Safety and Effectiveness of Rivaroxaban Versus Warfarin Across GFR Levels in Atrial Fibrillation: A Population-Based Study in Australia and Canada.

Rationale & Objective: The benefit-risk profile of rivaroxaban versus warfarin for atrial fibrillation (AF) in patients with chronic kidney disease is uncertain. We compared rivaroxaban with warfarin across the range of kidney function in adults with AF. Study Design: Multicenter retrospective cohort. Setting & Participants: Adults with AF and a measure of estimated glomerular filtration rate (eGFR); using administrative data from 5 jurisdictions across Australia and Canada (2011-2018). Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. Patients receiving dialysis and kidney transplant recipients were excluded. Exposures: New dispensation of either rivaroxaban or warfarin. Outcomes: Composite (1) effectiveness outcome (all-cause death, ischemic stroke, or transient ischemic attack) and (2) major bleeding events (intracranial, gastrointestinal, or other) at 1 year. Analytical Approach: Cox proportional hazards models accounting for propensity score matching were performed independently in each jurisdiction and then pooled using random-effects meta-analysis. Results: 55,568 patients (27,784 rivaroxaban-warfarin user matched pairs; mean age 74 years, 46% female, 33.5% with eGFR <60 mL/min/1.73 m2) experienced a total of 4,733 (8.5%) effectiveness and 1,144 (2.0%) bleeding events. Compared to warfarin, rivaroxaban was associated with greater or similar effectiveness across a broad range of kidney function (pooled HRs of 0.72 [95% CI, 0.66-0.78], 0.78 [95% CI, 0.58-1.06], 0.70 [95% CI, 0.57-0.87], and 0.78 [95% CI, 0.62-0.99]) for eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively). Rivaroxaban was also associated with similar risk of major bleeding across all eGFR categories (pooled HRs of 0.75 [95% CI, 0.56-1.00], 1.01 [95% CI, 0.79-1.30], 0.87 [95% CI, 0.66-1.15], and 0.63 [95% CI, 0.37-1.09], respectively). Limitations: Unmeasured treatment selection bias and residual confounding. Conclusions: In adults with AF, rivaroxaban compared with warfarin was associated with lower or similar risk of all-cause death, ischemic stroke and transient ischemic attack and similar risk of bleeding across a broad range of kidney function. Plain-Language Summary: This real-world study involved a large cohort of 55,568 adults with atrial fibrillation from 5 jurisdictions across Australia and Canada. It showed that the favorable safety (bleeding) and effectiveness (stroke or death) profile of rivaroxaban compared with warfarin was consistent across different levels of kidney function. This study adds important safety data on the use of rivaroxaban in patients with reduced kidney function, including those with estimated glomerular filtration rate <30 mL/min/1.73 m2 in whom the risks and benefits of rivaroxaban use is most uncertain. Overall, the study supports the use of rivaroxaban as a safe and effective alternative to warfarin for atrial fibrillation across differing levels of kidney function.

Pandemic fatigue impedes mitigation of COVID-19 in Hong Kong.

Hong Kong has implemented stringent public health and social measures (PHSMs) to curb each of the four COVID-19 epidemic waves since January 2020. The third wave between July and September 2020 was brought under control within 2 m, while the fourth wave starting from the end of October 2020 has taken longer to bring under control and lasted at least 5 mo. Here, we report the pandemic fatigue as one of the potential reasons for the reduced impact of PHSMs on transmission in the fourth wave. We contacted either 500 or 1,000 local residents through weekly random-digit dialing of landlines and mobile telephones from May 2020 to February 2021. We analyze the epidemiological impact of pandemic fatigue by using the large and detailed cross-sectional telephone surveys to quantify risk perception and self-reported protective behaviors and mathematical models to incorporate population protective behaviors. Our retrospective prediction suggests that an increase of 100 daily new reported cases would lead to 6.60% (95% CI: 4.03, 9.17) more people worrying about being infected, increase 3.77% (95% CI: 2.46, 5.09) more people to avoid social gatherings, and reduce the weekly mean reproduction number by 0.32 (95% CI: 0.20, 0.44). Accordingly, the fourth wave would have been 14% (95% CI%: -53%, 81%) smaller if not for pandemic fatigue. This indicates the important role of mitigating pandemic fatigue in maintaining population protective behaviors for controlling COVID-19.

Current and future therapy in haemochromatosis and Wilson's disease.

There have been several new developments in the treatment of iron and copper overload disorders, such as haemochromatosis, thalassaemia and Wilson's disease. Clinical trials of orally administered iron chelators, both as monotherapy and in combination with deferoxamine, are in progress around the world. Several new chelators are now being introduced in clinical trials. Future therapies for iron overload may comprise of oral iron binding agents capable of preventing dietary iron absorption from the diet. The characterisation of specific iron transporters such as the divalent metallic transporter and ferroportin may hold promise for the development of 'smart' compounds capable of blocking iron transport. Several new agents are now available for the management of Wilson's disease, including trientine, zinc and tetrathiomolybdate. This review, will discuss the pathogenesis, and current and future therapies for iron and copper overload disorders.