Ceftaroline fosamil demonstrated high clinical cure and microbiological response rates in hospitalized patients with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile similar to that of ceftriaxone and consistent with the cephalosporin class. In this study, ceftaroline fosamil was an effective and well-tolerated treatment option for CAP.

ObjectivesTo evaluate the efficacy and safety of different doses of filgotinib, an oral Janus kinase 1 inhibitor, as monotherapy in patients with active rheumatoid arthritis (RA) and previous inadequate response to methotrexate (MTX).MethodsIn this 24-week phase IIb study, patients with moderately to severely active RA were randomised (1:1:1:1) to receive 50, 100 or 200 mg filgotinib once daily, or placebo, after a ≥4-week washout from MTX. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR)20 response at week 12.ResultsOverall, 283 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib at any dose achieved ACR20 responses versus placebo (≥65% vs 29%, p<0.001). For other key end points at week 12 (ACR50, ACR70, ACR-N, Disease Activity Score based on 28 joints and C reactive protein, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index) significant differences from baseline in favour of filgotinib 100 and 200 mg versus placebo were seen; responses were maintained or improved through week 24. Rapid onset of action was observed for most efficacy end points. Dose-dependent increases in haemoglobin were observed. The percentage of patients with treatment-emergent adverse events (TEAE) was similar in the placebo and filgotinib groups (∼40%). Eight patients on filgotinib and one on placebo had a serious TEAE, and four patients, all of whom received filgotinib, experienced a serious infection. No tuberculosis or opportunistic infections were reported.ConclusionsOver 24 weeks, filgotinib as monotherapy was efficacious in treating the signs and symptoms of active RA, with a rapid onset of action. Filgotinib was generally well tolerated.Trial registration numberNCT01894516.

No abstract

BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

BACKGROUND Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. OBJECTIVES In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. METHODS ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3–74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2–111.0 mg/dL). RESULTS In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [Cl]: 0.52–0.90) and 1.11 (95% Cl: 0.83–1.49), with treatment-lipoprotein(a) interaction on MACE ( P interaction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% Cl: 0.72–0.92) and 0.89 (95% Cl: 0.75–1.06), with P interaction = 0.43. CONCLUSIONS In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402 )

Two doses of the MMRV vaccine and one dose of the varicella vaccine remain efficacious through six years post-vaccination.

COVID-19 has had a significant impact on health care systems, including drug use. The present study aimed to evaluate the patterns of community supply of antimicrobials from community pharmacies during the COVID-19 pandemic in five cities of Russia. In a cross-sectional study, a random sample of pharmacies reported all episodes of antimicrobials supply during a one-week period. Patterns of supply (age and gender of customer, drug name and formulation, prescription availability, indication, etc.) were analyzed. Altogether, 71 pharmacies took part in the study and 5270 encounters were recorded. In total, 4.2% of visits resulted in supply of more than one antimicrobial agent and 5.2% were for parenteral formulations. The rate of prescription-based purchase in participated cities varied from 40.5 to 99.1%. Systemic antibiotics and antivirals accounted for the majority of supplies (60.5 and 26.3%, respectively). Upper respiratory tract infections were reported as the indication for antimicrobials usage in 36.9% of cases, followed by skin and soft tissue infections (12.1%) and urinary tract infections (8.7%); COVID-19 accounted for 8.4% of all supplies. Amoxicillin with clavulanic acid, azithromycin and amoxicillin were indicated as the top three antimicrobials purchased for upper respiratory tract infections, and azithromycin, umifenovir and levofloxacin were the top three for COVID-19. In general, a high rate of drugs dispensing without prescription was revealed. Antibiotics for systemic use remained the most common antimicrobials, whereas presumably viral upper respiratory tract infections were the main reason for their purchase. COVID-19 infection itself was responsible for a small proportion of the supply of antimicrobial agents, but systemic antibiotics accounted for more than a half of supplies.

BackgroundFilgotinib (GLPG0634) is a novel oral, selective JAK1 inhibitor that was evaluated in a 24-week phase 2B study as monotherapy in active rheumatoid arthritis (RA) with inadequate response to methotrexate. The primary endpoint of proportion of patients achieving ACR20 response after 12 weeks of treatment was met.ObjectivesTo present the results of the 24-week analysis.MethodsPatients with active RA were randomized 1:1:1:1 in a double blinded manner to receive either placebo (PBO) or one of three doses of filgotinib (50mg, 100mg or 200mg) as a once daily regimen for 24 weeks (DARWIN 2 study). At Week 12 all patients on PBO and on 50mg daily whose tender and swollen joint counts did not improve by at least 20% (non-responders (NR)) were reassigned to 100mg daily.ResultsOf 283 randomized and treated patients, mean duration of RA of 9 years and DAS28(CRP) at baseline between 6.0–6.2. At Week 12, a statistically significant higher ACR20, ACR50, ACR70, DAS28(CRP) and CDAI response versus PBO was observed in filgotinib groups. These responses were similar or continued to improve through 24 weeks (Table 1). Increase in filgotinib dose from Week 12 improved efficacy in PBO and 50mg NR groups (at Week 24 ACR20 55% and 60% respectively). Serious Adverse Events and Treatment-Emergent Adverse Events (TEAE) were distributed over the dose groups including PBO: TEAE 39% PBO and 41% filgotinib groups. Infections occurred in 10% PBO and 19% filgotinib groups. No opportunistic infections, cancers or deaths occurred. In filgotinib groups, for the first 4 weeks, a dose dependent decrease in mean neutrophil and a small reduction in platelet counts was seen; mild increase in mean creatinine was apparent. These changes subsequently plateaued and remained stable up to Week 24. A dose dependent increase in haemoglobin was seen during the first 12 weeks and levels remained stable up to Week 24. Over 24 weeks no meaningful difference in transaminase changes was apparent.Table 1.Summary of the efficacy responses after 12 and 24 weeks treatmentPlacebo50mg100mg200mg(n=72)(n=72)(n=70)(n=69)12 weeks ACR20, NRI1, %2967***66***73** ACR50, NRI, %1135**37***44*** ACR70, NRI, %3819**13* DAS28(CRP), LOCF3, mean change from BL2−1.0−1.8***−2.0***−2.3*** CDAI4 mean change from BL, LOCF−12−21***−24***−25***24 weeks ACR20, NRI, %n/a577967 ACR50, NRI, %n/a333945 ACR70, NRI, %n/a192625 DAS28(CRP), LOCF, mean change from BLn/a−2.0−2.6−2.6 CDAI mean change from BL, LOCFn/a−22−30−28*p<0.05 vs. placebo; **p<0.01 vs. placebo; ***p<0.001 vs. placebo. ACR scores based on ITT analysis. 1Non-responder imputation. 2Baseline. 3Last observation carried forward. 4Clinical Disease Activity Index.ConclusionsSignificant improvement in signs and symptoms of active RA was observed after 12 weeks treatment with filgotinib monotherapy. Efficacy responses were sustained or increased at Week 24. The safety profile was acceptable.Disclosure of InterestA. Kavanaugh Grant/research support from: Galapagos, Pfizer, AbbVie, Amgen, Celgene, Janssen, Novartis, Eli Lilly, UCB, Cons...