Synovial fluid detection in intra-articular injections using a bioimpedance probe (BIP) needle-a clinical study

Intra-articular glucocorticoid injections are the recommended treatment for active arthritis, but accurate positioning of the needle may be challenging. Inexperienced physicians might decide not to inject because an unsuccessful injection impairs clinical outcome and may lead to complications; however, choosing not to inject may impair or delay the best possible treatment. Here, we address this problem by introducing a novel Bioimpedance Probe (BIP) Needle-guidance method that was tested in a clinical study. The BIP Needle was utilized for detection of synovial fluid. It measures real-time bioimpedance spectra and identifies when the needle tip is in contact with the synovial fluid. Injections into 80 joints with active arthritis were performed by an experienced rheumatologist using the BIP Needle. The location of the BIP Needle was ensured by aspiration of synovial fluid, absence of resistance during injection, and/or using real-time ultrasound imaging. Sensitivity and specificity of the device for synovial fluid detection were 86 % (CI 75-93 %) and 85 % (CI 74-92 %), respectively. The BIP Needles showed high spatial resolution and differentiated the synovial fluid from the surrounding tissues. However, lack of synovial fluid, anatomic variability, and intra-articular structures challenged the technology. The BIP Needles provided adequate results in intra-articular injections. Performance of the device was good even in small joints, which may be the most difficult for inexperienced physicians. Further performance improvement can be expected when more data is collected for mathematical models. Overall, this novel method showed potential to be used in real-time needle guidance.Peer reviewe

Modeled Health Economic Impact of a Hypothetical Certolizumab Pegol Risk-Sharing Scheme for Patients with Moderate-to-Severe Rheumatoid Arthritis in Finland

To model the American College of Rheumatology (ACR) outcomes, cost-effectiveness, and budget impact of certolizumab pegol (CZP) (with and without a hypothetical risk-sharing scheme at treatment initiation for biologic-na <ve patients) versus the current mix of reimbursed biologics for treatment of moderate-to-severe rheumatoid arthritis (RA) in Finland. A probabilistic model with 12-week cycles and a societal approach was developed for the years 2015-2019, accounting for differences in ACR responses (meta-analysis), mortality, and persistence. The risk-sharing scheme included a treatment switch and refund of the costs associated with CZP acquisition if patients failed to achieve ACR20 response at week 12. For the current treatment mix, ACR20 at week 24 determined treatment continuation. Quality-adjusted life years were derived on the basis of the Health Utilities Index. In the Finnish target population, CZP treatment with a risk-sharing scheme led to a estimated annual net expenditure decrease ranging from 1.7% in 2015 to 5.6% in 2019 compared with the current treatment mix. Per patient over the 5 years, CZP risk sharing was estimated to decrease the time without ACR response by 5%-units, decrease work absenteeism by 24 days, and increase the time with ACR20, ACR50, and ACR70 responses by 5%-, 6%-, and 1%-units, respectively, with a gain of 0.03 quality-adjusted life years. The modeled risk-sharing scheme showed reduced costs of a,notsign7866 per patient, with a more than 95% probability of cost-effectiveness when compared with the current treatment mix. The present analysis estimated that CZP, with or without the risk-sharing scheme, is a cost-effective alternative treatment for RA patients in Finland. The surplus provided by the CZP risk-sharing scheme could fund treatment for 6% more Finnish RA patients.Peer reviewe

YKL-40 was associated with disease activity and inflammation during intensive treatment with DMARDs.

<p>The figure shows quadratic relationships of YKL-40 with the disease activity measured as DAS28 (A) and with the inflammatory cytokine IL-6 (B) during the 26 weeks of treatment. The patients were treated for the first four weeks with a combination of sulphasalazine, methotrexate, hydroxychloroquine and low dose prednisolone, and thereafter randomized to receive either placebo infusions or infliximab infusions added to the treatment for another 22 weeks. Measurements were carried out at weeks 0, 4, 10, 18, and 26 during the treatment and area under the curve analysis over time (AUC_{0-26 weeks}) adjusted for age, gender and RF positivity was used. Gray-shaded areas represent 95% confidence intervals around the mean. YKL-40 AUC_{0-26 weeks} showed a statistically significant correlation to DAS28 AUC_{0-26 weeks} and IL-6 AUC_{0-26 weeks}.</p

CONSORT flow diagram for the NEO-RACo study.

<p>CONSORT flow diagram for the NEO-RACo study.</p

YKL-40 levels decreased during the intensive anti-rheumatic treatment with a combination of csDMARDs.

<p>The figure shows the mean change in plasma YKL-40 levels in 88 patients in the NEO-RACo -study treated with a combination of sulphasalazine, methotrexate, hydroxychloroquine and low dose prednisolone for the first four weeks, and thereafter randomized to receive either placebo infusions (Fin-RACo + Pla) or infliximab infusions (Fin-RACo + INFL) added on the csDMARD combination for another 22 weeks. YKL-40 levels decreased significantly (p<0.001) during the first four weeks of treatment with csDMARDs; when infliximab (or placebo) was added to the treatment there was a minor further decrease (groups combined, p = 0.031) but no difference between placebo and infliximab treatment groups was found. The change is presented as ng/ml, mean ± 95% CI, n = 88.</p

Generalized estimating equations models for the effect of YKL40, time and interaction in measures of disease activity from baseline to 26 weeks.

<p>Generalized estimating equations models for the effect of YKL40, time and interaction in measures of disease activity from baseline to 26 weeks.</p

The baseline characteristics of the patients.

<p>The baseline characteristics of the patients.</p