COVID-19 Therapeutics: Use, Mechanism of Action, and Toxicity (Xenobiotics).

SARS-CoV-2 emerged in 2019 and led to the COVID-19 pandemic. Efforts to develop therapeutics against SARS-Cov-2 led to both new treatments and attempts to repurpose existing medications. Here, we provide a narrative review of the xenobiotics and alternative remedies used or proposed to treat COVID-19. Most repositioned xenobiotics have had neither the feared toxicity nor the anticipated efficacy. Repurposed viral replication inhibitors are not efficacious and frequently associated with nausea, vomiting, and diarrhea. Antiviral medications designed specifically against SARS-CoV-2 may prevent progression to severe disease in at-risk individuals and appear to have a wide therapeutic index. Colloidal silver, zinc, and ivermectin have no demonstrated efficacy. Ivermectin has a wide therapeutic index but is not efficacious and acquiring it from veterinary sources poses additional danger. Chloroquine has a narrow therapeutic index and no efficacy. A companion review covers vaccines, monoclonal antibodies, and immunotherapies. Together, these two reviews form an update to our 2020 review.

Translator use not associated with longer time to pain medication in initial evaluation of low-severity geriatric trauma.

OBJECTIVES: Determine whether geriatric victims of blunt trauma who preferred to communicate in a language other than English waited longer for pain medication or received more imaging studies than English-speaking patients with the same age and injuries. Secondary outcomes were the type of medication administered and number of imaging studies. METHODS: We conducted a retrospective analysis of all trauma activations to a single academic urban medical center from January 2019 to October 2019. We included all hemodynamically stable patients older than 65, with head or torso trauma after a low energy injury, and on at least one medication that was an anti-coagulant, anti-platelet, or chemotherapeutic. RESULTS: We identified 1,153 unique patients (17, 379 radiologic studies) performed from January 2019 to October 2019, with a median of 5 (4-6) radiologic studies per patient. We excluded 419 patients for whom the language used was not reported (n = 7), no imaging was not reported (n = 16), or no medication was recorded as given (n = 409), leaving 734 patients for further analysis. Of those 734 patients, 460 preferred to communicate in English, 84 in Mandarin Chinese, 64 in Spanish, 37 in Cantonese Chinese, and 35 in Korean, and 29 in Russian. Across all languages patient age and Injury Severity Score (ISS) were comparable. Those who preferred to communicate in Spanish, Russian, or Korean were more likely to be female than those who preferred English, Mandarin, or Cantonese, but this tendency was not statistically significant (χ2-test; p = 0.051, 0.15 after Bonferroni correction). We did not find a statistically significant association between preferred language and time to medication, fraction of opioids used as first-line pain medication, or number of imaging studies performed. Across all patients, the most common medications administered were acetaminophen (524/734, 71%), any opioid (111/734, 15%), followed by local infiltration or nerve block with lidocaine (49/734, 6.7%). CONCLUSIONS: A retrospective analysis of patients with low-risk blunt trauma found no relationship between preferred language, time to pain medication, use of opioids or number of imaging studies.

Geospatial correlation between COVID-19 health misinformation and poisoning with household cleaners in the Greater Boston Area.

INTRODUCTION: Calls to poison control about exposure to household cleaners have increased during the COVID-19 pandemic. This dynamic may reflect increased exposure from public health efforts as well as health misinformation shared on social media. METHODS: We analyzed the dynamics of calls to the Regional Center for Poison Control and Prevention serving Massachusetts and Rhode Island (MARI PCC) and tweets discussing treating COVID-19 with house cleaners from January 20, 2020 to May 5, 2020. We obtained publicly available tweets discussing the use of household cleaners to "cure COVID" from the same time period with geographic co-ordinates indicating that they were emitted from the Greater Boston Area. RESULTS: Our main finding is that public health efforts were followed by a sustained increase in calls after March 15, 2020 (10 ± 2 calls per day before to 15 ± 2.5 after) while misinformation on social media was associated with intermittent spikes in calls. Overall, calls significantly increased during the study period by 34% as compared to the previous 8 years, mostly reporting unintentional ingestions with no serious effects. The daily volume of tweets and retweets was significantly correlated with daily call rates to MARI PCC for the surrounding 7-10 days. CONCLUSIONS: Health misinformation on social media about using household cleaning agents to treat COVID-19 and public health efforts lead to different dynamics in PCC calls. Public health efforts were followed by a sustained increase in calls after March 15, 2020 while misinformation on social media was followed by intermittent spikes in calls. This analysis is the first to link the geospatial dynamics of social media and public health interventions to poison center calls about exposure to household cleaners.

COVID-19: Therapeutics and Their Toxicities.

SARS-CoV-2 is a novel coronavirus that emerged in 2019 and is causing the COVID-19 pandemic. There is no current standard of care. Clinicians need to be mindful of the toxicity of a wide variety of possibly unfamiliar substances being tested or repurposed to treat COVID-19. The United States Food and Drug Administration (FDA) has provided emergency authorization for the use of chloroquine and hydroxychloroquine. These two medications may precipitate ventricular dysrhythmias, necessitating cardiac and electrolyte monitoring, and in severe cases, treatment with epinephrine and high-doses of diazepam. Recombinant protein therapeutics may cause serum sickness or immune complex deposition. Nucleic acid vaccines may introduce mutations into the human genome. ACE inhibitors and ibuprofen have been suggested to exacerbate the pathogenesis of COVID-19. Here, we review the use, mechanism of action, and toxicity of proposed COVID-19 therapeutics.

The Role and Promise of Artificial Intelligence in Medical Toxicology.

Artificial intelligence (AI) refers to machines or software that process information and interact with the world as understanding beings. Examples of AI in medicine include the automated reading of chest X-rays and the detection of heart dysrhythmias from wearables. A key promise of AI is its potential to apply logical reasoning at the scale of data too vast for the human mind to comprehend. This scaling up of logical reasoning may allow clinicians to bring the entire breadth of current medical knowledge to bear on each patient in real time. It may also unearth otherwise unreachable knowledge in the attempt to integrate knowledge and research across disciplines. In this review, we discuss two complementary aspects of artificial intelligence: deep learning and knowledge representation. Deep learning recognizes and predicts patterns. Knowledge representation structures and interprets those patterns or predictions. We frame this review around how deep learning and knowledge representation might expand the reach of Poison Control Centers and enhance syndromic surveillance from social media.

Operator experience determines performance in a simulated computer-based brain tumor resection task.

PURPOSE: Develop measures to differentiate between experienced and inexperienced neurosurgeons in a virtual reality brain surgery simulator environment. METHODS: Medical students (n = 71) and neurosurgery residents (n = 12) completed four simulated Glioblastoma multiforme resections. Simulated surgeries took place over four days with intermittent spacing in between (average time between surgeries of 4.77 ± 0.73 days). The volume of tumor removed (cc), volume of healthy brain removed (cc), and instrument path length (mm) were recorded. Additionally, surgical effectiveness (% tumor removed divided by % healthy brain removed) and efficiency (% tumor removed divided by instrument movement in mm) were calculated. Performance was compared (1) between groups, and (2) for each participant over time to assess the learning curve. In addition, the effect of real-time instruction ("coaching") was assessed with a randomly selected group of medical students. RESULTS: Neurosurgery residents removed less healthy brain, were more effective in removing tumor and sparing healthy brain tissue, required less instrument movement, and were more efficient in removing tumor tissue than medical students. Medical students approached the resident level of performance over serial sessions. Coached medical students showed more conservative surgical behavior, removing both less tumor and less healthy brain. In sum, neurosurgery residents removed more tumor, removed less healthy brain, and required less instrument movement than medical students. Coaching modified medical student performance. CONCLUSIONS: Virtual Reality brain surgery can differentiate operators based on both recent and long-term experience and may be useful in the acquisition and assessment of neurosurgical skills. Coaching alters the learning curve of naïve inexperienced individuals.