Chronic disease management often requires use of multiple drug regimens that lead to polypharmacy challenges and suboptimal utilization of healthcare services. While the rising costs and healthcare utilization associated with polypharmacy and drug interactions have been well documented, effective tools to address these challenges remain elusive. Emerging evidence that proactive medication management, combined with pharmacogenomic testing, can lead to improved health outcomes and reduced cost burdens may help to address such gaps. In this report, we describe informatic and bioanalytic methodologies that integrate weak signals in symptoms and chief complaints with pharmacogenomic analysis of ~90 single nucleotide polymorphic variants, CYP2D6 copy number, and clinical pharmacokinetic profiles to monitor drug–gene pairs and drug–drug interactions for medications with significant pharmacogenomic profiles. The utility of the approach was validated in a virtual patient case showing detection of significant drug–gene and drug–drug interactions of clinical significance. This effort is being used to establish proof-of-concept for the creation of a regional database to track clinical outcomes in patients enrolled in a bioanalytically-informed medication management program. Our integrated informatic and bioanalytic platform can provide facile clinical decision support to inform and augment medication management in the primary care setting.

Background: A large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19. We hypothesize that BCG vaccination can reduce SARS-CoV-2 infection and disease severity. Methods: This will be a placebo-controlled adaptive multi-center randomized controlled trial. A total of 1800 individuals considered to be at high risk, including those with comorbidities (hypertension, diabetes, obesity, reactive airway disease, smokers), racial and ethnic minorities, elderly, teachers, police, restaurant wait-staff, delivery personnel, health care workers who are defined as personnel working in a healthcare setting, at a hospital, medical center or clinic (veterinary, dental, ophthalmology), and first responders (paramedics, firefighters, or law enforcement), will be randomly assigned to two treatment groups. The treatment groups will receive intradermal administration of BCG vaccine or placebo (saline) with groups at a 1:1 ratio. Individuals will be tracked for evidence of SARS-CoV-2 infection and severity as well as obtaining whole blood to track immunological markers, and a sub-study will include cognitive function and brain imaging. The majority of individuals will be followed for 6 months, with an option to extend for another 6 months, and the cognitive sub-study duration is 2 years. We will plot Kaplan-Meier curves that will be plotted comparing groups and hazard ratios and p-values reported using Cox proportional hazard models. Discussion: It is expected this trial will allow evaluation of the effects of BCG vaccination at a population level in high-risk healthcare individuals through a mitigated clinical course of SARS-CoV-2 infection and inform policy making during the ongoing epidemic. Trial registration: ClinicalTrials.gov NCT04348370. Registered on April 16, 2020.

Background: The BCG vaccine induces trained immunity, an epigenetic-mediated increase in innate immune responsiveness. Therefore, this clinical trial evaluated if BCG-induced trained immunity could decrease coronavirus disease 2019 (COVID-19)–related frequency or severity. Methods: A double-blind, placebo-controlled clinical trial of healthcare workers randomized participants to vaccination with BCG TICE or placebo (saline). Enrollment included 529 healthcare workers randomized to receive BCG or placebo. Primary analysis evaluated COVID-19 disease frequency, while secondary analysis evaluated coronavirus immunity in a subset of participants. Study enrollment ceased early in December 2020 following introduction of COVID-19–specific vaccines. Results: Study enrollment was halted early, prior to reaching the targeted recruitment, and was not powered to detect a decrease in COVID-19 frequency. Symptomatic COVID-19 occurred in 21 of 263 and 10 of 266 participants in the BCG and placebo arms, respectively (P = .50, Fisher exact test). Participants vaccinated with BCG, but uninfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrated increased coronavirus vaccine immunity (increase spike-inducible levels of tumor necrosis factor, interleukin 6, and interleukin 1β) 12 months after BCG vaccination compared to participants receiving placebo. Immune responsiveness to SARS-CoV-2 antigens correlated with BCG-induced DNA methylation changes. Conclusions: Due to early study closure, the study was not powered to evaluate COVID-19 frequency. Secondary analysis demonstrated that 12 months following vaccination, BCG increased coronavirus vaccine immunity compared to those who did not receive BCG. This increase in COVID-19 vaccine immunity correlated with BCG-induced DNA methylation changes.

Background Selective serotonin reuptake inhibitors (SSRI) are commonly used for the treatment of depression and anxiety. Inhibition of serotonin reuptake in platelets increases bleeding risk in patients taking SSRIs. Case Here, we present the case of a 52-year-old patient who developed severe postsurgical bleeding requiring blood transfusion following panniculectomy. Conclusion SSRI-induced bleeding is dose-related and strongly influenced by individual variations in drug metabolizing enzymes and transporters. Video abstract Supplementary file1 (MP4 8441 KB)