Major Hemorrhage Risk Associated with Direct Oral Anticoagulants in Non-Valvular Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background: Real-world, observational studies have investigated the safety profile of Direct Oral Anticoagulants (DOACs) on Major Hemorrhage (MH) used for stroke prevention in Non-Valvular Atrial Fibrillation (NVAF). We performed a systematic review and meta-analysis to investigate the comparative safety of DOACs versus other DOACs and versus Vitamin K Antagonists (VKAs) adhering to PRISMA guidelines. We defined MH according to the International Society on Thrombosis and Haemostasis statement or as the composite outcome of intracranial, gastrointestinal, genitourinary, respiratory, cavitary and musculoskeletal bleeding in case of studies using International Statistical Classification of Diseases codes for patient selection. Methods: We systematically investigated two databases (Medline, Embase) until April of 2021, gathered observational studies and extracted hazard ratios (HRs) with 95% confidence intervals (CI) on our outcome of interest. Additional subgroup analyses according to DOAC dosing, prior diagnosis of chronic kidney disease, prior diagnosis of stroke, history of previous use of VKA, the users' age, the users' gender and study population geographic region were conducted. All analyses were performed with a random-effects model. Results: From this search, 55 studies were included and 76 comparisons were performed. The MH risk associated with Rivaroxaban use was higher than the risk with Dabigatran use (HR: 1.32, 95% CI: 1.21-1.45, I 2 : 12.39%) but similar to VKA use (HR: 0.94, 95% CI: 0.87-1.02, I 2 : 76.57%). The MH risk associated with Dabigatran use was lower than the risk with VKA use (HR: 0.75, 95% CI: 0.64-0.90, I 2 : 87.57%). The MH risk associated with Apixaban use was lower than the risk with Dabigatran use (HR: 0.75, 95% CI: 0.64-0.88, I 2 : 58.66%), with Rivaroxaban use (HR: 0.58, 95% CI: 0.50-0.68, I 2 : 74.16%) and with VKA use (HR: 0.60, 95% CI: 0.55-0.65, I 2 : 58.83%). Our aforementioned subgroup analyses revealed similar results. Conclusions: All in all, Apixaban was associated with a reduced MH risk compared to Dabigatran, Rivaroxaban and VKA. Dabigatran was associated with a reduced MH risk compared to both Rivaroxaban and VKA.

High versus Medium Dose of Inhaled Corticosteroid in Chronic Obstructive Lung Disease: A Systematic Review and Meta-Analysis.

Background: Inhaled corticosteroids (ICSs) combined with bronchodilators have been identified to improve outcomes in COPD but also to be associated with certain adverse effects. Objective: We performed a systematic review and meta-analysis to compile and summarize data on the efficacy and safety of dosing levels (high versus medium/low) of ICS alongside ancillary bronchodilators following PRISMA guidelines. Data Sources: Medline and Embase were systematically searched until December 2021. Randomized, clinical trials (RCTs) that met predefined inclusion criteria were included. Data Extraction: Risk ratios (RRs) with 95% confidence intervals (CI) were extracted. Any acute exacerbation of COPD (AECOPD) risk was chosen as the primary efficacy outcome, mortality rate as the primary safety outcome, moderate/severe AECOPD risk as the secondary efficacy outcome and pneumonia risk as the secondary safety outcome. Subgroup analyses of individual ICS agents, of patients with baseline moderate/severe/very severe COPD and of patients with recent COPD exacerbation history were also performed. A random-effects model was used. Results: We included 13 RCTs in our study. No data on low doses were included in the analysis. High dose ICS was not associated with a statistically significant difference in any AECOPD risk (RR: 0.98, 95% CI: 0.91-1.05, I2: 41.3%), mortality rate (RR: 0.99, 95% CI: 0.75-1.32, I2: 0.0%), moderate/severe AECOPD risk (RR: 1.01, 95% CI: 0.96-1.06, I2: 0.0%) or pneumonia risk (RR: 1.07, 95% CI: 0.86 -1.33, I2: 9.3%) compared to medium dose ICS. The same trend was identified with the several subgroup analyses. Conclusion: Our study collected RCTs investigating the optimal dosing level of ICS prescribed alongside ancillary bronchodilators to patients with COPD. We identified that the high ICS dose neither reduces AECOPD risk and mortality rates nor increases pneumonia risk relative to the medium dose.

Unusual Fusobacterium Nucleatum Infection Presenting as a Liver Abscess Associated With Cephalic Vein Thrombosis.

Pyogenic liver abscesses are uncommon entities with potentially devastating consequences requiring immediate diagnosis and treatment. Fusobacterium nucleatum is an anaerobic, gram-negative oral commensal that has been seldom reported as a cause of liver abscess, particularly in immunocompetent hosts. We describe a case of an 80-year-old female patient presenting with a fusobacterium liver abscess associated with thrombosis of the left cephalic vein.