Impact of social media "challenges" on poison center case volume for intentional ingestions among school-aged children: an observational study.

INTRODUCTION: Mental health problems among youth have escalated over the past decade, with increased rates of self-harm, including suicide attempts by ingestion. Social media use has been linked to youth mental health, including "challenges" urging youth to ingest substances for recreational and other purposes. We hypothesized that social media challenges for particular substances would temporally correspond with increased ingestions of these substances. METHODS: We identified peak Google Trends search times for social media ingestion challenges involving diphenhydramine, laundry pods, nutmeg, and cinnamon, and used data from America's Poison Centers National Poison Data System to plot reported ingestions 3 months before and after peak searches in school-aged children. RESULTS: There were 2,169 individuals in the analysis. Diphenhydramine was the most frequently reported ingestion for misuse/abuse and suicidal purposes (n = 266 and 1,609, respectively). For all ingestions together, 45 percent (n = 979) had a moderate health effect, and 6.35 percent (n = 137) had a major health effect. Time of peak searches corresponded with increased ingestions for each substance. DISCUSSION: We found a temporal relationship between peak Google Trends searches for ingestion challenges and ingestions of that substance reported to United States poison centers. Compared to misuse/abuse ingestions, most suicidal ingestions peaked 1-2 months later, suggesting a public health opportunity for intervention. LIMITATIONS: This retrospective observational study does not establish causal effect. All data are a result of self-reporting of the exposures, which may lead to a reporting bias. Google Trends is not the only search engine and likely underestimates the true incidence of social media posts. CONCLUSIONS: Additional research is needed on the relationship between social media and youth mental health, particularly around "challenges" that place youths' health at risk. There may be opportunities for intervention to decrease medical and mental health sequelae of these challenges.

The future of evolutionary medicine: sparking innovation in biomedicine and public health.

Evolutionary medicine - i.e. the application of insights from evolution and ecology to biomedicine - has tremendous untapped potential to spark transformational innovation in biomedical research, clinical care and public health. Fundamentally, a systematic mapping across the full diversity of life is required to identify animal model systems for disease vulnerability, resistance, and counter-resistance that could lead to novel clinical treatments. Evolutionary dynamics should guide novel therapeutic approaches that target the development of treatment resistance in cancers (e.g., via adaptive or extinction therapy) and antimicrobial resistance (e.g., via innovations in chemistry, antimicrobial usage, and phage therapy). With respect to public health, the insight that many modern human pathologies (e.g., obesity) result from mismatches between the ecologies in which we evolved and our modern environments has important implications for disease prevention. Life-history evolution can also shed important light on patterns of disease burden, for example in reproductive health. Experience during the COVID-19 (SARS-CoV-2) pandemic has underlined the critical role of evolutionary dynamics (e.g., with respect to virulence and transmissibility) in predicting and managing this and future pandemics, and in using evolutionary principles to understand and address aspects of human behavior that impede biomedical innovation and public health (e.g., unhealthy behaviors and vaccine hesitancy). In conclusion, greater interdisciplinary collaboration is vital to systematically leverage the insight-generating power of evolutionary medicine to better understand, prevent, and treat existing and emerging threats to human, animal, and planetary health.

Early-onset, conjugal, twin-discordant, and clusters of sporadic ALS: Pathway to discovery of etiology via lifetime exposome research.

The identity and role of environmental factors in the etiology of sporadic amyotrophic lateral sclerosis (sALS) is poorly understood outside of three former high-incidence foci of Western Pacific ALS and a hotspot of sALS in the French Alps. In both instances, there is a strong association with exposure to DNA-damaging (genotoxic) chemicals years or decades prior to clinical onset of motor neuron disease. In light of this recent understanding, we discuss published geographic clusters of ALS, conjugal cases, single-affected twins, and young-onset cases in relation to their demographic, geographic and environmental associations but also whether, in theory, there was the possibility of exposure to genotoxic chemicals of natural or synthetic origin. Special opportunities to test for such exposures in sALS exist in southeast France, northwest Italy, Finland, the U.S. East North Central States, and in the U.S. Air Force and Space Force. Given the degree and timing of exposure to an environmental trigger of ALS may be related to the age at which the disease is expressed, research should focus on the lifetime exposome (from conception to clinical onset) of young sALS cases. Multidisciplinary research of this type may lead to the identification of ALS causation, mechanism, and primary prevention, as well as to early detection of impending ALS and pre-clinical treatment to slow development of this fatal neurological disease.

Cataracts Across the Tree of Life: A Roadmap for Prevention and Biomedical Innovation.

PURPOSE: Spontaneous cataracts have been identified in the lenses of animals across a phylogenetically wide range of species. This can be a source of insights and innovation for human health professionals, but many persons may lack awareness of it. By providing a phylogenetic survey and analysis of species with cataract vulnerability, this paper demonstrates how a broad comparative perspective can provide critical information about environmental hazards to human visual health and can spark potential innovations in the prevention and treatment of cataracts in humans. DESIGN: Perspectives. METHODS: Review and synthesis of selected literature with interpretation and perspective. RESULTS: We found 273 recorded cases of spontaneously occurring cataracts in 113 species of birds, 83 species of mammals, 30 species of actinopterygii fish, 10 species of amphibians, 6 species of reptiles, and 1 species of cephalopod. CONCLUSION: A phylogenetically wide range of species, including many living in and around human environments, are vulnerable to cataracts. These animals may serve as sentinels for human visual health. Variation in cataract vulnerability across species may also facilitate the identification of resistance-conferring physiologies, leading to accelerated innovation in the prevention and treatment of cataracts in humans.

Trends in intentional abuse and misuse ingestions in school-aged children and adolescents reported to US poison centers from 2000-2020.

CONTEXT: Childhood and adolescent misuse and abuse exposures remain a serious public health challenge in the United States. This study aimed to describe recent trends and patterns of intentional substance misuse and abuse exposures among school-aged children and adolescents in the United States. METHODS: This study was a retrospective cohort study of intentional misuse and abuse exposures in children 6 through 18 years reported to the National Poison Data System (NPDS) from January 1, 2000, through December 31, 2020. Demographic trends, reported clinical effects, treatments, management sites, and health outcomes were assessed overall and within four age categories: 6-9, 10-12, 13-15, and 16-18. RESULTS: Between 2000 and 2020, there were 338,727 cases regarding intentional misuse and abuse exposures for children ages 6 through 18 years old. Overall, misuse/abuse ingestions fluctuated over time, with a peak in 2011. The majority of intentional misuse/abuse ingestions occurred in males (58.3%), and more than 80% of all reported exposure cases occurred in youth aged 13 to 18. 32.6% of ingestions resulted in worse than minor clinical outcomes. Older age groups had a greater number of severe medical outcomes compared to younger age groups. Major or life-threatening exposures (including those resulting in death) were more common in males. Overall, deaths were rare (n = 450), 0.1%). Male sex, older age, abuse ingestions, exposure site of a public area or other residence, and multiple ingested substances were other factors associated with increased mortality. Marijuana exposure rates had the highest average monthly increase overall, with the most dramatic rise occurring from 2017 to 2020. Edible marijuana preparations accounted for the highest increase in call rates compared with all other forms of marijuana. DISCUSSION AND CONCLUSION: With over 330,000 poison center cases reported during the 20-year study period, intentional substance misuse and abuse exposures substantially impact the pediatric population. The substances most commonly misused/abused are more widely available substances such as over-the-counter medications, household products and pharmaceuticals commonly prescribed to youth. Differences in age and sex were evident, with males and adolescents more likely to abuse and misuse substances. Our study describes an upward trend in marijuana misuse/abuse exposures among youth, especially those involving edible products. These findings highlight an ongoing concern about the impact of rapidly evolving cannabis legalization on this vulnerable population.

Continuous extracorporeal clearance in metformin-associated lactic acidosis and metformin-induced lactic acidosis: a systematic review.

INTRODUCTION: Metformin poisoning with lactic acidosis is an uncommon yet clinically serious condition related to the inhibition of normal aerobic metabolism. Toxicity may occur after an acute overdose although it is much more common after a systemic insult, such as acute kidney injury, in the setting of chronic use. Hemodialysis is currently the preferred extracorporeal treatment modality (Grade 1D evidence) although some patients may be too hemodynamically unstable to tolerate it. Continuous renal replacement therapy is considered an alternative if hemodialysis is unavailable but an evaluation of survival amongst this specific treatment class is lacking. OBJECTIVES: To assess overall survival and provide an updated review of the toxicokinetic elimination parameters of patients receiving continuous renal replacement therapy for metformin poisoning. METHODS: A comprehensive search was performed using the EMBASE and MEDLINE libraries from inception until November 30, 2021. Data was extracted and findings were summarized. Toxicokinetic parameters were analyzed and confirmed for accuracy when data permitted. RESULTS: Eighty-three reports met inclusion criteria. These consisted of only low-quality evidence including 75 case reports, four case series, and four descriptive retrospective reviews. Overall survival among patients suffering from metformin toxicity who received continuous extracorporeal treatment was 85.8%. When stratified between metformin-induced lactic acidosis and metformin-associated lactic acidosis, survival was 75.0% and 87.4%, respectively. Available continuous renal replacement therapy toxicokinetic parameters were quite heterogeneous. Errors in previously published toxicokinetic calculations were noted in only two instances. The overall average and median peak metformin concentrations were 70.5 mg/L and 41.9 mg/L, respectively. The average and median extracorporeal clearance rates were 39.0 mL/min and 42.1 mL/min (range 9.0-58.7 mL/min). The average and median elimination half-life parameters were 27.5 h and median 23.0 h. Elimination half-life ranged from seven to 74 h. There was no meaningful relationship between peak metformin concentration and continuous extracorporeal treatment half-life at lower concentrations, though at very high concentrations (over 200 mg/L), there was a trend towards a half-life below 20 h. There is insufficient data to robustly evaluate overall survival in relation to the extracorporeal clearance rate. Finally, there was no relevant relationship between maximal lactate concentration and survival, nor nadir pH and survival, for patients with either type of metformin toxicity. CONCLUSIONS: This retrospective systematic analysis of published cases treating metformin related lactic acidosis with continuous renal replacement therapy notes an overall slightly greater survival percentage compared to previous publications of individuals requiring any modality of renal replacement therapy. Because of publication bias, these results should be interpreted with caution and serve as hypothesis generating for future research. Prospective study focusing on the most clinically meaningful endpoint - survival - will help elucidate if continuous modalities are non-inferior to intermittent hemodialysis in metformin toxicity.

Silibinin: a toxicologist's herbal medicine?

Silymarin is an herbal remedy, commonly called milk thistle, or St. Mary's Thistle, and has been used for over 2000 years. It has been available as a capsule of the plant extract in Europe since 1974 to treat hepatic disorders. To date toxicologists have relied on animal studies, human case series, or retrospective reviews to decide on its use. In the U.S. the ability to use IV silibinin, its pharmacologically active purified flavonolignan, is hindered by its lack of availability as a Food and Drug Administration approved pharmaceutical preparation. This commentary reviews the in vitro studies, animal studies, and human retrospective analyses which form the basis for its clinical use. Despite the numerous publications, summarized in this issue in a systematic review, the mortality rate from Amanita mushroom ingestion remains stubbornly the same over four decades of use, and hovers around 10%. Although in the retrospective systematic review the use of silibinin, or penicillin, compared to routine care is statistically significantly superior when the primary outcome is fatality. Despite this there is no quality randomized trial to definitively demonstrate its utility. While, intravenous silibinin has a low toxicity, unanswered is whether it is useful in protecting the liver in cases of amanitin-containing mushrooms toxicity, and whether earlier administration would likely improve outcomes.

Did hypervitaminosis A have a role in Mawson's ill-fated Antarctic exploration?

Douglas Mawson is a national hero of Australia, having led the Australasian Antarctic expedition of 1911, and survived. His three-man sledging team was beset by a series of catastrophes. First, expert skier Belgrave Ninnis died after he fell into a deep crevasse taking with him half the dogs and a sledge of essential food and supplies. The remaining two explorers immediately turned back to base which was 315 miles away. With their rations diminished they resorted to eating their remaining six dogs over 23 days. Xavier Mertz became progressively ill with diarrhea, delirium, vocal outbursts in rages, and finally several seizures. He died after another seizure. Mawson, alone with negligible food and no dogs for transportation, through his own sheer grit made it back to base camp a month later and was saved. His journal records medical complications with skin desquamation, alopecia, and muscle pain. It has been proposed that these symptoms in both Mertz and Mawson were the manifestations of hypervitaminosis A. They likely consumed greater than a 1,200,000 IU of vitamin A each day from the dog liver they decided was essential to eat to survive. Mertz, a vegetarian, possibly consumed more of the liver than muscle meat, and consequently suffered the more severe encephalopathy and seizures associated with acute vitamin A poisoning.

Glaucoma through Animal's Eyes: Insights from the Evolution of Intraocular Pressure in Mammals and Birds.

Glaucoma, an eye disorder caused by elevated intraocular pressure (IOP), is the leading cause of irreversible blindness in humans. Understanding how IOP levels have evolved across animal species could shed light on the nature of human vulnerability to glaucoma. Here, we studied the evolution of IOP in mammals and birds and explored its life history correlates. We conducted a systematic review, to create a dataset of species-specific IOP levels and reconstructed the ancestral states of IOP using three models of evolution (Brownian, Early burst, and Ornstein-Uhlenbeck (OU)) to understand the evolution of glaucoma. Furthermore, we tested the association between life history traits (e.g., body mass, blood pressure, diet, longevity, and habitat) and IOP using phylogenetic generalized least squares (PGLS). IOP in mammals and birds evolved under the OU model, suggesting stabilizing selection toward an optimal value. Larger mammals had higher IOPs and aquatic birds had higher IOPs; no other measured life history traits, the type of tonometer used, or whether the animal was sedated when measuring IOP explained the significant variation in IOP in this dataset. Elevated IOP, which could result from physiological and anatomical processes, evolved multiple times in mammals and birds. However, we do not understand how species with high IOP avoid glaucoma. While we found very few associations between life history traits and IOP, we suggest that more detailed studies may help identify mechanisms by which IOP is decoupled from glaucoma. Importantly, species with higher IOPs (cetaceans, pinnipeds, and rhinoceros) could be good model systems for studying glaucoma-resistant adaptations.

Female Health Across the Tree of Life: Insights at the Intersection of Women's Health, One Health and Planetary Health.

Across the tree of life, female animals share biological characteristics that place them at risk for similar diseases and disorders. Greater awareness of these shared vulnerabilities can accelerate insight and innovation in women's health. We present a broadly comparative approach to female health that can inform issues ranging from mammary, ovarian, and endometrial cancer to preeclampsia, osteoporosis, and infertility. Our focus on female health highlights the interdependence of human, animal, and environmental health. As the boundaries between human and animal environments become blurred, female animals across species are exposed to increasingly similar environmental hazards. As such, the health of female animals has unprecedented relevance to the field of woman's health. Expanding surveillance of animal populations beyond zoonoses to include noncommunicable diseases can strengthen women's health prevention efforts as environmental factors are increasingly implicated in human mortality. The physiology of nonhuman females can also spark innovation in women's health. There is growing interest in those species of which the females appear to have a level of resistance to pathologies that claim millions of human lives every year. These physiologic adaptations highlight the importance of biodiversity to human health. Insights at the intersection of women's health and planetary health can be a rich source of innovations benefitting the health of all animals across the tree of life.

Trends Over 2 Decades in Adolescent Suicidal and Recreational Ingestions of Over-the-Counter Coricidin Preparations.

OBJECTIVE: The aim of this study was to assess national trends in recreational and suicidal ingestions of over-the-counter cough preparations that contain Coricidin. METHODS: Using the American Association of Poison Control Center's National Poison Data System, we obtained data from 2004 to 2017 on patients aged 13 to 19 years with an ingestion of "Coricidin." We examined trends over time overall and ingestion intent (recreational vs suicidal) using linear regression. We compared patient characteristics, substances ingested, clinical effects and therapies, and outcomes by suicidal versus misuse or recreational intention. RESULTS: An initial search with the inclusion criteria found 19,213 calls that matched study inclusion criteria. On average, there was a yearly linear increase of 180.0 (95% confidence interval [CI], 136.6-223.3; P < 0.01) ingestions per year. Within suicide ingestions, there was an average yearly increase of 97.9 (95% CI, 66.9-128.9; P < 0.01) ingestions, and within misuse/recreational ingestions, there was an average yearly increase of 82.1 (95% CI, 60.3-103.9; P < 0.01) ingestions. The most common clinical effect was tachycardia, which occurred in 42.4% of ingestions. Altered mental status, mydriasis, and ataxia were all more common in misuse/recreational ingestions. Suicidal ingestions resulted in more hospital admissions and need for medical treatment. Recreational-use coded calls peaked in 2013, whereas calls coded for suicide attempts have continued to rise dramatically, with a 50% increase in the 14-year study period. CONCLUSION: Combination Coricidin products are a major source of morbidity in adolescents. Targeted preventive measures in primary care offices or larger-scale policy/legislative efforts may be helpful to address this.

Nitrous oxide abuse induced subacute combined degeneration despite patient initiated B12 supplementation.

INTRODUCTION: Nitrous oxide (N2O) is a commonly used inhaled anesthetic that is legal to purchase as a food additive and is popular as a recreational euphoric drug. Abuse causes a functional B12 deficiency, leading to clinical features and imaging consistent with subacute combined spinal cord degeneration (SCD). CASES: Poison Center medical records from four patients are reviewed in this series. Four patients presented with lower extremity weakness, paresthesias and gait abnormalities in the setting of chronic N2O abuse. Each reported using 50-150 N2O cartridges ("whippets") almost daily for months to years, and reported supplementing with oral B12 at the recommendation of other users and online forums. None reported prior B12 deficiency or dietary restrictions, and none exhibited hematologic abnormalities. RESULTS: All patients had clinical signs of neurotoxicity including weakness and ataxia. Additionally, all had elevated methylmalonic acid and homocysteine concentrations with normal B12 indicating a functional B12 deficiency. Three had imaging consistent with SCD despite home supplementation The MRI in the fourth case was inconclusive due to movement artifact. CONCLUSION: We report four cases of subacute combined degeneration induced by recreational nitrous oxide abuse despite self-administered vitamin B12 supplementation.

Stress, Subordination, and Anomalies of Feeding Across the Tree of Life: Implications for Interpreting Human Eating Disorders.

Eating behaviors of animals living in naturalistic environments offer unique insights into several dysregulated eating patterns observed in humans. Social subordination is a known precipitant of hyperphagia and hypophagia in human beings, and examples of similar responses have been identified in a phylogenetically widespread range of vertebral species. This points to potentially conserved, patterned responses to animals navigating lives within social hierarchies. Self-imposed food restriction in subordinate fish and hyperphagic responses in socially subordinated bird and primate individuals may represent evolved adaptations to the stress of social subordination. As such, hyperphagic and hypophagic responses to social subordination in these species may model the natural history, neurobiology, and behavioral ecology of human dieting and bingeing more accurately than some current animal models. Phylogenetically widespread similarities in eating patterns under the stress of social subordination point to potentially shared biological benefits of these behaviors across species and the role of evolutionary trade-offs, adaptations, and other processes in shaping them. The application of a broadly comparative lens to disordered eating behaviors in other species exposes important similarities and differences between neurophysiology of eating across species. In doing so, it highlights the value of phylogenetic analyses and macroevolution as tools for identifying novel, naturally occurring models for understanding disordered human eating. Moreover, this approach introduces the intriguing possibility that human cultural influences on disordered eating may have far more ancient origins than previously considered.