Cardiovascular Burden of Narcolepsy Disease (CV-BOND): a real-world evidence study.

STUDY OBJECTIVES: Narcolepsy is associated with cardiovascular risk factors; however, the risk of new-onset cardiovascular events in this population is unknown. This real-world study evaluated the excess risk of new-onset cardiovascular events in U.S. adults with narcolepsy. METHODS: A retrospective cohort study using IBM MarketScan administrative claims data (2014-2019) was conducted. A narcolepsy cohort, comprising adults (≥18 years) with at least two outpatient claims containing a narcolepsy diagnosis, of which at least one was non-diagnostic, was matched to a non-narcolepsy control cohort (1:3) based on cohort entry date, age, sex, geographic region, and insurance type. The relative risk of new-onset cardiovascular events was estimated using a multivariable Cox proportional hazards model to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The narcolepsy and matched non-narcolepsy control cohorts included 12 816 and 38 441 individuals, respectively. At baseline, cohort demographics were generally similar; however, patients with narcolepsy had more comorbidities. In adjusted analyses, the risk of new-onset cardiovascular events was higher in the narcolepsy cohort compared with the control cohort: any stroke (HR [95% CI], 1.71 [1.24, 2.34]); heart failure (1.35 [1.03, 1.76]); ischemic stroke (1.67 [1.19, 2.34]); major adverse cardiac event (1.45 [1.20, 1.74]); grouped instances of stroke, atrial fibrillation, or edema (1.48 [1.25, 1.74]); and cardiovascular disease (1.30 [1.08, 1.56]). CONCLUSION: Individuals with narcolepsy are at increased risk of new-onset cardiovascular events compared with individuals without narcolepsy. Physicians should consider cardiovascular risk in patients with narcolepsy when weighing treatment options.

Development and Optimization of Chromosomally-Integrated Fluorescent Mycobacterium tuberculosis Reporter Constructs.

Mycobacterium tuberculosis resides in the lungs in various lesion types with unique microenvironmental conditions. This diversity is in line with heterogeneous disease progression and divergent drug efficiency. Fluorescent reporter strains can be used to decipher the micromilieu and to guide future treatment regimens. Current reporters using replicating plasmids, however, are not suitable for long-term mouse infections or studies in non-human primates. Using a combination of recombinant DNA and protein optimization techniques, we have developed reporter strains based on integrative plasmids, which exhibit stimulus-response characteristics and fluorescence intensities comparable to those based on replicating plasmids. We successfully applied the concepts by constructing a multi-color reporter strain able to detect simultaneous changes in environmental pH, Mg2+ concentrations, and protein expression levels.