Interventions for generalized anxiety disorder.

PURPOSE OF REVIEW: To provide an overview of recently published work on anxiety, focusing on generalized anxiety disorder (GAD) and its treatment. RECENT FINDINGS: Self-reported anxiety symptoms were highly prevalent during the COVID-19 global pandemic in both the general population and in selected groups. There remains divided opinion about whether internet-based cognitive behavioural therapy (CBT) is noninferior to face-to-face CBT for GAD. A systematic review of drug treatment for GAD showed efficacy for selective serotonin reuptake inhibitors (SNRIs), agomelatine, and quetiapine. There may be a place for repetitive transcranial magnetic stimulation in the treatment of GAD. There was some evidence of efficacy for complementary therapies, including physical exercise, yoga, acupuncture, and Withania somnifera (ashwagandha). However, a systematic review of cannabidiol and tetrahydrocannabinol found insufficient evidence of efficacy in anxiety disorders. SUMMARY: Antidepressants and quetiapine show efficacy in the treatment of GAD. Internet-based psychological interventions have a place in the treatment of GAD when face-to-face treatment is inaccessible. There is increasing evidence for the use of physical exercise in the management of GAD. Some other complementary therapies, including cannabinoids, require further, methodologically sound, research.

Investigating and Resolving Cardiotoxicity Induced by COVID-19 Treatments using Human Pluripotent Stem Cell-Derived Cardiomyocytes and Engineered Heart Tissues.

Coronavirus disease 2019 continues to spread worldwide. Given the urgent need for effective treatments, many clinical trials are ongoing through repurposing approved drugs. However, clinical data regarding the cardiotoxicity of these drugs are limited. Human pluripotent stem cell-derived cardiomyocytes (hCMs) represent a powerful tool for assessing drug-induced cardiotoxicity. Here, by using hCMs, it is demonstrated that four antiviral drugs, namely, apilimod, remdesivir, ritonavir, and lopinavir, exhibit cardiotoxicity in terms of inducing cell death, sarcomere disarray, and dysregulation of calcium handling and contraction, at clinically relevant concentrations. Human engineered heart tissue (hEHT) model is used to further evaluate the cardiotoxic effects of these drugs and it is found that they weaken hEHT contractile function. RNA-seq analysis reveals that the expression of genes that regulate cardiomyocyte function, such as sarcomere organization (TNNT2, MYH6) and ion homeostasis (ATP2A2, HCN4), is significantly altered after drug treatments. Using high-throughput screening of approved drugs, it is found that ceftiofur hydrochloride, astaxanthin, and quetiapine fumarate can ameliorate the cardiotoxicity of remdesivir, with astaxanthin being the most prominent one. These results warrant caution and careful monitoring when prescribing these therapies in patients and provide drug candidates to limit remdesivir-induced cardiotoxicity.