Background Hydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin.Methods New user cohort studies were conducted including 16 severe adverse events (SAEs).Rheumatoid arthritis patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine and followed up over 30 days. Self-controlled case series (SCCS) were conducted to further establish safety in wider populations. Separately, SAEs associated with hydroxychloroquineazithromycin (compared to hydroxychloroquine-amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, Netherlands, Spain, UK, and USA.Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (CalHRs) according to drug use. Estimates were pooled where I2<40%. ResultsOverall, 956,374 and 310,350 users of hydroxychloroquine and sulfasalazine, and 323,122 and 351,956 users of hydroxychloroquine-azithromycin and hydroxychloroquine-amoxicillin were included.No excess risk of SAEs was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. SCCS confirmed these findings. However, when azithromycin was added to hydroxychloroquine, we observed an increased risk of 30-day cardiovascular mortality (CalHR2.19 [1.22-3.94]), chest pain/angina (CalHR 1.15 [95% CI 1.05-1.26]), and heart failure (CalHR 1.22 [95% CI 1.02-1.45])

Introduction: Angiotensin converting enzyme inhibitors (ACEs) and angiotensin receptor blockers (ARBs) could influence infection risk of coronavirus disease (COVID-19). Observational studies to date lack pre-specification, transparency, rigorous ascertainment adjustment and international generalizability, with contradictory results. Methods: Using electronic health records from Spain (SIDIAP) and the United States (Columbia University Irving Medical Center and Department of Veterans Affairs), we conducted a systematic cohort study with prevalent ACE, ARB, calcium channel blocker (CCB) and thiazide diuretic (THZ) use to determine relative risk of COVID-19 diagnosis and related hospitalization outcomes. The study addressed confounding through large-scale propensity score adjustment and negative control experiments. Results: Following over 1.1 million antihypertensive users identified between November 2019 and January 2020, we observed no significant difference in relative COVID-19 diagnosis risk comparing ACE/ARB vs CCB/THZ monotherapy (hazard ratio: 0.98; 95% CI 0.84 - 1.14), nor any difference for mono/combination use (1.01; 0.90 - 1.15). ACE alone and ARB alone similarly showed no relative risk difference when compared to CCB/THZ monotherapy or mono/combination use. Directly comparing ACE vs. ARB demonstrated a moderately lower risk with ACE, non-significant for monotherapy (0.85; 0.69 - 1.05) and marginally significant for mono/combination users (0.88; 0.79 - 0.99). We observed, however, no significant difference between drug- classes for COVID-19 hospitalization or pneumonia risk across all comparisons. Conclusion: There is no clinically significant increased risk of COVID-19 diagnosis or hospitalization with ACE or ARB use. Users should not discontinue or change their treatment to avoid COVID-19.

Vitamin A (retinol) is essential for normal fetal development, but the recommendation for maternal dietary intake (Retinol Activity Equivalent, RAE) does not differ for singleton vs. twin pregnancy, despite the limited evaluation of retinol status. Therefore, this study aimed to evaluate plasma retinol concentrations and deficiency status in mother–infant sets from singleton vs. twin pregnancies as well as maternal RAE intake. A total of 21 mother–infant sets were included (14 singleton, 7 twin). The HPLC and LC-MS/HS evaluated the plasma retinol concentration, and data were analyzed using the Mann–Whitney U test. Plasma retinol was significantly lower in twin vs. singleton pregnancies in both maternal (192.2 vs. 312.1 vs. mcg/L, p = 0.002) and umbilical cord (UC) samples (102.5 vs. 154.4 vs. mcg/L, p = 0.002). The prevalence of serum-defined vitamin A deficiency (VAD) <200.6 mcg/L was higher in twins vs. singletons for both maternal (57% vs. 7%, p = 0.031) and UC samples (100% vs. 0%, p < 0.001), despite a similar RAE intake (2178 vs. 1862 mcg/day, p = 0.603). Twin pregnancies demonstrated a higher likelihood of vitamin A deficiency in mothers, with an odds ratio of 17.3 (95% CI: 1.4 to 216.6). This study suggests twin pregnancy may be associated with VAD deficiency. Further research is needed to determine optimal maternal dietary recommendations during twin gestation.

aureus(MRSA), streptococci and many common Gram-negative pathogens. The objective was to evaluate the efficacy of ceftaroline fosamil monotherapy versus other antibiotics routinely used in initial empiric treatment of MRSA-suspected CSSTI. METHODS: MEDLINE, Medline-In-Progress, EMBASE and the Cochrane Controlled Trials Registry were searched to identify published randomised controlled trials in which ceftaroline fosamil, daptomycin, linezolid, teicoplanin, tigecycline and vancomycin (with or without a Gram-negative antibiotic) were used to treat patients admitted to hospital with CSSTI. Primary outcomes were clinical success at test-of-cure visit in the modified intention-to-treat (MITT) and clinically evaluable (CE) populations using a NMA with uninformative priors. Clinical success for each antibiotic was reported with 95% credible intervals (CrI 95% ). A fixed effects model was used. RESULTS: Thirteen studies involving five antibiotics and a total of 8,152 patients with CSSTI were included. No data were found for teicoplanin. Pooled clinical success rates and CrI 95% in the MITT population for each antibiotic were: ceftaroline fosamil 81.2% (CrI 95% : 76.8% to 85.0%), daptomycin 81.4% (CrI 95% : 72.5% to 87.9%), linezolid 84.9% (CrI 95% : 80.0% to 88.8%), tigecycline 79.9% (CrI 95% : 74.1% to 84.7%) and vancomycin 80.4% (CrI 95% : 77.9% to 82.6%). Clinical success rates in the CE population were: ceftaroline fosamil 89.2% (CrI 95% : 85.3% to 92.3%), daptomycin 93.3% (CrI 95% : 88.5% to 96.2%), linezolid 94.2% (CrI 95% : 90.7% to 96.5%), tigecycline 88.1% (CrI 95% : 84.7% to 90.9%) and vancomycin 90.0% (CrI 95% : 88.2% to 91.6%). CONCLUSIONS: Although limited data were identified and differences across trials were noted, the results of this NMA suggest that ceftaroline fosamil is comparable in efficacy to other antibiotics used in the treatment of MRSA-suspected CSSTI.

Background Comparison of adalimumab (ADA), etanercept (ETN), and infliximab (INF) use in clinical practice may provide important insight into the comparative effectiveness and cost of approved therapies. Objectives To examine persistence, dose escalation, clinical outcomes, and treatment costs with ADA, ETN, and INF for patients (pts) enrolled in the US Veterans Affairs RA (VARA) registry. Methods VARA links to VA pharmacy and administrative databases, and documents longitudinal assessments of disease activity and outcomes. VARA pts initiating ADA, ETN, or INF from 3/18/2003 to 9/30/2010 were identified with follow-up data collected for ≥12 months. This analysis was limited to first treatment course beginning ≥180 days after VARA enrollment. A treatment course was defined as continuous medication dispensing in the absence of ≥90-day gap. Dose escalation was ≥25% increase in weekly dose. Cost was determined by drug costs alone and including drug administration (dispensing/infusion costs). Results Data from 563 pts (204 ADA; 290 ETN; 69 INF) were analyzed (Table). No differences in persistence were seen (Fig A). Dose escalation was most common with INF followed by ADA (Fig B). Persistence post-escalation was similar for all agents. Mean DAS28 and change in DAS28 in 61 evaluable pts were similar for each drug. Average annual costs were highest for INF. Image/graph: Conclusions In VARA, persistence on ADA, ETN and INF was similar. Escalation was most common with INF and least frequent with ETN, and did not impact persistence. Drug costs were higher for INF than ADA and ETN. Persistence and DAS scores were similar regardless of dose escalation. Acknowledgements Research funded by VA Research Program and Immunex Corporation, a wholly owned subsidiary of Amgen Inc., and by Wyeth, which was acquired by Pfizer Inc. in October 2009. Disclosure of Interest G. Cannon Grant/research support from: Amgen Inc., S. DuVall Grant/research support from: Amgen Inc, Anolinx LLC, Genentech Inc, F. Hoffmann-La Roche Ltd, Merck & Co Inc, Mylan Specialty LP, and Shire PLC, C. Hayden: None Declared, L. Caplan: None Declared, J. Curtis Grant/research support from: Roche/Genentech, UCB, Centocor, CORRONA, Amgen, Pfizer BMS, Janssen, AbbVie, K. Michaud: None Declared, T. Mikuls Grant/research support from: Genentech/Roche, A. Reimold Grant/research support from: Lilly, Novartis, Janssen, Ardea, Consultant for: UCB, D. Collier Shareholder of: Amgen Inc., Employee of: Amgen Inc., D. Harrison Shareholder of: Amgen Inc., Employee of: Amgen Inc., G. Joseph Shareholder of: Amgen Inc., Pfizer Inc., Employee of: Amgen Inc., B. Sauer Grant/research support from: Amgen Inc.