales. CONCLUSION: MRI-defined synovitis, BMLs, erosions and attrition were associated with joint tenderness. Synovitis and BMLs may be targets for therapeutic interventions in hand OA.

The AUSCAN subscales, AIMS-2 hand/finger subscale, and FIOHA were not unidimensional scales.

OBJECTIVES: Evaluate the internal construct validity of the Australian/Canadian (AUSCAN) index for hand osteoarthritis (HOA) and identify the physical function instrument with best performance. STUDY DESIGN AND SETTING: AUSCAN, AIMS-2 (Arthritis Impact Measurement Scale 2), and Functional Index of HOA (FIHOA) were self-completed by 209 HOA patients (mean [standard deviation] age 61.6 [5.7] years) at baseline and 128 at follow-up. Rasch analysis was performed. RESULTS: AUSCAN pain, physical function, and stiffness subscales comprised three constructs. AUSCAN scale performance was improved after removal of "Pain at rest" from the pain scale and division of physical function into two scales of high precision and grip strength tasks. AIMS-2 hand/finger subscale and FIHOA were improved after removal of one and two items, respectively and collapse of two AIMS-2 response categories. AUSCAN physical function scale showed better targeting to the sample and higher person reliability compared with FIHOA and especially AIMS-2 because of less "severe" items concerning grip strength tasks as opposed to precision tasks. CONCLUSION: The AUSCAN subscales, AIMS-2 hand/finger scale, and FIHOA were not unidimensional. However, deletion of misfitting items improved scale performance. The revised AUSCAN physical function and FIHOA scales are preferable for measurement of grip strength and precision tasks, respectively.