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.

Task shifting in the care for patients with hand osteoarthritis. Protocol for a randomized controlled non-inferiority trial.

BACKGROUND: Current health policy states that patients with osteoarthritis (OA) should mainly be managed in primary health care. Still, research shows that patients with hand OA have poor access to recommended treatment in primary care, and in Norway, they are increasingly referred to rheumatologist consultations in specialist care. In this randomized controlled non-inferiority trial, we will test if a new model, where patients referred to consultation in specialist health care receive their first consultation by an occupational therapy (OT) specialist, is as safe and effective as the traditional model, where they receive their first consultation by a rheumatologist. More specifically, we will answer the following questions: 1. What are the characteristics of patients with hand OA referred to specialist health care with regards to joint affection, disease activity, symptoms and function? 2. Is OT-led hand OA care as effective and safe as rheumatologist-led care with respect to treatment response, disease activity, symptoms, function and patient satisfaction? 3. Is OT-led hand OA care equal to, or more cost effective than rheumatologist-led care? 4. Which factors, regardless of hand OA care, predict improvement 6 and 12 months after baseline? METHODS: Participants will be patients with hand OA diagnosed by a general practitioner and referred for consultation at one of two Norwegian departments of rheumatology. Those who agree will attend a clinical assessment and report their symptoms and function in validated outcome measures, before they are randomly selected to receive their first consultation by an OT specialist (n = 200) or by a rheumatologist (n = 200). OTs may refer patients to a rheumatologist consultation and vice versa. The primary outcome will be the number of patients classified as OMERACT/OARSI-responders after six months. Secondary outcomes are pain, function and satisfaction with care over the twelve-month trial period. The analysis of the primary outcome will be done by logistic regression. A two-sided 95% confidence interval for the difference in response probability will be formed, and non-inferiority of OT-led care will be claimed if the upper endpoint of this interval does not exceed 15%. DISCUSSION: The findings will improve access to evidence-based management of people with hand OA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03102788. Registered April 6th, 2017, https://clinicaltrials.gov/ct2/show/NCT03102788?term=Kjeken&draw=2&rank=1 Date and version identifier: December 17th, 2020. First version.

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.

Exercise for hand osteoarthritis.

BACKGROUND: Hand osteoarthritis (OA) is a prevalent joint disease that may lead to pain, stiffness and problems in performing hand-related activities of daily living. Currently, no cure for OA is known, and non-pharmacological modalities are recommended as first-line care. A positive effect of exercise in hip and knee OA has been documented, but the effect of exercise on hand OA remains uncertain. OBJECTIVES: To assess the benefits and harms of exercise compared with other interventions, including placebo or no intervention, in people with hand OA. Main outcomes are hand pain and hand function. SEARCH METHODS: We searched six electronic databases up until September 2015. SELECTION CRITERIA: All randomised and controlled clinical trials comparing therapeutic exercise versus no exercise or comparing different exercise programmes. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, extracted data, assessed risk of bias and assessed the quality of the body of evidence using the GRADE approach. Outcomes consisted of both continuous (hand pain, physical function, finger joint stiffness and quality of life) and dichotomous outcomes (proportions of adverse events and withdrawals). MAIN RESULTS: We included seven studies in the review. Most studies were free from selection and reporting bias, but one study was available only as a congress abstract. It was not possible to blind participants to treatment allocation, and although most studies reported blinded outcome assessors, some outcomes (pain, function, stiffness and quality of life) were self-reported. The results may be vulnerable to performance and detection bias owing to unblinded participants and self-reported outcomes. Two studies with high drop-out rates may be vulnerable to attrition bias. We downgraded the overall quality of the body of evidence to low owing to potential detection bias (lack of blinding of participants on self-reported outcomes) and imprecision (studies were few, the number of participants was limited and confidence intervals were wide for the outcomes pain, function and joint stiffness). For quality of life, adverse events and withdrawals due to adverse events, we further downgraded the overall quality of the body of evidence to very low because studies were very few and confidence intervals were very wide.Low-quality evidence from five trials (381 participants) indicated that exercise reduced hand pain (standardised mean difference (SMD) -0.27, 95% confidence interval (CI) -0.47 to -0.07) post intervention. The absolute reduction in pain for the exercise group, compared with the control group, was 5% (1% to 9%) on a 0 to 10 point scale. Pain was estimated to be 3.9 points on this scale (0 = no pain) in the control group, and exercise reduced pain by 0.5 points (95% CI 0.1 to 0.9; number needed to treat for an additional beneficial outcome (NNTB) 9).Four studies (369 participants) indicated that exercise improved hand function (SMD -0.28, 95% CI -0.58 to 0.02) post intervention. The absolute improvement in function noted in the exercise group, compared with the control group, was 6% (0.4% worsening to 13% improvement). Function was estimated at 14.5 points on a 0 to 36 point scale (0 = no physical disability) in the control group, and exercise improved function by 2.2 points (95% CI -0.2 to 4.6; NNTB 9).One study (113 participants) evaluated quality of life, and the effect of exercise on quality of life is currently uncertain (mean difference (MD) 0.30, 95% CI -3.72 to 4.32). The absolute improvement in quality of life for the exercise group, compared with the control group, was 0.3% (4% worsening to 4% improvement). Quality of life was 50.4 points on a 0 to 100 point scale (100 = maximum quality of life) in the control group, and the mean score in the exercise group was 0.3 points higher (3.5 points lower to 4.1 points higher).Four studies (369 participants) indicated that exercise reduced finger joint stiffness (SMD -0.36, 95% CI -0.58 to -0.15) post intervention. The absolute reduction in finger joint stiffness for the exercise group, compared with the control group, was 7% (3% to 10%). Finger joint stiffness was estimated at 4.5 points on a 0 to 10 point scale (0 = no stiffness) in the control group, and exercise improved stiffness by 0.7 points (95% CI 0.3 to 1.0; NNTB 7).Three studies reported intervention-related adverse events and withdrawals due to adverse events. The few reported adverse events consisted of increased finger joint inflammation and hand pain. Low-quality evidence from the three studies showed an increased likelihood of adverse events (risk ratio (RR) 4.55, 95% CI 0.53 to 39.31) and of withdrawals due to adverse events in the exercise group compared with the control group (RR 2.88, 95% CI 0.30 to 27.18), but the effect is uncertain and further research may change the estimates.Included studies did not measure radiographic joint structure changes. Two studies provided six-month follow-up data (220 participants), and one (102 participants) provided 12-month follow-up data. The positive effect of exercise on pain, function and joint stiffness was not sustained at medium- and long-term follow-up.The exercise intervention varied largely in terms of dosage, content and number of supervised sessions. Participants were instructed to exercise two to three times a week in four studies, daily in two studies and three to four times daily in another study. Exercise interventions in all seven studies aimed to improve muscle strength and joint stability or function, but the numbers and types of exercises varied largely across studies. Four studies reported adherence to the exercise programme; in three studies, this was self-reported. Self-reported adherence to the recommended frequency of exercise sessions ranged between 78% and 94%. In the fourth study, 67% fulfilled at least 16 of the 18 scheduled exercise sessions. AUTHORS' CONCLUSIONS: When we pooled results from five studies, we found low-quality evidence showing small beneficial effects of exercise on hand pain, function and finger joint stiffness. Estimated effect sizes were small, and whether they represent a clinically important change may be debated. One study reported quality of life, and the effect is uncertain. Three studies reported on adverse events, which were very few and were not severe.

Increasing synovitis and bone marrow lesions are associated with incident joint tenderness in hand osteoarthritis.

OBJECTIVES: To explore whether changes of MRI-defined synovitis and bone marrow lesions (BMLs) are related to changes in joint tenderness in a 5-year longitudinal study of the Oslo hand osteoarthritis (OA) cohort. METHODS: We included 70 patients (63 women, mean (SD) age 67.9 (5.5) years). BMLs and contrast-enhanced synovitis in the distal and proximal interphalangeal joints were evaluated on 0-3 scales in n=69 and n=48 patients, respectively. Among joints without tenderness at baseline, we explored whether increasing/incident synovitis and BMLs were associated with incident joint tenderness using generalised estimating equations. Among joints with tenderness at baseline, we explored whether decreasing or resolution of synovitis and BMLs were associated with loss of joint tenderness. We adjusted for age, sex, body mass index, follow-up time and changes in radiographic OA. RESULTS: Among joints without tenderness at baseline, increasing/incident synovitis and BMLs were seen in 45 of 220 (20.5%) and 47 of 312 (15.1%) joints, respectively. Statistically significant associations to incident joint tenderness were found for increasing/incident synovitis (OR=2.66, 95% CI 1.38 to 5.11) and BMLs (OR=2.85, 95% CI 1.23 to 6.58) independent of structural progression. We found a trend that resolution of synovitis (OR=1.72, 95% CI 0.80 to 3.68) and moderate/large decreases of BMLs (OR=1.90, 95% CI 0.57 to 6.33) were associated with loss of joint tenderness, but these associations were non-significant. CONCLUSIONS: The Oslo hand OA cohort is the first study with longitudinal hand MRIs. Increasing synovitis and BMLs were significantly associated with incident joint tenderness, whereas no significant associations were found for decreasing or loss of synovitis and BMLs.

Ultrasound-detected inflammation predicts radiographic progression in hand osteoarthritis after 5†years.

OBJECTIVE: To examine whether ultrasound predicts radiographic hand osteoarthritis (OA) progression after 5 years. METHODS: We included 78 participants (71 women, mean (SD) age 67.8 (5.2) years) from the Oslo Hand OA cohort with ultrasound examination (gray-scale (GS) synovitis and power Doppler (PD) signals) at baseline and conventional radiographs and clinical examination at baseline and 5-year follow-up. Radiographic progression was defined as an increase in global OA according to the Kellgren-Lawrence (KL) scale or progression of individual radiographic OA features. We examined whether baseline ultrasound features and clinical examination predicted radiographic progression using generalised estimating equations, adjusted for age, sex, body mass index and follow-up time. RESULTS: Radiographic progression occurred in 17.9% joints for KL, 12.1% for joint space narrowing, 11.7% for osteophytes and 4.5% for erosions. Ultrasound-detected inflammation predicted KL progression, and dose-response associations were observed for GS synovitis grade 1 (OR=2.8, 95% CI 1.8 to 4.2), grade 2 (OR=3.6, 95% CI 2.2 to 5.8) and grade 3 (OR=15.2, 95% CI 6.9 to 33.6), and for PD signal grade 1 (OR=2.9, 95% CI 1.2 to 6.8) and grades 2-3 (OR=12.0, 95% CI 3.5 to 41.0). Significant associations were also observed between ultrasound inflammation and progression of all individual radiographic features, and between clinical soft tissue swelling at baseline and radiographic progression. CONCLUSIONS: Ultrasound-detected GS synovitis and PD signals were significantly associated with radiographic progression after 5 years. This study supports the use of ultrasound as a tool to detect patients with hand OA who are likely to progress.

MRI findings predict radiographic progression and development of erosions in hand osteoarthritis.

OBJECTIVES: To examine whether MRI features predict radiographic progression including erosive evolution in patients from the Oslo hand osteoarthritis (OA) cohort, which is the first longitudinal hand OA study with available MRI. METHODS: We included 74 patients (91% female, mean (SD) age of 67.9 (5.3) years) with MRI of the dominant hand and conventional radiographs taken at baseline and 5-year follow-up. Baseline MRIs were read according to the Oslo hand OA MRI score. We used three definitions of radiographic progression: Progression of joint space narrowing (JSN, grades 0-3), increased Kellgren-Lawrence score (grades 0-4) or incident erosions (absent/present). For each definition, we examined whether MRI features predicted radiographic progression in the same joint using Generalised Estimating Equations. We adjusted for age, sex, Body Mass Index, follow-up time and other erosive joints (the latter for analyses on incident erosions only). RESULTS: MRI-defined moderate/severe synovitis (OR=3.52, 95% CI 1.29 to 9.59), bone marrow lesions (BML) (OR=2.73, 95% CI 1.29 to 5.78) and JSN (severe JSN: OR=11.05, 95% CI 3.22 to 37.90) at baseline predicted progression of radiographic JSN. Similar results were found for increasing Kellgren-Lawrence score, except for weaker association for JSN. Baseline synovitis, BMLs, JSN, bone damage, osteophytes and malalignment were significantly associated with development of radiographic erosions, of which malalignment showed the strongest association (OR=10.18, 95% CI 2.01 to 51.64). CONCLUSIONS: BMLs, synovitis and JSN were the strongest predictors for radiographic progression. Malalignment was associated with incident erosions only. Future studies should explore whether reducing BMLs and inflammation can decrease the risk of structural progression.

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.].

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.

Hand, hip and knee osteoarthritis in a Norwegian population-based study--the MUST protocol.

BACKGROUND: Knowledge about the prevalence and consequences of osteoarthritis (OA) in the Norwegian population is limited. This study has been designed to gain a greater understanding of musculoskeletal pain in the general population with a focus on clinically and radiologically confirmed OA, as well as risk factors, consequences, and management of OA. METHODS/DESIGN: The Musculoskeletal pain in Ullensaker STudy (MUST) has been designed as an observational study comprising a population-based postal survey and a comprehensive clinical examination of a sub-sample with self-reported OA (MUST OA cohort). All inhabitants in Ullensaker municipality, Norway, aged 40 to 79 years receive the initial population-based postal survey questionnaire with questions about life style, general health, musculoskeletal pain, self-reported OA, comorbidities, health care utilisation, medication use, and functional ability. Participants who self-report OA in their hip, knee and/or hand joints are asked to attend a comprehensive clinical examination at Diakonhjemmet Hospital, Oslo, including a comprehensive medical examination, performance-based functional tests, different imaging modalities, cardiovascular assessment, blood and urine samples, and a number of patient-reported questionnaires including five OA disease specific instruments. Data will be merged with six national data registries. A subsample of those who receive the questionnaire has previously participated in postal surveys conducted in 1990, 1994, and 2004 with data on musculoskeletal pain and functional ability in addition to demographic characteristics and a number of health related factors. This subsample constitutes a population based cohort with 20 years follow-up. DISCUSSION: This protocol describes the design of an observational population-based study that will involve the collection of data from a postal survey on musculoskeletal pain, and a comprehensive clinical examination on those with self-reported hand, hip and/or knee OA. These data, in addition to data from national registries, will provide unique insights into clinically and radiologically confirmed OA with respect to risk factors, consequences, and management.

Minimum Core Data Elements for Transcatheter Mitral Therapies: Scientific Statement by PASSION CV, HVC, and TVTR.

Mitral regurgitation is the most common valvular disease and is estimated to affect over 5 million Americans. Real-world data collection contributes to safety and effectiveness evidence for the U.S. Food and Drug Administration, quality evaluation for the Centers for Medicare and Medicaid Services and hospitals, and clinical best practice research. We aimed to establish a minimum core data set in mitral interventions to promote efficient, reusable real-world data collection for all of these purposes. Two expert task forces separately evaluated and reconciled a list of candidate elements derived from: 1) 2 ongoing transcatheter mitral trials; and 2) a systemic literature review of high-impact mitral trials and U.S multicenter, multidevice registries. From 703 unique data elements considered, unanimous consensus agreement was achieved on 127 "core" data elements, with the most common reasons for exclusion from the minimum core data set being burden or difficulty in accurate assessment (41.2%), duplicative information (25.0%), and low likelihood of affecting outcomes (19.6%). After a systematic review and extensive discussions, a multilateral group of academicians, industry representatives, and regulators established and implemented into the national Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapies Registry 127 interoperable, reusable core data elements to support more efficient, consistent, and informative transcatheter mitral device evidence for regulatory submissions, safety surveillance, best practice development, and hospital quality assessments.

Comparison of features by MRI and radiographs of the interphalangeal finger joints in patients with hand osteoarthritis.

OBJECTIVES: To examine the construct validity of MRI in the detection of structural hand osteoarthritis features with conventional radiography (CR) as reference and explore the association between radiographic severity and MRI-defined pathology. METHODS: 106 hand osteoarthritis patients (97 women, mean age 68.9 years (SD 5.6)) had 1.0T contrast-enhanced MRI and CR of the dominant hand. The 2nd-5th interphalangeal joints were scored according to the preliminary Oslo hand osteoarthritis MRI score and Kellgren-Lawrence (KL) scale and Osteoarthritis Research Society International atlas for radiographs. The authors compared the number of joints with structural features by MRI and CR (Wilcoxon signed-rank test) and examined concordance at the individual joint level. The OR of MRI features in joints with doubtful (KL grade 1), mild (2) and moderate/severe (≥3) radiographic osteoarthritis was estimated by generalised estimating equations (KL grade 0 as reference). RESULTS: MRI detected approximately twice as many joints with erosions and osteophytes compared with CR (p<0.001), but identification of joint space narrowing, cysts and malalignment was similar. The sensitivity of MRI was very high for osteophytes (1.00) and erosions (0.95), while specificity was lower (0.22 and 0.63). The prevalence of most MRI features increased with radiographic severity, but synovitis was more frequent in joints with mild osteoarthritis (OR2.1, 95% CI 1.4 to 3.2) than in moderate/severe osteoarthritis (OR1.4, 95% CI 1.0 to 2.2). CONCLUSION: MRI detected more osteophytes and erosions than CR, suggesting that erosive osteoarthritis may be more common than indicated by CR. Synovitis was most common in mild osteoarthritis. Whether this is due to burn-out of inflammation in late disease must be investigated further.

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.

Associations of pain sensitisation with tender and painful joint counts in people with hand osteoarthritis: results from the Nor-Hand study.

OBJECTIVE: To examine associations of pain sensitisation with tender and painful joint counts and presence of widespread pain in people with hand osteoarthritis (OA). METHODS: Pressure pain thresholds (PPT) at a painful finger joint and the tibialis anterior muscle, and temporal summation (TS) were measured in 291 persons with hand OA. We examined whether sex-standardised PPT and TS values were associated with assessor-reported tender hand joint count, self-reported painful hand and total body joint counts and presence of widespread pain using linear and logistic regression analyses adjusted for age, sex, body mass index, education and OA severity. RESULTS: People with lower PPTs at the painful finger joint (measure of peripheral and/or central sensitisation) had more tender and painful hand joints than people with higher PPTs. PPT at tibialis anterior (measure of central sensitisation) was associated with painful total body joint count (beta=-0.82, 95% CI -1.28 to -0.35) and presence of widespread pain (OR=0.57, 95% CI 0.43 to 0.77). The associations between TS (measure of central sensitisation) and joint counts in the hands and the total body were statistically non-significant. CONCLUSION: This cross-sectional study suggested that pain sensitisation (ie, lower PPTs) was associated with joint counts and widespread pain in hand OA. This knowledge may be used for improved pain phenotyping of people with hand OA, which may contribute to better pain management through more personalised medicine. Further studies are needed to assess whether a reduction of pain sensitisation leads to a decrease in tender and painful joint counts.

Minimum Core Data Elements for Evaluation of TAVR: A Scientific Statement by PASSION CV, HVC, and TVT Registry.

Transcatheter aortic valve replacement (TAVR) is the standard of care for severe, symptomatic aortic stenosis. Real-world TAVR data collection contributes to benefit/risk assessment and safety evidence for the U.S. Food and Drug Administration, quality evaluation for the Centers for Medicare and Medicaid Services and hospitals, as well as clinical research and real-world implementation through appropriate use criteria. The essential minimum core dataset for these purposes has not previously been defined but is necessary to promote efficient, reusable real-world data collection supporting quality, regulatory, and clinical applications. The authors performed a systematic review of the published research for high-impact TAVR studies and U.S. multicenter, multidevice registries. Two expert task forces, one from the Predictable and Sustainable Implementation of National Cardiovascular Registries/Heart Valve Collaboratory and another from The Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry convened separately and then met to reconcile a final list of essential data elements. From 276 unique data elements considered, unanimous consensus agreement was achieved on 132 "core" data elements, with the most common reasons for exclusion from the minimum core dataset being burden or difficulty in accurate assessment (36.9%), duplicative information (33.3%), and low likelihood of affecting outcomes (10.7%). After a systematic review and extensive discussions, a multilateral group of academicians, industry representatives, and regulators established 132 interoperable, reusable essential core data elements essential to supporting more efficient, consistent, and informative TAVR device evidence for regulatory submissions, safety surveillance, best practice, and hospital quality assessments.

Minimum Core Data Elements for Evaluation of TAVR: A Scientific Statement by PASSION CV, HVC, and TVT Registry.

Transcatheter aortic valve replacement (TAVR) is the standard of care for severe, symptomatic aortic stenosis. Real-world TAVR data collection contributes to benefit/risk assessment and safety evidence for the U.S. Food and Drug Administration, quality evaluation for the Centers for Medicare and Medicaid Services and hospitals, as well as clinical research and real-world implementation through appropriate use criteria. The essential minimum core dataset for these purposes has not previously been defined but is necessary to promote efficient, reusable real-world data collection supporting quality, regulatory, and clinical applications. The authors performed a systematic review of the published research for high-impact TAVR studies and U.S. multicenter, multidevice registries. Two expert task forces, one from the Predictable and Sustainable Implementation of National Cardiovascular Registries/Heart Valve Collaboratory and another from The Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry convened separately and then met to reconcile a final list of essential data elements. From 276 unique data elements considered, unanimous consensus agreement was achieved on 132 "core" data elements, with the most common reasons for exclusion from the minimum core dataset being burden or difficulty in accurate assessment (36.9%), duplicative information (33.3%), and low likelihood of affecting outcomes (10.7%). After a systematic review and extensive discussions, a multilateral group of academicians, industry representatives, and regulators established 132 interoperable, reusable essential core data elements essential to supporting more efficient, consistent, and informative TAVR device evidence for regulatory submissions, safety surveillance, best practice, and hospital quality assessments.

Transcatheter Mitral Valve Therapy in the United States: A Report from the STS/ACC TVT Registry.

Data for nearly all patients undergoing transcatheter edge-to-edge repair (TEER) and transcatheter mitral valve replacement (TMVR) with an approved device in the United States is captured in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. All data submitted for TEER or TMVR between 2014 and March 31, 2020, are reported. A total of 37,475 patients underwent a mitral transcatheter procedure, including 33,878 TEER and 3,597 TMVR. Annual procedure volumes for TEER have increased from 1,152 per year in 2014 to 10,460 per year in 2019 at 403 sites and for TMVR from 84 per year to 1,120 per year at 301 centers. Mortality rates have decreased for TEER at 30 days (5.6%-4.1%) and 1 year (27.4%-22.0%). Early off-label use data on TMVR in mitral valve-in-valve therapy led to approval by the U.S. Food and Drug Administration in 2017, and the 2019 30-day mortality rate was 3.9%. Overall improvements in outcomes over the last 6 years are apparent. (STS/ACC TVT Registry Mitral Module; NCT02245763).

Reversal of endocrine resistance in breast cancer: interrelationships among 14-3-3ζ, FOXM1, and a gene signature associated with mitosis.

INTRODUCTION: Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. 14-3-3 ζ/YWHAZ, a member of the 14-3-3 family of conserved proteins, is over-expressed in several types of cancer, and our previous work showed that high expression of 14-3-3ζ in ER-positive breast cancers was associated with a poor clinical outcome for women on tamoxifen. Therefore, we now probe the role of 14-3-3ζ in endocrine resistance, and we examine the functional dimensions and molecular basis that underlie 14-3-3ζ activities. METHODS: From analyses of four independent breast cancer microarray datasets from nearly 400 women, we characterized a gene signature that correlated strongly with high expression of 14-3-3ζ in breast tumors and examined its association with breast cancer molecular subtypes and clinical-pathological features. We investigated the effects of altering 14-3-3ζ levels in ER-positive, endocrine sensitive and resistant breast cancer cells on the regulation of 14-3-3ζ signature genes, and on cellular signaling pathways and cell phenotypic properties. RESULTS: The gene signature associated with high 14-3-3ζ levels in breast tumors encompassed many with functions in mitosis and cytokinesis, including aurora kinase-B, polo-like kinase-1, CDC25B, and BIRC5/survivin. The gene signature correlated with early recurrence and risk of metastasis, and was found predominantly in luminal B breast cancers, the more aggressive ER-positive molecular subtype. The expression of the signature genes was significantly decreased or increased upon reduction or overexpression of 14-3-3ζ in ER-positive breast cancer cells, indicating their coregulation. 14-3-3ζ also played a critical role in the regulation of FOXM1, with 14-3-3ζ acting upstream of FOXM1 to regulate cell division-signature genes. Depletion of 14-3-3ζ markedly increased apoptosis, reduced proliferation and receptor tyrosine kinase (HER2 and EGFR) signaling, and, importantly, reversed endocrine resistance. CONCLUSIONS: This study reveals that 14-3-3ζ is a key predictive marker for risk of failure on endocrine therapy and serves a pivotal role impacting growth factor signaling, and promoting cell survival and resistance to endocrine therapies. Targeting 14-3-3ζ and its coregulated proteins, such as FOXM1, should prove valuable in restoring endocrine sensitivity and reducing risk of breast cancer recurrence.

Hand osteoarthritis and MRI: development and first validation step of the proposed Oslo Hand Osteoarthritis MRI score.

OBJECTIVES: MRI scoring systems for hand osteoarthritis (HOA) are currently not available. The present work proposes the Oslo HOA MRI (OHOA-MRI) score and examines the intrareader and inter-reader reliability. METHODS: Relevant HOA features were included in the initial version of the OHOA-MRI score after literature review and informal group discussions. After a training session and two calibration exercises (with three readers), features with low reliability and/or low prevalence were excluded, and feature definitions/gradings were improved. In the reliability exercise 3 readers independently evaluated MRI scans of distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints in 10 patients with HOA according to the final proposed score. The reading was repeated after 1 week. Intraclass correlation coefficients (ICCs), percentage exact agreement/percentage close agreement (PEA/PCA) and smallest detectable difference were calculated. RESULTS: The final proposed OHOA-MRI score includes assessment of synovitis, flexor tenosynovitis, erosions, osteophytes (OPs), joint space narrowing (JSN) and bone marrow lesions (BMLs) on a 0-3 scale, and absence/presence of cysts, malalignment (frontal/sagittal plane), collateral ligaments (CLs) and BMLs at CL insertion sites. Inter-reader reliability was very good for synovitis, erosions, OPs, JSN, malalignment (frontal) and BMLs (ICCs ≥ 0.83, PCA ≥ 89%), and good for flexor tenosynovitis (ICC 0.64, PCA 80%) and CL presence (ICC 0.79, PEA 63%). Cysts, malalignment (sagittal) and BMLs at CL insertion sites showed high PEA (≥ 85%), but poor to moderate ICCs (0.00-0.59). Intrareader reliability was similar. The reliability was generally highest in PIP joints. CONCLUSIONS: The proposed OHOA-MRI score could reliably assess HOA features. However, further validation is needed.