Background: Drug-coated balloons (DCBs) are an established treatment strategy for coronary artery disease. Randomized data on the application of DCBs in patients with an acute coronary syndrome (ACS) are limited. We evaluated the impact of clinical presentation (ACS versus chronic coronary syndrome) on clinical outcomes in patients undergoing DCB or drug-eluting stent (DES) treatment in a prespecified analysis of the BASKET-SMALL 2 trial (Basel Kosten Effektivitäts Trial–Drug-Coated Balloons Versus Drug-Eluting Stents in Small Vessel Interventions). Methods: BASKET-SMALL 2 randomized 758 patients with small vessel coronary artery disease to DCB or DES treatment and followed them for 3 years regarding major adverse cardiac events (cardiac death, nonfatal myocardial infarction, and target vessel revascularization). Results: Among 758 patients, 214 patients (28.2%) presented with an ACS (15 patients [7%], ST-segment–elevation myocardial infarction; 109 patients [50.9%], non–ST-segment–elevation myocardial infarction; 90 patients [42.1%], unstable angina pectoris). At 1-year follow-up, there was no significant difference in the incidence of the primary end point by randomized treatment in patients with ACS (hazard ratio, 0.50 [95% CI, 0.19–1.26] for DCB versus DES) or chronic coronary syndrome (hazard ratio, 1.29 [95% CI, 0.67–2.47] for DCB versus DES). There was no significant interaction between clinical presentation and treatment effect ( P for interaction, 0.088). For cardiac death ( P for interaction, 0.049) and nonfatal myocardial infarction ( P for interaction, 0.010), a significant interaction between clinical presentation and treatment was seen at 1 year with lower rates of these secondary end points in patients with ACS treated by DCB. At 3 years, there were similar major adverse cardiac event rates throughout groups without significant interaction between clinical presentation and treatment ( P for interaction, 0.301). All-cause mortality was higher in ACS compared with chronic coronary syndrome; however, there was no difference between DCB and DES irrespective of clinical presentation. Conclusions: In this subgroup analysis of the BASKET-SMALL 2 trial, there was no interaction between indication for percutaneous coronary intervention (acute versus chronic coronary syndrome) and treatment effect of DCB versus DES in patients with small vessel coronary artery disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01574534.

Stargardt disease is a currently untreatable, inherited neurodegenerative disease that leads to macular degeneration and blindness due to loss-of-function mutations in the ABCA4 gene. We have designed a dual adeno-associated viral vector encoding a split-intein adenine base editor to correct the most common mutation in ABCA4 (c.5882G>A, p.Gly1961Glu). We optimized ABCA4 base editing in human models, including retinal organoids, induced pluripotent stem cell-derived retinal pigment epithelial (RPE) cells, as well as adult human retinal explants and RPE/choroid explants in vitro. The resulting gene therapy vectors achieved high levels of gene correction in mutation-carrying mice and in female nonhuman primates, with average editing of 75% of cones and 87% of RPE cells in vivo, which has the potential to translate to a clinical benefit. No off-target editing was detectable in human retinal explants and RPE/choroid explants. The high editing rates in primates show promise for efficient gene editing in other ocular diseases that are targetable by base editing.

In both classical and Bayesian approaches, statistical inference is unified and generalized by the corresponding decision theory. This is not the case for the likelihood approach to statistical inference, in spite of the manifest success of the likelihood methods in statistics. The goal of the present work is to fill this gap, by extending the likelihood approach in order to cover decision making as well. The resulting likelihood decision functions generalize the usual likelihood methods (such as ML estimators and LR tests), while maintaining some of their key properties, and thus providing a theoretical foundation for established and new likelihood methods.