Cannabis use and involuntary admission may mediate long-term adherence in first-episode psychosis patients: a prospective longitudinal study

Background: This study aimed to examine factors associated with treatment adherence in first-episode psychosis (FEP) patients followed up over 8 years, especially involuntary first admission and stopping cannabis use. Methods: This prospective, longitudinal study of FEP patients collected data on symptoms, adherence, functioning,and substance use. Adherence to treatment was the main outcome variable and was categorized as ‘good’ or ‘bad’. Cannabis use during follow-up was stratified as continued use, stopped use, and never used. Bivariate and logistic regression models identified factors significantly associated with adherence and changes in adherence over the 8-year follow-up period. Results: Of the 98 FEP patients analyzed at baseline, 57.1% had involuntary first admission, 74.4% bad adherence,and 52% cannabis use. Good adherence at baseline was associated with Global Assessment of Functioning score (p = 0.019), Hamilton Depression Rating Scale score (p = 0.017) and voluntary admission (p < 0.001). Adherence patterns over 8 years included: 43.4% patients always bad, 26.1% always good, 25% improved from bad to good. Among the improved adherence group, 95.7% had involuntary first admission and 38.9% stopped cannabis use. In the subgroup of patients with bad adherence at baseline, involuntary first admission and quitting cannabis use during follow up were associated with improved adherence. Conclusions: The long-term association between treatment adherence and type of first admission and cannabis use in FEP patients suggest targets for intervention to improve clinical outcomes.

Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles

Self-amplifying RNA or RNA replicon is a form of nucleic acid-based vaccine derived from either positive-strand or negative-strand RNA viruses. The gene sequences encoding structural proteins in these RNA viruses are replaced by mRNA encoding antigens of interest as well as by RNA polymerase for replication and transcription. This kind of vaccine has been successfully assayed with many different antigens as vaccines candidates, and has been shown to be potent in several animal species, including mice, nonhuman primates, and humans. A key challenge to realizing the broad potential of self-amplifying vaccines is the need for safe and effective delivery methods. Ideally, an RNA nanocarrier should provide protection from blood nucleases and extended blood circulation, which ultimately would increase the possibility of reaching the target tissue. The delivery system must then be internalized by the target cell and, upon receptor-mediated endocytosis, must be able to escape from the endosomal compartment into the cell cytoplasm, where the RNA machinery is located, while avoiding degradation by lysosomal enzymes. Further, delivery systems for systemic administration ought to be well tolerated upon administration. They should be safe, enabling the multiadministration treatment modalities required for improved clinical outcomes and, from a developmental point of view, production of large batches with reproducible specifications is also desirable. In this review, the concept of self-amplifying RNA vaccines and the most promising lipid-based delivery systems are discussed.