Where the rubber meets the road: Emerging environmental impacts of tire wear particles and their chemical cocktails.

About 3 billion new tires are produced each year and about 800 million tires become waste annually. Global dependence upon tires produced from natural rubber and petroleum-based compounds represents a persistent and complex environmental problem with only partial and often-times, ineffective solutions. Tire emissions may be in the form of whole tires, tire particles, and chemical compounds, each of which is transported through various atmospheric, terrestrial, and aquatic routes in the natural and built environments. Production and use of tires generates multiple heavy metals, plastics, PAH's, and other compounds that can be toxic alone or as chemical cocktails. Used tires require storage space, are energy intensive to recycle, and generally have few post-wear uses that are not also potential sources of pollutants (e.g., crumb rubber, pavements, burning). Tire particles emitted during use are a major component of microplastics in urban runoff and a source of unique and highly potent toxic substances. Thus, tires represent a ubiquitous and complex pollutant that requires a comprehensive examination to develop effective management and remediation. We approach the issue of tire pollution holistically by examining the life cycle of tires across production, emissions, recycling, and disposal. In this paper, we synthesize recent research and data about the environmental and human health risks associated with the production, use, and disposal of tires and discuss gaps in our knowledge about fate and transport, as well as the toxicology of tire particles and chemical leachates. We examine potential management and remediation approaches for addressing exposure risks across the life cycle of tires. We consider tires as pollutants across three levels: tires in their whole state, as particulates, and as a mixture of chemical cocktails. Finally, we discuss information gaps in our understanding of tires as a pollutant and outline key questions to improve our knowledge and ability to manage and remediate tire pollution.

Cardiac Oscillations Complicating Brain Death Diagnosis.

Death by neurologic criteria (DNC) or brain death is a clinical diagnosis. It is often complicated by variations in policies as well as confounders on examination. We discuss here the case of a 27-year-old male who had a cardiac arrest following toxic gaseous exposure. He ultimately progressed to brain death but was identified as having cardiac oscillations during clinical assessments that complicated the diagnosis. We discuss the case as well as the maneuvers used to clarify that the "triggered breaths" on the ventilator were indeed cardiac oscillations.

Critical gaps in nanoplastics research and their connection to risk assessment.

Reports of plastics, at higher levels than previously thought, in the water that we drink and the air that we breathe, are generating considerable interest and concern. Plastics have been recorded in almost every environment in the world with estimates on the order of trillions of microplastic pieces. Yet, this may very well be an underestimate of plastic pollution as a whole. Once microplastics (<5 mm) break down in the environment, they nominally enter the nanoscale (<1,000 nm), where they cannot be seen by the naked eye or even with the use of a typical laboratory microscope. Thus far, research has focused on plastics in the macro- (>25 mm) and micro-size ranges, which are easier to detect and identify, leaving large knowledge gaps in our understanding of nanoplastic debris. Our ability to ask and answer questions relating to the transport, fate, and potential toxicity of these particles is disadvantaged by the detection and identification limits of current technology. Furthermore, laboratory exposures have been substantially constrained to the study of commercially available nanoplastics; i.e., polystyrene spheres, which do not adequately reflect the composition of environmental plastic debris. While a great deal of plastic-focused research has been published in recent years, the pattern of the work does not answer a number of key factors vital to calculating risk that takes into account the smallest plastic particles; namely, sources, fate and transport, exposure measures, toxicity and effects. These data are critical to inform regulatory decision making and to implement adaptive management strategies that mitigate risk to human health and the environment. This paper reviews the current state-of-the-science on nanoplastic research, highlighting areas where data are needed to establish robust risk assessments that take into account plastics pollution. Where nanoplastic-specific data are not available, suggested substitutions are indicated.

Postanoxia-Induced Chorea Treated with Intravenous Fentanyl.

The case presented is that of a young male with postanoxic brain injury secondary to cocaine overdose who began to exhibit choreiform movements of the left upper extremity. Traditional treatment options for chorea were unsuccessful, leading to the administration of fentanyl, which rapidly resolved the patient's choreiform movements. There is a limited research involving the treatment of chorea in anoxic brain injury as well as fentanyl's role in the movement pathway. We hypothesize that chorea can be caused or exacerbated by opioid withdrawal in a patient with chronic opioid use through modulation of dopamine transmission.

A Comparison of Variable Versus Fixed Insulin Infusion Rate on Resolution of Diabetic Ketoacidosis.

BACKGROUND: Diabetic ketoacidosis (DKA) is a well-known, potentially fatal complication of diabetes. The American Diabetes Association hyperglycemic crises guidelines suggest the use of intravenous insulin in patients presenting with DKA, along with a recommended rate of glucose reduction of 50-75 mg/dL/h. However, no specific guidance is provided regarding how to best achieve this rate of glucose decline. STUDY QUESTION: Is there a difference in time to DKA resolution between a variable intravenous insulin infusion strategy and a fixed infusion strategy in the absence of an institutional protocol? STUDY DESIGN: Single-center, retrospective cohort study of DKA patient encounters in 2018. MEASURES AND OUTCOMES: Insulin infusion strategy was considered to be variable if the infusion rate changed within the first 8 hours of therapy or was considered fixed if the rate remained unchanged for the same period. The primary outcome was time to resolution of DKA. Secondary outcomes were hospital length of stay, intensive care unit length of stay, hypoglycemia, mortality, and DKA recurrence. RESULTS: The median time to resolution of DKA was 9.3 hours in the variable infusion group compared with 7.8 hours in the fixed infusion group (HR, 0.82; 95% CI, 0.43-1.5, P = 0.5360). Severe hypoglycemia was observed in 13% of patients in the variable infusion group and in 50% of patients in the fixed infusion group ( P = 0.006). CONCLUSIONS: In this analysis, insulin infusion strategy (variable vs. fixed) was not associated with a significant difference in the time to resolution of DKA in the absence of an institutional protocol. The fixed infusion strategy was associated with a higher incidence of severe hypoglycemia.

Evaluation of intravenous lorazepam dosing strategies and the incidence of refractory status epilepticus.

INTRODUCTION: Status epilepticus (SE) is a neurological emergency associated with high mortality if not identified and treated promptly. For the emergent treatment of SE, the recommended intravenous (IV) lorazepam dose is 0.1 mg/kg/dose, up to a maximum of 4 mg. It has been shown that lorazepam is commonly under dosed in SE, but there is conflicting data on whether this has a negative impact on patient outcomes. This study assessed any dose less than 4 mg to help identify the effects of under dosing lorazepam in SE. METHODS: This was a retrospective cohort study of patients admitted to a quaternary health system between October 1, 2017 and September 30, 2019 that experienced SE and were initially treated with IV lorazepam. Patients were divided into two cohorts, less than 4 mg or 4 mg, based on the initial one-time dose of lorazepam received. The primary outcome was the proportion of patients that progressed to refractory status epilepticus (RSE) that received an initial IV lorazepam dose of 4 mg compared to less than 4 mg for the treatment of SE. Secondary outcomes evaluated include length of stay, mortality, time in SE, number of seizures, cumulative lorazepam dose prior to urgent therapy, number of lorazepam doses prior to urgent therapy, time to urgent therapy, appropriately dosed urgent therapy, and number of antiepileptic drugs given in SE. RESULTS: One hundred twenty patients were included in this study (107 patients received less than 4 mg and 13 patients received 4 mg). All patients included in the study were greater than 40 kg. The primary outcome of progression to RSE was observed in a significantly greater proportion of patients in the less than 4 mg group compared to the 4 mg group (93 [87%] vs. 8 [62%], p = 0.03). There was no difference in hospital or intensive care unit length of stay. However, there was an increased rate of in-hospital mortality in patients who received 4 mg compared to less than 4 mg (5 [39%] vs. 12[11%], p = 0.02). DISCUSSION: The majority of patients in the study received less than the recommended dose of IV lorazepam for SE. Patients who received less than 4 mg experienced an increased progression to RSE, which supports current guideline recommended dosing. While there was an increased rate of mortality in patients who received 4 mg compared to less than 4 mg, time in SE was prolonged in the patient population and severity of illness was only available for a limited number of patients included.

Comparison of 4F-PCC and aPCC time to administration and outcomes for oral anticoagulant-related ICH.

INTRODUCTION: Intracranial hemorrhages (ICHs) are associated with increased morbidity and mortality. Use of oral anticoagulants are a potential risk factor for ICH, and reversal of the anticoagulant with agents such as Four-Factor Prothrombin Complex Concentrate (4F-PCC) or Activated Prothrombin Complex Concentrate (aPCC) is vital to prevent hematoma expansion. The objective of the study was to the compare the time to administration and outcomes of 4F-PCC or aPCC in patients with ICH taking an oral anticoagulant. METHODS: This was a multicenter, retrospective cohort chart review of patients with ICH taking an oral anticoagulants who received 4F-PCC or aPCC over a two year period. The primary outcome of the study was to the compare the time to administration of 4F-PCC or aPCC in patients with ICH on an oral anticoagulant. Secondary outcomes included evaluating mortality rate, modified Rankin scale (mRs) score, presence of worsening bleed volume on first computed tomography (CT) six hours after the initial reading, and hospital and intensive care unit (ICU) length of stay. The tertiary outcome was to evaluate the effect of risk factors for delay on time to administration, with delay being greater than 60 min. RESULTS: A total of 350 patient charts were reviewed and 193 patients (4F-PCC [n = 99] and aPCC [n = 94]) were included in the study. There was no significant difference in the primary outcome of median time to administration for the 4F-PCC group (141 min, IQR [93-185]) compared to aPCC (121 min, IQR [107-194]; p = 0.08). No difference was identified between the two groups for all secondary outcomes. Only time to CT results was found to be a risk factor for administration delay (OR, 1.160; 95% CI, 1.073-1.255; p < 0.001). DISCUSSION: In patients with ICH taking oral anticoagulants, there was no significant difference in the time to administration between 4F-PCC and aPCC. More prospective randomized controlled trials are warranted to determine an ideal reversal time to improve patient outcomes.

Toxicity of micro and nano tire particles and leachate for model freshwater organisms.

Environmental sampling has documented a diversity of microplastics, including high levels of black rubber- generally identified as tire debris. Though organisms have been shown to ingest tire particles (TPs), past research focused on toxicity of leachate alone, overlooking potential effects of particles. To address these gaps, we assessed the toxicity of micro (1-20 µm) and nano (<1 µm) TPs for two model organisms, embryonic Zebrafish Danio rerio and the crustacean Daphnia magna. To assess effects on development, Zebrafish embryos were exposed to concentrations of TPs or leachate ranging from 0 to 3.0 × 109 particles/ml and 0-100% respectively (n = 4). Greater mortality and sublethal malformations were observed following nano TP and leachate exposures as compared to micro TPs. Unique abnormalities between the exposures indicates that there is both chemical and particle-specific toxicity. We also observed D. magna mortality following a 48 h exposure of neonate to TPs or leachate, ranging from 0 to 3.3 × 109 particles/ml and 0-100% respectively (n = 3). Though, particle-enhancement of toxicity was observed for both Zebrafish and D. magna, overall sensitivity to TPs differed. It is important to identify differential toxicities across species to achieve an understanding of the environmental impacts of TPs and the chemicals they leach.

Evaluation of levocarnitine, lactulose, and combination therapy for the treatment of valproic acid-induced hyperammonemia in critically ill patients.

INTRODUCTION: Critically ill patients treated with valproic acid are at risk for hyperammonemic encephalopathy. Both levocarnitine and lactulose, either alone or in combination, have been used for the treatment of hyperammonemia associated with valproic acid, however they have not been directly compared in the literature. The aim of this study was to compare the effect of levocarnitine, lactulose, and combination therapy for the treatment of valproic acid-induced hyperammonemia in critically ill patients. METHODS: This was a retrospective, system-wide, cohort study of critically ill patients who received valproic acid and levocarnitine, lactulose, or combination therapy from January 1, 2012 to October 31, 2019. The primary outcome of the study was the change in ammonia level from baseline to the lowest point within the first 48 h of treatment. Secondary outcomes included the change in ammonia levels within the first 7 days, the incidence of a clinically significant reduction, ICU length of stay, hospital length of stay, and hospital mortality. RESULTS: A total of 371 charts were reviewed and 114 patients (levocarnitine [n = 15], lactulose [n = 72], and combination [n = 27]) were included. No difference in the primary outcome was observed (levocarnitine [11umol/L] vs. lactulose [20 umol/L] vs. combination [23 umol/L], p = 0.605). The incidence of a clinically significant reduction in ammonia levels at 48 h did not differ between groups, nor did mortality. CONCLUSION: In critically ill patients with valproic acid-induced hyperammonemia, there was no significant difference in the reduction in ammonia levels in the first 48 h of treatment between levocarnitine, lactulose, and combination therapy.

Specialized Medical Weight Management Intervention for High-Risk Obesity.

Background: Bundled payments are services rendered at pre-determined costs with the goal of providing high value care. Our institution's Episodes of Care team partnered with its tertiary care obesity center to design a novel medical weight management bundle for employers that would collectively deliver high value obesity services. Objective: As a first step, we sought to evaluate short-term medical weight loss outcomes over 6 months at the obesity center. Methods: We retrospectively analyzed weight loss outcomes on 157 patients with commercial insurance coverage over a period of 6 months. Results: Patients ranged in age from 18-72 years, and 77.7% were female. Patients ranged in weight from 160-443 pounds, with a mean body mass index (BMI) of 42.7 kg/m2 (Class 3a severe obesity; BMI range 28.4-74.5). The prevalence of any obesity-related medical condition was 54.1%; at least a quarter of the patients had either prediabetes or Type 2 diabetes mellitus, approximately a third had hypertension, and over 8% had hyperlipidemia. Mean weight loss from the initial program start date was 6.28% (+/-0.48% standard error of mean [SEM]; 95% confidence interval [CI] 5.34-7.23%). Completers (defined as having at least 6 visits with a medical provider) achieved a higher percentage of weight loss (7.06%) from the initial program start compared to non-completers (4.68%; at least 4-5 visits with a medical provider; P<0.0158). Approximately 50% of patients were able to achieve >7% weight loss, with over 55% of patients achieving at least 3% weight loss or higher irrespective of BMI classification. Conclusions: Specialized medical weight intervention is effective in treating high-risk obesity with complications. This has implications for enhanced long-term cost savings related to employer coverage of such programs for their employees with obesity.

Silver Nanoparticles Stable to Oxidation and Silver Ion Release Show Size-Dependent Toxicity In Vivo.

Silver nanoparticles (AgNPs) are widely used in commerce, however, the effect of their physicochemical properties on toxicity remains debatable because of the confounding presence of Ag+ ions. Thus, we designed a series of AgNPs that are stable to surface oxidation and Ag+ ion release. AgNPs were coated with a hybrid lipid membrane comprised of L-phosphatidylcholine (PC), sodium oleate (SOA), and a stoichiometric amount of hexanethiol (HT) to produce oxidant-resistant AgNPs, Ag-SOA-PC-HT. The stability of 7-month aged, 20-100 nm Ag-SOA-PC-HT NPs were assessed using UV-Vis, dynamic light scattering (DLS), and inductively coupled plasma mass spectrometry (ICP-MS), while the toxicity of the nanomaterials was assessed using a well-established, 5-day embryonic zebrafish assay at concentrations ranging from 0-12 mg/L. There was no change in the size of the AgNPs from freshly made samples or 7-month aged samples and minimal Ag+ ion release (<0.2%) in fishwater (FW) up to seven days. Toxicity studies revealed AgNP size- and concentration-dependent effects. Increased mortality and sublethal morphological abnormalities were observed at higher concentrations with smaller nanoparticle sizes. This study, for the first time, determined the effect of AgNP size on toxicity in the absence of Ag+ ions as a confounding variable.

The chemistry and toxicology of vaping.

Vaping is the process of inhaling and exhaling an aerosol produced by an e-cigarette, vape pen, or personal aerosolizer. When the device contains nicotine, the Food and Drug Administration (FDA) lists the product as an electronic nicotine delivery system or ENDS device. Similar electronic devices can be used to vape cannabis extracts. Over the past decade, the vaping market has increased exponentially, raising health concerns over the number of people exposed and a nationwide outbreak of cases of severe, sometimes fatal, lung dysfunction that arose suddenly in otherwise healthy individuals. In this review, we discuss the various vaping technologies, which are remarkably diverse, and summarize the use prevalence in the U.S. over time by youths and adults. We examine the complex chemistry of vape carrier solvents, flavoring chemicals, and transformation products. We review the health effects from epidemiological and laboratory studies and, finally, discuss the proposed mechanisms underlying some of these health effects. We conclude that since much of the research in this area is recent and vaping technologies are dynamic, our understanding of the health effects is insufficient. With the rapid growth of ENDS use, consumers and regulatory bodies need a better understanding of constituent-dependent toxicity to guide product use and regulatory decisions.

Lighting Strikes Twice: Recurrent Guillain-Barré Syndrome (GBS) after Influenza Vaccination.

Guillain-Barré syndrome (GBS) is a rare acute demyelinating syndrome of the peripheral nervous system that is commonly preceded by infection. Vaccinations have also been associated with an increased incidence of GBS, though the risk is low. Caution with revaccination is recommended in patients with a history of GBS. Risks of revaccination compared with the risks of influenza complications should be considered. Patients who experience GBS after vaccination have not been shown to have an increased incidence of recurrent GBS after the influenza vaccine, though evidence is limited. We report a case of recurrent GBS in a patient following the influenza vaccine.

Impact of Early Reinitiation of Neuropsychiatric Medications on Agitation and Delirium in the Intensive Care Unit: A Retrospective Study.

BACKGROUND: Approximately 17% of intensive care unit (ICU) patients are prescribed at least 1 home neuropsychiatric medication (NPM). When abruptly discontinued, withdrawal symptoms may occur manifesting as agitation or delirium in the ICU setting. OBJECTIVE: To evaluate the impact of early reinitiation of NPMs. METHODS: This was a retrospective, observational cohort of adult ICU patients in a tertiary care hospital. Patients were included if admitted to the ICU and prescribed a NPM prior to arrival. Study groups were based on the timing of reinitiation of at least 50% of NPMs: ≤72 hours (early group) versus >72 hours (late group). RESULTS: The primary outcome was the proportion of patients with at least 1 agitation or delirium episode in the first 72 hours. Agitation and delirium were defined as at least 1 RASS assessment between +2 to +4 and a positive CAM-ICU assessment, respectively. A total of 300 patients were included, with 187 (62%) and 113 (38%) in the early and late groups, respectively. There was no difference in agitation or delirium (late 54 [48%] vs early 62 [33%]; adjusted odds ratio [aOR] = 1.5; 95% CI = 0.8-2.8; P = 0.193). Independent risk factors found to be associated with the primary outcome were restraints (aOR = 12.9; 95% CI = 6.9-24.0; P < 0.001) and benzodiazepines (BZDs; aOR = 2.0; 95% CI = 1.0-3.7; P = 0.038). CONCLUSIONS: After adjustment for baseline differences, there was no difference in agitation or delirium. Independent risk factors were restraint use and newly initiated BZDs.

Effects of three zinc-containing sunscreens on development of purple sea urchin (Strongylocentrotus purpuratus) embryos.

The growing popularity of physical sunscreens will lead to an increased release of ingredients from zinc oxide (ZnO) sunscreens into marine environments. Though zinc (Zn) is a necessary micronutrient in the ocean, greater than natural Zn concentrations may be released into marine environments by use of sunscreens. The extent of the consequences of this addition of Zn to the ocean are not fully understood. We investigated the effects of materials released by ZnO- sunscreens on the development of California purple sea urchin, Strongylocentrotus purpuratus. Embryos incubated in various concentrations of Zn (0.01, 0.05, 0.1, 0.5, and 1 mg/L), the sources of which included zinc-containing compounds: ZnO and zinc sulfate (ZnSO4); and ZnO sunscreens: All Good, Badger, and Raw Elements brands. Based on EC50 values, ZnO-containing sunscreens were slightly, but not significantly, more toxic than ZnO and ZnSO4, suggesting that sunscreens may release additional unknown materials that are detrimental to sea urchin embryo development. All concentrations of Zn-exposure resulted in significant malformations (skeletal abnormality, stage arrest, axis determination disruption), which were identified using light and fluorescence confocal microscopy. The concentration of Zn2+ internalized by the developing embryos correlated positively with the concentration of Zn in seawater. Additionally, exposure to both ZnO sunscreens and ZnO and ZnSO4 at 1 mg/L Zn, significantly increased calcein-AM (CAM) accumulation, indicating decreased multidrug resistant (MDR) transporter activity. This is one of the first studies documenting ZnO-containing sunscreens release high concentrations of Zn that are internalized by and have detrimental effects on aquatic organisms.

Predictors of ambulance transport in patients with ST-elevation myocardial infarction.

INTRODUCTION: Despite intense public awareness campaigns, many patients with ST-elevation myocardial infarction (STEMI) do not utilize Emergency Medical Services (EMS) transportation to the Emergency Department (ED). Predictors for mode of transport by EMS versus private vehicle in patients with an acute STEMI were investigated. Hypothesis It was hypothesized that patient characteristics, specifically older age, male sex, and a history of a prior cardiac intervention, would be associated with a higher likelihood of EMS utilization. METHODS: A retrospective, observational cohort study was performed for all STEMI patients treated from April 1, 2007 through June 30, 2010 at an urban, academic ED with 24-hour cardiac catheterization available. Multivariable analyses with predetermined predictors (age, sex, prior cardiac intervention, weekend/evening arrival) were performed to investigate associations with mode of transport. Door-to-balloon (D2B) times were calculated. RESULTS: Of the 209 STEMI patients, 11 were excluded, leaving 198 for analysis. Median age was 60 years (IQR: 53-70), 138 (70%) arrived by private vehicle, and 60 (30%) by EMS. The primary analysis did not identify significant predictors for EMS, but a post-hoc model found that private insurance (OR 0.18; 95% CI, 0.07-0.45) was associated with fewer EMS transports. Although not statistically significant due to the great variability in time of arrival for STEMI patients transported by private vehicle, EMS transports had shorter D2B times. During business hours and weekend/evenings, EMS had D2B times of 50 (IQR: 42-61) and 58 minutes (IQR: 47-63), respectively, while private vehicle transports had median D2B times of 62 (IQR: 50-74) and 78 minutes (IQR: 66-106). Conclusion No associations between mode of transport and patient age, sex, weekend/evening presentation and history of a prior cardiac intervention were identified. Privately insured patients were less likely to use EMS when experiencing a STEMI. More effective ways are needed to educate the public on the importance of EMS activation when one is concerned for acute coronary syndrome.