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BackgroundOcular rosacea is common and is often managed with long-term antibiotic treatment. Doxycycline is the most commonly selected antibiotic for the treatment of rosacea. As there is no established standard of care treatment dose for rosacea, prescribed doses of doxycycline vary widely. The FDA classifies 40 mg daily dose of doxycycline for ocular rosacea as sub-microbial in comparison to an antibiotic dose of 200 mg daily. However, this "sub-microbial" dose has never been evaluated in patients with ocular rosacea, and even the sub-microbial dose has potential to alter systemic mucosa flora. Here, we present a randomized controlled trial using RNA sequencing to fully characterize the impact of sub-microbial antibiotic dosing of doxycycline on antimicrobial resistance and bacterial composition of the ocular and gut flora.MethodsIn a triple-masked parallel randomized control trial, patients with ocular rosacea will be randomized to three arms: a 40-mg dose of doxycycline, a 200-mg antibiotic dose of doxycycline, or placebo. Collected rectal and lower eyelid samples will be compared for frequency of antimicrobial resistance genetic determinants and microbiome diversity. A subjective ocular surface disease index survey and objective tear breakup time measurement will be determined.DiscussionThese results will enhance our understanding of the overall systemic impact of long-term systemic sub-microbial antibiotic dosing for the treatment of chronic recurrent ocular inflammatory diseases.Trial registrationThis trial was registered on ClinicalTrials.org (NCT05296837) on March 22, 2022.

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Background: The optimal management of patients with spontaneous coronary artery dissection remains debated. Methods: Patients enrolled in the DISCO (Dissezioni Spontanee Coronariche) Registry up to December 2020 were included. The primary end point was major adverse cardiovascular events, a composite of all-cause death, nonfatal myocardial infarction, and repeat percutaneous coronary intervention (PCI). Independent predictors of PCI and medical management were investigated. Results: Among 369 patients, 129 (35%) underwent PCI, whereas 240 (65%) were medically managed. ST-segment–elevation myocardial infarction (68% versus 35%, P <0.001), resuscitated cardiac arrest (9% versus 3%, P <0.001), proximal coronary segment involvement (32% versus 7%, P <0.001), and Thrombolysis in Myocardial Infarction flow 0 to 1 (54% versus 20%, P <0.001) were more frequent in the PCI arm. In-hospital event rates were similar. Between patients treated with PCI and medical therapy, there were no differences in terms of major adverse cardiovascular events at 2 years (13.9% versus 11.7%, P =0.467), all-cause death (0.7% versus 0.4%, P =0.652), myocardial infarction (9.3% versus 8.3%, P =0.921) and repeat PCI (12.4% versus 8.7%, P =0.229). ST-segment–elevation myocardial infarction at presentation (odds ratio [OR], 3.30 [95% CI, 1.56–7.12]; P =0.002), proximal coronary segment involvement (OR, 5.43 [95% CI, 1.98–16.45]; P =0.002), Thrombolysis in Myocardial Infarction flow grade 0 to 1 and 2 (respectively, OR, 3.22 [95% CI, 1.08–9.96]; P =0.038; and OR, 3.98 [95% CI, 1.38–11.80]; P =0.009) and luminal narrowing (OR per 5% increase, 1.13 [95% CI, 1.01–1.28]; P =0.037) were predictors of PCI, whereas the 2B-angiographic subtype predicted medical management (OR, 0.25 [95% CI, 0.07–0.83]; P =0.026). Conclusions: Clinical presentation and procedural variables drive the choice of the initial therapeutic approach in spontaneous coronary artery dissection. If PCI is needed, it seems to be associated with a similar risk of short-to-mid-term adverse events compared to medical treatment. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04415762. [ABSTRACT FROM AUTHOR]