Effect of meditation or escitalopram on work performance in patients with anxiety disorders.

OBJECTIVE: This study aimed to 1) examine how psychopharmacotherapy and mindfulness-based stress reduction (MBSR) influence absenteeism and job performance among individuals with anxiety disorders and 2) compare the effectiveness of these treatments in improving work performance. METHODS: Adults (N = 67) with a primary anxiety disorder were recruited to participate in the study. Participants were randomized to escitalopram, a common treatment for anxiety disorders, or MBSR. Absenteeism and job performance were measured with the Health and Work Performance (HPQ) questionnaire prior to treatment and at the week 24 follow up. RESULTS: At week 24, individuals in the escitalopram arm and the MBSR arm showed significant improvements in partial days of missed work due to mental/physical health problems from baseline (1.00 [0.00-2.50] to 0.00 [0.00 = 1.00], p = .034 and 0.00 [0.00-2.00] to 0.00 [0.00 = 1.00], p = .001, respectively). In the MBSR arm only, job performance increased from baseline to week 24 (65.00 [50.00-80.00] to 75.00 [67.50-82.50], p = .017). None of the outcome variables significantly varied by group at baseline or week 24. CONCLUSIONS: Our study finds evidence that MBSR improves work performance equivalently to SSRI medication among individuals with anxiety disorders. Given the limitations of SSRIs, MBSR should be considered as an alternative to individuals who desire improved anxiety symptoms and work outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03522844.

A Review of Protein- and Peptide-Based Chemical Conjugates: Past, Present, and Future.

Over the past few decades, the complexity of molecular entities being advanced for therapeutic purposes has continued to evolve. A main propellent fueling innovation is the perpetual mandate within the pharmaceutical industry to meet the needs of novel disease areas and/or delivery challenges. As new mechanisms of action are uncovered, and as our understanding of existing mechanisms grows, the properties that are required and/or leveraged to enable therapeutic development continue to expand. One rapidly evolving area of interest is that of chemically enhanced peptide and protein therapeutics. While a variety of conjugate molecules such as antibody-drug conjugates, peptide/protein-PEG conjugates, and protein conjugate vaccines are already well established, others, such as antibody-oligonucleotide conjugates and peptide/protein conjugates using non-PEG polymers, are newer to clinical development. This review will evaluate the current development landscape of protein-based chemical conjugates with special attention to considerations such as modulation of pharmacokinetics, safety/tolerability, and entry into difficult to access targets, as well as bioavailability. Furthermore, for the purpose of this review, the types of molecules discussed are divided into two categories: (1) therapeutics that are enhanced by protein or peptide bioconjugation, and (2) protein and peptide therapeutics that require chemical modifications. Overall, the breadth of novel peptide- or protein-based therapeutics moving through the pipeline each year supports a path forward for the pursuit of even more complex therapeutic strategies.

Direct Tie2 Agonists Stabilize Vasculature for the Treatment of Diabetic Macular Edema.

Purpose: Diabetic macular edema (DME) is the leading cause of vision loss and blindness among working-age adults. Although current intravitreal anti-vascular endothelial growth factor (VEGF) therapies improve vision for many patients with DME, approximately half do not achieve the visual acuity required to drive. We therefore sought additional approaches to resolve edema and improve vision for these patients. Methods: We explored direct agonists of Tie2, a receptor known to stabilize vasculature and prevent leakage. We identified a multivalent PEG-Fab conjugate, Tie2.1-hexamer, that oligomerizes Tie2 and drives receptor activation and characterized its activities in vitro and in vivo. Results: Tie2.1-hexamer normalized and stabilized intercellular junctions of stressed endothelial cell monolayers in vitro, suppressed vascular leak in mice under conditions where anti-VEGF alone was ineffective, and demonstrated extended ocular exposure and robust pharmacodynamic responses in non-human primates. Conclusions: Tie2.1-hexamer directly activates the Tie2 pathway, reduces vascular leak, and is persistent within the vitreal humor. Translational Relevance: Our study presents a promising potential therapeutic for the treatment of DME.