Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study

Background: Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis. Methods: In this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the I2 value was less than 0·4. Findings: The study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Self-controlled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1·65 [95% CI 1·12–2·44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2·19 [95% CI 1·22–3·95]), chest pain or angina (1·15 [1·05–1·26]), and hear

Measurement of the D+D^+- Meson Production Cross Section at Low Transverse Momentum in ppˉp\bar{p} Collisions at s=1.96\sqrt{s}=1.96 TeV

International audienceWe report on a measurement of the D+-meson production cross section as a function of transverse momentum (pT) in proton-antiproton (pp¯) collisions at 1.96 TeV center-of-mass energy, using the full data set collected by the Collider Detector at Fermilab in Tevatron Run II and corresponding to 10  fb-1 of integrated luminosity. We use D+→K-π+π+ decays fully reconstructed in the central rapidity region |y|<1 with transverse momentum down to 1.5  GeV/c, a range previously unexplored in pp¯ collisions. Inelastic pp¯-scattering events are selected online using minimally biasing requirements followed by an optimized offline selection. The K-π+π+ mass distribution is used to identify the D+ signal, and the D+ transverse impact-parameter distribution is used to separate prompt production, occurring directly in the hard-scattering process, from secondary production from b-hadron decays. We obtain a prompt D+ signal of 2950 candidates corresponding to a total cross section σ(D+,1.5<pT<14.5  GeV/c,|y|<1)=71.9±6.8(stat)±9.3(syst)  μb. While the measured cross sections are consistent with theoretical estimates in each pT bin, the shape of the observed pT spectrum is softer than the expectation from quantum chromodynamics. The results are unique in pp¯ collisions and can improve the shape and uncertainties of future predictions