Ikram, Jibran

ABSTRACT Background Factor XI/XIa inhibitors are emerging anticoagulants with potential to reduce bleeding complications in atrial fibrillation (AF) patients. This meta‐analysis evaluated their efficacy and safety compared to direct oral anticoagulants (DOACs) and explored dose optimization. Methods A systematic search of PubMed, Cochrane, and Embase was conducted through March 2025 following PRISMA guidelines. Randomized controlled trials (RCTs) comparing Factor XI/XIa inhibitors with DOACs in AF patients were included. Outcomes assessed were major bleeding, stroke, systemic embolism, all‐cause and cardiovascular mortality and serious adverse events. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a Mantel‐Haenszel random‐effects model. Heterogeneity was evaluated with the I² statistic, and evidence certainty assessed by the GRADE approach. Trial Sequential Analysis (TSA) was performed. Results Three RCTs including 16,772 patients (mean age 73 years, CHA₂DS₂‐VASc 3.9–5) were analyzed. Factor XI/XIa inhibitors significantly reduced major bleeding (RR: 0.41, 95% CI: 0.36–0.46, I² = 0%) compared to DOACs. However, stroke risk was increased (RR: 3.42, 95% CI: 2.62–4.46), particularly with asundexian 50 mg (RR: 4.02). No significant differences were observed in all‐cause mortality (RR: 0.82) or cardiovascular death (RR: 1.05). Systemic embolism risk was higher (RR: 4.26), while serious adverse events were comparable (RR: 0.95). TSA indicated encouraging safety outcomes but highlighted the need for further large‐scale studies. Conclusion Factor XI/XIa inhibitors lower major bleeding risk in AF patients but increase stroke and systemic embolism rates without impacting mortality.

e16076 Background: Gastric cancer is the fourth leading cause of global cancer deaths. Despite declining incidence and mortality, it remains a significant contributor to the global disease burden. This study analyzes regional gastric cancer DALYs and mortality trends from 1990-2021 using the GBD database. Methods: The regional DALYs and mortality rates per 100,000 individuals aged 70+ from GBD 2021 were analyzed, with trends from 1990 to 2021 evaluated using AAPC, and statistical significance assessed by p-values. Results: In 2021, the greatest Age-standardized DALYs rates were recorded in Andean Latin America, with 3068.04 per 100,000; the lowest was found in High-income North America with 386.08 per 100,000. The most significant increase of DALYs rate from 1990 to 2021 was in Southern Sub-Saharan Africa, (AAPC = -0.3068%; 95% CI: -0.3852 to -0.2234; p < 0.000001), while in Western Europe, the largest decline was noted (AAPC = -2.9999%; 95% CI: -3.0164 to -2.9841; p < 0.000001). Andean Latin America was the region with the highest Age-standardized mortality rates (ASMRs) in 2021, at 207.58 per 100,000 while High-income North America had the lowest at 27.18 per 100,000. In Western Sub-Saharan Africa, the ASMRs were rising with an AAPC of -0.2601% (95% CI: -0.2872 to -0.2368; p < 0.000001), while Western Europe had the highest decline with an AAPC of -2.7658% (95% CI: -2.7895 to -2.7471; p < 0.000001). Conclusions: The global burden of diseases from 1990 to 2021 is regional in nature. In 2021, DALYs and mortality were predominantly high in Andean Latin America and East Asia and notably low in High-income North America. DALYs have risen across Southern Sub-Saharan Africa over three decades, and mortality increased over Western Sub-Saharan Africa, while both declined sharply in Western Europe. These trends underscore the importance of regionalized health solutions. DALY per 100,000. Metric Region 1990 2021 AAPC (1990-2021) HIGHEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PER 100,000 Andean Latin America 4469.23 3068.04 -1.14 East Asia 5507.72 2958.98 -1.99 High Income Asia Pacific 4849.23 2130.43 -2.71 LOWEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PER 100,000 High Income North America 758.59 386.09 -2.22 Australasia 1116.91 567.32 -2.16 South Asia 794.81 680.50 -0.46 HIGHEST MORTALITY RATE PER 100,000 Andean Latin America 293.65 207.58 -1.04 East Asia 324.60 188.92 -1.72 High Income Asia Pacific 316.44 161.94 -2.22 LOWEST MORTALITY RATE PER 100,000 High Income North America 51.24 27.19 -2.02 Australasia 74.36 41.81 -1.85 South Asia 47.50 41.95 -0.39

e16456 Background: Gastric cancer is one of the significant contributors of mortality and morbidity, especially in older patients. Analyzing national trends in the Disability adjust life years (DALY) helps identify the evolving burden of this disease among patients older than 70 years and highlights the regions requiring particular interventions. Methods: Using Global burden of disease data from 2021, national DALY rates per 100,000 people aged 70 and over with gastric cancer were assessed. The Estimated Annual Percentage Change (EAPCs) with p value taken as a statistical measure of significance, was used to evaluate trends from 1990 to 2021. Results: The analysis displays considerable contrasts in the trends of gastric cancer burden across nations. From 1990 to 2021, a rising trend in DALY EAPC was seen in Egypt (1.01883; 95% CI: -0.1931- 1.958) followed by Honduras (0.3262; 95% CI: 0.0177- 0.7456) and Lesotho (0.2253; 95% CI:-0.1326- 0.6995). Conversely, Austria (-0.7368; 95% CI: -0.7646 to -0.7087), Republic of Korea (-0.7095; 95% CI: -0.7620 to -0.6442) and Singapore (-0.6923; 95% CI: -0.7286 to -0.6553) reported a prominent decline in DALY EAPCs, reflecting significant progress in reducing burden. The DALY rates in 2021 also varied dramatically among nations. Highest DALY rate was observed in Bolivia (4882.7; 95% CI:3782.9- 6349.7) underscoring highest impact on healthcare system. Conversely, Morocco (329.69; 95% CI: 234.64- 410.12) recorded lowest DALY rate indicating comparatively better disease control or lower incidence. Conclusions: While some nations demonstrate remarkable progress in mitigating the burden of gastric cancer, others still face significant challenges. Highest increase in EAPC in Egypt, Honduras and Lesotho whereas significant decline in Austria, Korea, and Singapore indicates areas of target public health efforts. Future research should focus on understanding the causes of these disparities and evaluating the impact of interventions across it. DALY and EPAC. Country 2021 DALY rate EAPC(1990-2021) EAPC, 95% CI Egypt 1272.146 1.018834(highest) -0.193 to 1.959 Honduras 2880.563 0.32617 0.018 to 0.746 Lesotho 1555.79 0.225384 -0.133 to 0.699 Singapore 806.6098 -0.692396 -0.729 to -0.655 Republic of Korea 1961.151 -0.709502 -0.762 to -0.644 Austria 662.5105 -0.736826(lowest) -0.765 to -0.709 Morocco 410.1227(lowest) -0.17817 -0.387 to 0.097 Bolivia 4882.718(highest) -0.32185 -0.473 to -0.103