Plant identification applications do not reliably identify toxic and edible plants in the American Midwest.

INTRODUCTION: Exposure to potentially toxic plants is a global problem, resulting in thousands of calls to poison centers and emergency department visits annually and occasional deaths. Persons with limited botanical knowledge may be tempted to rely on smartphone applications to determine if plants are safe to forage. This study evaluated the reliability of several popular smartphone applications to identify foraged foods and distinguish them from potentially toxic plants in the Midwestern United States. METHODS: Sixteen plant species were selected based on local availability, attractiveness as foraged food, and potential for misidentification. Of the 16 species, five are edible, three are potentially toxic if improperly harvested or prepared, and eight are considered to be toxic. Plant specimens were identified by graduate-level botanists and photographed during multiple stages of their growth cycles. LeafSnap, PictureThis, Pl@ntNet and PlantSnap were used to identify the plants. RESULTS: Overall accuracy of the applications in identifying plant genus was 76% (95% confidence interval: 73-79, range 96% for PictureThis to 53% for PlantSnap). Accuracy for identification of plant species was 58% (95% confidence interval 55-62%, range 94% for PictureThis to 34% for PlantSnap). Five of eleven potentially toxic species were identified as an edible species by at least one application. CONCLUSION: Accuracy of the smartphone applications varies, with PictureThis outperforming other apps. At this time, apps cannot be used to safely identify edible plants. Foragers must have adequate botanical knowledge to ensure safe harvesting of wild plants.

Methanol toxicity in a pediatric patient treated with fomepizole and hemodialysis.

Methanol toxicity is an important cause of toxic alcohol exposure resulting in morbidity and mortality in both adult and pediatric populations. Methanol is metabolized into formaldehyde and formic acid: toxic metabolites that can cause altered mental status, visual disturbances, multisystem organ failure, and death. Recognition of methanol intoxication and rapid treatment are critical for the prevention of long-term sequelae. We present the case of a 16-year-old male with a past medical history of depression who intentionally ingested windshield wiper fluid containing methanol. Based on the patient's osmolal gap, he was estimated to have a serum methanol level of 374 mg/dL; a send-out laboratory measurement later revealed a serum methanol level of 436 mg/dL. Therapy included two hemodialysis treatments as well as fomepizole and supportive care. The patient recovered remarkably with no long-term sequelae. This case demonstrates the effectiveness of swift recognition and treatment of methanol ingestion. Optimization of methods of measuring serum methanol and evidence-based guidelines for therapy are needed to improve the care of patients with methanol intoxication.

Healthcare Provider Characteristics and Cardiopulmonary Resuscitation Quality During Infant Resuscitation: A Simulation Study.

INTRODUCTION: Healthcare providers' anthropometric characteristics can adversely affect adult cardiopulmonary resuscitation (CPR) performance quality. However, their effects on infant CPR are unknown. We aimed to determine any relationships between healthcare provider characteristics (anthropomorphic, demographics, training, occupational data) and simulated infant CPR performance at multiple international sites. Our secondary aim was to examine provider's CPR performance degradation. METHODS: Providers from 4 international hospitals performed 2 minutes of single-rescuer simulated infant CPR using 2015 American Heart Association Basic Life Support criteria with guidance from a real-time visual performance feedback device. Providers' characteristics were collected, and the simulator collected compression and ventilation data. Multivariate analyses examined the entire 2 minutes and performance degradation. RESULTS: Data from 127 participants were analyzed. Although median values for all compression variables (depth, rate, lean) and ventilation volume were within guideline target ranges, when looking at individuals, only 52% chest compressions and 20% ventilations adhered to the American Heart Association guidelines. Age was found to be independently associated with ventilation volume (direct-relationship), and height was associated with chest compression lean (shorter participant-deeper lean). No significant differences were noted based on sex or body mass index. Neonatal intensive care unit participants were noted to perform shallower chest compressions (P < 0.001). Overall, there was minimal evidence of performance degradation over 2 minutes. CONCLUSIONS: Isolated provider characteristics were noted among a diverse cohort of healthcare providers that may affect the CPR quality on a simulated infant. Understanding the relationships between provider characteristics and CPR quality could inform future infant CPR guidelines customized for the provider and not just the patient.

Fomepizole as an adjunct in acetylcysteine treated acetaminophen overdose patients: a case series.

INTRODUCTION: Acetaminophen (N-acetyl-para-aminophenol or APAP) is the leading cause of acute liver failure worldwide. Standard therapy for APAP overdose is with IV N-acetylcysteine (NAC). However, overdose patients treated with NAC can still incur hepatotoxicity in some circumstances. Fomepizole has proven safety in methanol and ethylene glycol poisoning and is a potent CYP2E1 and c-Jun-N-terminal Kinase (JNK) inhibitor that is effective even in the metabolic phase. METHODS: We present a prospective case series of 14 consecutive, high-risk patients who had elevated APAP levels after overdose who were treated with fomepizole as an adjunct to standard IV-NAC. The attending toxicologist utilized clinical judgement to determine the use of fomepizole, especially if APAP levels persisted due to altered half-life or risk factors for toxicity. RESULTS: There were no unfavorable outcomes in any patient, which were better than expected. CONCLUSIONS: This case series has demonstrated the safety of fomepizole in high-risk APAP overdose. The efficacy of fomepizole needs to be further elucidated through controlled clinical trials on a larger scale. In massive APAP overdoses, fomepizole should be considered as an adjunct due to the known failure rate of NAC and the safety profile of fomepizole.

Gabapentin prevalence: clinical and forensic experience in St. Louis, Missouri, USA.

Gabapentin (Neurontin) is an anti-epileptic drug that has had wide off-label prescription use since market release due to presumed negligible abuse potential. However, trends in drug misuse have demonstrated that gabapentin misuse is occurring, particularly in those with a history of opioid misuse. This is concerning, because although gabapentin has no direct ligand activity at opioid receptors, it does potentiate the analgesic effect of opioids, and concurrent use of gabapentin and opioids may increase the risk of respiratory depressive effects of opioids. This study investigates the incidence of gabapentin detected in urine samples collected for clinical drug screening purposes in a local hospital emergency department and in postmortem samples submitted by medical examiners in the St. Louis metropolitan area. The prevalence of gabapentin and co-detected drugs in both populations is contrasted, compared, and discussed. This study found that 30% of urine samples collected from patients with suspected drug intoxication presenting to SSM Health Saint Louis University Hospital, a quaternary care medical center, were positive for gabapentin, and nearly two thirds of those were also positive for oxycodone. Over a 6-month period, the incidence of gabapentin positive postmortem cases increased from 18% to 20%. Nearly all gabapentin positive postmortem cases were also positive for an opioid, the most significant being fentanyl, suggesting that gabapentin misuse may be due to its potentiating effect of opioid drug action. This study also highlights the limited utility of immunoassay-based urine drug screens.

Propylene glycol neurotoxicity due to sodium citrate therapy in an infant with renal tubular acidosis.

Sodium citrate in its liquid formulation is commonly used as therapy for renal tubular acidosis in pediatric patients. Convenient dosing and administration is important to ensure long-term medication adherence and normal growth in the chronic forms of this condition. Liquid sodium citrate formulations contain propylene glycol, a commonly used excipient, which can be toxic at high doses. Propylene glycol toxicity due to medication excipients has been reported in the literature, including many cases secondary to sustained exposure to intravenous anti-epileptics, however toxicity associated with oral sodium citrate therapy has not been described. We report the first case of propylene glycol neurotoxicity in a 6-week-old infant with renal tubular acidosis treated with sodium citrate. Clinical suspicion of risk for medication-related toxicity and awareness of propylene glycol content in sodium citrate led to timely diagnosis and management. Awareness of increased risk of toxicity in pediatric patients due to high sodium citrate requirement and low propylene glycol metabolism capacity is important for optimal care for pediatric patients with renal tubular acidosis.

Severe Noncardiogenic Pulmonary Edema Secondary to Massive Verapamil Overdose and Treatment with Venovenous Extracorporeal Membrane Oxygenation.

Calcium channel blocker (CCB) poisoning frequently presents with cardiovascular complications such as cardiogenic shock and arrhythmia. We present a case of massive verapamil overdose causing refractory noncardiogenic pulmonary edema successfully treated with extracorporeal membrane oxygenation. To our knowledge, this is the first case with these features reported in literature. A 27-year-old female patient presented with an overdose of 18,000 mg of verapamil. Her clinical condition deteriorated to severe hypoxic respiratory failure despite being treated with calcium, high-dose insulin, and full invasive ventilation support. She eventually required venovenous extracorporeal membrane oxygenation (VV-ECMO) for three days with full recovery. Large ingestion of verapamil could lead to noncardiogenic pulmonary edema. VV-ECMO might play an important role to support the treatment in severe cases with refractory hypoxia.

Heightened Immune Response to Presumed Loxosceles reclusa Envenomation.

Loxoscelism is a systemic inflammatory reaction in response to a brown recluse spider bite (BRSB). In this case we describe a patient with a heightened inflammatory response to a presumed BRSB, with Coomb's positive hemolysis, cytoplasmic antineutrophil cytoplasmic antibody (cANCA) vasculitis, and features of hemophagocytic lymphohistiocytosis (HLH). A 24-y-old female presented with sudden pain and swelling to her lower back, nausea, fever, and tachycardia after a presumed BRSB. Hemolysis began on hospital day 3 (15.9 g·dL-1) with a nadir on hospital day 5 (6.3 g·dL-1). She had an lactate dehydrogenase of 1415 U·L-1, ferritin of 15534 ng·mL-1, persistent fever, and signs of bone marrow suppression despite hemolysis, with thrombocytopenia (100,000 µL-1) and an inadequate reticulocyte response (1.7%) suggestive of HLH. The patient's blood was Coomb's and cANCA/antiproteinase 3 positive. She had signs of toxin-induced vasculitis, with respiratory failure requiring bilevel positive airway pressure, radiographs with bilateral pulmonary infiltrates, and a desquamating rash. She received 6 U of packed red blood cells, furosemide for pleural and pericardial effusions, antibiotics, and symptomatic treatment during the acute phase of her illness. Hemolysis improved without glucocorticoids by hospital day 6. The patient demonstrated a dysregulated immunologic and complement-mediated response to the presumed BRSB. The triad of Coomb's positive hemolysis, cANCA vasculitis, and HLH-like reaction associated with a presumed BRSB is described for the first time in the literature and brings up questions for future research regarding the role of immune modulators and complement inhibitors in the treatment of severe loxoscelism as well as the genetic factors that predispose certain individuals to such reactions.

Poisoning, Overdoses, Toxic Exposures.

The national poison center movement originated in the Midwest with actions of the American Academy of Pediatrics in Chicago, Illinois, in 1972. The Missouri Poison Center (MPC) was established in 1974. The MPC and other regional poison centers are essential to the public health locally and nationally. Trends in serious poisoning outbreaks such as the release of synthetic cannabinoids have been detected by real-time electronic surveillance by specialists in poison information and medical toxicologists.

Validity Evidence for a Serious Game to Assess Performance on Critical Pediatric Emergency Medicine Scenarios.

INTRODUCTION: We developed a first-person serious game, PediatricSim, to teach and assess performances on seven critical pediatric scenarios (anaphylaxis, bronchiolitis, diabetic ketoacidosis, respiratory failure, seizure, septic shock, and supraventricular tachycardia). In the game, players are placed in the role of a code leader and direct patient management by selecting from various assessment and treatment options. The objective of this study was to obtain supportive validity evidence for the PediatricSim game scores. METHODS: Game content was developed by 11 subject matter experts and followed the American Heart Association's 2011 Pediatric Advanced Life Support Provider Manual and other authoritative references. Sixty subjects with three different levels of experience were enrolled to play the game. Before game play, subjects completed a 40-item written pretest of knowledge. Game scores were compared between subject groups using scoring rubrics developed for the scenarios. Validity evidence was established and interpreted according to Messick's framework. RESULTS: Content validity was supported by a game development process that involved expert experience, focused literature review, and pilot testing. Subjects rated the game favorably for engagement, realism, and educational value. Interrater agreement on game scoring was excellent (intraclass correlation coefficient = 0.91, 95% confidence interval = 0.89-0.9). Game scores were higher for attendings followed by residents then medical students (Pc < 0.01) with large effect sizes (1.6-4.4) for each comparison. There was a very strong, positive correlation between game and written test scores (r = 0.84, P < 0.01). CONCLUSIONS: These findings contribute validity evidence for PediatricSim game scores to assess knowledge of pediatric emergency medicine resuscitation.

Can Residents Assess Other Providers' Infant Lumbar Puncture Skills?: Validity Evidence for a Global Rating Scale and Subcomponent Skills Checklist.

OBJECTIVES: The aims of this study were to provide validity evidence for infant lumbar puncture (ILP) checklist and global rating scale (GRS) instruments when used by residents to assess simulated ILP performances and to compare these metrics to previously obtained attending rater data. METHODS: In 2009, the International Network for Simulation-based Pediatric Innovation, Research, and Education (INSPIRE) developed checklist and GRS scoring instruments, which were previously validated among attending raters when used to assess simulated ILP performances. Video recordings of 60 subjects performing an LP on an infant simulator were collected; 20 performed by subjects in 3 categories (beginner, intermediate, and expert). Six blinded pediatric residents independently scored each performance (3 via the GRS, 3 via the checklist). Four of the 5 domains of validity evidence were collected: content, response process, internal structure (reliability and discriminant validity), and relations to other variables. RESULTS: Evidence for content and response process validity is presented. When used by residents, the checklist performed similarly to what was found for attending raters demonstrating good internal consistency (Cronbach α = 0.77) and moderate interrater agreement (intraclass correlation coefficient = 0.47). Residents successfully discerned beginners (P < 0.01, effect size = 2.1) but failed to discriminate between expert and intermediate subjects (P = 0.68, effect size = 0.34). Residents, however, gave significantly higher GRS scores than attending raters across all subject groups (P < 0.001). Moderate correlation was found between GRS and total checklist scores (P = 0.49, P < 0.01). CONCLUSIONS: This study provides validity evidence for the checklist instrument when used by pediatric residents to assess ILP performances. Compared with attending raters, residents appeared to over-score subjects on the GRS instrument.

Ly49C Impairs NK Cell Memory in Mouse Cytomegalovirus Infection.

NK cells possess inhibitory receptors that are responsible for self-MHC class I recognition; beyond their inhibitory function, accumulating evidence indicates that such receptors confer NK cell functional competence through an unclear process termed "licensing." Ly49C is the main self-specific inhibitory Ly49 receptor in H-2(b) C57BL/6 (B6) mice. We used B6 Ly49C-transgenic and B6 ß2 microglobulin (ß2m)-knockout Ly49C-transgenic mice to investigate the impact of licensing through this inhibitory receptor in precursor and mature NK cells. We found that self-specific inhibitory receptors affected NK cell precursor survival and proliferation at particular developmental stages in an MHC class I-dependent manner. The presence of Ly49C impacted the NK cell repertoire in a ß2m-dependent manner, with reduced Ly49A(+), Ly49G2(+), and Ly49D(+) subsets, an increased DNAM-1(+) subset, and higher NKG2D expression. Licensed NK cells displayed a skewed distribution of the maturation stages, which was characterized by differential CD27 and CD11b expression, toward the mature phenotypes. We found that Ly49C-mediated licensing induced a split effect on NK cell functions, with increased cytokine-production capabilities following engagement of various activating receptors while cytotoxicity remained unchanged. Analysis of licensed NK cell functions in vivo, in a system of mouse CMV infection, indicated that licensing did not play a major role in the NK cell antiviral response during acute infection, but it strongly impaired the generation and/or persistence of memory NK cells. This study unravels multifaceted effects of licensing on NK cell populations and their functions.

Modafinil Moderates the Relationship Between Cancer-Related Fatigue and Depression in 541 Patients Receiving Chemotherapy.

OBJECTIVE: The aim of this study was to examine the effect of modafinil on depression via a secondary data analysis of a randomized clinical trial of modafinil for fatigue in cancer patients. The primary aim is to elucidate factors that contributed to the effectiveness of modafinil in the parent trial. METHODS: Five hundred forty-one cancer patients receiving chemotherapy and experiencing fatigue (Brief Fatigue Inventory [BFI] item 3 of ≥3) were randomized to receive 200 mg modafinil (n = 260) or placebo (n = 281) daily from baseline (cycle 2) to posttest (cycle 4). Patients completed the Center for Epidemiological Studies-Depression Scale (CES-D) and Profile of Mood States depression-dejection subscale at baseline and posttest. We used linear regression to address the hypothesis that modafinil would be associated with reduced depression, particularly in those experiencing severe fatigue (BFI ≥7). RESULTS: Modafinil did not have a significant effect on depression, even for those patients with severe fatigue. However, for subjects with severe fatigue (BFI ≥7), those receiving modafinil had lower depression scores than did control subjects. Modafinil significantly moderated the relationship between baseline fatigue and CES-D total scores (P = 0.04) and was marginally significant as a moderator for the relationship between baseline fatigue and Profile of Mood States depression-dejection subscale scores (P = 0.07). Modafinil also significantly moderated the relationship between baseline fatigue and CES-D positive affect subscale scores (P = 0.003), but not CES-D somatic, negative affect, or interpersonal subscale scores. CONCLUSIONS: Modafinil differentially impacts depression based on a patient's level of fatigue and reduced depressive symptoms only in those with extreme fatigue. This effect may be driven by increases in positive affective symptoms. These results have significant implications for intervention; in patients with high levels of fatigue, modafinil might also reduce depression. Future randomized clinical trials are needed to confirm these results.

Evidence for Persistence of Ectromelia Virus in Inbred Mice, Recrudescence Following Immunosuppression and Transmission to Naïve Mice.

Orthopoxviruses (OPV), including variola, vaccinia, monkeypox, cowpox and ectromelia viruses cause acute infections in their hosts. With the exception of variola virus (VARV), the etiological agent of smallpox, other OPV have been reported to persist in a variety of animal species following natural or experimental infection. Despite the implications and significance for the ecology and epidemiology of diseases these viruses cause, those reports have never been thoroughly investigated. We used the mouse pathogen ectromelia virus (ECTV), the agent of mousepox and a close relative of VARV to investigate virus persistence in inbred mice. We provide evidence that ECTV causes a persistent infection in some susceptible strains of mice in which low levels of virus genomes were detected in various tissues late in infection. The bone marrow (BM) and blood appeared to be key sites of persistence. Contemporaneous with virus persistence, antiviral CD8 T cell responses were demonstrable over the entire 25-week study period, with a change in the immunodominance hierarchy evident during the first 3 weeks. Some virus-encoded host response modifiers were found to modulate virus persistence whereas host genes encoded by the NKC and MHC class I reduced the potential for persistence. When susceptible strains of mice that had apparently recovered from infection were subjected to sustained immunosuppression with cyclophosphamide (CTX), animals succumbed to mousepox with high titers of infectious virus in various organs. CTX treated index mice transmitted virus to, and caused disease in, co-housed naïve mice. The most surprising but significant finding was that immunosuppression of disease-resistant C57BL/6 mice several weeks after recovery from primary infection generated high titers of virus in multiple tissues. Resistant mice showed no evidence of a persistent infection. This is the strongest evidence that ECTV can persist in inbred mice, regardless of their resistance status.

A NK complex-linked locus restricts the spread of herpes simplex virus type 1 in the brains of C57BL/6 mice.

The most frequent cause of sporadic viral encephalitis in western countries is Herpes simplex virus (HSV). Despite treatment, mortality rates reach 20-30% while survivors often suffer from significant morbidity. In mice, resistance to lethal Herpes simplex encephalitis (HSE) is multifactorial and influenced by mouse and virus strain as well as route of infection. The ability to restrict viral spread in the brain is one factor contributing to resistance. After infection of the oral mucosa with HSV type 1 (HSV-1), virus spreads throughout the brains of susceptible strains but is restricted in resistant C57BL/6 mice. To further investigate restriction of viral spread in the brain, mendelian analysis was combined with studies of congenic, intra-natural killer complex (intra-NKC) recombinant and antibody-depleted mice. Results from mendelian analysis support the restriction of viral spread as a dominant trait and consistent with a single gene effect. In congenic mice, the locus maps to the NKC on chromosome 6 and is provisionally termed Herpes Resistance Locus 2 (Hrl2). In intra-NKC recombinants, the locus is further mapped to the segment Cd69 through D6Wum34; a different location from previously identified loci (Hrl and Rhs1) also associated with HSV-1 infection. Studies with antibody-depleted mice indicate the effect of this locus is mediated by NK1.1(+) expressing cells. This model increases our knowledge of lethal HSE, which may lead to new treatment options.

Ly49C-dependent control of MCMV Infection by NK cells is cis-regulated by MHC Class I molecules.

Natural Killer (NK) cells are crucial in early resistance to murine cytomegalovirus (MCMV) infection. In B6 mice, the activating Ly49H receptor recognizes the viral m157 glycoprotein on infected cells. We previously identified a mutant strain (MCMVG1F) whose variant m157 also binds the inhibitory Ly49C receptor. Here we show that simultaneous binding of m157 to the two receptors hampers Ly49H-dependent NK cell activation as Ly49C-mediated inhibition destabilizes NK cell conjugation with their targets and prevents the cytoskeleton reorganization that precedes killing. In B6 mice, as most Ly49H+ NK cells do not co-express Ly49C, the overall NK cell response remains able to control MCMVm157G1F infection. However, in B6 Ly49C transgenic mice where all NK cells express the inhibitory receptor, MCMV infection results in altered NK cell activation associated with increased viral replication. Ly49C-mediated inhibition also regulates Ly49H-independent NK cell activation. Most interestingly, MHC class I regulates Ly49C function through cis-interactions that mask the receptor and restricts m157 binding. B6 Ly49C Tg, ß2m ko mice, whose Ly49C receptors are unmasked due to MHC class I deficient expression, are highly susceptible to MCMVm157G1F and are unable to control a low-dose infection. Our study provides novel insights into the mechanisms that regulate NK cell activation during viral infection.