I Can’t Believe It’s Not Toothpaste! Poison Control Center Calls Regarding Dental and Oral-Care Products

Background: A cluster of incidents in which non-toothpaste products were used to brush teeth prompted a review of all calls to one Poison Control Center (PCC) regarding exposures to dental and oral-care products to determine if any resulted in significant toxicity. Methods: Retrospective review of 65,849 calls to one PCC during one calendar year. All inquiries about exposures to substances used as dental or oral-care products were analyzed by a single reviewer for reported adverse effects, including hospital admission or PCC referral for emergent medical evaluation. Results: 798 calls involved exposure to dental or oral-care products, comprising 1.21% of all calls received. Toothbrushing incidents with non-toothpaste products (122 cases) did not result in any significant recognized toxicity. Twenty-four patients were either referred for emergent medical evaluation (14) or were admitted to the hospital (10). In 23 of these patients (96%), the toxic agent was either an over-the-counter analgesic or a local anesthetic used to treat dental pain. Conclusions: Among PCC calls received regarding dental and oral-care products, over-the-counter analgesics and local anesthetics used for dental pain resulted in the most frequent need for emergent medical evaluation or for hospital admission

Fatal Metformin Overdose Presenting with Progressive Hyperglycemia

A 29-year-old man with no history of diabetes ingested over 60 grams of metformin in a suicide attempt. He presented to the emergency department with acute renal insufficiency, severe lactic acidosis, and rapidly-progressive hyperglycemia. The patient’s peak serum glucose level of 707 mg/dL is the highest yet reported in a case of metformin toxicity. Treatment included sodium bicarbonate infusion and hemodialysis, but the patient suffered several cardiac arrests with pulseless electrical activity and ultimately expired 25 hours after the ingestion

Bayesian inference of evolutionary histories under time-dependent substitution rates

Many factors complicate the estimation of time scales for phylogenetic histories, requiring increasingly complex evolutionary models and inference procedures. The widespread application of molecular clock dating has led to the insight that evolutionary rate estimates may vary with the time frame of measurement. This is particularly well established for rapidly evolving viruses that can accumulate sequence divergence over years or even months. However, this rapid evolution stands at odds with a relatively high degree of conservation of viruses or endogenous virus elements over much longer time scales. Building on recent insights into time-dependent evolutionary rates, we develop a formal and flexible Bayesian statistical inference approach that accommodates rate variation through time. We evaluate the novel molecular clock model on a foamy virus cospeciation history and a lentivirus evolutionary history and compare the performance to other molecular clock models. For both virus examples, we estimate a similarly strong time-dependent effect that implies rates varying over four orders of magnitude. The application of an analogous codon substitution model does not implicate long-term purifying selection as the cause of this effect. However, selection does appear to affect divergence time estimates for the less deep evolutionary history of the Ebolavirus genus. Finally, we explore the application of our approach on woolly mammoth ancient DNA data, which shows a much weaker, but still important, time-dependent rate effect that has a noticeable impact on node age estimates. Future developments aimed at incorporating more complex evolutionary processes will further add to the broad applicability of our approach.status: publishe

Accelerated evolution of SARS-CoV-2 in free-ranging white-tailed deer

The zoonotic origin of the COVID-19 pandemic virus highlights the need to fill the vast gaps in our knowledge of SARS-CoV-2 ecology and evolution in non-human hosts. Here, we detected that SARS-CoV-2 was introduced from humans into white-tailed deer more than 30 times in Ohio, USA during November 2021-March 2022. Subsequently, deer-to-deer transmission persisted for 2–8 months, disseminating across hundreds of kilometers. Newly developed Bayesian phylogenetic methods quantified how SARS-CoV-2 evolution is not only three-times faster in white-tailed deer compared to the rate observed in humans but also driven by different mutational biases and selection pressures. The long-term effect of this accelerated evolutionary rate remains to be seen as no critical phenotypic changes were observed in our animal models using white-tailed deer origin viruses. Still, SARS-CoV-2 has transmitted in white-tailed deer populations for a relatively short duration, and the risk of future changes may have serious consequences for humans and livestock

Context-specific emergence and growth of the SARS-CoV-2 Delta variant

The SARS-CoV-2 Delta (Pango lineage B.1.617.2) variant of concern spread globally, causing resurgences of COVID-19 worldwide1,2. The emergence of the Delta variant in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 SARS-CoV-2 genomes from England together with 93,649 genomes from the rest of the world to reconstruct the emergence of Delta and quantify its introduction to and regional dissemination across England in the context of changing travel and social restrictions. Using analysis of human movement, contact tracing and virus genomic data, we find that the geographic focus of the expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced more than 1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers reduced onward transmission from importations; however, the transmission chains that later dominated the Delta wave in England were seeded before travel restrictions were introduced. Increasing inter-regional travel within England drove the nationwide dissemination of Delta, with some cities receiving more than 2,000 observable lineage introductions from elsewhere. Subsequently, increased levels of local population mixing-and not the number of importations-were associated with the faster relative spread of Delta. The invasion dynamics of Delta depended on spatial heterogeneity in contact patterns, and our findings will inform optimal spatial interventions to reduce the transmission of current and future variants of concern, such as Omicron (Pango lineage B.1.1.529)

Virus genomes reveal factors that spread and sustained the Ebola epidemic.

The 2013-2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic 'gravity' model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics