Hamza Janjua

Introduction: Hemophilia A and B are among the most common inherited bleeding disorders in humans with lifelong risk of spontaneous and recurrent bleeding. While prophylaxis with clotting factors has improved outcomes, challenges like inhibitor development and treatment burden persist. We aim for a comparative effectiveness between these agents and traditional therapy with this study. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. Studies were identified through PubMed, Cochrane Central, and ClinicalTrials.gov up to May 30th, 2025. Eligible studies were double-arm RCTs comparing non-clotting factor prophylaxis (emicizumab, fitusiran, concizumab) and on-demand therapy in patients with hemophilia A or B. Results: Non-clotting factor prophylaxis significantly reduced the annualized bleeding rate (ABR) for all treated bleeds [ n = 399, (RR = 0.13; 95% CI: 0.09–0.19), I ² = 63.8%, p = 0.0107], spontaneous bleeds [RR = 0.08; 95% CI: (0.06, 0.11), I ² = 0.0%, p = 0.5933)] and joint bleeds [RR = 0.09; 95% CI: (0.06, 0.14), : I ² = 26.2%, p = 0.2468 ]. Haem-A-QoL total score improved with prophylaxis [MD = −11.08 [−16.34, −5.83], I ² = 57.5%, p = 0.0949]. Prophylaxis increased the likelihood of achieving zero treated bleeds [RR = 4.11; 95% CI: (1.48%, 11.45%), I ² = 88.5%, p < 0.0001]. An exploratory network meta-analysis comparing fitusiran, emicizumab, and concizumab reported no statistically significant difference in the ABR for all treated bleeds. Conclusion: Compared to on-demand therapy, non-factor prophylactic therapies significantly reduce bleeding episodes, improve quality of life, and increase the likelihood of zero bleeds in patients with hemophilia.

BACKGROUND: Heart failure (HF) is associated with high mortality rates and substantial health care costs. While there is growing emphasis on integrating palliative care for patients with HF, limited data exist on the locations where adults with HF spend their final days. The study aimed to analyze the location and circumstances of death among adults with HF in the United States using Centers for Disease Control and Prevention’s Wide-ranging Online Data for epidemiological Research data. METHODS: Mortality data from individuals aged ≥20 years, with HF listed as the cause of death between 1999 and 2023, were analyzed. The places of death were categorized as the emergency room, hospice/nursing home, inpatient medical facility, or home. Multinomial logistic regression was performed to examine the associations between demographic factors and death location. RESULTS: HF-related mortality rates declined from 1999 (3.60% and 143.6 age-adjusted mortality rate) to 2010 (3.47% and 123.1 age-adjusted mortality rate). However, rates gradually increased thereafter, reaching 5.18% and 168.1 age-adjusted mortality rate in 2023. Deaths at home nearly doubled, rising from 18.41% (50 648 of 275 132) in 1999 to 33.47% (132 470 of 395 826) in 2023. Hospice/nursing home deaths increased from 30.95% (85 144 of 275 132) in 1999 to 34.71% (116 634 of 336 014) in 2017, but declined to 29.54% (116 931 of 395 826) by 2023. Young adults (20–34 years) had the highest proportion of inpatient deaths. Sex, ethnicity, and urbanization were significant predictors of death location, with men, White individuals, and those in large metropolitan areas more likely to die in medical facilities. CONCLUSIONS: This study underscores the shifting trends in the locations of death among patients with HF, with a ≈2-fold increase in HF-related deaths occurring at home over the past 2 decades. The recent decline in hospice/nursing home deaths, following a period of steady growth, calls for an in-depth examination of contributing barriers. Further research is essential to understand the sociodemographic factors driving disparities in HF-related death locations.