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An amendment to this paper has been published and can be accessed via the original article.

Abstract Background With diabetes incidence growing globally and metformin still being the first-line for its treatment, metformin’s toxicity and overdose have been increasing. Hence, its mortality rate is increasing. For the first time, we aimed to study the efficacy of machine learning algorithms in predicting the outcome of metformin poisoning using two well-known classification methods, including support vector machine (SVM) and decision tree (DT). Methods This study is a retrospective cohort study of National Poison Data System (NPDS) data, the largest data repository of poisoning cases in the United States. The SVM and DT algorithms were developed using training and test datasets. We also used precision-recall and ROC curves and Area Under the Curve value (AUC) for model evaluation. Results Our model showed that acidosis, hypoglycemia, electrolyte abnormality, hypotension, elevated anion gap, elevated creatinine, tachycardia, and renal failure are the most important determinants in terms of outcome prediction of metformin poisoning. The average negative predictive value for the decision tree and SVM models was 92.30 and 93.30. The AUC of the ROC curve of the decision tree for major, minor, and moderate outcomes was 0.92, 0.92, and 0.89, respectively. While this figure of SVM model for major, minor, and moderate outcomes was 0.98, 0.90, and 0.82, respectively. Conclusions In order to predict the prognosis of metformin poisoning, machine learning algorithms might help clinicians in the management and follow-up of metformin poisoning cases.

Abstract The global COVID-19 pandemic has affected the world’s population by causing changes in behavior, such as social distancing, masking, restricting people’s movement, and evaluating existing medication as potential therapies. Many pre-existing medications such as tocilizumab, ivermectin, colchicine, interferon, and steroids have been evaluated for being repurposed to use for the treatment of COVID-19. None of these agents have been effective except for steroids and, to a lesser degree, tocilizumab. Ivermectin has been one of the suggested repurposed medications which exhibit an in vitro inhibitory activity on SARS-CoV-2 replication. The most recommended dose of ivermectin for the treatment of COVID-19 is 150–200 µg/kg twice daily. As ivermectin adoption for COVID-19 increased, the Food and Drug Administration (FDA) issued a warning on its use during the pandemic. However, the drug remains of interest to clinicians and has shown some promise in observational studies. This narrative reviews the toxicological profile and some potential therapeutic effects of ivermectin. Based on the current dose recommendation, ivermectin appears to be safe with minimum side effects. However, serious questions remain about the effectiveness of this drug in the treatment of patients with COVID-19.

Abstract Today, COVID-19 is spreading around the world. Information about its mechanism, prognostic factors, and management is minimal. COVID-19, as a human disease, has several identifying phases. Physicians of patients with COVID-19 may be interested in knowing whether opioid use disorder may affect their patients’ course or prognosis. This information may be crucial when considering the opioid epidemic in the US and other parts of the world. Opioid use at high doses and over several months duration can mitigate the immune system’s function, which may complicate the course of COVID-19 disease. Potential suppression of parts of the immune response may be important in prevention, clinical support, and therapeutic use of medications in various phases of the COVID-19. Specifically, opioid use disorders via an inhalation route may enhance the “late hyper-inflammatory phase” or result in end-organ damage. It is well established that opioids decrease ventilation as their effect on the medullary respiratory centers increases the risk of pneumonia. This increased risk has been associated with immune-suppressive opioids. The ultimate role of opioids in COVID-19 is not clear. This paper endorses the need for clinical studies to decipher the role and impact of chronic opioid use on viral diseases such as COVID-19.

Introduction: Snakebite is an urgent, unmet global medical need causing significant morbidity and mortality worldwide. Varespladib is a potent inhibitor of venom secretory phospholipase A2 (sPLA2) that can be administered orally via its prodrug, varespladib-methyl. Extensive preclinical data support clinical evaluation of varespladib as a treatment for snakebite envenoming (SBE). The protocol reported here was designed to evaluate varespladib-methyl for SBE from any snake species in multiple geographies. Methods and Analysis: BRAVO (Broad-spectrum Rapid Antidote: Varespladib Oral for snakebite) is a multicenter, randomized, double-blind, placebo-controlled, phase 2 study to evaluate the safety, tolerability, and efficacy of oral varespladib-methyl plus standard of care (SoC) vs. SoC plus placebo in patients presenting with acute SBE by any venomous snake species. Male and female patients 5 years of age and older who meet eligibility criteria will be randomly assigned 1:1 to varespladib-methyl or placebo. The primary outcome is the Snakebite Severity Score (SSS) that has been modified for international use. This composite outcome is based on the sum of the pulmonary, cardiovascular, nervous, hematologic, and renal systems components of the updated SSS. Ethics and Dissemination: This protocol was submitted to regulatory authorities in India and the US. A Clinical Trial No Objection Certificate from the India Central Drugs Standard Control Organisation, Drug Controller General-India, and a Notice to Proceed from the US Food and Drug Administration have been obtained. The study protocol was approved by properly constituted, valid institutional review boards or ethics committees at each study site. This study is being conducted in compliance with the April 1996 ICH Guidance for Industry GCP E6, the Integrated Addendum to ICH E6 (R2) of November 2016, and the applicable regulations of the country in which the study is conducted. The trial is registered on Clinical trials.gov, NCT#04996264 and Clinical Trials Registry-India, 2021/07/045079 000062.

Introduction Snakebite envenoming (SBE) results in over 500 000 deaths or disabling injuries annually. Varespladib methyl, an oral inhibitor of secretory phospholipase A2, is a nearly ubiquitous component of snake venoms. We conducted a phase II clinical trial to assess efficacy and safety of oral varespladib methyl in patients bitten by venomous snakes.Methods This double-blind, randomised, placebo-controlled trial enrolled patients in emergency departments in India and the USA. Patients with SBE were randomly assigned (1:1) to receive varespladib methyl or placebo two times per day for 1 week. All patients received standard of care, including antivenom. The primary outcome was change in the composite Snakebite Severity Score (SSS) measuring the severity of envenoming, from baseline to the average composite SSS at 6 and 9 hours.Results Among 95 patients randomised August 2021 through November 2022, the most common snakebites were from Russell’s vipers (n=29), copperheads (n=18) and rattlesnakes (n=14). The SSS improved from baseline to the average at 6 and 9 hours by 1.1 (95% CI, 0.7 to 1.6) in the varespladib group versus 1.5 (95% CI, 1.0 to 2.0) in the placebo group (difference −0.4, 95% CI, −0.8 to 0.1, p=0.13). While key secondary outcomes were not statistically different by treatment group, benefit was seen in the prespecified subgroup initiating study drug within 5 hours of bite (n=37). For this early treatment group, clinically important differences were observed for illness severity over the first week, patient-reported function on days 3 and 7 and complete recovery. No death or treatment emergent serious adverse event occurred.Conclusion For emergency department treatment of snakebites, the addition of varespladib to antivenom did not find evidence of difference for the primary outcome based on the SSS. A potentially promising signal of benefit was observed in patients initiating treatment within 5 hours of snakebite.