Objective To evaluate fenebrutinib, an oral and highly selective noncovalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arthritis (RA). Methods Patients with RA and an inadequate response to methotrexate (MTX) (cohort 1; n = 480) were randomized to receive fenebrutinib (50 mg once daily, 150 mg once daily, or 200 mg twice daily), adalimumab (40 mg every other week), or placebo. Patients with RA and an inadequate response to tumor necrosis factor inhibitors (cohort 2; n = 98) received fenebrutinib (200 mg twice daily) or placebo. Both cohorts continued MTX therapy. Results In cohort 1, the percentages of patients in whom American College of Rheumatology 50% improvement criteria (ACR50) was achieved at week 12 were similar in the fenebrutinib 50 mg once daily and placebo groups, and were higher in the fenebrutinib 150 mg once daily group (28%) and 200 mg twice daily group (35%) than in the placebo group (15%) (P = 0.016 and P = 0.0003, respectively). Fenebrutinib 200 mg twice daily and adalimumab (36%) were comparable (P = 0.81). In cohort 2, ACR50 was achieved in more patients receiving fenebrutinib 200 mg twice daily (25%) than placebo (12%) (P = 0.072). The most common adverse events in the fenebrutinib groups included nausea, headache, anemia, and upper respiratory tract infections. Fenebrutinib had significant effects on myeloid and B cell biomarkers (CCL4 and rheumatoid factor). Fenebrutinib and adalimumab caused overlapping as well as distinct changes in B cell and myeloid biomarkers. Conclusion Fenebrutinib demonstrates efficacy comparable to adalimumab in patients with an inadequate response to MTX, and safety consistent with existing immunomodulatory therapies for RA. These data support targeting both B and myeloid cells via this novel mechanism for potential efficacy in the treatment of RA.

Background and Aims Proctitis is the least extensive type of ulcerative colitis, for which rectal therapy is rarely studied and underused. This study evaluated the efficacy, safety, and patient’s preference of a novel formulation of budesonide suppository 4 mg, compared with a commercially available budesonide rectal foam 2 mg, for the treatment of mild to moderate ulcerative proctitis. Methods This was a randomised, double-blind, double-dummy, active-controlled trial. Patients were randomly assigned in a 1:1 ratio to receive either budesonide 4 mg suppository or budesonide 2 mg foam once daily for 8 weeks. The co-primary endpoints were changes from baseline to week 8 in clinical symptoms, for which clinical remission was defined as having a modified Ulcerative Colitis-Disease Activity Index (UC-DAI) subscore for stool frequency of 0 or 1 and a subscore for rectal bleeding of 0, and mucosal healing, defined as having a modified UC-DAI subscore for mucosal appearance of 0 or 1. Using a more stringent criterion we additionally analysed deepened mucosal healing, which was defined as a mucosal appearance subscore of 0. Patient’s preference, physician’s global assessment, and quality of life were also assessed and analysed. Results Overall, 286 and 291 patients were included in the 4 mg suppository and 2 mg foam groups, respectively. Budesonide 4 mg suppository met the prespecified criterion for non-inferiority to the 2 mg foam in both co-primary endpoints of clinical remission and mucosal healing. Secondary endpoints consistently supported the non-inferiority of the suppository. Trends in favour of the suppository were observed in the subgroup of mesalazine non-responders. More patients reported a preference for the suppository over rectal foam. Conclusions In patients with ulcerative proctitis, budesonide 4 mg suppository was non-inferior to budesonide 2 mg foam in efficacy, and both were safe and well tolerated. EudraCT no. 2016-001921-15

Introduction: Mirror therapy requires a minimum of equipment, is relatively simple to perform and effective for various pathological conditions. The effect of mirror therapy on body schema disturbances registered in complex regional pain syndrome type I (CRPS I) patients has not yet been determined. Methods: The study is based on the analysis of the treatment results of 30 patients with CRPS I, developed as a result of the distal radius fractures, with help of mirror therapy together with exercise therapy and medications. The control group consisted of 20 patients with CRPS I developed as a result of the distal radius fractures treated only with exercise therapy and medications. We evaluated the results before the treatment, after 3 days and after 6 weeks of treatment according to The Bath CRPS Body Perception Disturbance Scale. Results: A total of 83.33% patients experienced the positive effect of mirror therapy on the perception of the 'body schema' after 6 weeks of treatment, and 35% underwent standard treatment without mirror therapy. The positive effect was statistically significant for the first five points of the Bath scale after 6 weeks of treatment compared to the control group. Improvements observed in some patients after 3 days of treatment were less pronounced and statistically insignificant. Conclusion: Mirror therapy can improve the perception of the body schema as an element of integrated treatment of CRPS I developed after fractures of the distal radius less than 3 years duration.

The use of neural network computations and the modification of the algorithm through the construction of individual training samples for different age intervals, and the creation of individual ensembles of classification neural networks, therefore achieved a prediction of the age of examined persons based on the values of their time and frequency domain heart rate variability indices, with 87% accuracy for women and 85% accuracy for men in the 66-85 years age interval and at least 85% for age groups across the entire sample.

No abstract