Background and Objective Identifying international differences in the epidemiology of acute poisonings in children may help in improving prevention. We sought to evaluate the international epidemiological differences in acute poisonings in children presenting to emergency departments (EDs) from 8 different global regions. Methods This was an international multicenter cross-sectional prospective study including children younger than 18 years with acute poisonings presenting to 105 EDs in 20 countries was conducted. Data collection started at each ED between January and September 2013, and continued for 1 year. Results During the study period, we registered 363,245 pediatric ED presentations, of which 1727 were for poisoning (0.47%; 95% confidence interval, 0.45%–0.50%), with a significant variation in incidence between the regions. Full data were obtained for 1688 presentations. Most poisonings (1361 [80.6%]) occurred at home with either ingestion (1504 [89.0%]) or inhalation of the toxin (126 [7.6%]). Nonintentional exposures accounted for 1157 poisonings (68.5%; mainly in South America and Eastern Mediterranean region), with therapeutic drugs (494 [42.7%]), household products (310 [26.8%]), and pesticides (59 [5.1%]) being the most common toxins. Suicide attempts accounted for 233 exposures (13.8%; mainly in the Western Pacific region and North America), with therapeutic drugs (214 [91.8%], mainly psychotropics and acetaminophen) being the most common toxins. Significant differences between regions were found in both types of poisonings. Recreational poisonings were more common in Europe and Western Pacific region. No patient died. Conclusions There are substantial epidemiological differences in acute poisonings among children in different countries and regions of the globe. International best practices need to be identified for prevention of acute poisonings in childhood.

Study objective: The antivenom currently available for treatment of systemic black widow envenomation (latrodectism) is composed of equine whole immunoglobin. Although considered effective, it has been associated with anaphylaxis and 2 reported fatalities. We test the efficacy and safety of new equine antivenom composed of purified F(ab')(2) antibody fragments. Methods: A randomized, double-blind, placebo-controlled trial was conducted at 16 sites across the United States. Subjects aged 10 years or older with moderate to severe pain because of black widow spider envenomation received F(ab')(2) antivenom or placebo. The primary outcome measure was treatment failure, which was defined as failure to achieve and maintain clinically significant reduction in pain for 48 hours posttreatment. Secondary measures of pain intensity differences and summed pain intensity difference were computed. Adverse events were recorded. Results: Sixty patients were treated (29 antivenom and 31 placebo). The mean age was 39 years and 68% were male. There were 15 treatment failures in the antivenom group and 24 in the placebo group (P=.019). Differences in pain intensity difference between groups were lower at each postbaseline point, and the mean summed pain intensity difference was greater for the antivenom group (difference 2,133; 95% confidence interval 177 to 4,090). No deaths or serious drug-related adverse events were detected. Conclusion: The F(ab')(2) antivenom met the predefined primary outcome of reduced treatment failures. Secondary outcomes of pain intensity difference and summed pain intensity difference also supported efficacy. The rate of symptom improvement in the placebo group was higher than expected, which may be related to enrollment criteria or placebo effect.

ABSTRACTHaving sufficient medical countermeasures (MCMs) available for the treatment of acetylcholinesterase-inhibiting nerve agent poisoned patients following a mass chemical exposure is a challenge for communities. After stockpiles containing auto-injectors are exhausted, communities need to be aware of alternative pharmaceutical options. The Department of Homeland Security Chemical Defense Program convened a federal interagency working group consisting of first responders, clinicians, and experts from the fields of medical toxicology, pharmacology, and emergency management. A literature review of pharmaceutical alternatives for treating nerve agent toxicity was performed. Pharmaceuticals that met the federal Public Health Emergency Medical Countermeasures Enterprise Product Specific Requirements were prioritized. Food and Drug Administration approval for one indication, market availability, and alignment to government procurement strategy were considered. This article summarizes the literature on comparative pharmacokinetics and efficacy against nerve agents (where available) of Food and Drug Administration approved drugs with muscarinic acetylcholine receptor antagonist and gamma-aminobutyric acid receptor agonist effects. This work is intended to serve as a resource of pharmaceutical options that may be available to communities (ie, emergency managers, planners, clinicians, and poison centers) when faced with a mass human exposure to a nerve agent and inadequate supplies of MCMs. (Disaster Med Public Health Preparedness. 2019;13:605-612)

INTRODUCTION:Rhabdomyolysis and delayed acetaminophen hepatotoxicity may be associated with elevated serum transaminase values. Establishing the cause of elevated transaminases may be especially difficult because of limited or inaccurate histories of acetaminophen ingestion. We hypothesized that the comparative ratios of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) can differentiate acetaminophen hepatotoxicity from rhabdomyolysis.METHODS:A retrospective chart review of patients in four hospitals from 2006 to 2011 with a discharge diagnosis of acetaminophen toxicity or rhabdomyolysis was performed. Subjects were classified into three groups: rhabdomyolysis, acetaminophen overdose (all), and acetaminophen overdose with undetectable serum acetaminophen concentrations [acetaminophen(delayed)]. Ratios of AST, ALT, and CK were compared using non-parametric statistical methods.RESULTS:1,353 subjects were identified and after applying our exclusion criteria there were 160 in the rhabdomyolysis group, 68 in the acetaminophen overdose (all) group, and 29 in the acetaminophen (delayed) group. The AST/ALT ratio for the rhabdomyolysis group was 1.66 (Interquartile range: 1.18-2.22), for the acetaminophen overdose (all) group was 1.38 (1.08-1.69, statistically lower than the rhabdomyolysis group, p = 0.018), and for the acetaminophen (delayed)group was 1.30 (1.06-1.63, p = 0.037). CK/AST ratios were 21.3 (12.8-42.2), 5.49 (2.52-15.1, p < 0.001), and 3.80 (1.43-13.8, p < 0.001) respectively. CK/ALT ratios were 37.1 (16.1-80.0), 5.77 (2.79-25.2, p < 0.001), and 5.03 (2.20-17.4, p < 0.001) respectively. Increasing CK to transaminase ratio cutoffs resulted in increasing test sensitivity but lower specificity.CONCLUSION:AST/ALT, CK/AST and CK/ALT ratios are significantly larger in rhabdomyolysis when compared to patients with acetaminophen toxicity. This result suggests that the ratios could be used to identify patients with rhabdomyolysis who otherwise might have been diagnosed as delayed acetaminophen toxicity. Such patients may not require treatment with N-acetylcysteine, resulting in cost savings and improved resource utilization.

Introduction: Prolongation of the QT interval is a well-recognized complication associated with many commonly used medications. Emergency Department monitoring of the corrected QT (QTc) both before and after medication administration is typically performed using the 12 lead electrocardiogram (ECG). The purpose of this study is to compare the QTc reported on the 12 lead ECG to that reported by single brand of bedside monitor. Methods: A convenience sample of emergency department patients over the age of 18 undergoing bedside monitoring and who had an ECG ordered by their treating physician were enrolled. These patients underwent simultaneous ECG and monitor QTc calculation. The primary outcome of interest was the correlation between the monitor and ECG QTc. Secondary outcomes included ability of each method to identify patients with a QTc > 500 ms and the ability of each method to identify patients with a QTc < 450 ms. Results: A total of 125 patients had simultaneous ECG and monitor QTc measurements recorded. There was moderate correlation between the monitor and ECG QTc (Pearson's correlation coefficient = 0.55). The median difference between the ECG QTc and the monitor QTc (ECG QTc minus monitor QTc) was -7 ms (IQR - 23 to 11 ms). Conclusion: We found that there wasmoderate correlation between the QTc reported on the 12 lead ECG and that reported by the bedside monitor. This correlation is not strong enough to support the use of the bedside monitor as a substitute for the 12 lead ECG when evaluating a patient's QTc. (C) 2017 Elsevier Inc. All rights reserved.

Introduction: Parasympathetic neurons utilize the neurotransmitter acetylcholine to modulate and constrict airway smooth muscles at the muscarinic acetylcholine receptor. Inhaled agents that antagonize the muscarinic (M) acetylcholine receptor, particularly airway M3 receptors, have increasing data supporting use in persistent asthma. Areas covered: Use of inhaled long-acting muscarinic antagonists (LAMA) in asthma is explored. The LAMA tiotropium is approved for maintenance in symptomatic asthma patients despite the use of inhaled corticosteroids (ICS), leukotriene receptor antagonists (LTRA) and/or long-acting beta(2) agonists (LABA). LAMA agents currently approved for chronic obstructive pulmonary disease (COPD) include tiotropium, glycopyrrolate/glycopyrronium, umeclidinium and aclidinium. These agents are reviewed for their pharmacological differences and clinical trials in asthma. Expert opinion: Current guidelines place inhaled LAMAs as adjunctive maintenance therapy in symptomatic asthma not controlled by an ICS and/or a LTRA. LAMA agents will play an increasing role in moderate to severe symptomatic asthma patients. Additional LAMA agents are likely to seek a maintenance indication perhaps as a combined inhaler with an ICS or with an ICS and a LABA. These fixeddose combination inhalers are being tested in COPD and asthma patients. Once-a-day dosing of inhaled LAMA agents in severe asthma patients will likely become the future standard.

INTRODUCTION:Dabigatran etexilate was the first direct-acting oral anticoagulant approved in the United States. The prevalence of intracranial hemorrhage after blunt head trauma in patients on dabigatran is currently unknown, complicating adequate ability to accurately compare the risks and benefits of dabigatran to alternative anticoagulants. We aimed to determine the prevalence of intracranial hemorrhage for patients on dabigatran presenting to a Level I trauma center. METHODS:This is a retrospective observational study of adult patients on dabigatran who presented to a Level I trauma center and received cranial computed tomography (CT) following blunt head trauma. Patients who met inclusion criteria underwent manual chart abstraction. Our primary outcome was intracranial hemorrhage on initial cranial CT. RESULTS:We included a total of 33 eligible patient visits for analysis. Mean age was 74.8 years (SD 11.2, range 55-91). The most common cause of injury was ground-level fall (n = 22, 66.7%). One patient (3.0%, 95% confidence interval [CI] 0.[1-15.8%]) had intracranial hemorrhage on cranial CT. No patients (0%, 95% CI [0-8.7%]) required neurosurgical intervention. One in-hospital death occurred from infection. CONCLUSION:To our knowledge, this is the first study to evaluate the prevalence of intracranial hemorrhage after blunt head trauma for patients on dabigatran presenting to the emergency department, including those not admitted. The intracranial hemorrhage prevalence in our study is similar to previous reports for patients on warfarin. Further studies are needed to determine if the prevalence of intracranial hemorrhage seen in our patient population is true for a larger patient population in more diverse clinical settings.

The Salford Lung Study (SLS) of patients with asthma and chronic obstructive pulmonary disease (COPD) is a practical, community-based, randomized, open-label pragmatic study on the efficacy and safety of the once-daily dry powder inhaler that combines the inhaled corticosteroid fluticasone furoate (FF) with the long-acting beta2 agonist vilanterol (VI). The asthma component of the SLS is not yet reported but the COPD component, done over a 12-month period, found a statistically significant 8.4% reduction in COPD exacerbations when compared to usual care. No differences in adverse events, including serious adverse events and pneumonia, were noted. The importance of real-world findings, such as those found in the SLS COPD trial with inhaled FF/VI, is discussed in comparison to classical randomized controlled trials (RCTs) with inhaled FF/VI in COPD patients. The real-world, community-based pragmatic RCT like the SLS provides additional generalizable data with direct clinical applicability and potential usefulness in the development of practice guidelines. The results from the SLS, along with those of large and small RCTs, are supportive of the use of once-daily FF/VI in COPD maintenance therapy.

The major psychoactive compounds in marijuana (cannabis) are cannabinoids, the most significant of which is delta-9-tetrahydrocannabinol. There are also two synthetic pharmaceutical cannabinoids, nabilone and dronabinol, available by prescription in the United States. The use of marijuana has increased in the United States with passage of medical marijuana laws in many states and legalization of recreational marijuana use in several states. In addition, the potency of marijuana has increased in recent years. Marijuana has been used for a variety of medical purposes, including management of nausea and vomiting, appetite and immunologic stimulation in patients with HIV infection and AIDS, glaucoma, neurologic disorders, and pain relief. Studies on the benefits of marijuana as a treatment for various conditions have been inconsistent, except for those on pain management. Marijuana has adverse effects, and has been associated with driving impairment, psychosis, dependence and withdrawal syndromes, hyperemesis, acute cardiac events, some cancers, and impaired lung function. As with studies on the benefits of marijuana, studies of adverse effects have yielded inconsistent results. Except for impaired driving and the occurrence of dependence and withdrawal syndromes, the adverse effects of marijuana use have not been fully studied.

OBJECTIVE The current national opioid epidemic is a public health emergency. We have identified an outbreak of exaggerated opioid toxicity caused by fentanyl adulterated tablets purchased on the street as hydrocodone/acetaminophen. METHODS Over an 8-day period in late March 2016, a total of 18 patients presented to our institution with exaggerated opioid toxicity. The patients provided a similar history: ingesting their "normal dose" of hydrocodone/acetaminophen tablets but with more pronounced symptoms. Toxicology testing and analysis was performed on serum, urine, and surrendered pills. RESULTS One of the 18 patients died in hospital. Five patients underwent cardiopulmonary resuscitation, one required extracorporeal life support, three required intubation, and two received bag-valve-mask ventilation. One patient had recurrence of toxicity after 8 hours after naloxone discontinuation. Seventeen of 18 patients required boluses of naloxone, and four required prolonged naloxone infusions (26-39 hours). All 18 patients tested positive for fentanyl in the serum. Quantitative assays conducted in 13 of the sera revealed fentanyl concentrations of 7.9 to 162 ng/mL (mean = 52.9 ng/mL). Pill analysis revealed fentanyl amounts of 600-6,900 μg/pill. The pills are virtually indistinguishable from authentic hydrocodone/acetaminophen tablets and are similar in weight. To date, our county has reported 56 cases of fentanyl opioid toxicity, with 15 fatalities. In our institution, the outbreak has stressed the capabilities and resources of the emergency department and intensive care units. CONCLUSIONS A serious outbreak of exaggerated opioid toxicity caused by fentanyl-adulterated tablets purchased on the street as hydrocodone/acetaminophen is under way in California. These patients required higher dosing and prolonged infusions of naloxone. Additionally, observation periods off naloxone were extended due to delayed, recurrent toxicity. The outbreak has serious ramifications for public health and safety, law enforcement, and healthcare facilities and resources.

In recent years, there has been a large increase in the number of synthetic drugs used recreationally. One class of drugs is synthetic cannabinoids, which are sprayed onto herbal preparations and marketed under names such as K2 and spice. Others include amphetaminelike compounds, such as cathinones (eg, bath salts) and methylenedioxymethamphetamine (MDMA) (eg, ecstasy, Molly). New hallucinogens, such as Bromo-Dragonfly, and hallucinogens that have been used for centuries, such as Salvia divinorum, also are gaining popularity. Because these substances are sold labeled as not for human consumption and because the chemicals in them frequently change, they often are unregulated, and many users consider them legal, although they are not. Their use often goes undetected because testing for them is not included in routine drug screening. Nonetheless, these substances can be associated with significant toxicities, often because their concentrations are unpredictable. Adverse effects of synthetic cannabinoids include psychosis and other effects. Amphetaminelike drugs have stimulant effects and can cause hyponatremia and seizures. The new hallucinogens can cause serious vasoconstriction with ischemia. Clinicians, especially those working with adolescents and young adults (ie, the main users of these drugs), should be aware of these new substances and counsel patients about their adverse effects.

Objective Contrast induced nephropathy (CIN) is a result of injury to the proximal tubules. The incidence of CIN is around 11% for imaging done in the acute care setting. We aim to analyze the metabolic patterns in the urine, before and after dosing with intravenous contrast for computed tomography (CT) imaging of the chest, to determine if metabolomic changes exist in patients who develop CIN. Methods A convenience sample of high risk patients undergoing a chest CT with intravenous contrast were eligible for enrollment. Urine samples were collected prior to imaging and 4 to 6 hours post imaging. Samples underwent gas chromatography/mass spectrometry profiling. Peak metabolite values were measured and data was log transformed. Significance analysis of microarrays and partial least squares was used to determine the most significant metabolites prior to CT imaging and within subject. Analysis of variance was used to rank metabolites associated with temporal change and CIN. CIN was defined as an increase in serum creatinine level of ≥ 0.5 mg/dL or ≥ 25% above baseline within 48 hours after contrast administration. Results We sampled paired urine samples from 63 subjects. The incidence of CIN was 6/63 (9.5%). Patients without CIN had elevated urinary citric acid and taurine concentrations in the pre-CT urine. Xylulose increased in the post CT sample in patients who developed CIN. Conclusion Differences in metabolomics patterns in patients who do and do not develop CIN exist. Metabolites may be potential early identifiers of CIN and identify patients at high-risk for developing this condition prior to imaging.

There has been an increase in diagnoses of attention-deficit/hyperactivity disorder (ADHD), with approximately 9% of American children now diagnosed, and a concomitant increase in the use of stimulants (eg, amphetamines, methylphenidate) to manage ADHD. Nonstimulant drugs (eg, atomoxetine, guanfacine, clonidine) also are used, but most patients are treated with stimulants. All of these drugs are effective for management of ADHD, and, overall, use in childhood does not seem to increase the risk of substance abuse later in life. However, widespread use has resulted in prescription stimulants being diverted for nonmedical uses, particularly by high school and college students seeking cognitive enhancement for improved academic performance. Studies of ADHD drugs for improving cognition in patients without ADHD have mixed results, and any improvements appear to be modest and short-term. Other substances also are used for cognitive enhancement. Drugs for Alzheimer disease are being used for mild cognitive impairment, though there is no evidence that they are effective. Creatine may have mild cognition-enhancing properties, but study results often are confounded by the addition of exercise, which by itself is thought to improve cognition. There is no evidence that other supplements, such as vitamins and omega-3 fatty acids, improve cognitive function.

The use of inhaled corticosteroids (ICSs) plays a key role in the treatment of asthmatic patients, and international guidelines have designated ICSs as an early maintenance therapy in controlling asthma symptoms. When asthmatic patients remain symptomatic on ICSs, one common option is to add a long-acting beta2 agonist (LABA) to the maintenance treatment. Fixed combination inhalers that contain both an ICS and a LABA have been popular for both chronic obstructive pulmonary disease (COPD) and asthma. Historically, these inhalers have been dosed twice daily. However, currently, there is a once-daily combination therapy with the ICS fluticasone furoate (FF) and the LABA vilanterol trifenatate (VI) with indications for use in both COPD and asthma. This dry powder inhaler (DPI) comes in two doses of FF (100 or 200 μg) both combined with VI (25 μg). This article reviews the clinical trial data for FF, VI and FF/VI combination inhalers and documents the efficacy and safety of once-daily inhaled maintenance therapy by DPI in asthmatic patients.

INTRODUCTION:Government agencies are increasingly emphasizing opioid safety in hospitals. In 2012, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) started a sentinel event program, the "Safe Use of Opioids in Hospitals." We sought to determine if opioid use patterns in our emergency department (ED) changed from 2011, before the program began, to 2013, after start of the program.METHODS:This was a retrospective study of all adult ED patients who received an intravenous opioid and had a serum creatinine measured. We recorded opioids used, dose prescribed, and serum creatinine. As an index of the safety of opioids, uses of naloxone after administration of an opioid was recorded.RESULTS:Morphine is still the most commonly used opioid by doses given, but its percentage of opioids used decreased from 68.9% in 2011 to 52.8% in 2013. During the same period, use of hydromorphone increased from 27.5% to 42.9%, while the use of fentanyl changed little (3.6% to 4.3%). Naloxone administration was rare after an opioid had been given. Opioids were not dosed in an equipotent manner.CONCLUSION:The use of hydromorphone in our ED increased by 56% (absolute increase of 15.4%), while the use of morphine decreased by 30.5% (absolute decrease 16.1%) of total opioid use from 2011 to 2013. The JCAHO program likely was at least indirectly responsible for this change in relative dosing of the opioids. Based on frequency of naloxone administered after administration of an opioid, the use of opioids was safe.