Introduction Hand osteoarthritis (OA) is a prevalent joint disorder with limited treatment options. Accumulating evidence suggests that the antidiabetic drug metformin has beneficial effects on knee OA and may likewise be beneficial for hand OA. The objective of this randomised, double-blinded, placebo-controlled trial is to investigate the effect of metformin 1000 mg two times a day, or maximum tolerated dose, compared with placebo on reducing finger joint pain after 16 weeks of treatment.Methods and analysis The participants will be enrolled from the OA clinic at the Parker Institute at Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark and from the Department of Rheumatology, Hospitalsenhed Midt, Silkeborg, Denmark. 150 participants with painful hand OA according to the American College of Rheumatology criteria will be randomly allocated in a 1:1 ratio to receive either metformin or a matching placebo for 16 weeks. The initial dose of 500 mg of metformin or placebo once daily is increased by 500 mg every week until the target dose of 1000 mg two times a day, or the maximum tolerated dose, is reached. The participants will have clinical visits every 4 weeks, except the week 12 visit, which is by telephone. The primary endpoint is the between-group difference in least squares means for the change in the Visual Analogue Scale (VAS) finger joint pain scores between the metformin and placebo groups at 16 weeks. The main analysis will be conducted on the intention-to-treat population, comprising all participants assessed and randomly assigned at baseline. Least squares means and the differences between them, along with their respective 95% CIs, will be derived from a mixed-effects model for repeated measurements (outcomes collected at baseline and at weeks 4, 8, 12 and 16). Adverse events will be registered systematically.Ethics and dissemination Approval has been obtained from the European Medicines Agency (EudraCT: 2023-509181-38-00), which also includes approval from the local health research ethics committee. Written informed consent will be obtained from all participants. Study findings will be published in international peer-reviewed journals and will be presented in relevant media and at international scientific conferences.Trial registration number EudraCT, 2023-509181-38-00; ClinicalTrials.gov, NCT06367283.

BACKGROUND:People with hand osteoarthritis (HOA) experience difficulties performing activities of daily living (ADL). Referral for occupational therapy is rare despite support for non-pharmacological interventions by international treatment recommendations. HANDY, a multidisciplinary cross-sectorial management program for people with HOA, includes procedures for needs evaluation and referral for occupational therapy performed by general practitioners (GPs) as well as a group-based occupational therapy intervention delivered in municipal rehabilitation settings. The present study aimed to evaluate the feasibility of this first version of the HANDY program (HANDY 1.0). METHODS:A feasibility study will be conducted in two municipalities and related general practices to evaluate aspects of the content and delivery of the HANDY program. In accordance with international guidelines for evaluation of feasibility, the aspects evaluated include: intervention development, intervention components, perceived values, benefits, harms or unintended consequences, acceptability in principle, feasibility and acceptability in practice, and fidelity, reach, and dose. Participants will be recruited among people with HOA when visiting their GP, GPs themselves, and occupational therapy clinicians employed in municipal rehabilitation settings. Each municipality will offer the group-based occupational therapy intervention twice, each time involving up to eight participants with HOA. Qualitative and quantitative data will be collected based on registration forms, logbooks, assessments of ADL ability, and qualitative interviews. CONCLUSIONS:This study will be the first to examine the feasibility of the content and delivery of the multidisciplinary, cross-sectorial management program HANDY for people living with HOA. It will enable us to determine whether to proceed to a pilot randomized controlled trial evaluating aspects related to trial design, conduct, and processes. TRIAL REGISTRATION:Clinicaltrials.gov PRS registry, registration number NCT06254105. Registered 22nd January 2024-retrospectively registered, https://clinicaltrials.gov/study/NCT06254105 . Estimated date of study completion was 28th June 2024. However, participant follow-up is still ongoing at the time of submission of the present paper.

Purpose (the aim of the study): To assess change in function after 6 weeks treatment with electrically heated mittens compared to sham mittens (electrical heating disabled) in participants with hand OA.

OBJECTIVE To assess the effect of electrically heated mittens on physical hand function in people with osteoarthritis of the hands compared with control mittens. DESIGN Randomised controlled trial. SETTING Osteoarthritis outpatient clinic, Copenhagen, Denmark. PARTICIPANTS 200 people with hand osteoarthritis aged 42-90 years. 100 participants were assigned to the intervention group and 100 to the control group. INTERVENTIONS Electrically heated mittens or control mittens (heating elements disconnected) worn for at least 15 minutes daily for six weeks. MAIN OUTCOME MEASURES The primary outcome was change in hand function measured on the function subscale of the Australian/ Canadian hand osteoarthritis index (AUSCAN; score 0-100 points) at six weeks. Key secondary outcomes included changes in the AUSCAN hand pain subscale (score 0-100 points), global rating of hand osteoarthritis related problems (0-100 visual analogue scale), and grip strength (newtons) at six weeks. Analysis of secondary outcomes was performed using a hierarchical gatekeeping approach. RESULTS 91 participants in the intervention group and 95 in the control group completed the trial. The mean age of participants was 71 years, 87% (n=173) were women, and mean body mass index was 24.9 (SD 4.4). Median disease duration was 10 years (interquartile range 5-15 years). The between group difference for change in AUSCAN function at week 6 was 3.0 points (95% confidence interval (CI) -0.4 to 6.3; P=0.09) in favour of heated mittens. For the key secondary outcome, change in AUSCAN hand pain score from baseline, a group difference was observed of 5.9 points (95% CI 2.2 to 9.5) in favour of heated mittens. Changes in global rating of hand osteoarthritis related problems and grip strength did not differ between the groups with an observed difference between groups of 2.8 points (95% CI -3.7 to 9.2) and 2.3 newtons (95% CI -16.3 to 21.0) in favour of heated mittens, respectively. CONCLUSION Use of electrically heated mittens for six weeks was not related to a positive change in physical hand function compared with control mittens. Heated mittens provided no additional benefits on global rating of hand osteoarthritis related problems and grip strength. A small benefit was detected for hand pain, but this could have been overestimated. TRIAL REGISTRATION ClinicalTrials.gov NCT04576403.

OBJECTIVE:To compare the effect of an illness perception conversation (IPC), relative to a research participation conversation (RPC), on 2-week changes in knee pain in patients with knee osteoarthritis. METHOD:This was a randomised single-blind trial. Patients were randomised to two matched conversations. An IP conversation concerning the participant's knee pain-related illness perception (IP) or an RPC concerning the participant's motivation for participating in research. Both conversations were followed by an open-label intraarticular saline injection in the most symptomatic knee. The primary outcome was change in knee pain from baseline to 2 weeks follow-up on a 100 mm visual analogue scale (VAS). Key secondary outcomes included the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales: Activities of daily living (ADL) and Quality of life (QoL). Main analyses were based on the intention-to-treat population using repeated measures mixed effects linear models. RESULTS:103 patients were randomised to the IPC group (n = 52) and the RPC group (n = 51). VAS knee pain scores changed statistically significantly from baseline to end of treatment in both groups, -13.7 (standard error [SE]: 3.2) in the IPC group and -13.0 (SE: 3.1) in the RPC group with an adjusted between-group difference of -0.7 (95% CI: -8.3 to 6.9; P = 0.85). Likewise, no group differences were seen in KOOS ADL and KOOS QoL. CONCLUSION:A conversation concerning knee pain-related IP did not augment the pain-relieving effect of an open-label placebo injection when compared to a similar control conversation concerning motivations for participating in research. TRIAL REGISTRATION:NCT05225480.

ObjectiveTo examine the pain relief effects of comparators (placebos and untreated control groups) in hand osteoarthritis trials and the impact of contextual factors.MethodsWe systematically searched PubMed, EMBASE and CENTRAL from inception to December 26, 2021. We included randomised controlled trials of people with hand osteoarthritis with a placebo or an untreated control group. We assessed the Risk of Bias with Cochrane Risk-of-Bias tool version 2. Each comparator was contrasted with a null-arm, imputed as having a zero change from baseline with the same standard deviation as the comparator. We combined the standardised mean differences with a random effects meta-analysis. The contextual factors’ effect was explored in meta-regression and stratified models with pain as the dependent variable.Results84 trials (7,262 participants) were eligible for quantitative synthesis, of which 76 (6,462 participants) were eligible for the stratified analyses. Placebos were superior to their matched null-arms in relieving pain with an effect size of -0.51 (95 % confidence interval -0.61 to -0.42), while untreated control groups were not. When analysing all comparators, blinded trial designs and low risk of bias were associated with higher pain relief compared to an open-label trial design and some concern or high risk of bias.ConclusionThe placebo response on pain for people with hand osteoarthritis was increased by appropriate blinding and a lower risk of bias assessment. Placebos were superior to a null-arm, while untreated control groups were not. Results emphasise the importance of using appropriate comparators in clinical trials.PROSPERO registration IDCRD42022298984

BACKGROUND:Colchicine has been suggested for osteoarthritis treatment, but evidence is contradictory. We aimed to investigate colchicine's efficacy and safety compared with placebo in people with hand osteoarthritis. METHODS:In this single-centre, double-blind, randomised, placebo-controlled trial we recruited adults with symptomatic hand osteoarthritis and finger pain of at least 40 mm on a 100 mm visual analogue scale from an outpatient clinic in Denmark. The hand with the most severe finger pain at inclusion was the target hand. Participants were randomly assigned (1:1) to 0·5 mg colchicine or placebo taken orally twice a day for 12 weeks, stratified by BMI (≥30 kg/m2), sex, and age (≥75 years). Participants, outcome assessors, and data analysts were masked to treatment allocation. The primary endpoint was change from baseline to week 12 in target hand finger pain, assessed on a 100 mm visual analogue scale with a pre-specified minimal clinically important difference of 15 mm, in the intention-to-treat population. Safety was assessed at week 12 in the intention-to-treat population. The study was registered with ClinicalTrials.gov, NCT04601883, and with EudraCT, 2020-002803-20. FINDINGS:Between Jan 15, 2021, and March 3, 2022, 186 people were screened for eligibility, and 100 were randomly assigned to receive colchicine (n=50) or placebo (n=50). Participants had a mean age of 70·9 (SD 7·5) years, 69 (69%) of 100 were women and 31 (31%) were men. All participants completed the study. The mean change from baseline to week 12 in finger pain were -13·9 mm (SE 2·8) in the colchicine group and -13·5 mm (2·8) in the placebo group, with a between-group difference (colchicine vs placebo) of -0·4 mm (95% CI -7·6 to 6·7; p=0·90). In the colchicine group, there were 76 adverse events in 36 (72%) of 50 participants and one serious adverse advent (migraine attack leading to hospital admission). In the placebo group, there were 42 adverse events in 22 (44%) of 50 participants and two serious adverse events (cholecystitis and elevated alanine aminotransferase concentrations, in the same patient). INTERPRETATION:In people with painful hand osteoarthritis, treatment with 0·5 mg of colchicine twice day for 12 weeks did not effectively relieve pain, and treatment with colchicine was associated with more adverse events. FUNDING:The Oak Foundation, IMK Almene Fond, Minister Erna Hamilton's Scholarship for Science and Art, AP Moller and Wife Chastine McKinney Moller's Foundation for Medical Science Advancement, The Danish Medical Association, the Velux Foundation, Aase and Ejnar Danielsen's Foundation, and Director Emil C Hertz and Wife Inger Hertz's foundation.

Summary Near-earth UAV magnetic surveying has recently become a competitive approach to traditional approaches. UAV surveys can safely and cost-effectively be conducted with a dense line spacing while tightly draping the topography, significantly improving the data resolution. For UAV magnetic surveying, the sensors are often placed in a gradiometer system towed underneath the UAV and far away from any onboard electronics to minimise the magnetic noise. In gradiometry surveys, even the sensor-specifics can result in line-to-line striping. In addition, imperfect draping and orientational deviations from the set survey heading will also result in line-to-line striping. This study discusses the processing of a multi-sensor UAV-towed magnetic survey. The raw total-field data and the across-, along-, and vertical-track differences (gradients) show significant line-to-line striping. The proposed processing method relies on modelling the along-track differences using an equivalent sources model to remove the noise responses from both sensor-specific noise and noise responses from attitude/attitude deviations. After the processing, the modelled differences show significantly less line-to-line striping. The results suggest that filter and edge detection methods can be used after the proposed processing method to locate the edge of structures that might host mineral pockets.

Objective To explore the comparative effectiveness of pharmacological interventions for hand osteoarthritis (OA). Methods We systematically searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception until 26 December 2021, for randomised trials of pharmacological interventions for people with hand OA. Two reviewers independently extracted study data and assessed the risk of bias. We calculated the effect sizes for pain (standardised mean differences) using Bayesian random effects models for network meta-analysis (NMA) and pairwise meta-analysis. Based on a pre-specified protocol, we prospectively registered the study at PROSPERO, CRD42021215393. Results We included 72 trials with 7609 participants. 65 trials (n=5957) were eligible for the quantitative synthesis, investigating 29 pharmacological interventions. Oral non-steroidal anti-inflammatory drugs (NSAIDs) and oral glucocorticoids’ NMA effect sizes were −0.18 (95% credible interval −0.36 to 0.02) and −0.54 (−0.83 to −0.24), respectively, compared with placebo, and the result was consistent when limiting evidence to the pairwise meta-analysis of trials without high risk of bias. Intra-articular hyaluronate, intra-articular glucocorticoids, hydroxychloroquine, and topical NSAIDs’ NMA effect sizes were 0.22 (−0.08 to 0.51), 0.25 (0.00 to 0.51), −0.01 (−0.19 to 0.18), and −0.14 (−0.33 to 0.08), respectively, compared with placebo. Oral NSAIDs were inferior to oral glucocorticoids with an NMA effect size of 0.36 (0.01 to 0.72). No intervention was superior to placebo when stratifying for thumb and finger OA. Conclusion Oral NSAIDs and glucocorticoids are apparently effective pharmacological interventions in hand OA. Intra-articular therapies and topical NSAIDs were not superior to placebo.

Osteoarthritis is the most common chronic joint disorder. The prevalence of symptomatic hand osteoarthritis for adults (aged 40–84 years) is 16% among women and 8% among men in the USA.2 Base-of-thumb osteoarthritis is located at the first carpometacarpal joint, which causes pain and is particularly challenging given the joint's central role in hand function, making it hard to perform everyday activities, especially when requiring a pinch grip (eg, when eating and dressing).

Objectives The aim of this study was to determine the diagnostic performance of dual-energy computed tomography (DECT) to detect and distinguish crystal deposits in a phantom. The primary objective was to determine the cutoff DECT ratio and the cross-sectional area (CSA) of a crystal deposit necessary to differentiate monosodium urate (MSU), calcium pyrophosphate (CPP), and calcium hydroxyapatite (HA) using DECT. Our secondary objective was to determine the concentration for limit of detection for MSU, CPP, and HA crystal deposits. Exploratory objectives included the comparison between 2 generations of DECT scanners from the same manufacturer as well as different scanner settings. Materials and Methods We used a cylindrical soft tissue phantom with synthetic MSU, CPP, and HA crystals suspended in resin. Crystal suspension concentration increased with similar attenuation between MSU, CPP, and HA in conventional CT. The phantom was scanned on 2 dual-source DECT scanners, at 2 dose levels and all available tube voltage combinations. Both scanners had a tin (Sn) filter at the high-energy spectra. Dual-energy CT ratios were calculated for a given tube voltage combination by dividing linear regression lines of CT numbers against concentration. Dual-energy CT ratios were compared using an analysis of covariance. Receiver operating characteristic curves and corresponding areas under the curve (AUCs) were calculated for individual crystal suspension comparisons (HA vs CPP, MSU vs CPP, and MSU vs HA). Results At standard clinical scan settings with 8 mGy and 80/Sn150 kV, the DECT ratios were as follows: CPP, 2.02 (95% confidence interval [CI], 1.98-2.07); HA, 2.00 (95% CI, 1.96-2.05); and MSU, 1.09 (95% CI, 1.06-1.11). Ratios varied numerically depending on the scanner and tube voltage combination. Monosodium urate crystal DECT ratios were significantly different from HA and CPP (P < 0.001), whereas DECT ratios for HA and CPP crystals did not differ significantly (P = 0.99). The differentiation of MSU crystals from both calcium crystals (HA and CPP) was excellent with an AUC of 1.00 (95% CI, 1.00-1.00) and an optimal cutoff DECT ratio of 1.43:1.40 depending on the scanner. In addition, differentiation of MSU and calcium-containing crystals (HA and CPP) required a CSA of minimum 4 pixels of crystal at standard clinical scan conditions. In contrast, differentiation between CPP and HA crystals was moderate with AUCs ranging from 0.66 (95% CI, 0.52-0.80) to 0.80 (95% CI, 0.69-0.91) and an optimal cutoff DECT ratio of 2.02:2.06 depending on the scanner. Furthermore, differentiation between CPP and HA crystals required a CSA of minimum 87 pixels of crystal at standard clinical scan conditions, corresponding to a region of interest of 3.7 mm diameter. When scanning at highest possible spectral separation and maximum dose of 50 mGy, the limit of detection for crystals within a region of interest of 50 pixels was 14 mg/cm(3) for MSU and 2 mg/cm(3) for both CPP and HA. Conclusions This phantom study shows that DECT can be used to detect MSU, CPP, and HA crystal deposits. Differentiation of CPP and HA was not possible in crystals deposits less than 3.7 mm in diameter, but MSU could accurately be differentiated from CPP and HA crystal deposits at standard clinical scan conditions.

Summary Getting reliable geophysical and geological 3D models of the subsurface is an absolute necessity for successful resources exploration. Here, we show how novel UAV-borne geophysical mapping can be extremely valuable for mapping potential new exploration areas that are difficult to access by foot, such as hard rock inter-tidal zones and boulder beaches. We show the results from a multidisciplinary geophysical campaign of highly magnetic dikes and granites along a boulder beach in Brittany, France. Our mapping is carried out using customized geophysical sensor systems with high quality sensors. These include in particular a special designed UAV-towed magnetometer bird and multispectral system for large area mapping purposes. The UAV-borne mapping is supplemented by ground-based gamma-ray spectrometry data and ground-based magnetic gradiomety data. The results clearly demonstrate the value of UAV-borne systems in difficult areas as compared to traditional mapping methods as well as the value of combining various geophysical sensors for exploring the economic geology. All UAV-borne data were collected during two days, while the ground-based data – covering only the inner and dry part of the beach - were collected over seven days.

Reducing the electromagnetic signal from the UAV by towing the frequency-domain electromagnetic induction instrumentation in a suspension system underneath the UAV, at 6 meters separation the noise from the UAV appears to be neglectable compared to other sources of electromagnetic noise.

Summary Characterization and discrimination of UXO in magnetic offshore seabed surveys usually have limited success. We investigate how to utilize available prior knowledge on UXO type and quantity in a probabilistic framework, in order to improve on discrimination capabilities. It has previously been demonstrated how Bayesian inference can be utilized in a Markov chain Monte Carlo (MCMC) framework, where the solution can be sampled in a stochastic process. In this project, we extend the previous work containing independent 1-D prior distributions to a more complex case, introducing real quantitative data of actual UXO findings in the North Sea. Here, we develop the methodology to take into account knowledge about known size and shape of different UXO as well as the expected quantities of each type. This enables us to not only sample the posterior distribution of the model parameters, but also assign a probability of each UXO type with respect to the data at hand.

In Denmark, about 50% of patients with chronic hepatitis C virus (HCV) infection are undiagnosed. Since 2014, therapy containing direct-acting antivirals (DAA) has proven efficient and is available to all patients, who have a chronic HCV infection and a Danish personal identification number. The World Health Organization has a goal of elimination of viral hepatitis in 2030. Elimination of HCV in Denmark should focus on reducing HCV transmission, incidence and prevalence, combined with treatment with DAA of all infected patients. Micro-elimination strategies may play a major role, but a national strategy is lacking.

Background Methotrexate (MTX) is considered the anchor drug in rheumatoid arthritis (RA) treatment, based on efficacy, safety, and its ability to increase the efficacy of biologic agents when used in combination. Both the “American College of Rheumatology” (ACR) and the “European League Against Rheumatism” (EULAR) recommend the use of biologic agents with concomitant MTX in RA. However, analyses from health care claims suggest that the MTX prescribed in conjunction with a biologic disease-modifying antirheumatic drug (bDMARD), is not collected at the pharmacy by more than half of the patients. Despite claims from pivotal trial data, the empirical evidence supporting combination MTX plus bDMARD in terms of the actual benefit-harm has not been evaluated extensively. Objectives To review the evidence for benefit and harm associated with combining MTX with a biologic agent in RA patients. Methods A systematic review and meta-analysis of randomised controlled trials (RCTs) was performed to identify all trials relating treatment of RA with MTX in combination with bDMARD compared to a bDMARD in monotherapy. Random-effects models were applied for meta-analyses with risk ratio and 95% confidence intervals (RR, 95%CI) and inconsistency (I2, %) estimated using Review Manager. According to the protocol the major outcomes were ACR50 for benefit and withdrawals due to adverse events (AEs) for harm (PROSPERO: CRD42014014633). Results From the 4,405 identified references, 14 trials were eligible for inclusion in the meta-analysis. The overall likelihood of responding to therapy (ie, RR according to ACR50) was 1.36 [1.24 to 1.49] - with a low degree of inconsistency (28%) - in favour of concomitant use of MTX when treating with a biologic (P<0.001). There was no reason to suspect that added value of MTX varied with the choice of bDMARD (Test for subgroup differences P=0.38): abatacept 1.27 [0.97 to 1.67], adalimumab 1.42 [1.24 to 1.61], etanercept 1.44 [1.22 to 1.69], golimumab 1.60 [1.13 to 2.27], infliximab 3.54 [1.38 to 9.08], rituximab 1.31 [0.74 to 2.32], and tocilizumab 1.24 [1.03 to 1.51]. The overall estimate of discontinuing therapy due to AEs from concomitant use of MTX was 1.17 [0.94 to 1.44] (P=0.16) compared to bDMARD in monotherapy - corresponding to a possible 17% increased risk. Conclusions This systematic review and meta-analysis of RCTs provides empirical evidence about the clinical value of combining the prescribed bDMARD with the recommended concomitant use of MTX. Combination therapy increases the probability of achieving treatment success at the level of ACR50 by approximately 40% compared to patients using biologics in monotherapy. Although the precision around the estimate of concomitant MTX use does not rule out an increased risk of clinically important harms, these findings justify the recommendation that all patients prescribed biologics should be encouraged to continue MTX therapy. Acknowledgements This study was supported by unrestricted grants from The Oak foundation, and AbbVie (Denmark). Disclosure of Interest T. S. Jørgensen Grant/research support from: has received research grants paid to institute: AbbVie and Roche, S. Tarp: None declared, D. E. Furst: None declared, A. Døssing: None declared, P. Taylor: None declared, H. Bliddal Grant/research support from: has received research grants paid to institute: AbbVie and Roche, R. Christensen Grant/research support from: has received research grants paid to institute: AbbVie and Roche