Non-medical use of loperamide in the UK and the USA.

BACKGROUND: Loperamide is a mu-opioid receptor agonist that is available as an over-the-counter anti-motility agent in the US and UK; recommended maximum doses of 12-16 mg/day. Anecdotal reports of non-medical use (NMU) have increased over the past decade with supra-therapeutic doses (70-800 mg/day) associated with cardiotoxicity. Little data exists on the prevalence of loperamide NMU. AIM: The aim of this study was to determine the prevalence of loperamide NMU in the UK and US and to describe characteristics of non-medical loperamide users. DESIGN: The Researched, Abuse, Diversion and Addiction Related Surveillance (RADARS® ) Survey of Nonmedical Use of Prescription Drugs (NMURx) was utilized to study NMU of loperamide among the adult population in the UK and US in 2017. The RADARS® NMURx is anonymous and self-administered online. METHODS: A total of 40,029 completed surveys were included (10,019 from the UK and 30,010 from the US). Respondents were asked questions about medical and NMU of loperamide, frequency of and reasons for NMU, route of use problematic drug use markers, and demographics. RESULTS: Prevalence of lifetime loperamide use (95% CI) and lifetime NMU of loperamide were: UK 28.5% (27.67-29.4), and 0.66% (0.5-0.8), respectively; US 33.7% (33.1-34.2), and 5.19% (4.9-5.5), respectively. Problematic drug use markers were elevated in those who reported NMU of loperamide in both the UK and US, however high-risk use was more prevalent in the UK than in the US. CONCLUSION: NMU of loperamide is common. In the current international environment of opioid addiction involving both therapeutic and illicit opioids, awareness of the NMU of loperamide is important.

Trends in intentional abuse or misuse of benzodiazepines and opioid analgesics and the associated mortality reported to poison centers across the United States from 2000 to 2014.

CONTEXT: Prior works demonstrates an increased risk of death when opioid analgesics and benzodiazepines are used concomitantly to gain a high. Using poison center data, we described trends in abuse or misuse of benzodiazepines and opioid analgesics. We quantified mortality risk associated with abuse or misuse of benzodiazepines, opioid analgesics and the combination of opioid analgesics and benzodiazepines. METHODS: This was a retrospective chart review of data from the National Poison Data System which collects information from 55 poison centers located across the United States. We identified reported cases of "intentional abuse or misuse" of benzodiazepine and/or opioid analgesic exposures. Poisson regression was used to compare the number of cases from each year between 2001 and 2014 to the year 2000. Logistic regression was used to determine whether cases exposed to both benzodiazepines and opioids had greater odds of death relative to cases exposed to opioid analgesics alone. RESULTS: From 2000 to 2014, there were 125,485 benzodiazepine exposures and 84,627 opioid exposures among "intentional abuse or misuse" cases. Of the benzodiazepine exposures, 17.3% (n = 21,660) also involved an opioid. In 2010, exposures involving both opioids and benzodiazepines were 4.26-fold (95% CI: 3.87-4.70; p < .001) higher than in 2000. The risk of death was 1.55 (95% CI: 1.01-2.37; p = .04) times greater among those who used both an opioid and a benzodiazepine compared to opioids alone. This association held after adjusting for gender and age. CONCLUSION: Intentional abuse or misuse of benzodiazepines and opioids in combination increased significantly from 2000 to 2014. Benzodiazepine abuse or misuse far exceeded cases of opioid abuse or misuse. Death was greater with co-abuse or misuse of benzodiazepines and opioids. Population-level campaigns to inform the public about the risk of death with co-abuse or misuse of benzodiazepines and opioids are urgently needed to address this overdose epidemic.

The effect of an abuse-deterrent opioid formulation (OxyContin) on opioid abuse-related outcomes in the postmarketing setting.

An extended-release opioid analgesic (OxyContin, OC) was reformulated with abuse-deterrent properties to deter abuse. This report examines changes in abuse through oral and nonoral routes, doctor-shopping, and fatalities in 10 studies 3.5 years after reformulation. Changes in OC abuse from 1 year before to 3 years after OC reformulation were calculated, adjusted for prescription changes. Abuse of OC decreased 48% in national poison center surveillance systems, decreased 32% in a national drug treatment system, and decreased 27% among individuals prescribed OC in claims databases. Doctor-shopping for OC decreased 50%. Overdose fatalities reported to the manufacturer decreased 65%. Abuse of other opioids without abuse-deterrent properties decreased 2 years later than OC and with less magnitude, suggesting OC decreases were not due to broader opioid interventions. Consistent with the formulation, decreases were larger for nonoral than oral abuse. Abuse-deterrent opioids may mitigate abuse and overdose risks among chronic pain patients.

A model to improve the accuracy of US Poison Center data collection.

CONTEXT: Over 2 million human exposure calls are reported annually to United States regional poison information centers. All exposures are documented electronically and submitted to the American Association of Poison Control Center's National Poison Data System. This database represents the largest data source available on the epidemiology of pharmaceutical and non-pharmaceutical poisoning exposures. The accuracy of these data is critical; however, research has demonstrated that inconsistencies and inaccuracies exist. OBJECTIVE: This study outlines the methods and results of a training program that was developed and implemented to enhance the quality of data collection using acetaminophen exposures as a model. METHODS: Eleven poison centers were assigned randomly to receive either passive or interactive education to improve medical record documentation. A task force provided recommendations on educational and training strategies and the development of a quality-measurement scorecard to serve as a data collection tool to assess poison center data quality. Poison centers were recruited to participate in the study. Clinical researchers scored the documentation of each exposure record for accuracy. Results. Two thousand two hundred cases were reviewed and assessed for accuracy of data collection. After training, the overall mean quality scores were higher for both the passive (95.3%; + 1.6% change) and interactive intervention groups (95.3%; + 0.9% change). Data collection accuracy improved modestly for the overall accuracy score and significantly for the substance identification component. There was little difference in accuracy measures between the different training methods. CONCLUSION: Despite the diversity of poison centers, data accuracy, specifically substance identification data fields, can be improved by developing a standardized, systematic, targeted, and mandatory training process. This process should be considered for training on other important topics, thus enhancing the value of these data in relation to public health safety.

A single-arm clinical trial of a 48-hour intravenous N-acetylcysteine protocol for treatment of acetaminophen poisoning.

INTRODUCTION: Acetylcysteine prevents hepatic injury when administered soon after acetaminophen overdose. The most commonly used treatment protocols are a 72-hour oral and a 21-hour intravenous (IV) protocol. Between 1984 and 1994, 409 patients were enrolled in a study to describe the outcomes of patients who were treated using a 48-hour IV protocol. In 1991, an interim analysis reported the first 223 patients. The objective of this manuscript is to report the rates of hepatotoxicity and adverse events occurring during a 48-hour IV acetylcysteine protocol in the entire 409 patient cohort. METHODS: This was a multicenter, single-arm, open-label clinical trial enrolling patients who presented with a toxic serum acetaminophen concentration within 24 h of acute acetaminophen ingestion. Patients were treated with 140 mg/kg loading dose followed by 70 mg/kg every 4 h for 12 doses. Serum aminotransferase activities were measured every 8 h during the protocol, and adverse events were recorded. The primary outcome was the percentage of subjects who developed hepatotoxicity defined as a peak serum aminotransferase greater than 1000 IU/L. RESULTS: Four hundred and nine patients were enrolled, and 309 met inclusion for the outcome analysis. The overall percentage of patients developing hepatotoxicity was 18.1%, and 3.4% of patients treated within 10 h developed hepatotoxicity. One acetaminophen-related death occurred in a patient treated at 22 h. Adverse events occurred in 28.9% of enrolled subjects; the most common adverse events were nausea, vomiting, and flushing, and no events were rated as serious by the investigator. CONCLUSIONS: Acetaminophen-overdosed patients treated with IV acetylcysteine administered as 140 mg/kg loading dose followed by 70 mg/kg every 4 h for 12 doses had a low rate of hepatotoxicity and few adverse events. This protocol delivers a higher dose of acetylcysteine which may be useful in selected cases involving very large overdoses.

Cardiovascular risk in patients without known cardiovascular disease.

Understanding the risks of atherosclerotic cardiovascular disease (CVD) allows for better patient education and management. Multiple risk models have been validated in large patient populations and provide insights into the risks associated with CVD. When assessing such risks, we suggest using a model that predicts myocardial infarction, cardiovascular death, and/or cerebrovascular events. In this review, we analyze several risk models and stratify the risks associated with CVD. We suggest that appropriate profiling of patients at-risk of CVD will lead to better physician recognition and treatment of modifiable risk factors, appropriate application of ATP III treatment for hyperlipidemia, and achieving optimal blood pressure control.

Reassessment of Crohn's disease treated with at least 12†months of anti-TNF therapy: how likely is treatment withdrawal?

OBJECTIVE: To assess methods of disease reassessment and rates of treatment withdrawal in patients with Crohn's disease (CD) treated with biologics and to report retrospective risk stratification for treatment withdrawal as suggested by the STORI trial in the context of this cohort. DESIGN: A retrospective observational cohort study of all patients with CD treated with antitumour necrosis factor (anti-TNF) therapy for >12 months in 2011. SETTING: Tertiary care. PATIENTS: Patients with CD treated with anti-TNF therapy. MAIN OUTCOME MEASURES: Method and outcome of reassessment and whether patient was withdrawn from therapy; also, whether patients met low-risk criteria for withdrawal as identified by the STORI trial, and outcome of those meeting low-risk criteria. RESULTS: 73 patients (infliximab n=48, adalimumab n=25) underwent disease reassessment. Nine patients were deemed to have achieved remission and were withdrawn from treatment: 6 (67%) maintained remission at 12 months, three patients relapsed and were successfully retreated. 52 patients had sufficient data available for STORI criteria to be applied retrospectively. 37% (19/52) fulfilled low-risk criteria for withdrawal-of these, 26% (5/19) were withdrawn from anti-TNF therapy and three had sustained clinical remission at 1 year. Reasons for non-withdrawal included ongoing endoscopic activity (n=8), radiological activity (n=2) and clinical concern due to previous disease behaviour (n=4). CONCLUSIONS: Relatively few patients were deemed in sufficient depth of remission to warrant a trial of withdrawal of anti-TNF therapy. Many patients were not withdrawn, despite meeting STORI low-risk criteria, due to ongoing disease activity highlighting the limitations of applying such criteria in a 'real world' setting.

The effects of paracetamol (acetaminophen) on hepatic tests in patients who chronically abuse alcohol - a randomized study.

BACKGROUND: Retrospective accounts suggest that therapeutic doses of paracetamol can produce severe hepatic injury in patients with putative high-risk conditions, including alcoholism and infectious hepatitis. Metabolism of paracetamol to its hepatotoxic metabolite is enhanced in patients who abuse alcohol, who also have compromised liver defences from depressed hepatic glutathione. AIM: To determine the effect of paracetamol on serum liver tests of newly abstinent subjects who abuse alcohol, including subjects with hepatitis C infection. METHODS: A randomized, double-blind, placebo-controlled study. Adult alcohol abusers with a current drinking episode longer than 7 days received either placebo or paracetamol 4 g/day for 5 days. RESULTS: Of 142 subjects enrolled, 74 received paracetamol and 68 received placebo. Mean ALT activity during treatment increased from 48 to 62 IU/L in the paracetamol group and from 47 to 49 IU/L in the placebo group. Maximum ALT was 238 and 249 IU/L in the paracetamol and control groups respectively. The INR remained unchanged and serum bilirubin decreased in both groups. Subgroup analyses for subjects with alcoholic hepatitis, hepatitis C virus antibody and other subgroups showed no statistical difference between groups. CONCLUSION: Administration of paracetamol 4 g/day appears safe in newly abstinent patients who abuse alcohol.

A randomized trial to determine the change in alanine aminotransferase during 10 days of paracetamol (acetaminophen) administration in subjects who consume moderate amounts of alcohol.

BACKGROUND: Previous studies have suggested that therapeutic doses of paracetamol (acetaminophen) are safe in alcoholic patients when administered for up to 3 days. However, 14 days of therapeutic doses of paracetamol has been associated with an increase in serum transaminases. AIM: To determine the effect of 10 days of the maximal therapeutic dose of paracetamol on serum alanine aminotransferase (ALT) activity in subjects who consume 1 to 3 alcoholic beverages per day. METHODS: This was a randomized, double blind, placebo-controlled trial. Subjects took 4 g of paracetamol (or placebo) daily for 10 days. Serum aspartate aminotransferase (AST), ALT, bilirubin and INR were measured at baseline, day 4 and day 11. Symptoms potentially related to liver injury were also recorded. RESULTS: Paracetamol and placebo groups had no change from baseline values at day 4, but the paracetamol group had an increase in mean ALT at day 11 of 8.7 IU/L. No subject developed symptoms of liver injury or met predefined criteria for hepatotoxicity or liver failure. CONCLUSION: Therapeutic dosing of paracetamol administered for 10 days appears to elevate serum ALT in moderate drinkers, but does not produce clinically evident liver injury.

The effect of acetaminophen (four grams a day for three consecutive days) on hepatic tests in alcoholic patients--a multicenter randomized study.

BACKGROUND: Hepatic failure has been associated with reported therapeutic use of acetaminophen by alcoholic patients. The highest risk period for alcoholic patients is immediately after discontinuation of alcohol intake. This period exhibits the largest increase in CYP2E1 induction and lowest glutathione levels. Our hypothesis was that common liver tests would be unaffected by administration of the maximum recommended daily dosage of acetaminophen for 3 consecutive days to newly-abstinent alcoholic subjects. METHODS: Adult alcoholic subjects entering two alcohol detoxification centers were enrolled in a prospective double-blind, randomized, placebo-controlled trial. Subjects were randomized to acetaminophen, 4 g/day, or placebo for 3 consecutive days. The study had 95% probability of detecting a 15 IU/L difference in serum ALT. RESULTS: A total of 443 subjects were enrolled: 308 (258 completed) received acetaminophen and 135 subjects (114 completed) received placebo. Study groups did not differ in demographics, alcohol consumption, nutritional status or baseline laboratory assessments. The peak mean ALT activity was 57 +/- 45 IU/L and 55 +/- 48 IU/L in the acetaminophen and placebo groups, respectively. Subgroup analyses for subjects presenting with an elevated ALT, subjects fulfilling a diagnosis of alcoholic hepatitis and subjects attaining a peak ALT greater than 200 IU/L showed no statistical difference between the acetaminophen and control groups. The one participant developing an increased international normalized ratio was in the placebo group. CONCLUSION: Alcoholic patients treated with the maximum recommended daily dose of acetaminophen for 3 consecutive days did not develop increases in serum transaminase or other measures of liver injury. Treatment of pain or fever for 3 days with acetaminophen appears safe in newly-abstinent alcoholic patients, such as those presenting for acute medical care.

Educação em saúde para a prevenção de Febre Reumática

Introdução: A Febre Reumática, doença resultante de uma faringoamigdalite estreptocócica não tratada adequadamente, pode cursar com seqüelas cardíacas graves e incapacitantes. Apesar de sua fácil prevenção, sua prevalência ainda é alta nos países subdesenvolvidos e em desenvolvimentos, em especial no Brasil, segundo dados do Data SUS. A falta de informação da população e dos próprios profissionais de saúde, é uma das causas que contribui para tais índices. No Rio de Janeiro, o Hospital Geral de Bonsucesso é um centro de referência para o acompanhamento de crianças e adolescentes portadores de febre reumática, sendo este, portanto cenário de atuação do presente trabalho. Materiais e métodos: Análise de 480 questionários elaborados e aplicados por estudantes de medicina do nono período e residentes; supervisionados por médicos do setor de cardiologia pediátrica e professores da UNESA. Objetivo: O objetivo geral do estudo é avaliar o grau de conhecimento de usuários, funcionários, estudantes e profissionais de saúde do HGB, a respeito da enfermidade - febre reumática. Com base nos dados obtidos são delineadas estratégias de atuação educacional visando à conscientização da prevenção da doença. Conclusão: Após análise dos dados colhidos de 480 questionários respondidos, constata-se a necessidade de uma maior divulgação interna do centro de referência de febre reumática do HGB e de seu campo de atuação, alem de se criar para a população leiga uma dinâmica de informação do diagnóstico precoce e tratamento correto das faringoamigdalites bacterianas, e reciclagem periódica para profissionais da área de saúde.

Rethinking the toxic methanol level.

INTRODUCTION: Treatment thresholds for methanol poisoning are based on case reports and published opinion. Most guidelines recommend treatment for a methanol level > or = 20 mg/dL in a nonacidotic patient. No supportive data have been offered nor has the time of the exposure been addressed. For instance, no distinction has been drawn between a methanol level drawn 1 hr vs. 24 hr from ingestion. We analyzed all published cases of methanol poisoning to determine the applicability of the 20 mg/dL threshold in a nonacidotic patient, specifically those arriving early for care (within 6 hr) with a peak or near-peak blood methanol concentration. METHODS: Using predefined search criteria, a systematic review of the world literature was performed using MEDLINE and EMBASE. In addition, each article's references were hand searched for pre-1966 articles, as were fatality abstracts from all U.S. poison centers. Human cases were included if they reported a known time of a single methanol exposure, acid-base data, blood methanol, and blood ethanol (if not acidotic). RESULTS: Dating to 1879, 372 articles in 18 languages were abstracted using a standard format; 329 articles (2433 patients) involved methanol poisoning, and 70 articles (173 patients) met inclusion criteria. Only 22 of these patients presented for care within 6hr of ingestion with an early methanol level. All but 1 patient was treated with an inhibitor of alcohol dehydrogenase (ADH). A clear acidosis developed only with a methanol level > or = 126 mg/dL. The patient that did not receive an ADH inhibitor was an infant with an elevated early methanol level (46 mg/dL) that was given folate alone and never became acidotic. Intra and inter-rater reliability were 0.95. CONCLUSIONS: Nearly all reports of methanol poisoning involve acidotic patients far removed from ingestion. The small amount of data regarding patients arriving early show that 126 mg/dL is the lowest early blood methanol level ever clearly associated with acidosis. Contrary to conventional teaching, there are case reports of acidosis after only a few hours of ingestion. The data are insufficient to apply 20 mg/dL as a treatment threshold in a nonacidotic patient arriving early for care. Prospective studies are necessary to determine if such patients may be managed without antidotal therapy or dialysis.

Mechanisms for enhanced biodegradation of petroleum hydrocarbons by a microbe-colonized gas-liquid foam.

AIMS: A microbe-colonized gas-liquid foam formulation has been previously shown to provide enhanced biodegradation capabilities in soil microcosms. The present study considers the reservoir properties of this foam and how this affects hydrocarbon degradation rates. METHODS AND RESULTS: Oxygen solubility in protein hydrolysate solutions draining from aerated and oxygenated foams was measured. The suitability of oxygenated foam to enhance the degradation of n-hexadecane in soil microcosms was assessed. Sorption of bacterial isolates at the gas-liquid interface was also investigated using a range of microscopy techniques. CONCLUSIONS: Oxygenated bioactive foam enhanced biodegradation rates by improving oxygen availability and transfer. Biodegradation of n-hexadecane was also stimulated by the protein hydrolysate used and by the inclusion of known bacterial hydrocarbon-degrading bacteria. The interaction of bacteria with the gas-liquid interface was shown to be a significant factor governing the drainage of the bacteria from the bioactive foam. SIGNIFICANCE AND IMPACT OF THE STUDY: Protein hydrolysate-based bioactive foam may be a suitable treatment technology to enhance the biodegradation of petroleum hydrocarbons in soil.

Tricyclic antidepressants directly depress human myocardial mechanical function independent of effects on the conduction system.

OBJECTIVES: To measure the effect of tricyclic antidepressant drugs (TCAs) on human myocardial contractility. METHODS: Human atrial tissue was obtained during cardiac bypass surgery. The tissue was harvested, suspended in a Tyrode buffer at 37 degrees C, and perfused with a 95%/5% oxygen-carbon dioxide mixture. Developed force was continuously measured using a force transducer and recorded by computer. After an equilibration period, escalating doses of amitriptyline or desipramine were added to the bath. All strips were exposed to the following five concentrations of each drug: 0 (control) 0.4, 4, 40, and 400 microM. The results for each experiment were expressed as the difference between the developed force measured prior to the addition of each concentration of drug and the developed force measured after a 30-minute exposure to the drug. RESULTS: Desipramine decreased the developed force by 27%, 49%, and 74% at concentrations of 0.4, 40, and 400 microM, respectively. Amitriptyline decreased the developed force by 38% at the 40-microM concentration and by 89% at the 400-microM concentration. Untreated strips retained 94% of baseline developed force at 150 minutes. CONCLUSIONS: Tricyclic antidepressants depress human myocardial function in a dose-dependent fashion independent of the effects on the cardiac conduction system. While previous work has demonstrated the effect of therapies for the reversal of impaired cardiac conduction following TCA poisoning, to the best of the authors' knowledge, no reports have documented the effects of therapy on direct myocardial depression. Additional therapies targeted at reversing the direct cardiodepressive effects of TCA may improve outcome following TCA poisoning.

Effect of maximal daily doses of acetaminophen on the liver of alcoholic patients: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Retrospective reports suggest that therapeutic doses of acetaminophen may be associated with fulminant hepatic failure and death in alcoholic patients. Millions of patients use acetaminophen; the prevalence of alcoholism in the United States is 5% to 10%. OBJECTIVE: To determine if hepatic injury was associated with maximal therapeutic dosing of acetaminophen to chronic alcohol abuse patients immediately following cessation of alcohol intake (the presumed time of maximal vulnerability). METHODS: Patients entering an alcohol detoxification center were enrolled in a randomized, double-blind, placebo-controlled trial. Exclusion criteria were baseline values of aspartate or alanine aminotransferase greater than 120 U/L, international normalized ratio greater than 1.5, serum acetaminophen level greater than 20 mg/L, or a history of ingesting more than 4 g/d of acetaminophen. Acetaminophen, 1000 mg, or placebo was administered orally 4 times daily for 2 consecutive days and liver test results were monitored for 2 more days. Acetaminophen was not administered until the alcohol had been eliminated. RESULTS: There were 102 patients in the acetaminophen-treated group and 99 patients in the placebo-treated (control) group. Demographic data, alcohol history, and baseline blood test results were similar in both groups. The mean (SD) aspartate aminotransferase level on day 4 was 38.0 +/- 26.7 U/L in the acetaminophen-treated group and 37.5 +/- 27.6 U/L in the placebo-treated group. There were 4 patients in the acetaminophen-treated group and 5 in the placebo-treated group who developed an increase in their serum aspartate aminotransferase level to greater than 120 U/L; it did not exceed 200 U/L in any patient. The mean (SD) international normalized ratio on day 4 was 0.96 +/- 0.09 in the acetaminophen-treated group and 0.98 +/- 0.11 in the placebo-treated group. CONCLUSION: Repeated administration of the maximum recommended daily doses of acetaminophen to long-term alcoholic patients was not associated with evidence of liver injury.

Attenuation of verapamil-induced myocardial toxicity in an ex-vivo rat model using a verapamil-specific ovine immunoglobin.

OBJECTIVE: To determine whether an ovine verapamil-specific immunoglobin G (V-IgG) attenuates verapamil toxicity in an ex-vivo rat left ventricular papillary muscle model. METHODS: The authors dissected left ventricular papillary muscle strips from male Sprague-Dawley rats (350-410 g) and suspended them in an oxygen-perfused Tyrode buffer bath at 37.5 degrees C. Muscle strips equilibrated for 90 minutes under electrical stimulation of 1 Hz. Resting and developed tension (mg) were monitored continuously. A concentration-response trial was performed with verapamil concentrations ranging from 31 to 1,020 nM; 510 nM produced consistent reduction in developed tension. A trial of V-IgG was then conducted by administering the following treatments to papillary muscle strips in a randomized manner: V-IgG + 510 nM verapamil, nonspecific ovine IgG (N-IgG) + 510 nM verapamil (protein control), and 510 nM verapamil alone. Immunoglobin G was administered in equimolar concentrations to verapamil. Attenuation was expressed as inhibition of the verapamil-induced reduction of developed tension. RESULTS: The V-IgG comparative trial indicated the V-IgG + verapamil treatment had a mean reduction in developed tension of 14.1% (SD +/- 12.2) compared with 36.2% (SD +/- 14.9) for N-IgG + verapamil and 34.9% (SD +/- 8.1) for verapamil alone (p < 0.05). There was no difference between the two control groups. CONCLUSION: Verapamil-specific IgG attenuated verapamil-induced reduction of developed tension in an ex-vivo rat model.

Emergency management of the nonviable intrauterine pregnancy.

Fetal death early in gestation is common. Patients in the first trimester of pregnancy with abdominal pain or vaginal bleeding often present to the emergency department for care. Over the past 20 years, the technology available to confirm or exclude the diagnosis of a nonviable pregnancy has improved dramatically. These improvements have altered the diagnostic approach to these patients and have lead to a change in the terminology used to categorize the pregnancy status. In addition, the therapeutic options available to manage patients with a confirmed nonviable pregnancy have expanded greatly. In this article, we re-evaluate the classification scheme used to categorize patients with first trimester pain or bleeding given the improved technology that is available to the emergency physician today. We discuss the role of ultrasound and biochemical markers in confirming or excluding the diagnosis of a nonviable pregnancy. Finally, we review the therapeutic options, including expectant, surgical as well as medical management that are available once the diagnosis of a nonviable intrauterine pregnancy has been confirmed.

A randomized multicenter trial of crotalinae polyvalent immune Fab (ovine) antivenom for the treatment for crotaline snakebite in the United States.

BACKGROUND: Current therapy for crotaline snakebite includes antivenin (Crotalidae) polyvalent, an antivenom with numerous adverse effects. We compared the efficacy and safety of 2 dosing regimens with a new antivenom, Crotalinae polyvalent immune Fab (Fab AV). METHODS: A single dose of Fab AV alone (as-needed [PRN] group) was compared with an initial dose plus repeated treatments during 18 hours (scheduled group) in a multicenter randomized trial. The study included patients with minimal or moderate envenomation by a crotaline snake within the preceding 6 hours, aged 10 years or older, in whom worsening of the envenomation syndrome was observed before Fab AV treatment. After treatment with Fab AV to achieve initial control, patients were randomized to the scheduled or PRN treatment group. Scheduled group patients received additional doses of Fab AV every 6 hours for 3 doses. The PRN group received no planned additional doses of antivenom. RESULTS: The mean severity score of the 31 patients decreased from 4.35 to 2.39 points (P<.001); there was no difference between scheduled and PRN groups. No patient in the scheduled group received unplanned Fab AV doses, but 8 of 16 patients in the PRN group received unplanned doses (P =.002). Acute reactions occurred in 6 patients (19%), and serum sickness occurred in 6 (23%) of 26 patients who returned for follow-up. CONCLUSIONS: In the first randomized trial of antivenom in the United States, Fab AV effectively terminated venom effects. Since the unplanned use of Fab AV in the PRN group was common, the treatment regimen may require more than 1 initial dose.

Calcium neutralizes fluoride bioavailability in a lethal model of fluoride poisoning.

OBJECTIVES: Acute systemic fluoride poisoning can result in systemic hypocalcemia, cardiac dysrhythmias, and cardiovascular collapse. Topical and intraarterial therapy with calcium or magnesium salts reduces dermal injury from fluoride burns. The mechanism of these therapies is to bind and inactivate the fluoride ion. The purpose of this study is to evaluate the effect of calcium and magnesium to decrease the bioavailability of fluoride in a lethal model of fluoride poisoning. METHODS: In preliminary studies, we determined that fluoride 3.6 mM/kg intraperitoneally in the form of sodium fluoride was uniformly and rapidly fatal in a mouse model. Using this fluoride dose, we performed a controlled, randomized, blinded study of low- and high-dose calcium chloride (1.8 and 3.6 mM/kg intraperitoneally, respectively) and magnesium sulfate (3.6 mM/kg intraperitoneally) to decrease the bioavailability of the fluoride ion. After injection with sodium fluoride, animals were immediately treated with injections of sodium chloride (control), calcium chloride (low- or high-dose), or magnesium sulfate. The major outcome was 6-hour survival using a Cox Proportional Hazard model. RESULTS: All untreated animals died within 60 minutes. Using a Cox Proportional Hazard model, each 1.8 mM/kg dose of calcium chloride administered reduced the risk of death by 33%. Magnesium sulfate treatment was not associated with a hazard reduction. CONCLUSION: Calcium chloride administered simultaneously with sodium fluoride reduces the bioavailability of fluoride poisoning in a mouse model. The equivalent dose of magnesium sulfate does not significantly decrease fluoride bioavailability.