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The use of N-acetylcysteine (NAC) remains the standard of care for treatment of acetaminophen (APAP) toxicity and overdose. Currently, there is growing evidence to suggest that massive acetaminophen overdose is associated with increased hepatotoxicity despite timely administration of NAC. This raises the question as to whether an increased dose of intravenous (IV) NAC should be used in the setting of massive APAP ingestion. This study aimed to evaluate the rate of hepatotoxicity after massive APAP overdose treated with 3 different NAC treatment regimens.This was a retrospective cohort study conducted by electronic medical record review of cases reported to a statewide poison control system between 2007 and 2020. Inclusion criteria were single APAP or APAP combination-medication ingestion; acute massive acetaminophen (APAP) ingestion (defined as APAP concentration ≥ 2 times above the Rumack-Matthew 150 nomogram); received one of the three NAC regimens: standard dose IV NAC, oral (PO) NAC, or high dose IV NAC. The risk of hepatotoxicity was evaluated using a multivariate logistic regression model with standard dose IV NAC as the base variable for comparison.A total of 373 patients met inclusion for the study. Of those, 135 cases were treated with standard dose IV NAC, 121 cases treated with PO NAC, and 117 cases treated with high dose IV NAC. The risk of developing hepatotoxicity was not statistically significant between the high dose IV NAC (OR 1.05, 95% CI 0.52 - 2.09) or oral NAC (OR 0.69, 95% CI 0.33 - 1.46) when compared to standard dose IV NAC. When adjusted for APAP combination medications, initial APAP ratio, initial elevated AST/ALT, and treatment within 8 h, there remained no difference between treatment regimens.This study was unable to detect a large absolute reduction in the rate of hepatotoxicity after massive APAP ingestion in patients treated with high dose IV NAC or PO NAC when compared to standard dose IV NAC; even when treatment was initiated within 8 h of ingestion.

Septic and vasoplegic shock are common types of vasodilatory shock (VS) with high mortality. After fluid resuscitation and the use of catecholamine-mediated vasopressors (CMV), vasopressin, angiotensin II, methylene blue (MB), and hydroxocobalamin can be added to maintain blood pressure.VS treatment utilizes a phased approach with secondary vasopressors added to vasopressor agents to maintain an acceptable mean arterial pressure (MAP). This review covers additional vasopressors and adjunctive therapies used when fluid and catecholamine-mediated vasopressors fail to maintain target MAP.Evidence supporting additional vasopressor agents in catecholamine-resistant VS is limited to case reports, series, and a few randomized control trials (RCTs) to guide recommendations. Vasopressin is the most common agent added next when MAPs are not adequately supported with CMV. VS patients failing fluids and vasopressors with cardiomyopathy may have cardiotonic agents such as dobutamine or milrinone added before or after vasopressin. Angiotensin II, another class of vasopressor, is used in VS to maintain adequate MAP. MB and/or hydroxocobalamin, vitamin C, thiamine, and corticosteroids are adjunctive therapies used in refractory VS. More RCTs are needed to confirm the utility of these drugs, at what doses, which combinations and in what order they should be given.

Introduction Hydrazines are highly toxic inorganic liquids that are used as propellants in military and aviation industries, such as the U.S. Air Force F-16 Emergency Power Unit and SpaceX SuperDraco Rockets. The most commonly used derivatives include hydrazine, monomethylhydrazine, and 1,1-dimethylhydrazine (unsymmetrical dimethylhydrazine). Industrial workers in close contact with hydrazines during routine maintenance tasks can be exposed to levels well above the National Institute for Occupational Safety and Health relative exposure limits. Materials and Methods A systematic review was performed using PubMed, Web of Science, Google Scholar, National Aeronautics and Space Administration Technical Server, and Defense Technical Information Center, and data related to hydrazine exposures were searched from inception to April 2020. Publications or reports addressing hydrazine toxicity, pathophysiology, and treatment of hydrazine fuel exposure were selected. Results Acute toxic exposures to hydrazine and its derivatives are rare. There are few case reports of acute toxic exposure in humans, and data are largely based on animal studies. The initial search identified 741 articles, manuscripts, and government reports. After screening for eligibility, 51 were included in this review. Eight articles reported acute exposures to hydrazine propellant in humans, and an additional 14 articles reported relevant animal data. Conclusions Exposure to small amounts of hydrazine and its derivatives can cause significant soft tissue injury, pulmonary injury, seizures, coma, and death. Neurologic presentations can vary based on exposure compound and dose. Decontamination is critical as treatment is mainly supportive. High-dose intravenous pyridoxine has been suggested as treatment for hydrazine-related neurologic toxicity, but this recommendation is based on limited human data. Despite recent research efforts to generate less toxic alternatives to hydrazine fuel, it will likely continue to have a role in military and aviation industries. Aerospace and military physicians should be aware of the toxicity associated with hydrazine exposure and be prepared to treat hydrazine toxicity in at-risk populations.

Asthma is a heterogeneous syndrome with variable phenotypes. Reversible airway obstruction and airway hyper-responsiveness often with an atopic or eosinophilic component is common in the elderly asthmatic. Asthma chronic obstructive pulmonary disease overlap syndrome (ACOS), a combination of atopy-mediated airway hyper-responsiveness and a history of smoking or other environmental noxious exposures, can lead to some fixed airway obstruction and is also common in elderly patients. Little specific data exist for the treating the elderly asthmatic, thus requiring the clinician to extrapolate from general adult data and asthma treatment guidelines.A stepwise approach to pharmacotherapy of the elderly patient with asthma and ACOS is offered and the literature supporting the use of each class of drugs reviewed.Inhaled, long-acting bronchodilators in combination with inhaled corticosteroids represent the backbone of treatment for the elderly patient with asthma or ACOS . Beyond these medications used as direct bronchodilators and topical anti-inflammatory agents, a stepwise approach to escalation of therapy includes multiple options such as oral leukotriene receptor antagonist or 5-lipoxygense inhibitor therapy, oral phosphodiesterase inhibitors, systemic corticosteroids, oral macrolide antibiotics and if evidence of eosinophilic/atopic component disease exists then modifying monoclonal antibody therapies.

Context: Point-of-care glucose meters are an integral part in the assessment of patients with altered mental status. For this reason, glucose meters are checked for interference from commonly encou...

Carbon monoxide is a colorless, odorless, highly toxic gas primarily produced through the incomplete combustion of organic material. Carbon monoxide binds to hemoglobin and other heme molecules, causing tissue hypoxia and oxidative stress. Symptoms of carbon monoxide poisoning can vary from a mild headache to critical illness, which can make diagnosis difficult. When there is concern for possible carbon monoxide poisoning, the diagnosis can be made via blood co-oximetry. The primary treatment for patients with carbon monoxide poisoning is supplemental oxygen, usually delivered via a nonrebreather mask. Hyperbaric oxygen can also be used, but the exact indications are controversial.

Author(s): Betting, David J.; Chenoweth, James A.; Jarman, Angela F. | Abstract: Introduction: Loperamide is a non-prescription anti-diarrheal agent targeting µ-opioid receptors in the intestinal tract. At high doses it crosses the blood-brain barrier, where µ-opioid agonism can cause euphoric effects. Misuse has been increasing for both the euphoric effects and as an alternative treatment for opioid dependence and withdrawal.Case Report: Here we report the case of a 30-year-old woman presenting with syncope, who was found to have severe myocardial conduction delays in the setting of chronic loperamide abuse.Conclusion: Treatment with sodium bicarbonate and hypertonic sodium resulted in improvement of her conduction abnormalities. Prior to discharge she was initiated on buprenorphine for her opioid use disorder.

Author(s): Elder, Joshua W; Wu, Evan F; Chenoweth, James A; Holmes, James F; Parikh, Aman K; Moulin, Aimee K; Trevino, Tommie G; Richards, John R | Abstract: BackgroundScreening for unhealthy alcohol and drug use in the emergency department (ED) can be challenging due to crowding, lack of privacy, and overburdened staff. The objectives of this study were to determine the feasibility and utility of a brief tablet-based screening method in the ED and if patients would consider a face-to-face meeting with a certified alcohol and drug counselor (CADC) for more in-depth screening, brief intervention, and referral to treatment (SBIRT) helpful via this interface.MethodsA tablet-based questionnaire was offered to 500 patients. Inclusion criteria were age ≥18, Emergency Severity Index 2-5, and English comprehension. Subjects were excluded if they had evidence of acute intoxication and/or received sedating medication.ResultsA total of 283 (57%) subjects were enrolled over a 4-week period, which represented an increase of 183% over the monthly average of patients referred for SBIRT by the CADC prior to the study. There were 131 (46%) who screened positive for unhealthy alcohol and drug use, with 51 (39%) and 37 (28%) who screened positive for solely unhealthy alcohol use and drug use/drug use disorders, respectively. There were 43 (33%) who screened positive for combined unhealthy alcohol and drug use. Despite willingness to participate in the tablet-based questionnaire, only 20 (15%) with a positive screen indicated via the tablet that a face-to-face meeting with the CADC for further SBIRT would be helpful.ConclusionBrief tablet-based screening for unhealthy alcohol and drug use in the ED was an effective method to increase the number of adult patients identified than solely by their treating clinicians. However, only a minority of subjects screening positive using this interface believed a face-to-face meeting with the CADC for further SBIRT would be helpful.

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 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 was moderate 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.

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 beta2 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 fixed-dose 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.

BACKGROUND AND AIMS The Psychoactive Surveillance Consortium and Analysis Network (PSCAN) is a national network of academic emergency departments (ED), analytical toxicologists and pharmacologists that collects clinical data paired with biological samples to identify and improve treatments of medical conditions arising from use of new psychoactive substances (NPS). The aim of this study was to gather clinical data with paired drug identification from NPS users who presented to EDs within PSCAN during its first year (2016-17). DESIGN Observational study involving patient records and biological samples. SETTING Seven academic emergency medical centers across the United States. PARTICIPANTS ED patients (n = 127) > 8 years of age with possible NPS use who were identified and enrolled in PSCAN by clinical providers or research personnel. MEASUREMENTS Clinical signs, symptoms and treatments were abstracted from the patients' health records. Biological samples were collected from leftover urine, serum and whole blood. Biological and drug samples, when available, were tested for drugs and drug metabolites via liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). FINDINGS Patients in whom synthetic opioids were detected (n = 9) showed higher rates of intubation (four of nine), impaired mental status (four of nine) and respiratory acidosis (five of nine) compared with the rest of the cohort (nine of 118, P-value

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.

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.

Study Objective: Dabigatran etexilate was the first direct-acting oral anticoagulant approved in the United States. The rate 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 aim to determine the prevalence of intracranial hemorrhage for patients on dabigatran presenting to a level 1 trauma center. Methods: This is a retrospective observational study of adult patients on dabigatran who presented to a Level 1 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: A total of 33 eligible patient visits were included 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% 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. Results: A total of 33 eligible patient visits were included 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% 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. Conclusion: To our knowledge, this is the first study to evaluate the rate of intracranial hemorrhage after blunt head trauma for patients on dabigatran presenting to the emergency department. The intracranial hemorrhage rate in our study is similar to previous reports for patients on warfarin. Further studies are needed to determine if the rate of intracranial hemorrhage seen in our patient population is true for a larger patient population in more diverse clinical settings.

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.

Purpose of review The review aims to describe the scope of the problem and potential therapeutic intervention for the management and risk stratification of patients with atrial fibrillation in the emergency department and acute care setting. Recent findings Atrial fibrillation is the most common arrhythmia prompting admission to the hospital. Management strategies include determining the trigger of the arrhythmia, rate control, and potential cardioversion. In the acute care setting the treatment is often dependent on the timing of the onset of arrhythmia. In those patients presenting with symptoms of less than 48 h of duration management may consist of rate control, pharmacologic, or electrical cardioversion. Recent studies suggest no difference in long-term outcomes with rate and rhythm control. In patients with symptoms greater that 48 h rate control is the initial option with potential for cardioversion as an outpatient. There are recent advances in ablation that provide additional options to patients with paroxysmal atrial fibrillation. An essential component of the treatment strategy for these patients is risk stratification for stroke and the initiation of long-term anticoagulation in appropriate patients. Summary Management of atrial fibrillation is guided by underlying causes of the atrial fibrillation and duration of symptoms.

Importance Current guidelines conflict on the management of older adults who have blunt head trauma taking anticoagulant and antiplatelet medications. This is partially due to the limited data comparing patients who are taking these medications with those who are not. Objective To investigate the incidence of delayed traumatic intracranial hemorrhage in older adults with head trauma, including those taking anticoagulant and antiplatelet medications. Design, Setting, and Participants This prospective observational cohort study included patients 55 years and older who had blunt head trauma and were transported via emergency medical services between August 1, 2015, and September 30, 2016. The setting was a multicenter study conducted at 11 hospitals in northern California. Patients were excluded if they had traumatic intracranial hemorrhage on the initial cranial computed tomographic scan, did not have a cranial computed tomographic scan performed at the initial emergency department visit, refused consent for a follow-up telephone call, or did not have reliable means of follow-up. Main Outcome and Measure The primary outcome of this study was the incidence of delayed traumatic intracranial hemorrhage within 14 days of injury. Results Among 859 patients enrolled in the study, the median age was 75 years (interquartile range, 64-85 years), and 389 (45.3%) were male. A total of 343 patients (39.9%) were taking an anticoagulant or antiplatelet medication. Three patients (0.3%; 95% CI, 0.1%-1.0%) had a delayed traumatic intracranial hemorrhage. Of the 3 patients, 1 of 75 patients (1.3%; 95% CI, 0.0%-7.2%) who were taking warfarin sodium alone and 2 of 516 patients (0.4%; 95% CI, 0.1%-1.4%) who were not taking any anticoagulant or antiplatelet medication had a delayed traumatic intracranial hemorrhage. Thirty-nine patients (4.5%; 95% CI, 3.2%-6.2%) were lost to follow-up. Conclusions and Relevance Overall, the incidence of delayed intracranial hemorrhage in older adults who have blunt head trauma is low, including patients taking an anticoagulant or antiplatelet medication. These findings suggest that routine observation and serial cranial computed tomography may not be necessary in these patients.

Awareness of the prevalence of the use of appearance- and performance-enhancing drugs (APEDs) is increasing. Users range from professional athletes and bodybuilders to amateurs and adolescents. Anabolic androgenic steroids (AASs) are the most widely used APEDs, typically for purposes of building muscle mass, in forms that include pills, injections, topical preparations, and transdermal systems. AASs are often used in combination with augmenting drugs taken to enhance androgen production and, for men, to decrease estrogen production. These include aromatase inhibitors, clomiphene, selective estrogen receptor modulators, and human chorionic gonadotropin. Other drugs used with the intention of improving athletic performance include human growth hormone, insulinlike growth factor 1, insulin, erythropoietin, stimulants, diuretics, levothyroxine, and gamma-hydroxybutyrate. Use of APEDs is increasing, with up to 5% of male and 2% of female college athletes using AASs and reports of a more than 20% usage rate among teenagers. Although many of these substances can increase muscle mass when combined with high levels of exercise and specific diets, it is not clear that they improve athletic performance. Furthermore, they are associated with a variety of serious adverse effects. AASs, in particular, can cause hepatotoxicity and acute cardiac events. Behavioral and psychiatric symptoms also can occur.

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.

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 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.

The management of overdoses of cardioactive medications in the emergency department can be challenging. The reversal of severe toxicity from one or more types of cardioactive medication may fail maximal medical therapies and require extreme invasive measures such as transvenous cardiac pacing and extracorporeal life support. We present a case of massive diltiazem and metoprolol overdose refractory to maximal medical therapy, including intravenous calcium, glucagon, vasopressors, high dose insulin, and lipid emulsion. The patient experienced refractory bradydysrhythmia that responded only to transvenous pacing. Extracorporeal life support was initiated and resulted in successful organ perfusion and complete recovery of the patient. This case highlights the potential utility of extracorporeal life support in cases of severe toxicity due to multiple cardioactive medications.

The need to treat withdrawal syndromes is a common occurrence in outpatient, inpatient ward, and intensive care unit (ICU) settings. A PubMed and Google Scholar search using alpha2-adrenoreceptor agonist (A2AA), specific A2AA agents, withdrawal syndrome and nicotine, and alcohol and opioid withdrawal terms was performed. A2AA agents appear to be able to modulate many of the signs and symptoms of significant withdrawal syndromes but are also capable of significant side effects, which can limit clinical use. Non-opioid oral A2AA agent use for opioid withdrawal has been well established. Pharmacologic combination therapy that utilizes A2AA agents for withdrawal syndromes appears promising but requires further formal testing to better define which other agents, under what condition(s), and at what A2AA doses are needed. The A2AA dexmedetomidine may be useful as an adjunctive agent in treating severe alcohol withdrawal syndromes in the ICU. In general, the current data does not support the routine use of A2AA as the primary or sole agent to treat ethanol/alcohol or nicotine withdrawal syndromes. Specific A2AA agents such as lofexidine has been shown to have a primary role in non-opioid-based treatment of opioid withdrawal syndrome and dexmedetomidine in combination with benzodiazepines has been shown to have potential in the treatment of severe ICU-based alcohol withdrawal syndrome.

IntroductionOver the past decade, there has been a sharp increase in the number of newly identified synthetic drugs. These new drugs are often derivatives of previously abused substances but have unpredictable toxicity. One of these drugs is gacyclidine, a derivative of phencyclidine (PCP). Gacyclidine has been studied as a neuroprotective agent in trauma and as a therapy of soman toxicity. There are no previous reports of its use as a drug of abuse.Case reportsDuring a two-month period in the summer of 2013, a series of patients with severe agitation and end-organ injury were identified in an urban academic Emergency Department (ED). A urine drug of abuse screen was performed on all patients, and serum samples were sent for comprehensive toxicology analysis. A total of five patients were identified as having agitation, rhabdomyolysis, and elevated troponin (Table 1). Three of the five patients reported use of methamphetamine, and all five patients had urine drug screens positive for amphetamine. Comprehensive serum analysis identified methamphetamine in three cases, cocaine metabolites in one case, and a potential untargeted match for gacyclidine in all five cases. No other drugs of abuse were identified.DiscussionThis is the first series of cases describing possible gacyclidine intoxication. The possible source of the gacyclidine is unknown but it may have been an adulterant in methamphetamine as all patients who were questioned reported methamphetamine use. These cases highlight the importance of screening for new drugs of abuse when patients present with atypical or severe symptoms. Gacyclidine has the potential to become a drug of abuse both by itself and in conjunction with other agents and toxicity from gacyclidine can be severe. It is the role of the medical toxicology field to identify new agents such as gacyclidine early and to attempt to educate the community on the dangers of these new drugs of abuse.

Current V-shaped stainless steel pyrovalve initiators have rectified many of the deficiencies of the heritage Y-shaped aluminum design. However, a credible failure mode still exists for dual simultaneous initiator (NSI) firings in which low temperatures were detected at the booster cap and less consistent ignition was observed than when a single initiator was fired. In order to asses this issue, a numerical framework has been developed for predicting the flow through pyrotechnically actuated valves. This framework includes a fully coupled solution of the gas-phase equation with a non-equilibrium dispersed phase for solid particles as well as the capability to model conjugate gradient heat transfer to the booster cap. Through a hierarchy of increasingly complex simulations, a hypothesis for the failure mode of the nearly simultaneous dual NSI firings has been proven. The simulations indicate that the failure mode for simultaneous dual NSI firings may be caused by flow interactions between the flame channels. The shock waves from each initiator interact in the booster cavity resulting in a high pressure that prevents the gas and particulate velocity from rising in the booster cap region. This impedes the bulk of the particulate phase from impacting the booster cap and reduces the heat transfer to the booster cap since the particles do not impact it. Heat transfer calculations to the solid metal indicate that gas-phase convective heat transfer may not be adequate by itself and that energy transfer from the particulate phase may be crucial for the booster cap burn through.

This study evaluates whether unsteady simulations of swirling jets that resolve a large range of scales can better predict the enhanced mixing in swirling flows particularly since two-equation RANS models have been shown to be very poor at accurately predicting both the axial and swirl velocity mixing rates in swirling flows. Unsteady, three-dimensional, hybrid RANS/LES results for a swirling jet are presented. The configuration chosen has a moderate swirl number of 0.23 for which an experimental database with detailed mean and turbulence measurements exists (Gilchrist and Naughton 1 ). The simulation results show very good comparison with the experiment and demonstrate that an unsteady framework employing hybrid RANS-LES methodology is able to resolve the disparate length scales of mixing seen in the axial and swirl directions. Furthermore, the hybrid RANS/LES methodology reduces computational cost, and makes the methodology practical from an "engineering" perspective on present day computational resources. The jet flow field shows that the swirl decays very rapidly by x/D~5, and further downstream the jet behaves similar to a non-swirling one with a linear growth rate and exhibiting self-similarity in the axial velocity profiles. Results from a second-order and a higher-order (4 th order) spatial scheme do not show much difference in prediction of the mean flow, but the turbulent fluctuations, particularly the axial component, is better predicted by the higher-order scheme.

(1990). Final Report of the HTRI/TEMA Joint Committee to Review the Fouling Section of the TEMA Standards. Heat Transfer Engineering: Vol. 11, No. 1, pp. 73-107.

The ability to accurately model axisymmetric, turbulent swirling jet flows over a variety of inflow conditions is evaluated. The deficiency of the standard k-e turbulence model in predicting mixing rates in flows with streamline curvature is well known. A relatively straightforward modification to this model is made based on a local value of the flux Richardson number which accounts for the azimuthal velocity and its variation. To evaluate the effectiveness of this modification two different experimental data sets are used to compare the computational results against. All calculations were performed using the structured, density based, CRAFT CFD code utilizing a preconditioning methodology. Both cases have initial swirl distributions that are equivalent to a solid-body rotation profile, and have swirl numbers that are low enough to remain below the vortex breakdown regime. They also have non-swirling jet data available for the same geometries and operating conditions which allows the increased jet mixing rate of swirling jets over purely axial jets to be confirmed. All calculations showed a significant improvement of centerline velocity decay as well as downstream radial velocity profiles when the Richardson number correction was activated. For the case with turbulence data, the centerline decay of turbulent kinetic energy was also much improved. An important result that was discovered was the extreme sensitivity of the downstream evolution of the jet to the specification of the initial k and e profiles, highlighting the critical need for a comprehensive experimental characterization of all flow properties at the jet exit.

Flow-induced tube vibration in shell-and-tube heat exchangers has resulted in tube failure that has caused industrial plants and power stations to be shut down for costly repairs. As a result, possible flow-induced tube vibration problems have joined thermal, hydraulic, and mechanical design considerations. There have been few vibration research studies made with actual shell-and-tube heat exchangers. Most tests have been made with ideal tube banks, and there is a serious question as to whether the methods developed from these tests apply to the complex geometry in a shell-and-tube heat exchanger. Although not providing the best solution, data banks of field experience offer a practical way of evaluating proposed methods for predicting vibration problems. This paper follows the evolution of various data banks, discusses the essential need for vibration data banks, notes the difficulties in collecting and using their content, and describes the latest project to develop the new DOE/ANL/HTRI Heat Ex...

Air Force development of various types of space-based surveillance systems is expected to become increasingly important during the 1980's. Sensors carried on orbiting spacecraft can detect and track targets both in space and in the atmosphere. Those sensors which detect infrared radiation from a target and have higher sensitivity than present operational systems will require very low temperature (cryogenic) cooling of focal planes and optical elements in the sensor. For long duration missions, this cooling should be provided by direct, passive thermal radiation or by several types of closed cycle refrigerators (cryo-coolers) now being developed. The particular cooling method chosen depends on the required temperature, the amount of cooling needed, and other factors such as the satellite orbit and weight or size restrictions. This paper will describe the development status, and projected capabilities of several cryo-coolers being developed by the Flight Dynamics Laboratory for space applications.© (1981) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Monitoring fouling can provide useful information to permit the effective operation of heat exchangers. Different techniques are used to detect fouling by observing the buildup of a fouling layer, the accompanying deterioration in the thermal performance, and the increase in the overall pressure drop. Some monitors determine the relative performance of particular heat exchangers to signal the time for cleaning. Other monitors are used to evaluate the effectiveness of various treatment programs to control corrosion and minimize fouling. All have the objective of understanding more about the fouling characteristics of plant streams that are known to foul heat exchangers.

Not all heat exchangers have serious problems with fouling. Many operate satisfactorily for long periods without being cleaned. Garret-Price et al. [1] assembled Table 1 which identifies the kind and typical extent of fouling for fluids in various industry groups. This is useful in determining which heat exchangers must seriously consider fouling when they are being designed.

targets consist of one small circle strategically placed adjacent to some distracting influence such as a heavy dark area or an area containing broken lines moving off at an angle. While it is too early to evaluate the results of using this target, it provides an interesting change of pace for the shooter whose only instructions are to fire at the circle; shots missing the circle tend to be concentrated on the side opposite to the distracting

On September 29, 1829, the Metropolitan Police of London, England, entered upon their first day of duty. Of the first 2800 men recruited into that organization, at least 2238 (or approximately 80%) had to be dismissed from the force. All 2800 officers had been hand-picked by a very careful system of selection. Each candidate had to submit three written testimonials of character, one of them being from his last employer; the writers of these testimonials were personally interviewed. If a candidate passed through this stage, he reported for a medical examination, which in practice meant an inquiry into both his physical qualifications and his general intelligence. Less than one in three of the applicants was successful in passing through this stage. Those who did were then interviewed by an experienced personnel officer who eliminated the candidates obviously not suited to police work and passed the survivors on to the first two Commissioners