Best practices for design, conduct, analysis, and interpretation of randomized controlled trials should adhere to rigorous statistical principles. The reliable detection of small effects of treatment should be based on results reported from the primary pre-specified endpoints of large-scale randomized trials designed a priori to test relevant hypotheses. Inference about treatment should not be based on undue reliance on individual small trials, meta-analyses of small trials, subgroups, or post hoc analyses. Failure to follow these principles can lead to conclusions inconsistent with the totality of evidence and to inappropriate recommendations made by guideline committees. The American Heart Association/American College of Cardiology Task Force published guidelines to restrict aspirin for primary prevention of cardiovascular disease to patients below 70 years of age, and the United States Preventive Services Task Force to below 60 years. These guidelines were both unduly influenced by the Aspirin in Reducing Events in the Elderly trial, the results of which were uninformative; they did not provide evidence that aspirin showed no benefit in these age groups. We present several major methodological pitfalls in interpreting the results from the Aspirin in Reducing Events in the Elderly trial of aspirin in the primary prevention of cardiovascular disease. We believe that undue reliance on this uninformative trial has led to misinformed guidelines. Furthermore, given the totality of evidence, we believe that general guidelines for aspirin in the primary prevention of cardiovascular disease are unwarranted. Prescription should be based on an assessment of an individual’s benefit to risk; age should be only one component of that assessment.

As of October 28, 2021, the United States was the epicenter of the coronavirus disease 2019 (COVID-19) pandemic. The United States accounts for >45.6 million of the >244 million cases of COVID-19 worldwide, or 18.5% in a population of 940,000 of the >4.95 million deaths worldwide have occurred in the United States since February 2020, a...

Guinea worm disease is approaching eradication, with only 10 human cases reported worldwide in 2025, the lowest annual total recorded. Yet the final phase of eradication presents complex clinical and public health challenges that differ from earlier stages of control. Persistent animal infections, particularly in dogs, civil conflict, fragile health systems, financing disruptions, and the need for prolonged surveillance threaten progress at the point when global attention may wane. Unlike smallpox, Guinea worm has been driven to near-eradication without a vaccine, curative drug, or rapid diagnostic test, relying instead on safe water, filtration, vector control, case containment, community education, reporting incentives, and sustained field operations. This Perspective argues that eradication remains achievable but requires a specific policy agenda: protected financing for surveillance, animal-source transmission control, safe-water measures, operational access, and certification through 2030. Completing the final mile would represent a permanent preventive achievement and a durable victory for neglected populations too often overlooked.