Efficacy and safety of canakinumab as a second line biologic after tocilizumab treatment failure in children with systemic juvenile idiopathic arthritis: A single-centre cohort study using routinely collected health data.

Background: A significant number of systemic juvenile idiopathic arthritis (sJIA) patients discontinue biologic disease-modifying antirheumatic drugs (bDMARDs) due to lack of efficacy or safety concerns. Studies of biologic therapy switch regimens in sJIA are required. Methods: Patients with sJIA who switched from tocilizumab (due to lack of efficacy or safety) to canakinumab (4 mg/kg every 4 weeks) and were hospitalized at the rheumatology department from August 2012 to July 2020 were included. Primary efficacy outcomes were 30% or greater improvement based on the paediatric criteria of the American College of Rheumatology (ACR30), achievement of inactive disease (JADAS-71 = 0) and clinical remission (ACR sJIA clinical inactive disease criteria). Follow-up from time first canakinumab dose administered was 12 months or the closest time point (not less than 6 and not more than 18 months). Data were extracted from electronic outpatient medical records. Results: During the study period, 46 patients with sJIA switched from tocilizumab to canakinumab. Median age at baseline was 8.2 [interquartile range (IQR) 4.0-12.9] years, with the median sJIA duration being 1.8 (IQR 0.8-5.8) years; 37 (80%) patients received at least one conventional DMARD (cDMARD; oral corticosteroids, methotrexate and/or cyclosporine A). Study outcomes were followed up in 45 patients (one patient did not attend the follow-up for an unknown reason); median follow-up was 359 (IQR 282-404) days. During the follow-up, 1 patient discontinued canakinumab due to tuberculosis detection and the dose was reduced or the injection interval increased in 4 (9%) patients. In total, 27 (60%) patients continued to receive at least one cDMARD. Improvement according to the ACR30 criteria was achieved in 43 patients [96%; 95% confidence interval (CI) 85-99], inactive disease in 42 (93%; 95%CI 82-98), and remission in 37 (82%; 95% CI 69-91); after adjustment for actual time-at-risk, the rates were 83, 85 and 73 events per 100 person-years, respectively. During follow-up, 23 AEs (most frequently infections) were reported in 19/45 (42%) patients; 5/45 (11%) patients developed macrophage activation syndrome, with a favorable outcome in all cases. Conclusions: One-year canakinumab therapy was found to be potentially effective as second-line biologic therapy after discontinuation of tocilizumab in patients with sJIA.

Blood urea nitrogen and creatinine levels at admission for mortality risk assessment in patients with acute coronary syndromes.

PURPOSE: To compare the prognostic significance of blood urea nitrogen (BUN) versus creatinine levels for estimating the risk of death in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: A prospective study of all patients admitted with suspected (n=1613) and retrospectively confirmed (n=54) myocardial infarction or unstable angina was conducted. The ROC analysis established that the area under the curve for BUN was higher than that of creatinine: 0.76 (95% CI 0.70 to 0.82) and 0.69 (95% CI 0.63 to 0.76), respectively (p=0.005). The threshold level (that maximised the combined sensitivity and specificity) was 8.8 mmol/l for BUN and 110 mumol/l for creatinine. Sensitivity (true positive cases) was 60% and 55% for threshold levels of BUN and creatinine, respectively, and specificity (true negative cases) was 82% and 77%, respectively. An increase of only BUN levels and a combination of increased BUN and creatinine levels, but not isolated hypercreatinaemia, proved to be the independent risk factors of death from ACS. Separate inclusion of BUN and creatinine as continuous variables in the regression model showed that both were associated with the risk of death: OR 1.22 (95% CI 1.17 to 1.28) and 1.016 (95% CI 1.011 to 1.021) per unit increase (R(2)=14.5 and 8.4%, respectively). When both were simultaneously included, only an increased BUN level was pertinent to the prognosis of ACS: OR after multivariate adjustment 1.17 (95% CI 1.08 to 1.27). CONCLUSION: An increased level of BUN is a more significant risk factor for ACS outcomes than that of creatinine.

The impact of funding through the RF President's grants for young scientists (the field--medicine) on research productivity: a quasi-experimental study and a brief systematic review.

The impact of grants on research productivity has been investigated by a number of retrospective studies. The results of these studies vary considerably. The objective of my study was to investigate the impact of funding through the RF President's grants for young scientists on the research productivity of awarded applicants. The study compared the number of total articles and citations for awarded and rejected applicants who in 2007 took part in competitions for young candidates of science (CoS's) and doctors of science (DoS's) in the scientific field of medicine. The bibliometric analysis was conducted for the period from 2003 to 2012 (five years before and after the competition). The source of bibliometric data is the eLIBRARY.RU database. The impact of grants on the research productivity of Russian young scientists was assessed using the meta-analytical approach based on data from quasi-experimental studies conducted in other countries. The competition featured 149 CoS's and 41 DoS's, out of which 24 (16%) and 22 (54%) applicants, respectively, obtained funding. No difference in the number of total articles and citations at baseline, as well as in 2008-2012, for awarded and rejected applicants was found. The combination of data from the Russian study and other quasi-experimental studies (6 studies, 10 competitions) revealed a small treatment effect--an increase in the total number of publications over a 4-5-year period after the competition by 1.23 (95% CI 0.48-1.97). However, the relationship between the number of total publications published by applicants before and after the competition revealed that this treatment effect is an effect of the "maturation" of scientists with a high baseline publication activity--not of grant funding.