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.

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, this review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.

Goals and Background: Since the introduction of Direct Oral Anticoagulants (DOACs), “real-world” studies have investigated their safety profile on gastrointestinal hemorrhage (GIH) when used by patients with Non-Valvular Atrial Fibrillation. We performed a systematic review and meta-analysis to compile and summarize this data after Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Study: Medline and Embase were systematically searched until April 2021. Observational studies that met predefined inclusion criteria were included and hazard ratios (HRs) with 95% CI were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, prior exposure to VKA (vitamin K antagonist), age, gender, geographic location of population samples, as well as Leave-One-Out and Low/Moderate Risk of Bias sensitivity analyses were performed. A random effects model was used. Results: A total of 46 studies were included. Apixaban was associated with a reduced risk of GIH compared with Dabigatran (HR: 0.67, 95% CI, 0.56 to 0.81, I ²: 53.28%), Rivaroxaban (HR: 0.56, 95% CI, 0.44 to 0.70, I ²: 79.17%), and VKA (HR: 0.68, 95% CI, 0.60 to 0.78, I ²: 71.93%). Rivaroxaban was associated with increased GIH risk compared with Dabigatran (HR: 1.19, 95% CI, 1.02 to 1.40, I ²: 72.96%) and VKA (HR: 1.16, 95% CI, 1.05 to 1.27, I ²: 81.95%). Dabigatran was associated with similar GIH risk compared with VKA (HR: 1.11, 95% CI, 0.98 to 1.26, I ²: 87.28%). Conclusions: Our study shows that Apixaban was associated with a reduction in GIH risk compared with Dabigatran, Rivaroxaban and VKA, whereas Rivaroxaban was associated with an increase in GIH risk compared with both Dabigatran and VKA.

Background: Patients with atrial fibrillation (AF) on oral anticoagulation (OAC) who have a history of intracranial hemorrhage (ICrH) or cerebral amyloid angiopathy (CAA) have an elevated risk of ICrH recurrence. Left atrial appendage occlusion (LAAO) has emerged as a potential alternative to OAC for stroke prevention in high-bleeding-risk AF patients. Small observational studies suggest that LAAO may be safe and feasible in patients with ICrH, when using single or dual antiplatelet therapy or short-term OAC post-procedure, though data remain limited. This systematic review and meta-analysis aims to consolidate evidence on the safety and efficacy of LAAO in patients with prior ICrH or CAA. Methods: We conducted a systematic review and meta-analysis examining the safety and efficacy of LAAO in patients with non-valvular AF and prior ICrH and/or CAA. PubMed/MEDLINE and EMBASE (via Scopus) databases were systematically searched from inception until 29 February 2024. Eligible studies included randomized control trials, observational studies, and case series (⩾10 participants) reporting stroke events in patients with AF and previous history of ICrH and/or CAA undergoing LAAO. Pooled incidence rates (IRs) with corresponding 95% confidence intervals (CIs) were calculated for primary outcomes (post-procedural ischemic stroke and recurrent ICrH) and secondary outcomes. Results: Fourteen studies including 1235 patients met inclusion criteria. The pooled average follow-up period was 17.1 months. The pooled IRs for ischemic stroke, recurrent ICrH, and major hemorrhage were 2% (95% CI: 1–3%, I ² = 2%), 2% (95% CI: 0.4–3%, I ² = 45%) and 3% (95% CI: 1–5%, I ² = 54%), respectively. In prespecified subgroup analyses of studies focusing on patients with intraparenchymal hemorrhage and/or CAA, pooled IRs for ischemic stroke, recurrent ICrH, and major hemorrhage IR of 4% (95% CI: 1–8%), 4% (95% CI: 0.4–10%) and 6% (95% CI: 3–12%), respectively. Conclusions: LAAO may be a safe and effective treatment for selected AF patients with a history of ICrH and/or CAA, but the quality of evidence is poor. Future randomized controlled trials are essential to validate LAAO’s efficacy and long-term safety.