Phenotypic characteristics of patients with chronic widespread pain and fibromyalgia: a cross-sectional cluster analysis.

OBJECTIVE: This study aimed to explore whether phenotypic characteristics of patients with chronic widespread pain (CWP) and fibromyalgia (FM) can be aggregated into definable clusters that may help to tailor treatments. METHOD: Baseline variables (sex, age, education, marital/employment status, pain duration, prior CWP/FM diagnosis, concomitant rheumatic disease, analgesics, tender point count, and disease variables derived from standardized questionnaires) collected from 1099 patients (93.4% females, mean age 44.6 years) with a confirmed CWP or FM diagnosis were evaluated by hierarchical cluster analysis. The number of clusters was based on coefficients in the agglomeration schedule, supported by dendrograms and silhouette plots. Simple and multiple regression analyses using all variables as independent predictors were used to assess the likelihood of cluster assignment, reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Only one cluster emerged (Cluster 1: 455 patients). Participants in this cluster were characterized as working (OR 66.67, 95% CI 7.14 to 500.00), with a medium-term/higher education (OR 16.80, 95% CI 1.94 to 145.41), married/cohabiting (OR 14.29, 95% CI 1.26 to 166.67), and using mild analgesics (OR 25.64, 95% CI 0.58 to > 999.99). The odds of being an individual in Cluster 1 were lower when having a worse score on the PDQ (score ≥ 18) (OR < 0.001, 95% CI < 0.001 to 0.02). CONCLUSION: We identified one cluster, where participants were characterized by a potentially favourable clinical profile. More studies are needed to evaluate whether these characteristics could be used to guide the management of patients with CWP and FM.

Validity of the Brief Illness Perception Questionnaire in people with knee pain: a Rasch analysis.

OBJECTIVE: The Brief Illness Perception Questionnaire (B-IPQ) is a frequently used measure of illness perception (IP). The aim of this study was to explore the psychometric properties of the questionnaire when used in elderly people with knee pain. METHOD: Based on data from the Frederiksberg Cohort on elderly people reporting knee pain (N = 836), the psychometric properties of the eight B-IPQ items (1 'Consequences', 2 'Timeline', 3 'Personal control', 4 'Treatment control', 5 'Identity', 6 'Concern', 7 'Coherence', and 8 'Emotions') were analysed using Rasch analysis to establish whether the questionnaire provides reliable and valid measures of IP. RESULTS: Threshold disordering was found on the 1-10 rating scale in all items. When rescaling to a 0-2 rating scale, disordering was resolved in six items. Item goodness-of-fit analyses revealed that two items displayed underfit misfit and four items overfit misfit; hence, the B-IPQ does not present unidimensionality. The person separation index indicated that items separate respondents into only two IP levels. Finally, floor and ceiling effects were found, indicating that the B-IPQ may not fully describe the extent of IP in this population. CONCLUSION: The 1-10 rating scale used in the Danish B-IPQ targeting knee pain is suboptimal, while a 0-2 scale improves the psychometric properties of the scale. The B-IPQ does not present unidimensionality and the use of a sum score is therefore not recommended when assessing IP. The B-IPQ may not cover the extent of IP in elderly people with knee pain.

Exercise and education vs intra-articular saline for knee osteoarthritis: a 1-year follow-up of a randomized trial.

OBJECTIVE: To assess the longer-term effect of the Good Life with osteoarthritis in Denmark (GLAD) exercise and education program relative to open-label placebo (OLP) on changes from baseline in core outcomes in individuals with knee osteoarthritis (OA). METHODS: In this 1-year follow-up of an open-label, randomized trial, patients with symptomatic and radiographically confirmed knee OA were monitored after being randomized to either the 8-week GLAD program or OLP given as 4 intra-articular saline injections over 8 weeks. The primary outcome was the change from baseline in the Knee injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale after 1 year in the intention-to-treat population. Key secondary outcomes were the KOOS function and quality of life subscales, and Patients' Global Assessment of disease impact. RESULTS: 206 adults were randomly assigned: 102 to GLAD and 104 to OLP, of which only 137 (63/74 GLAD/OLP) provided data at 1 year. At one year the mean changes in KOOS pain were 8.4 for GLAD and 7.0 for OLP (Difference: 1.5 points; 95% CI -2.6 to 5.5). There were no between-group differences in any of the secondary outcomes. CONCLUSIONS: In this 1-year follow-up of individuals with knee OA, the 8-week GLAD program and OLP both provided minor longer-term benefits with no group difference. These results require confirmation given the significant loss to follow-up. TRIAL REGISTRATION NUMBER: NCT03843931.

Who are likely to benefit from the Good Life with osteoArthritis in Denmark (GLAD) exercise and education program? An effect modifier analysis of a randomised controlled trial.

OBJECTIVE: To identify contextual factors that modify the treatment effect of the 'Good Life with osteoArthritis in Denmark' (GLAD) exercise and education programme compared to open-label placebo (OLP) on knee pain in individuals with knee osteoarthritis (OA). METHODS: Secondary effect modifier analysis of a randomised controlled trial. 206 participants with symptomatic and radiographic knee OA were randomised to either the 8-week GLAD programme (n = 102) or OLP given as 4 intra-articular saline injections over 8 weeks (n = 104). The primary outcome was change from baseline to week 9 in the Knee injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale (range 0 (worst) to 100 (best)). Subgroups were created based on baseline information: BMI, swollen study knee, bilateral radiographic knee OA, sports participation as a young adult, sex, median age, a priori treatment preference, regular use of analgesics (NSAIDs or paracetamol), radiographic disease severity, and presence of constant or intermittent pain. RESULTS: Participants who reported use of analgesics at baseline seem to benefit from the GLAD programme over OLP (subgroup contrast: 10.3 KOOS pain points (95% CI 3.0 to 17.6)). Participants with constant pain at baseline also seem to benefit from GLAD over OLP (subgroup contrast: 10.0 points (95% CI 2.8 to 17.2)). CONCLUSIONS: These results imply that patients who take analgesics or report constant knee pain, GLAD seems to yield clinically relevant benefits on knee pain when compared to OLP. The results support a stratified recommendation of GLAD as management of knee OA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03843931. EudraCT number 2019-000809-71.

Influence of procedural factors on patient procedural pain in relation to diagnostic lumbar puncture.

OBJECTIVE: The aim of this study is to investigate the influence of local anesthetic (LA), operator experience level and needle type on patient procedural pain in relation to diagnostic lumbar puncture (LP). METHODS: LP was performed with either a 22 gauge traumatic needle (22 TN) or a 22 gauge atraumatic needle (22 ATN). Immediately after LP patients documented a procedural pain score (PPS) on a 10-point Likert scale. Use of LA, needle type, anesthetic time interval (ATI), number of needle insertions and the LP operator experience level were registered. ATI was defined as the time from administration of LA to first needle insertion. RESULTS: 104 patients had the LP procedure performed by 66 physicians (40 novices and 26 experienced physicians). Patients having the procedure performed by novices had a lower PPS of 2.56 if LA was administered compared to a higher PPS of 5.80 if LA was not administered (P = .046). Among experienced physicians there was no difference in PPS regardless of administration of LA. If novices administered LA, patient PPS was equal to patients having the procedure performed by an experienced operator. If novices performed the procedure with a 22 TN PPS decreased with increasing ATI (P = .01). No similar correlation was identified with the 22 ATN. CONCLUSION: Our study suggests that LP operator experience level, the needle type used and ATI may influence patient PPS. Further studies are necessary for final conclusions. These studies must consider these factors to avoid fault conclusions.

Facile generation of monoclonal antibodies suitable for conjugation.

Monoclonal antibodies (mAb) are unique tools in therapeutics and immunodiagnostics applications but many of these applications rely on conjugated mAbs. Whether conjugating drugs or tracers, the conjugation process, frequently taking advantage of primary amines on lysine residues, may affect the binding activity of the antibodies. Furthermore, due to the sticky nature of many mAbs, unfavorable interactions may become eminent, with the result of high background signals. The workload associated with producing mAbs, able to withstand conjugation, preserving stability and affinity and avoiding off-target interactions, is comprehensive and related with only incidental success. We designed a method, where uncloned hybridomas were pre-selected for secretion of mAbs with the above characteristics. Using human collectin K1 (CL-K1, alias CL-11, Colec11) as a model antigen, mAbs present in culture supernatant from uncloned hybridomas were immobilized on Protein A beads, followed by solid phase biotinylation and subsequent elution. ELISA was employed to compare the binding activity of conjugated vs. unconjugated mAbs, and furthermore for their application in combination with other antibodies. From a group of 96 uncloned hybridomas we accomplished in obtaining five suitable mAbs, among which, two mAbs were superior. The successful conjugation of the selected mAbs with fluorophores and subsequent applications in microscopy and flow cytometry were further demonstrated. In conclusion, pre-selection of uncloned hybridomas, by testing of their mAbs' ability to withstand conjugation with tracers or drugs, is a successful strategy to avoid a huge workload of cloning numerous hybridomas, in order to obtain conjugatable mAbs.

The impact of a significant weight loss on inflammation assessed on DCE-MRI and static MRI in knee osteoarthritis: a prospective cohort study.

OBJECTIVE: To study the impact of weight loss on inflammation in individuals with overweight and knee osteoarthritis (OA) using both static- and dynamic contrast-enhanced (DCE)-MRI and assess the association of these changes to pain. DESIGN: Individuals with overweight (BMI > 27) and knee OA were examined before and after a >5% weight loss over 8 weeks (ClinicalTrials.gov NCT02905864). Using 3-T MRI, inflammation was quantified from non-contrast enhanced static-MRI according to MOAKS and contrast enhanced static MRI according to BLOKS and 11-point whole-knee synovitis score. DCE-MRI was used to assess the inflammation in the infra patellar fat pad (IPFP). Pain was assessed using KOOS. RESULTS: Complete data were available in 117 participants with a mean age of 60 years, BMI of 35 kg/m2 and KOOS pain score of 64. Mean weight loss was 12 kg and KOOS pain was improved by 13 points at follow-up. Change in inflammation was not associated with weight loss in static MRI. None of the MRI variables correlated with the change in KOOS pain. CONCLUSION: Weight loss did not induce a significant change in inflammation in individuals with overweight and OA. The significant clinical beneficial effect of weight loss on knee pain in individuals with overweight and knee OA seems uncoupled to changes in imaging markers of synovitis.

Home visits in the Danish High Risk and Resilience Study - VIA 7: assessment of the home environment of 508 7-year-old children born to parents diagnosed with schizophrenia or bipolar disorder.

OBJECTIVE: The home environment provided by the caregivers of a child is an influential single factor for development and well-being. We aimed to compare the quality of the home environment of children at familial high risk of schizophrenia or bipolar disorder with population-based controls. METHODS: Danish nationwide registers were used to retrieve a cohort of 522 7-year-old children of parents diagnosed with schizophrenia (N = 202), bipolar disorder (N = 120) or none of these diagnoses (N = 200). The home environment was assessed using the Middle Childhood-Home Observation for Measurement of the Environment Inventory (MC-HOME Inventory). RESULTS: The proportion of children living in home environments that were evaluated not to meet the needs of a 7-year-old child was significantly larger in the two familial high-risk groups. This was true for 21% of the children with familial predisposition for schizophrenia and 7% of children with familial disposition for bipolar disorder. CONCLUSION: Children born to parents diagnosed with schizophrenia and to a lesser extent bipolar disorder are at an increased risk of growing up in a home environment with an insufficient level of stimulation and support. Identifying families with inadequate home environments is a necessary step towards specialized help and support to at-risk families.

Explosion characteristics for Li-ion battery electrolytes at elevated temperatures.

Li-ion batteries are used in electronic devices and electric cars, yet they create safety concerns due to the possibility of the release of combustible materials. The electrolyte, one of the main components in a Li-ion cell, consists of organic carbonates. Venting and thermal runaway release organic carbonates and when mixed with air, it can result in fires and explosions. A 20-liter explosion sphere was used to determine the explosion characteristics for three typical carbonates used in electrolytes, at 373 K, and 100 kPa absolute pressure. The explosion pressure and the maximum rate of explosion pressure rise are presented for the carbonates and for hydrogen, methane, and propane, and the explosive limits for the carbonates are also identified at the same conditions. This allowed a comparison of the explosion characteristics for the carbonates with those for hydrogen, methane, and propane. Theoretical calculations gave a higher explosion pressure than that from the experimental results most likely due to losses in the hydrocarbon experiments. The carbonates analyzed have very similar explosion pressures and rate of explosion pressure rise as propane. The explosion characteristics found for the three carbonates can be used in future consequence and risk assessments for Li-ion battery installations.

Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial.

BACKGROUND AND OBJECTIVES: The 52-week, randomized, double-blind, noninferiority, government-funded NOR-SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT-P13 was not inferior to continued treatment with infliximab originator. The NOR-SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT-P13 throughout the 78-week study period (maintenance group) versus patients switched to CT-P13 at week 52 (switch group). The primary outcome was disease worsening during follow-up based on disease-specific composite measures. METHODS: Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis. RESULTS: Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per-protocol set). Adjusted risk difference was 5.9% (95% CI -1.1 to 12.9). Frequency of adverse events, anti-drug antibodies, changes in generic disease variables and disease-specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases. CONCLUSION: The NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.

Poor replicability of recommended exercise interventions for knee osteoarthritis: a descriptive analysis of evidence informing current guidelines and recommendations.

OBJECTIVE: To examine the reporting completeness of exercise-based interventions for knee osteoarthritis (OA) in studies that form the basis of current clinical guidelines, and examine if the clinical benefit (pain and disability) from exercise is associated with the intervention reporting completeness. DESIGN: Review of clinical OA guidelines METHODS: We searched MEDLINE and EMBASE for guidelines published between 2006 and 2016 including recommendations about exercise for knee OA. The studies used to inform a recommendation were reviewed for exercise reporting completeness. Reporting completeness was evaluated using a 12-item checklist; a combination of the Template for Intervention Description and Replication (TIDieR) and Consensus on Exercise Reporting Template (CERT). Each item was scored 'YES' or 'NO' and summarized as a proportion of interventions with complete descriptions and each intervention's completeness was summarized as the percentage of completely described items. The association between intervention description completeness score and clinical benefits was analyzed with a multilevel meta-regression. RESULTS: From 10 clinical guidelines, we identified 103 original studies of which 100 were retrievable (including 133 interventions with 6,926 patients). No interventions were completely described on all 12 items (median 33% of items complete; range 17-75%). The meta-regression analysis indicated that poorer reporting was associated with greater effects on pain and no association with effects on disability. CONCLUSION: The inadequate description of recommended interventions for knee OA is a serious problem that precludes replication of effective interventions in clinical practice. By consequence, the relevance and usability of clinical guideline documents and original study reports are diminished. PROSPERO: CRD42016039742.

Asymptomatic hypoglycaemia in Type 1 diabetes: incidence and risk factors.

AIM: The epidemiology of asymptomatic (silent) hypoglycaemia is not well-described. We investigated incidence and risk factors for asymptomatic hypoglycaemia in Type 1 diabetes. METHODS: A cohort of 153 people with Type 1 diabetes participated in 6 days of blinded continuous glucose monitoring (CGM) and recording of hypoglycaemia symptoms. At entry, hypoglycaemia awareness was classified (by three different methods) and HbA1c and C-peptide were measured. Hypoglycaemic episodes were defined as interstitial glucose ≤ 3.9 mmol/l (IG3.9 ) or ≤ 3.0 mmol/l (IG3.0 ) for ≥ 15 min, and were considered asymptomatic if no hypoglycaemic symptoms were reported. RESULTS: At thresholds IG3.9 and IG3.0 , the incidence rates of hypoglycaemic episodes were 5.0 (7.9) [median (IQR)] and 1.3 (3.4) episodes/person-week, respectively. Three-quarters of episodes were asymptomatic. In total, 77% and 52% of participants experienced one or more episode of asymptomatic hypoglycaemia at IG3.9 and IG3.0 [3.0 (6.2) and 1.0 (2.3) asymptomatic episodes/person-week]. At multivariate analysis, reduced awareness was positively associated with asymptomatic hypoglycaemia, particularly nocturnal events, and negatively with symptomatic hypoglycaemia. High insulin dose was associated with increased risk of both asymptomatic and symptomatic hypoglycaemia, whereas low HbA1c and long diabetes duration were risk factors only for symptomatic hypoglycaemia. CONCLUSIONS: Asymptomatic hypoglycaemia constitutes the majority of hypoglycaemic events in Type 1 diabetes. Reduced hypoglycaemia awareness and high insulin dose are risk factors for asymptomatic hypoglycaemia but other conventional risk factors for severe hypoglycaemia do not correlate with risk of asymptomatic episodes.

Day-to-Day Reliability of Nonlinear Methods to Assess Walking Dynamics.

The present study investigated the day-to-day reliability (quantified by the absolute and relative reliability) of nonlinear methods used to assess human locomotion dynamics. Twenty-four participants of whom twelve were diagnosed with knee osteoarthritis completed 5 min of treadmill walking at self-selected preferred speed on two separate days. Lower limb kinematics were recorded at 100 Hz and hip, knee, and ankle joint angles, three-dimensional (3D) sacrum marker displacement and stride time intervals were extracted for 170 consecutive strides. The largest Lyapunov exponent and correlation dimension were calculated for the joint angle and sacrum displacement data using three different state space reconstruction methods (group average, test-retest average, individual time delay and embedding dimension). Sample entropy and detrended fluctuation analysis (DFA) were applied to the stride time interval time series. Relative reliability was assessed using intraclass correlation coefficients and absolute reliability was determined using measurement error (ME). For both joint angles and sacrum displacement, there was a general pattern that the group average state space reconstruction method provided the highest relative reliability and lowest ME compared to the individual and test-retest average methods. The DFA exhibited good reliability, while the sample entropy showed poor reliability. The results comprise a reference material that can inspire and guide future studies of nonlinear gait dynamics.

The effect of intra-articular glucocorticosteroids and exercise on symptoms and bone marrow lesions in knee osteoarthritis: a secondary analysis of results from a randomized controlled trial.

OBJECTIVE: To evaluate if the relative volume of bone marrow lesions (BMLs) changed in patients with knee osteoarthritis (OA) during a therapeutic study. DESIGN: This study is a sub-study to a larger clinical trial which compared the clinical effects of intra-articular corticosteroid injection in knee OA to placebo injection, both given prior to exercise therapy. Clinical assessment using the Knee injury and Osteoarthritis Outcome Score (KOOS) and magnetic resonance imaging (MRI) examinations with BML assessments were performed at baseline and follow-up after 14 weeks and 26 weeks, respectively. The BML volume was determined using a computer assisted method focusing on participants with valid baseline and follow-up MRI examinations. Any changes in BML and KOOS were analyzed and investigated for associations. RESULTS: Fifty participants received steroid and placebo injection, respectively, of which 41 and 45 had complete MRI examinations at week 14, and 36 and 33 at week 26, respectively. All participants received 12 weeks of exercise. A significant change in relative BML volume was observed between the corticosteroid group and the placebo group after 14 weeks [-1.1% vs 2.7%; between-group difference, 3.8% (95% CI 0.5-7.0)] but not after 26 weeks [0.8% vs 1.6%; between-group difference, 0.8% (95% CI -2.8 to 4.4)]. No significant association was found between changes in relative BML volume and KOOS. CONCLUSIONS: Despite the statistically significant difference in BML volume at 14 weeks after corticosteroid injection and 12 weeks exercise therapy compared to placebo injection and exercise, there is very little evidence on a relationship between corticosteroids and BML volume. EU CLINICAL TRIALS REGISTER: EudraCT number: 2012-002607-18.

Relationship between weight loss in obese knee osteoarthritis patients and serum biomarkers of cartilage breakdown: secondary analyses of a randomised trial.

OBJECTIVE: To explore effects of weight loss and maintenance on serum cartilage biomarkers denaturation neoepitope for Collagen2 (Coll2-1) and Fibulin3 fragment (Fib3-2), as well as correlations between Coll2-1 and Fib3-2 and symptomatic improvement, in a knee osteoarthritis (KOA) population. DESIGN: 192 obese KOA patients followed a 16 week weight loss intervention and 52 weeks weight maintenance (ClinicalTrials.gov identifier: NCT00655941). Assessments were at 0, 8, 16 and 68 weeks. Serum Coll2-1 and Fib3-2 were determined with ELISA, and symptoms by the Knee Osteoarthritis Outcome Score (KOOS) questionnaire. Changes from week 0 and association between changes from baseline in body weight and Coll2-1, Fib3-2, and the 5 KOOS domains were assessed at all time points. RESULTS: Coll2-1 changes from baseline showed a decrease at week 8 (P = 0.0002), no change at week 16 (P = 0.49), and an increase at week 68 (P = 0.036). Fib3-2 showed an increase from baseline at week 8 (P = 0.0015) and 16 (P < 0.0001), but none at week 68 (P = 0.23). No statistically significant correlations were found between changes in body weight and Coll2-1 and Fib3-2 at any time point (r < 0.05; P > 0.49). At all time-points there were significant positive correlations between changes from baseline in Coll2-1 and in KOOSSports/Recreation (week 8, 16, 68: r = 0.17; P = 0.03; r = 0.16; P = 0.04; and r = 0.17; P = 0.04, respectively). CONCLUSION: The clinical improvement after a substantial weight loss and weight maintenance in KOA patients was not associated with decrease in markers of cartilage breakdown Coll2-1 or Fib3-2, even with indications of a slightly negative effect.

Osteoarthritis year in review 2016: imaging.

PURPOSE: The current narrative review covers original research related to imaging in osteoarthritis (OA) in humans published in English between April 1st 2015 and March 31st 2016, in peer reviewed journals available in Medline via PubMed (http://www.ncbi.nlm.nih.gov/pubmed/). METHODS: Relevant studies in humans, subjectively decided by the authors, contributing significantly to the OA imaging field, were selected from an extensive Medline search using the terms "Osteoarthritis" in combination with "MRI", "Imaging", "Radiography", "X-rays", "Ultrasound", "Computed tomography", "Nuclear medicine", "PET-CT", "PET-MRI", "Scintigraphy", "SPECT". Publications were sorted according to relevance for the OA imaging research community with an emphasis on high impact special interest journals using the software for systematic reviews www.covidence.org. RESULTS: An overview of newly published studies compared to studies reported previous years is presented, followed by a review of selected imaging studies of primarily knee, hip and hand OA focussing on (1) results for detection of OA and OA-related pathology (2) studies dealing with treatments and (3) studies focussing on prognosis of disease progression or joint replacement. A record high number of 1420 articles were published, among others, of new technologies and tools for improved morphological and pathophysiological understanding of OA-related changes in joints. Also, imaging data were presented of monitoring treatment effect and prognosis of OA progression, primarily using established radiographic, magnetic resonance imaging (MRI), and ultrasound (US) methods. CONCLUSION: Imaging continues to play an important role in OA research, where several exciting new technologies and computer aided analysis methods are emerging to complement the conventional imaging approaches.

The effects of intra-articular glucocorticoids and exercise on pain and synovitis assessed on static and dynamic magnetic resonance imaging in knee osteoarthritis: exploratory outcomes from a randomized controlled trial.

OBJECTIVE: The aims of the present knee osteoarthritis (KOA)-study were to: (1) describe and compare the changes in magnetic resonance imaging (MRI)-measures of synovitis following an exercise program preceded by an intra-articular injection of either corticosteroid or isotonic saline and (2) investigate if any of the changes in patient reported outcome measures (PROMs) were associated with changes in MRI-measures of synovitis. DESIGN: We performed a randomized, double-blinded, placebo-controlled clinical trial evaluating the effects of intra-articular corticosteroid vs placebo injections given before exercise therapy in KOA-patients. PROMs were assessed using the KOOS (knee injury and osteoarthritis outcome score). Synovitis was assessed on conventional non-contrast-enhanced, conventional contrast-enhanced (CE) and dynamic contrast-enhanced (DCE) MRI. PROMs and MRIs were obtained prior to the intra-articular injection, after termination of the exercise program (week 14-primary time point) and week 26. RESULTS: Of 100 randomized participants (50 in each allocation group), 91 had complete MRI-data at baseline (63% female, mean age: 62 years, median Kellgren-Lawrence-grade: 3). There were no statistically significant differences between the two interventions in regards of changes in MRI-measures of synovitis at any time-point. At week 14, we found no statistical significant MRI-explanatory variables of either of the PROMs. CONCLUSIONS: The present study does not justify the use of intra-articular corticosteroids over intra-articular saline when combined with an exercise program for reduction of synovitis in KOA. The improvement in pain and function following the intervention with intra-articular corticosteroids/saline and exercise could not be explained by a decrease in synovitis on MRI indicating other pain causing/relieving mechanisms in KOA.

The association between histological, macroscopic and magnetic resonance imaging assessed synovitis in end-stage knee osteoarthritis: a cross-sectional study.

OBJECTIVES: To investigate the association between magnetic resonance imaging (MRI), macroscopic and histological assessments of synovitis in end-stage knee osteoarthritis (KOA). METHODS: Synovitis of end-stage osteoarthritic knees was assessed using non-contrast-enhanced (CE), contrast-enhanced magnetic resonance imaging (CE-MRI) and dynamic contrast-enhanced (DCE)-MRI prior to (TKR) and correlated with microscopic and macroscopic assessments of synovitis obtained intraoperatively. Multiple bivariate correlations were used with a pre-specified threshold of 0.70 for significance. Also, multiple regression analyses with different subsets of MRI-variables as explanatory variables and the histology score as outcome variable were performed with the intention to find MRI-variables that best explain the variance in histological synovitis (i.e., highest R2). A stepped approach was taken starting with basic characteristics and non-CE MRI-variables (model 1), after which CE-MRI-variables were added (model 2) with the final model also including DCE-MRI-variables (model 3). RESULTS: 39 patients (56.4% women, mean age 68 years, Kellgren-Lawrence (KL) grade 4) had complete MRI and histological data. Only the DCE-MRI variable MExNvoxel (surrogate of the volume and degree of synovitis) and the macroscopic score showed correlations above the pre-specified threshold for acceptance with histological inflammation. The maximum R2-value obtained in Model 1 was R2 = 0.39. In Model 2, where the CE-MRI-variables were added, the highest R2 = 0.52. In Model 3, a four-variable model consisting of the gender, one CE-MRI and two DCE-MRI-variables yielded a R2 = 0.71. CONCLUSION: DCE-MRI is correlated with histological synovitis in end-stage KOA and the combination of CE and DCE-MRI may be a useful, non-invasive tool in characterising synovitis in KOA.

Short communication: Iodine concentrations in serum, milk, and tears after feeding Ascophyllum nodosum to dairy cows-A pilot study.

Kelp (Ascophyllum nodosum) is rich in iodine and often fed by organic dairy producers as a mineral supplement to support animal health. A commonly held belief is that kelp supplementation decreases susceptibility to infectious bovine keratoconjunctivitis due to increased iodine concentrations in tears. Whereas serum and milk iodine concentrations are positively correlated and modulated by oral iodine supplementation, nothing is known about the iodine concentration of tears. Therefore, the 3 objectives of this pilot study were to determine (1) the iodine content of tears, milk, and serum of cows after being fed kelp for 30d; (2) the trace mineral and thyroid status of cows before (d 0) and after being fed kelp for 30d; and (3) the in vitro growth rate of bacteria in tears (Moraxella bovis) or milk (Staphylococcus aureus, Escherichia coli, Streptococcus uberis) collected from cows fed no kelp (d 0) or kelp (d 30). Cows (n=3/treatment) were individually fed 56g of kelp per day (n=3/treatment) or not (n=3/no treatment) for 30 d. Daily feed intake of the TMR was recorded and weekly TMR, kelp, milk, blood and tear samples were collected and analyzed for iodine. The feed samples were pooled and further analyzed for other minerals. On d 0 and 30, liver biopsies and blood samples were collected and analyzed for mineral content and thyroid hormone concentrations, respectively. An inhibition test used milk and tear-soaked plates from kelp-fed cows (d 0 and 30) as well as 1 and 7.5% iodine as positive and distilled water as negative control. As expected, serum iodine concentrations were positively correlated with milk and tear iodine concentrations. Whereas the iodine concentrations in serum increased significantly in the kelp-fed cows during the 30-d study, milk and tear iodine concentrations increased only numerically in these cows compared with the control group. Liver mineral profiles were comparable between groups and generally did not change over the course of the study. Thyroid hormones remained overall within the reference range throughout the trial. Neither milk nor tears from kelp-fed cows inhibited in vitro growth of any of the plated bacteria. In summary, serum iodine concentration was correlated with the iodine concentration in milk and tears and feeding kelp increased only the serum iodine levels of cows in this trial. Bacterial growth was not inhibited in milk and tears of kelp-fed cattle in vitro, and prevention of infectious bovine keratoconjunctivitis would not be based solely on increased iodine concentrations in tears.

Changes in ultrasound assessed markers of inflammation following intra-articular steroid injection combined with exercise in knee osteoarthritis: exploratory outcome from a randomized trial.

OBJECTIVE: Knee osteoarthritis (KOA) is a multifactorial joint disease affecting many people worldwide. Recommended treatments for KOA include exercise and steroid injections, or a combination of these. The objective of this exploratory outcome analysis of a randomized trial was to assess changes in inflammation markers assessed by ultrasound imaging (US) in KOA secondary to intra-articular corticosteroid injection given prior to exercise therapy. DESIGN: This study is a sub-study to a larger clinical trial which compared the clinical effects of steroid injection in KOA to placebo injection, both given prior to exercise therapy. The US outcomes were changes from baseline in US-assessed synovial size, Doppler activity presence in the synovial membrane, and numbers of US-detected Baker's cysts. US was performed at baseline, week 14 (exercise stop), and week 26 (follow-up). RESULTS: Fifty participants received steroid injection, and 50 received placebo injection. All participants received 12 weeks of exercise. Forty-five and 44, respectively, completed the study. At week 14, the group difference in the change in synovium thickness was 2.2 mm (95%, confidence interval (CI) -0.5 to 4.8), P = 0.11. There were no group differences in the changes in distribution of patients with presence of synovial Doppler activity (P = 0.98) or Baker's cysts (P = 0.35). There were no statistically significant differences between groups at week 26 in any outcome. CONCLUSION: Intra-articular steroid injection of KOA-patients prior to a 3 months exercise programme did not reduce synovial hypertrophy, synovial Doppler activity, or Baker's cyst presence more than a placebo saline injection according to US-assessments. TRIAL REGISTRATION: EudraCT: 2012-002607-18.