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Objectives: Acetaminophen toxicity is a common cause of pediatric liver failure. The diagnosis may be limited by the short window of detection of acetaminophen in serum. Recently acetaminophen protein adducts (APAP-CYS) have been used as a biomarker with a longer duration of detection. The objective of this study was to describe the serum concentrations of APAP-CYS in pediatric patients with and without reported therapeutic acetaminophen exposure., Methods: A cross-sectional study of children age 1 to <12 years presenting to a pediatric emergency department. Subjects were stratified by recent acetaminophen use and had serum APAP-CYS measured using LC/MS., Results: One hundred patients were enrolled. All of the patients whose caregivers denied acetaminophen exposure had nondetectable APAP-CYS. Fifty-two percent of subjects who were reported to have taken acetaminophen in the preceding 2 weeks had detectable serum APAP-CYS. The APAP-CYS concentrations were positively correlated with higher overall dose and more recent ingestion., Conclusions: APAP-CYS is detectable in the majority of children taking acetaminophen and not detected in the majority of children who are not exposed to acetaminophen.

Spondylocarpotarsal synostosis (SCT) is a skeletal disorder characterized by progressive vertebral, carpal and tarsal fusions, and mild short stature. The majority of affected individuals have an autosomal recessive form of SCT and are homozygous or compound heterozygous for nonsense mutations in the gene that encodes the cytoskeletal protein filamin B (FLNB), but a subset do not have FLNB mutations. Exome sequence analysis of three SCT patients negative for FLNB mutations identified an autosomal dominant form of the disease due to heterozygosity for missense or nonsense mutations in MYH3, which encodes embryonic myosin. Cells transfected with the MYH3 missense mutations had reduced TGFβ signaling, revealing a regulatory role for embryonic myosin in the TGFβ signaling pathway. In wild-type mice, there was persistent postnatal expression of embryonic myosin in the small muscles joining the neural arches of the spine suggesting that loss of myosin function in these muscles contribute to the disease. Our findings demonstrate that dominant mutations in MYH3 underlie autosomal dominant SCT, identify a postnatal role for embryonic myosin and suggest that altered regulation of signal transduction in the muscles within the spine may lead to the development of vertebral fusions.

Objective: To determine whether an Early Warning System could identify patients wishing to focus on palliative care measures., Design: Prospective, randomized, pilot study., Setting: Barnes-Jewish Hospital, Saint Louis, MO (January 15, 2015, to December 12, 2015)., Patients: A total of 206 patients; 89 intervention (43.2%) and 117 controls (56.8%)., Interventions: Palliative care in high-risk patients targeted by an Early Warning System., Measurements and Main Results: Advanced directive documentation was significantly greater prior to discharge in the intervention group (37.1% vs 15.4%; p < 0.001) as were first-time requests for advanced directive documentation (14.6% vs 0.0%; p < 0.001). Documentation of resuscitation status was also greater prior to discharge in the intervention group (36.0% vs 23.1%; p = 0.043). There was no difference in the number of patients requesting a change in resuscitation status between groups (11.2% vs 9.4%; p = 0.666). However, changes in resuscitation status occurred earlier and on the general medicine units for the intervention group compared to the control group. The number of patients transferred to an ICU was significantly lower for intervention patients (12.4% vs 27.4%; p = 0.009). The median (interquartile range) ICU length of stay was significantly less for the intervention group (0 [0-0] vs 0 [0-1] d; p = 0.014). Hospital mortality was similar (12.4% vs 10.3%; p = 0.635)., Conclusions: This study suggests that automated Early Warning System alerts can identify patients potentially benefitting from directed palliative care discussions and reduce the number of ICU transfers.

Objectives: To identify differences in emergency department (ED) pain-care based on the type of fracture sustained and to examine whether fracture type may influence the more aggressive analgesic use previously demonstrated in older patients., Design: Secondary analysis of retrospective cohort study., Setting: Five EDs (four academic, one community) in the United States., Participants: Patients (1,664) who presented in January, March, July, and October 2009 with a final diagnosis of fracture (774 long bone [LBF], 890 shorter bone [SBF])., Measurements: Primary-predictor was type of fracture (LBF vs. SBF). Pain-care process outcomes included likelihood of analgesic administration, opioid-dose, and time to first analgesic. General estimating equations were used to control for age, gender, race, baseline pain score, triage acuity, comorbidities and ED crowding. Subgroup analyses were conducted to analyze age-based differences in pain care by fracture type., Results: A larger proportion of patients with LBF (30%) were older (>65 years old) compared to SBF (13%). Compared with SBF, patients with LBF were associated with greater likelihood of analgesic-administration (OR = 2.03; 95 CI = 1.58 to 2.62; P  < 0.001) and higher opioid-doses (parameter estimate = 0.268; 95 CI = 0.239 to 0.297; P  < 0.001). When LBF were examined separately, older-patients had a trend to longer analgesic wait-times (99 [55-163] vs. 76 [35-149] minutes, P  = 0.057), but no other differences in process outcomes were found., Conclusion: Long bone fractures were associated with more aggressive pain care than SBF. When fracture types were examined separately, older patients did not appear to receive more aggressive pain care. This difference should be accounted for in further research., (© 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: Falls are a common cause of morbidity and hospitalisation in older people. Inappropriate prescribing and polypharmacy contribute to falls risk in elderly patients. This study's aim was to quantify the problem and find out if medication review in the hospital setting led to deprescribing of medicines associated with falls risk., Methods: Admissions records for elderly patients were examined to identify those whose presenting complaint included a fall. Inpatient medication charts, pharmaceutical care notes, medical notes and discharge summaries were examined to identify any falls-risk medicines from admission histories and to determine if any medication review took place, and whether or not changes were made as a result. In particular deprescribing and dose reduction details were analysed., Results: 100 patients over 70 years old were admitted following a fall during the 2 months study period. The mean number of medicines on admission was 6.8 per patient with polypharmacy found in 62/100 (62%). One or more falls-risk medicine was found in 65/100 (65%) patients. Medicines review was carried out in 86/100 (86%) of patients, and 59/697 (8.5%) medicines were deprescribed. Pharmacist involvement in medication review led to a significant reduction in the number of falls-risk medicines per patient (p=0.002)., Conclusions: Inappropriate prescribing and polypharmacy are found frequently in elderly patients at admission following a fall. Comprehensive medicines reviews should be carried out in all such patients with the objective of deprescribing or reducing doses to minimise risk of harm. Involvement of a pharmacist improves the rate of reduction of falls-risk medicines., Competing Interests: Conflicts of Interest: None declared.

A study was performed to determine the potential influence of a rapid response system (RRS) employing real-time clinical deterioration alerts (RTCDAs) on patient outcomes involving 8 general medicine units. Introduction of the RRS occurred in 2006 with staged addition of the RTCDAs in 2009. Statistically significant year-to-year decreases in mortality were observed through 2014 ( r = -.794; P = .002). Similarly, year-to-year decreases in the number of cardiopulmonary arrests (CPAs; r = -.792; P = .006) and median lengths of stay ( r = -.841; P = .001) were observed. There was a statistically significant year-to-year increase in the number of RRS activations for these units ( r = .939; P < .001) that was inversely correlated with the occurrence of CPAs ( r = -.784; P = .007). In this single-institution retrospective study, introduction of a RRS employing RTCDAs was associated with lower hospital mortality, CPAs, and hospital length of stay.

Objective: Aggressive lymphomas (aNHL) including diffuse large B-cell lymphoma (DLBCL) have poor outcomes in relapsed refractory patients. Prior studies have demonstrated that loss of major histocompatibility complex class II (MHCII) expression in DLBCL is associated with poor survival. The objective of this single-arm phase II study was to evaluate if PXD-101 would increase MHCII expression, synergize with Zevalin, and improve clinical outcomes., Methods: This was a single-center open-label phase II trial (NCT01686165) geared toward heavily pretreated patients with CD20-positive aNHL. The primary endpoint was overall response rate (ORR) in aNHL patients treated with 2 cycles of PXD-101 followed by restaging CT and 1 cycle of Zevalin., Results: Five patients were enrolled, and all were heavily pretreated. Therapy was well tolerated, with nausea and vomiting being the most frequent adverse events. All patients progressed after receiving therapy; the study did not achieve the required ORR to proceed to the next stage., Conclusion: The pleotropic effects of histone deacetylase inhibition and lack of clinical biomarkers have precluded a priori identification of responding patients. Thus, while we report a negative trial of PXD-101 in combination with Zevalin, this study highlights the importance of a clinically feasible biomarker., (© 2017 S. Karger AG, Basel.)

Introduction: Clinical deterioration alerts (CDAs) are increasingly employed to identify deteriorating patients., Methods: We performed a retrospective study to determine whether CDAs predict 30-day readmission. Patients admitted to 8 general medicine units were assessed for all-cause 30-day readmission., Results: Among 3015 patients, 567 (18.8%) were readmitted within 30 days. Patients triggering a CDA (n = 1141; 34.4%) were more likely to have a 30-day readmission (23.6% vs 15.9%; P < 0.001). Logistic regression identified triggering of a CDA to be independently associated with 30-day readmission (odds ratio [OR]: 1.40; 95% confidence interval [CI]: 1.26-1.55; P = 0.001). Other predictors were: an emergency department visit in the previous 6 months (OR: 1.23; 95% CI:, 1.20-1.26; P < 0.001), increasing age (OR: 1.01; 95% CI: 1.01-1.02; P = 0.003), presence of connective tissue disease (OR: 1.63; 95% CI: 1.34-1.98; P = 0.012), diabetes mellitus with end-organ complications (OR: 1.23; 95% CI: 1.13-1.33; P = 0.010), chronic renal disease (OR: 1.16; 95% CI: 1.08-1.24; P = 0.034), cirrhosis (OR: 1.25; 95% CI: 1.17-1.33; P < 0.001), and metastatic cancer (OR: 1.12; 95% CI: 1.08-1.17; P = 0.002). Addition of the CDA to the other predictors added only modest incremental value for the prediction of hospital readmission., Conclusions: Readily identifiable clinical variables can be identified that predict 30-day readmission. It may be important to include these variables in existing prediction tools if pay for performance and across-institution comparisons are to be "fair" to institutions that care for more seriously ill patients. Journal of Hospital Medicine 2016;11:768-772. © 2016 Society of Hospital Medicine., (© 2016 Society of Hospital Medicine.)

Background: This study investigated the effect of Vibram FiveFingers Bikila minimalist shoes on intrinsic foot musculature. We hypothesized that a gradual transition into minimalist shoes will increase the thickness of the abductor hallucis muscle., Methods: Forty-one individuals were divided into four groups: control (traditional shod) (n = 9), restricted walking in Vibram FiveFingers (n = 11), running in Vibram FiveFingers (n = 10), and unlimited walking in Vibram FiveFingers (n = 11). At baseline, 12 weeks, and 24 weeks, the thickness of the abductor hallucis muscle was determined using ultrasound. Statistical analysis was performed to determine the significance of differences in muscle thickness at the three different time points., Results: The mean thickness of the abductor hallucis muscle at 24 weeks was significantly greater than that at baseline for the restricted walking (P = .005) and running (P < .001) groups. In the unlimited walking group, the mean thickness of the muscle at 12 weeks was significantly greater than that at baseline (P < .05) but not at 24 weeks. There were no significant differences in muscle thickness among the three time points for the control group (P = .432)., Conclusions: This study demonstrated that wearing Vibram FiveFinger Bikila footwear over a controlled period of time, an unlimited amount of time, as well as transitioning runners over a 6-month period of time using the 10% philosophy for increasing mileage, significantly increases intrinsic muscle thickness of the abductor hallucis. The abductor hallucis muscle aids in support of the medial longitudinal arch, and an increase in this muscle thickness may help reduce running-related injuries thought to arise from arch weakness.

Study Objective: Medication histories are collected to measure drug exposure in epidemiologic studies, to identify adverse drug events and in clinical practice. The objective of this study was to compare the accuracy of a structured medication history obtained by using the Medication History Assessment Tool (MedHAT) with a medication diary in which subjects recorded real-time medication use., Design: Prospective observational study., Setting: Outpatient research center., Subjects: Sixty-seven adult healthy volunteers., Interventions: Subjects were provided diaries to record the product name, dose quantity, and time that they used a prescription or nonprescription medication, supplement, or vitamin. After a minimum of 30 continuous days of diary use, a final interview was conducted, and medication history data were collected by using the MedHAT., Measurements and Main Results: We compared the medications reported during the interview with the medications recorded in the diary for each day to determine the accuracy of the verbal history. The primary outcome was the proportion of matches for each day for each subject. Overall accuracy for medication use for the day preceding the interview was 90%, and accuracy during the 30 days preceding the interview was 76%. Recall was higher for subjects taking prescription medications, those who had more recent medication use, older subjects, and subjects taking a higher proportion of prescription medications., Conclusion: The MedHAT system provided relatively high accuracy for immediate past use and for prescription medications and may offer better accuracy than other methods. Medication histories are often inaccurate, however, and may represent an important source of misclassification in epidemiologic studies. Thus medication histories alone should be used cautiously when measuring associations between drug exposure and health outcomes., (© 2016 Pharmacotherapy Publications, Inc.)

Background: The minimum recommended treatment duration for i.v. N-acetylcysteine (NAC) after an acute, single acetaminophen (APAP) overdose is 21 h. Some have questioned whether shorter courses may be sufficient in carefully selected cases., Objective: We sought to describe the incidence of hepatotoxicity in a cohort of acute APAP overdose patients who received <21 h of i.v. NAC for any reason., Methods: We performed a secondary analysis of a large multicenter retrospective cohort of patients hospitalized for APAP poisoning. We selected patients with a potentially toxic serum APAP concentration measured between 4 and 24 h post ingestion, in whom i.v. NAC was initiated but discontinued before completing the full 21-h course. We further characterized outcomes in these patients as a function of two novel risk-prediction tools, the psi (ψ) parameter and APAP × aminotransferase (AT) product. The ψ parameter is an estimate of the cellular burden of injury based on the area under the concentration-time curve before treatment, and calculated with respect to the APAP concentration and time to initiation of NAC., Results: Fifty-nine patients met inclusion criteria. Intravenous NAC was initiated a median of 11.3 h post ingestion and administered for a median of 11.0 h. Hepatotoxicity (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] > 1,000 IU/L) occurred in one patient (1.7%; 95% confidence interval 0.04-9.1), and eight additional patients developed hepatic injury (AST or ALT > 100 IU/L). No fatalities occurred. A multiplication product of APAP and AT (APAP × AT) that falls below 10,000 μmol/L/IU-L, or pretreatment ψ < 5 mmol/L-h suggested a low risk of hepatic injury., Conclusions: In this retrospective analysis of patients treated with < 21 h of i.v. NAC for acute APAP overdose, the incidence of hepatotoxicity and coagulopathy was low, despite delays to NAC treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: In cases of paracetamol (acetaminophen, APAP) overdose, an accurate estimate of tissue-specific paracetamol pharmacokinetics (PK) and ingested dose can offer health care providers important information for the individualized treatment and follow-up of affected patients. Here a novel methodology is presented to make such estimates using a standard serum paracetamol measurement and a computational framework., Methods: The core component of the computational framework was a physiologically-based pharmacokinetic (PBPK) model developed and evaluated using an extensive set of human PK data. Bayesian inference was used for parameter and dose estimation, allowing the incorporation of inter-study variability, and facilitating the calculation of uncertainty in model outputs., Results: Simulations of paracetamol time course concentrations in the blood were in close agreement with experimental data under a wide range of dosing conditions. Also, predictions of administered dose showed good agreement with a large collection of clinical and emergency setting PK data over a broad dose range. In addition to dose estimation, the platform was applied for the determination of optimal blood sampling times for dose reconstruction and quantitation of the potential role of paracetamol conjugate measurement on dose estimation., Conclusions: Current therapies for paracetamol overdose rely on a generic methodology involving the use of a clinical nomogram. By using the computational framework developed in this study, serum sample data, and the individual patient's anthropometric and physiological information, personalized serum and liver pharmacokinetic profiles and dose estimate could be generated to help inform an individualized overdose treatment and follow-up plan., (© 2015 The British Pharmacological Society.)

Background: Paracetamol protein adducts (PPA) are a biomarker of paracetamol exposure. PPA are quantified as paracetamol-cysteine (APAP-CYS), and concentrations above 1.1 μmol l(-1) have been suggested as a marker of paracetamol-induced hepatotoxicity. However, there is little information on the range of concentrations observed during prolonged therapeutic dosing., Aim: The aim of the present study was to describe the concentration of PPA in the serum of subjects taking therapeutic doses of paracetamol for at least 16 days., Methods: Preplanned secondary aim of a prospective randomized controlled (placebo vs. 4g day(-1) paracetamol) trial. We measured subjects' serum PPA concentrations every 3 days for a minimum of 16 days. We also measured concentrations on study days 1-3 and 16-25 in subsets of patients. PPA were quantified as APAP-CYS after gel filtration and protein digestion using liquid chromatography/mass spectrometry., Results: Ninety per cent of subjects had detectable PPA after five doses. Median APAP-CYS concentrations in paracetamol-treated subjects increased to a plateau of 0.1 μmol l(-1) on day 7, where they remained. The highest concentration measured was 1.1 μmol l(-1) and two subjects never had detectable PPA levels. PPA were detected in the serum of 78% of subjects 9 days after their final dose., Conclusions: PPA are detectable in the vast majority of subjects taking therapeutic doses of paracetamol. While most have concentrations well below the threshold associated with hepatotoxicity, concentrations may approach 1.1 μmol l(-1) in rare cases. Adducts are detectable after a few doses and can persist for over a week after dosing is stopped., (© 2015 The British Pharmacological Society.)

Over the last few decades, machine learning and data mining have been increasingly used for clinical prediction in ICUs. However, there is still a huge gap in making full use of the time-series data generated from ICUs. Aiming at filling this gap, we propose a novel approach entitled Time Slicing Cox regression (TS-Cox), which extends the classical Cox regression into a classification method on multi-dimensional time-series. Unlike traditional classifiers such as logistic regression and support vector machines, our model not only incorporates the discriminative features derived from the time-series, but also naturally exploits the temporal orders of these features based on a Cox-like function. Empirical evaluation on MIMIC-II database demonstrates the efficacy of the TS-Cox model. Our TS-Cox model outperforms all other baseline models by a good margin in terms of AUC&#95;PR, sensitivity and PPV, which indicates that TS-Cox may be a promising tool for mortality prediction in ICUs.

Background and Objective: Legitimate opioid use is associated with an increased risk of long-term opioid use and possibly misuse in adults. The objective of this study was to estimate the risk of future opioid misuse among adolescents who have not yet graduated from high school., Methods: Prospective, panel data come from the Monitoring the Future study. The analysis uses a nationally representative sample of 6220 individuals surveyed in school in 12th grade and then followed up through age 23. Analyses are stratified by predicted future opioid misuse as measured in 12th grade on the basis of known risk factors. The main outcome is nonmedical use of a prescription opioid at ages 19 to 23. Predictors include use of a legitimate prescription by 12th grade, as well as baseline history of drug use and baseline attitudes toward illegal drug use., Results: Legitimate opioid use before high school graduation is independently associated with a 33% increase in the risk of future opioid misuse after high school. This association is concentrated among individuals who have little to no history of drug use and, as well, strong disapproval of illegal drug use at baseline., Conclusions: Use of prescribed opioids before the 12th grade is independently associated with future opioid misuse among patients with little drug experience and who disapprove of illegal drug use. Clinic-based education and prevention efforts have substantial potential to reduce future opioid misuse among these individuals, who begin opioid use with strong attitudes against illegal drug use., (Copyright © 2015 by the American Academy of Pediatrics.)

Background: Previous studies examining sex-based disparities in emergency department (ED) pain care have been limited to a single pain condition, a single study site, and lack rigorous control for confounders., Objective: A multicenter evaluation of the effect of sex on abdominal pain (AP) and fracture pain (FP) care outcomes., Research Design: A retrospective cohort review of ED visits at 5 US hospitals in January, April, July, and October 2009., Subjects: A total of 6931 patients with a final ED diagnosis of FP (n=1682) or AP (n=5249) were included., Measures: The primary predictor was sex. The primary outcome was time to analgesic administration. Secondary outcomes included time to medication order, and the likelihood of receiving an analgesic and change in pain scores 360 minutes after triage: Multivariable models, clustered by study site, were conducted to adjust for race, age, comorbidities, initial pain score, ED crowding, and triage acuity., Results: On adjusted analyses, compared with men, women with AP waited longer for analgesic administration [AP women: 112 (65-187) minutes, men: 96 (52-167) minutes, P<0.001] and ordering [women: 84 (41-160) minutes, men: 71 (32-137) minutes, P<0.001], whereas women with FP did not (Administration: P=0.360; Order: P=0.133). Compared with men, women with AP were less likely to receive analgesics in the first 90 minutes (OR=0.766; 95% CI, 0.670-0.875; P<0.001), whereas women with FP were not (P=0.357)., Discussion: In this multicenter study, we found that women experienced delays in analgesic administration for AP, but not for FP. Future research and interventions to decrease sex disparities in pain care should take type of pain into account.

Ahead of Print article withdrawn by publisher.

Background: Hospital readmission occurs often and is difficult to predict. Polypharmacy has been identified as a potential risk factor for hospital readmission. However, the overall impact of the number of discharge medications on hospital readmission is still undefined., Methods: To determine whether the number of discharge medications is predictive of thirty-day readmission using a retrospective cohort study design performed at Barnes-Jewish Hospital from January 15, 2013 to May 9, 2013. The primary outcome assessed was thirty-day hospital readmission. We also assessed potential predictors of thirty-day readmission to include the number of discharge medications., Results: The final cohort had 5507 patients of which 1147 (20.8 %) were readmitted within thirty days of their hospital discharge date. The number of discharge medications was significantly greater for patients having a thirty-day readmission compared to those without a thirty-day readmission (7.2 ± 4.1 medications [7.0 medications (4.0 medications, 10.0 medications)] versus 6.0 ± 3.9 medications [6.0 medications (3.0 medications, 9.0 medications)]; P < 0.001). There was a statistically significant association between increasing numbers of discharge medications and the prevalence of thirty-day hospital readmission (P < 0.001). Multiple logistic regression identified more than six discharge medications to be independently associated with thirty-day readmission (OR, 1.26; 95 % CI, 1.17-1.36; P = 0.003). Other independent predictors of thirty-day readmission were: more than one emergency department visit in the previous six months, a minimum hemoglobin value less than or equal to 9 g/dL, presence of congestive heart failure, peripheral vascular disease, cirrhosis, and metastatic cancer. A risk score for thirty-day readmission derived from the logistic regression model had good predictive accuracy (AUROC = 0.661 [95 % CI, 0.643-0.679])., Conclusions: The number of discharge medications is associated with the prevalence of thirty-day hospital readmission. A risk score, that includes the number of discharge medications, accurately predicts patients at risk for thirty-day readmission. Our findings suggest that relatively simple and accessible parameters can identify patients at high risk for hospital readmission potentially distinguishing such individuals for interventions to minimize readmissions.

Study Objective: Acute pain complaints are commonly treated in the emergency department (ED). Short courses of opioids are presumed to be safe for acute pain; however, the risk of recurrent opioid use after receipt of an ED opioid prescription is unknown. We describe the risk of recurrent opioid use in patients receiving an opioid prescription from the ED for an acute painful condition., Methods: This is a retrospective cohort study of all patients discharged from an urban academic ED with an acute painful condition during a 5-month period. Clinical information was linked to data from Colorado's prescription drug monitoring program. We compared opioid-naive patients (no opioid prescription during the year before the visit) who filled an opioid prescription or received a prescription but did not fill it to those who did not receive a prescription. The primary outcome was the rate of recurrent opioid use, defined as filling an opioid prescription within 60 days before or after the first anniversary of the ED visit., Results: Four thousand eight hundred one patients were treated for an acute painful condition; of these, 52% were opioid naive and 48% received an opioid prescription. Among all opioid-naive patients, 775 (31%) received and filled an opioid prescription, and 299 (12%) went on to recurrent use. For opioid-naive patients who filled a prescription compared with those who did not receive a prescription, the adjusted odds ratio for recurrent use was 1.8 (95% confidence interval 1.3 to 2.3). For opioid-naive patients who received a prescription but did not fill it compared with those who did not receive a prescription, the adjusted odds ratio for recurrent use was 0.8 (95% confidence interval 0.5 to 1.3)., Conclusion: Opioid-naive ED patients prescribed opioids for acute pain are at increased risk for additional opioid use at 1 year., (Copyright © 2014 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Intravenous lipid emulsion (ILE) has been broadly attempted in the resuscitation of neurologic and cardiac toxic drug overdoses, however, the role of ILE in the emergency department is poorly defined., Objective: This review aims to identify recent literature on the use of ILE in humans as an antidote and to familiarize emergency providers with the indications, availability, dosing recommendations, and adverse reactions associated with ILE use., Methods: A systemic literature search of MEDLINE, EMBASE, and major toxicology conference abstracts was performed for human cases using ILE as an antidote with documented clinical outcomes through January 2014., Results: Ninety-four published articles and 40 conference abstracts were identified, 85% of which had positive outcomes. The most common indication for ILE was for local anesthetic systemic toxicity (LAST). The most common nonlocal anesthetic xenobiotics were tricyclic-antidepressants and verapamil., Discussion: No standard of care is defined for the use of ILE, although the American Heart Association recommends use in LAST, and the American College of Medical Toxicology recommends consideration for circumstances of hemodynamic instability resultant from lipid-soluble xenobiotics. ILE should be administered per American Society of Regional Anesthesia and Pain Medicine dosing recommendations. Laboratory interference, pancreatitis, respiratory distress syndrome, and interference with vasopressors should be considered as risks but are uncommon., Conclusions: In the setting of severe hemodynamic compromise by lipid-soluble xenobiotics, ILE may be considered for resuscitation by emergency physicians. As such, ILE may be stocked in emergency departments in close proximity to resuscitation rooms and areas where local nerve blocks are performed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Simulation-based teaching (SIM) is a common method for medical education. SIM exposes residents to uncommon scenarios that require critical, timely actions. SIM may be a valuable training method for critically ill poisoned patients whose diagnosis and treatment depend on key clinical findings. Our objective was to compare medical simulation (SIM) to traditional lecture-based instruction (LEC) for training emergency medicine (EM) residents in the acute management of critically ill poisoned patients. EM residents completed two pre-intervention questionnaires: (1) a 24-item multiple-choice test of four toxicological emergencies and (2) a questionnaire using a five-point Likert scale to rate the residents' comfort level in diagnosing and treating patients with specific toxicological emergencies. After completing the pre-intervention questionnaires, residents were randomized to SIM or LEC instruction. Two toxicologists and three EM physicians presented four toxicology topics to both groups in four 20-min sessions. One group was in the simulation center, and the other in a lecture hall. Each group then repeated the multiple-choice test and questionnaire immediately after instruction and again at 3 months after training. Answers were not discussed. The primary outcome was comparison of immediate mean post-intervention test scores and final scores 3 months later between SIM and LEC groups. Test score outcomes between groups were compared at each time point (pre-test, post-instruction, 3-month follow-up) using Wilcoxon rank sum test. Data were summarized by descriptive statistics. Continuous variables were characterized by means (SD) and tested using t tests or Wilcoxon rank sum. Categorical variables were summarized by frequencies (%) and compared between training groups with chi-square or Fisher's exact test. Thirty-two EM residents completed pre- and post-intervention tests and comfort questionnaires on the study day. Both groups had higher post-intervention mean test scores (p < 0.001), but the LEC group showed a greater improvement compared to the SIM group (5.6 [2.3] points vs. 3.6 [2.4], p = 0.02). At the 3-month follow-up, 24 (75 %) tests and questionnaires were completed. There was no improvement in 3-month mean test scores in either group compared to immediate post-test scores. The SIM group had higher final mean test scores than the LEC group (16.6 [3.1] vs. 13.3 [2.2], p = 0.009). SIM and LEC groups reported similar diagnosis and treatment comfort level scores at baseline and improved equally after instruction. At 3 months, there was no difference between groups in comfort level scores for diagnosis or treatment. Lecture-based teaching was more effective than simulation-based instruction immediately after intervention. At 3 months, the SIM group showed greater retention than the LEC group. Resident comfort levels for diagnosis and treatment were similar regardless of the type of education.

Pain is highly prevalent in health care settings; however, disparities continue to exist in pain care treatment. Few studies have investigated if differences exist based on patient-related characteristics associated with aging. The objective of this study was to determine if there are differences in acute pain care for older vs younger patients. This was a multicenter, retrospective, cross-sectional observation study of 5 emergency departments across the United States evaluating the 2 most commonly presenting pain conditions for older adults, abdominal and fracture pain. Multivariable adjusted hierarchical modeling was completed. A total of 6,948 visits were reviewed. Older (⩾ 65 years) and oldest (⩾ 85 years) were less likely to receive analgesics compared to younger patients (<65 years), yet older patients had greater reductions in final pain scores. When evaluating pain treatment and final pain scores, differences appeared to be based on type of pain. Older patients with abdominal pain were less likely to receive pain medications, while older patients with fracture were more likely to receive analgesics and opioids compared to younger patients. Differences in pain care for older patients appear to be driven by the type of presenting pain., (Published by Elsevier B.V.)

Background: Severe hypoglycemia (SH), defined as a blood glucose (BG) <40 mg/dL, is associated with an increased risk of adverse clinical outcomes in inpatients., Objective: To determine whether a predictive informatics hypoglycemia risk-alert supported by trained nurse responders would reduce the incidence of SH in our hospital., Design: A 5-month prospective cohort intervention study., Setting: Acute care medical floors in a tertiary care academic hospital in St. Louis, Missouri., Patients: From 655 inpatients on designated medical floors with a BG of <90 mg/dL, 390 were identified as high risk for hypoglycemia by the alert system., Measurements: The primary outcome was the incidence of SH occurring in high-risk intervention versus high-risk control patients. Secondary outcomes included: number of episodes of SH in all study patients, incidence of BG < 60 mg/dL and severe hyperglycemia with a BG >299 mg/dL, length of stay, transfer to a higher level of care, the frequency that high-risk patient's orders were changed in response to the alert-intervention process, and mortality., Results: The alert process, when augmented by nurse-physician collaboration, resulted in a significant decrease by 68% in the rate of SH in alerted high-risk patients versus nonalerted high-risk patients (3.1% vs 9.7%, P = 0.012). Rates of hyperglycemia were similar on intervention and control floors at 28% each. There was no difference in mortality, length of stay, or patients requiring transfer to a higher level of care., Conclusion: A real-time predictive informatics-generated alert, when supported by trained nurse responders, significantly reduced inpatient SH., (© 2014 Society of Hospital Medicine.)

Those medical providers deployed to remote countries and tasked with caring for military personnel must diagnose and treat diseases and nonbattle injuries that result from exposures rarely seen in developed countries. Military providers must also function with limited resources and a lack of access to physician specialists, to include medical toxicologists. There have been limited published approaches to addressing this clinical gap for medical toxicology. To address this void, the US Army Medical Department deployed an electronic mail telemedicine system to provide teleconsultations for remote health-care providers worldwide, including Iraq and Afghanistan. This study aimed to describe the types and the frequency of toxicology teleconsultation and consultant responses using electronic mail to assist physicians serving in resource-limited locations. This was a retrospective observational study in which an unblinded data extractor independently reviewed all medical toxicology email consultations. Using a previously developed data collection worksheet, the extractor recorded the type of question asked by the consultant (overdose case, envenomation, occupational exposure, etc.) and the duration of time from when the teleconsultation was placed until the consultant replied. The extractor also recorded if the patient was adult or pediatric and if the patient was US military, US contractor, or local national. The extractor also recorded how often the toxicologist provided the consulting physician with information, resources, or protocols to aid in the management of future cases. In addition, for clinical teleconsultations, the extractor documented the frequency that the consulted toxicologist (i) provided a differential diagnosis or specific diagnosis, (ii) provided specific management guidelines for a patient, and (iii) recommended to evacuate or not evacuate a patient. The results were analyzed using descriptive statistics. Of the 99 consultations evaluated, the most common consultation was for snake envenomation and antivenom recommendations (n = 23, 23 %) followed by accidental chemical exposures (n = 14, 14 %), drug testing (n = 13, 13 %), and substance abuse (n = 10, 10 %). In 41 % of consults, the toxicologist provided a differential diagnosis or specific diagnosis, and in 60 % of cases, the toxicologist provided specific management or evaluation guidelines. In 11 % of cases, the toxicologist recommended for or against evacuation of the patient. In 25 % of consults, the toxicologist provided the consulting physician with information, resources, or protocols to aid in the management of future cases. The most frequent consultations for the military telemedicine consultation service were for direct patient cases, specifically snake envenomation management and accidental chemical exposures. Our results may be used to educate physicians prior to military deployment or international humanitarian efforts and to create toxicology clinical guidelines for remote locations. Expansion of the current military teleconsultation program capabilities to include video teleconsultation may improve the effectiveness of military medical toxicology teleconsultation.

Background: Acetaminophen administration for more than 4 days causes aminotransferase elevation in some subjects. The objective of this randomized, placebo-controlled trial is to describe the course of alanine aminotransferase (ALT) elevation in subjects administered 4 g/day of acetaminophen for at least 16 days., Methods: A randomized, placebo controlled trial of acetaminophen (4 g/day) vs placebo. Subjects were healthy volunteers with normal liver enzymes. The primary outcome was the course of ALT during acetaminophen administration. All subjects were treated for a minimum of 16 days. Subjects with ALT elevation at day 16 were continued on treatment until these elevations resolved up to a maximum of 40 days. Subjects were also evaluated for elevation of INR or serum bilirubin as evidence of hepatic dysfunction., Results: 157/205 (77%) completed acetaminophen subjects had no ALT elevation or transient elevations that resolved by day 16. Of the 48 subjects who had ALT elevations at study day 16, 47 continued on acetaminophen and had resolution by study day 40. One acetaminophen subject did not have resolution by study day 40, and the course of aminotransferase elevation suggests an alternative cause. One placebo subject had an ALT elevation at day 16 that resolved by day 22. The highest observed ALT among all acetaminophen subjects was 191 IU/L. The mean ALT at day 16 was 4.4 IU/L higher for the acetaminophen than for the placebo group. No subject developed liver dysfunction., Conclusions: A minority of subjects treated with 4 g/day of acetaminophen for 16 days will have low-grade aminotransferase elevations that are not accompanied by liver dysfunction and resolve if administration is continued., Trials Registration: Clintrials.gov NCT00743093 registered August 26, 2008.

Background: Episodes of patient deterioration on hospital units are expected to increasingly contribute to morbidity and healthcare costs., Objective: To determine if real-time alerts sent to the rapid response team (RRT) improved patient care., Design: Randomized, controlled trial., Setting: Eight medicine units (Barnes-Jewish Hospital)., Patients: Five hundred seventy-one patients., Intervention: Real-time alerts generated by a validated deterioration algorithm were sent real-time to the RRT (intervention) or hidden (control)., Measurements: Intensive care unit (ICU) transfer, hospital mortality, hospital duration., Results: ICU transfer (17.8% vs 18.2%; odds ratio: 0.972; 95% confidence interval [CI]: 0.635-1.490) and hospital mortality (7.3% vs 7.7%; odds ratio: 0.947; 95% CI: 0.509-1.764) were similar for the intervention and control groups. The number of patients requiring transfer to a nursing home or long-term acute care hospital was similar for patients in the intervention and control groups (26.9% vs 26.3%; odds ratio: 1.032; 95% CI: 0.712-1.495). Hospital duration (8.4 ± 9.5 days vs 9.4 ± 11.1 days; P = 0.038) was statistically shorter for the intervention group. The number of RRT calls initiated by the primary care team was similar for the intervention and control groups (19.9% vs 16.5%; odds ratio: 1.260; 95% CI: 0.823-1.931)., Conclusions: Real-time alerts sent to the RRT did not reduce ICU transfers, hospital mortality, or the need for subsequent long term care. However, hospital length of stay was modestly reduced., (© 2014 Society of Hospital Medicine.)

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.

Study Objective: We compare state trends in unintentional pediatric marijuana exposures, as measured by call volume to US poison centers, by state marijuana legislation status., Methods: A retrospective review of the American Association of Poison Control Centers National Poison Data System was performed from January 1, 2005, to December 31, 2011. States were classified as nonlegal if they have not passed legislation, transitional if they enacted legislation between 2005 and 2011, and decriminalized if laws passed before 2005. Our hypotheses were that decriminalized and transitional states would experience a significant increase in call volume, with more symptomatic exposures and more health care admissions than nonlegal states., Results: There were 985 unintentional marijuana exposures reported from 2005 through 2011 in children aged 9 years and younger: 496 in nonlegal states, 93 in transitional states, and 396 in decriminalized states. There was a slight male predominance, and the median age ranged from 1.5 to 2.0 years. Clinical effects varied, with neurologic effects the most frequent. More exposures in decriminalized states required health care evaluation and had moderate to major clinical effects and critical care admissions compared with exposures from nonlegal states. The call rate in nonlegal states to poison centers did not change from 2005 to 2011. The call rate in decriminalized states increased by 30.3% calls per year, and transitional states had a trend toward an increase of 11.5% per year., Conclusion: Although the number of pediatric exposures to marijuana reported to the National Poison Data System was low, the rate of exposure increased from 2005 to 2011 in states that had passed marijuana legislation., (Copyright © 2014 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

N-Acetylcysteine (NAC) dosing for acetaminophen (APAP) overdose is weight based (150 mg/kg intravenous or 140-mg/kg oral loading dose) and, in the United States, the dosing protocol recommends using a maximum patient weight of 100 and 110 kg, respectively. Little clinical data describe the use of NAC for APAP poisoning in patients weighing >100 kg. The aim of this study was to describe the demographics, outcomes, and adverse event (AE) rates of patients weighing >100 kg treated with oral or IV NAC for APAP poisoning. Patients were identified from a multicenter retrospective NAC safety study for APAP overdose. We included patients with a recorded weight. Trained chart abstractors used a standardized form. Selected data included age, gender, weight, serum alanine transaminase, and aspartate transaminases, coingestants, NAC administration route, ingestion type, AEs, and outcome [hepatotoxicity (alanine transaminase > 1000 U/L), liver transplant, or death]. Descriptive statistics were used. Of 503 study patients, 37 (7.4%) had recorded weights >100 kg. The median (range) weight was 110 kg (101-160). The median (range) dosing for patients treated with oral NAC was 140 mg/kg (127-143 mg/kg) and 150 (108-168) mg/kg for IV NAC. Hepatotoxicity occurred in 12/36 (33.3%) patients. Death occurred in 4/36 (11.1%) patients. Thirteen NAC-related AEs occurred in 8 patients (1.6 per person). All AEs were related to NAC and were rated nonserious by the reviewer. Clinicians use an actual weight-based NAC dose rather than a maximum weight cutoff dose. Hepatotoxicity was common in our cohort. AEs were relatively common but not serious.

Liver injury has been reported in children treated with repeated doses of acetaminophen. The objective of this study was to identify and validate reports of liver injury or death in children younger than 6 years who were administered repeated therapeutic doses of acetaminophen. We reviewed US Poison Center data, peer-reviewed literature, US Food and Drug Administration Adverse Event Reports, and US Manufacturer Safety Reports describing adverse effects after acetaminophen administration. Reports that described hepatic abnormalities (description of liver injury or abnormal laboratory testing) or death after acetaminophen administration to children younger than 6 years were included. The identified reports were double abstracted and then reviewed by an expert panel to determine if the hepatic injury was related to acetaminophen and whether the dose of acetaminophen was therapeutic (≤75 mg/kg) or supratherapeutic. Our search yielded 2531 reports of adverse events associated with acetaminophen use. From these cases, we identified 76 cases of hepatic injury and 26 deaths associated with repeated acetaminophen administration. There were 6 cases of hepatic abnormalities and no deaths associated with what our panel determined to be therapeutic doses. A large proportion of cases could not be fully evaluated due to incomplete case reporting. Although we identified numerous examples of liver injury and death after repeated doses of acetaminophen, all the deaths and all but 6 cases of hepatic abnormalities involved doses more than 75 mg/kg per day. This study suggests that the doses of less than 75 mg/kg per day of acetaminophen are safe for children younger than 6 years.

Introduction: There are 161 emergency medicine residency programs in the United States, many of which have medical students rotating through the emergency department (ED). Medical students are typically supervised by senior residents or attendings while working a regular shift. Many believe that having students see and present patients prolongs length of stay (LOS), as care can be delayed. Our institution implemented a unique method of educating medical students while in the ED with the creation of a teaching service, whose primary goal is education in the setting of clinical care. The objective of this study was to explore the effect of the teaching service on efficiency by describing LOS and number of patients seen on shifts with and without a teaching service., Methods: This was a retrospective chart review performed over a 12-month period of visits to an urban academic ED. We collected data on all patients placed in a room between 14:00 and 19:59, as these were the hours that the teaching shift worked in the department. We categorized shifts as 1) a teaching service with students (TWS); 2) a teaching service without students (TWOS); and 3) no teaching service (NTS). LOS and median number of patients seen on days with a teaching service, both with and without students (TWS and TWOS), was compared to LOS on days without a teaching service (NTS)., Results: The median LOS on shifts with a dedicated teaching service without students (TWOS) was 206 minutes, while the median LOS on shifts with a teaching service with students (TWS) was 220 minutes. In comparison, the median LOS on shifts when no teaching service was present (NTS) was 202.5 minutes. The median number of patients seen on shifts with the teaching service with students (TWS) was 44, identical to the number seen on shifts when the teaching service was present without students (TWOS). When the teaching service was absent (NTS), the median number of patients seen was 40., Conclusion: A teaching service in the ED is a novel educational model for medical student and resident instruction that increases total ED patient throughput and has only a modest effect on increased median length of stay for patients.

In this article, we explore the nature of good postnatal care through a hermeneutic unpacking of the notion of tact, drawing on the philosophical writings of Heidegger, Gadamer, and van Manen. The tactful encounters considered were from a hermeneutic research study within a small, rural birthing center in New Zealand. Insights drawn from the analysis were as follows: the openness of listening, watching and being attuned that builds a positive mode of engagement, recognizing that the distance the woman needs from her nurse/midwife is a call of tact, that tact is underpinned by a spirit of care, within tact there are moods and tact might require firmness, and that all of these factors come together to build trust. We conclude that the attunement of tact requires that the staff member has time to spend with a woman, enough energy to engage, and a spirit of care. Women know that tactful practice builds their confidence and affects their mothering experience. Tact cannot be assumed; it needs to be nurtured and sheltered.

Objective: To investigate national trends in unintentional pediatric exposures to 3 common alpha-2 agonists: clonidine, guanfacine, and tizanidine. Secondary objectives were to describe outcomes, symptoms, treatments, and death., Study Design: Retrospective chart review from the American Association of Poison Control Centers National Poison Data System from January 2000 to December 2011 for unintentional exposure to clonidine, guanfacine, and tizanidine in children ≤ 12 years of age., Results: From 2000-2011, there was a significant increase (5.9% per year, CI 3.6, 8.2) in unintentional pediatric exposures to National Poison Data System for central alpha-2 agonists. There were 27,825 clonidine exposures (67.3% male, median age: 4 years), 6143 guanfacine exposures (69.8% male, median age: 6 years), and 856 tizanidine exposures (51.9% male, median age: 2 years). Guanfacine had the greatest proportional increase among the medications. Clonidine was associated with the most respiratory (799, 2.9%) and central nervous system symptoms (12,612, 45.3%), as well as the most episodes of bradycardia (2847, 10.2%) and hypotension (2365, 8.5%). Seven-hundred twenty-eight (2.0%) patients were intubated, and 141 patients (0.5%) were administered vasopressors. There were 7 cardiac arrests and 3 deaths from clonidine., Conclusions: The number of unintentional pediatric exposures to alpha-2 agonists increased from 2000-2011. Clonidine exposures were the most commonly reported, more symptomatic, and associated with 3 deaths. Despite central nervous system depression, bradycardia, and hypotension being common, the need for intubation and vasopressors was rare., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: Cesium chloride (CsCl) is sold as a treatment for several types of cancers. The purported mechanism of action is alkalinization of relatively acidic neoplastic cells. The efficacy of CsCl has not been demonstrated in controlled experiments. Oral and intravenous CsCl use has been associated with seizures, cardiotoxicity, syncope, and death. Although intratumoral treatment with various antineoplastic agents is described, no cases of intratumoral cancer treatment with CsCl have been found in the medical literature. The case described here appears to be of the first reported patient with CsCl toxicity secondary to subcutaneous exposure after attempted intratumoral injection., Case Details: A 61-year-old woman presented in cardiac arrest 20 hours after injecting 9 mL of an oral CsCl preparation around a mass in her breast. She had been taking the CsCl orally for approximately 1 year to treat her breast mass. The patient had a headache and nausea for several hours after injection and then experienced ventricular tachycardia arrest at home. She received advanced cardiac life support care and multiple antiarrhythmic medications and underwent electrical cardioversion early in the course of the arrest. After stabilization, her electrocardiogram revealed QT interval prolongation to >700 milliseconds. Upon discovery of her CsCl exposure, she was treated with Prussian blue. Her initial whole blood cesium level was 100,000 μg/L (reference range <10 μg/L). Her QT prolongation resolved after several days, but she experienced no meaningful postarrest neurologic recovery and died at home less than a week after exposure., Discussion: CsCl is sold as an alternative treatment for cancer. There is no demonstrable efficacy, and clear evidence shows life-threatening toxicity. Reported here is a case of fatal CsCl toxicity after attempted intratumoral injection.

Although women incarcerated by the criminal justice system encounter significant challenges to their health, there has been little research focusing on their health practices. To contribute to the research literature on the health experiences of criminalized women, the authors conducted a multi-method study as part of a program of research exploring the health promotion and health-literacy skills of women in conflict with the law. Conducting research in an incarcerated setting posed unique challenges and ethical dilemmas that problematized each phase of data collection. The authors share their experiences as health researchers conducting research in an incarcerated setting and with criminalized women. They document some of the challenges, successes, and valuable lessons learned during the research process in the hope that by sharing their knowledge with other health researchers they will support future studies with criminalized women.

Background: Suspected ingestions are a common chief complaint to the emergency department although the majority of ingestions by children are insignificant., Objective: Assess the utility of screening laboratory tests and Electrocardiograms (ECGs) in unintentional asymptomatic pediatric poisonings., Methods: Retrospective chart review at a tertiary care children's hospital and a regional poison center of patients less than 12 years of age using ICD-9 codes from January 2005 through December 2008. Laboratory or ECG results requiring intervention and/or direct treatment, a non-RPC subspecialty consultation, and/or prolonged Emergency Department stay was considered changed management., Results: Five hundred ninety five suspected ingestions met our criteria. The median age was 2.6 years (IQR 1.6, 3.0 years) and 56% were male. One laboratory test or ECG was obtained in 233 patients (39%). Of 24 screening ECGs, 32 complete blood counts and 34 blood gases, none were clinically significant. Fifty-two patients received screening metabolic panels, 3 were abnormal and 2 changed management (anion gap metabolic acidosis with unsuspected salicylate ingestions). None of the 127 (21%) screening acetaminophen levels changed management. Two of sixty-five (13%) screening salicylate levels changed management. Three screening urine toxicology tests on patients with altered mental status were positive without ingestion history. No patient under the age of 12 years with normal vital signs and normal mental status had positive screening tests., Conclusions: Screening laboratory tests and ECGs were of limited utility and rarely changed management despite being ordered in a significant number of patients. Screening tests are rarely indicated in unintentional overdoses in children who are asymptomatic., (Copyright © 2013. Published by Elsevier Inc.)

Importance: An increasing number of states are decriminalizing the use of medical marijuana, and the effect on the pediatric population has not been evaluated., Objective: To compare the proportion of marijuana ingestions by young children who sought care at a children's hospital in Colorado before and after modification of drug enforcement laws in October 2009 regarding medical marijuana possession., Design: Retrospective cohort study from January 1, 2005, through December 31, 2011., Setting: Tertiary-care children's hospital emergency department in Colorado., Participants: A total of 1378 patients younger than 12 years evaluated for unintentional ingestions: 790 patients before September 30, 2009, and 588 patients after October 1, 2009., Main Exposure: Marijuana ingestion., Main Outcomes and Measures: Marijuana exposure visits, marijuana source, symptoms, and patient disposition., Results: The proportion of ingestion visits in patients younger than 12 years (age range, 8 months to 12 years)that were related to marijuana exposure increased after September 30, 2009, from 0 of 790 (0%; 95% CI, 0%-0.6%) to 14 of 588 (2.4%; 95% CI, 1.4%-4.0%) (P < .001). Nine patients had lethargy, 1 had ataxia, and 1 had respiratory insufficiency. Eight patients were admitted, 2 to the intensive care unit. Eight of the 14 cases involved medical marijuana, and 7 of these exposures were from food products., Conclusions and Relevance: We found a new appearance of unintentional marijuana ingestions by young children after modification of drug enforcement laws for marijuana possession in Colorado. The consequences of unintentional marijuana exposure in children should be part of the ongoing debate on legalizing marijuana.

Introduction: To use Colorado's prescription drug monitoring program (PDMP) to describe the recent opioid prescription history of patients discharged from our emergency department (ED) with a prescription for opioid pain medications., Methods: Retrospective cohort study of 300 adult ED patients who received an opioid prescription. We abstracted prescription histories for the six months prior to the ED visit from the PDMP, and abstracted clinical and demographic variables from the chart., Results: There were 5,379 ED visits during the study month, 3,732 of which were discharged. Providers wrote 1,165 prescriptions for opioid analgesics to 1,124/3,732 (30%) of the patients. Median age was 36 years. Thirty-nine percent were male. Patients were 46% Caucasian, 26% African American, 22% Hispanic, 2% Asian and 4% other. These were similar to our overall ED population. There was substantial variability in the number of prescriptions, prescribers and total number of pills. A majority (205/296) of patients had zero or one prescription. The 90th percentile for number of prescriptions was seven, while the 10th percentile was zero. Patients in the highest decile tended to be older, with a higher proportion of Caucasians and females. Patients in the lowest decile resembled the general ED population. The most common diagnoses associated with opioid prescriptions were abdominal pain (11.5%), cold/flu symptoms (9.5%), back pain (5.4%), flank pain (5.0%) and motor vehicle crash (4.7%)., Conclusion: Substantial variability exists in the opioid prescription histories of ED patients, but a majority received zero or one prescription in the preceding six months. The top decile of patients averaged more than two prescriptions per month over the six months prior to ED visit, written by more than 6 different prescribers. There was a trend toward these patients being older, Caucasian and female.

Study Objective: Black widow spider antivenom has never been tested in a randomized clinical trial, to our knowledge. We explore various efficacy measures for a novel F(ab)2 antivenom in patients with moderate to severe pain caused by black widow spider envenomation., Methods: A randomized, placebo-controlled, double-blind, clinical trial was conducted in 12 academic emergency departments. We included patients at least 10 years old with moderate to severe latrodectism. Subjects received either a single intravenous infusion of antivenom or placebo. Pain was assessed with the visual analog scale. The primary efficacy outcome was the difference in pre- and posttreatment visual analog scale score. Prospectively defined secondary outcomes included treatment failures and time to clinically important decrease in pain., Results: Twenty-four subjects were enrolled between October 2005 and October 2006; 13 were randomized to antivenom and 11 to placebo. The median change in visual analog scale at 150 minutes posttreatment was -50.0 mm (Interquartile Range [IQR] -67, -41 mm) in the antivenom treatment group and -46.0 mm (IQR -51, 0 mm) in the placebo treatment group (P=.14). There were 7 treatment failures (64%; 95% confidence interval 35% to 92%) in the placebo group and 3 (23%; 95% confidence interval 0.2% to 46%) in the antivenom group (P=.06). The median time to a clinically important decrease in pain after treatment was shorter in the antivenom group compared with the placebo group (30 minutes [IQR 30, 60 minutes] versus 90 minutes [IQR 30, 90 minutes]; P=.03). No serious adverse events or deaths were reported., Conclusion: Although the overall reduction in pain was similar for antivenom- and placebo-treated subjects, antivenom reduced pain more rapidly than placebo. No significant adverse events occurred in either group., (Copyright © 2012. Published by Mosby, Inc.)

Duloxetine is a serotonin and norepinephrine reuptake inhibitor, which is mainly used to treat depression. This retrospective study describes the demographic and clinical effects of duloxetine ingestions reported to the National Poison Data System (NPDS). NPDS data were searched for duloxetine exposures between 2004 and 2010. A total of 11,373 patients were included and exposures were divided into three groups of ages ≤6 years old, 7-12 years and >12 years. Neurological clinical effects occurred in 6.1% of the patients aged ≤6 years, 13.0% of the patients aged 7-12 years and 24.6% of the patients aged >12 years. Cardiovascular effects occurred in 1.4% of the patients aged ≤6 years old, 2.5% of the patients aged 7-12 years and 11.6% of the patients aged >12 years. Gastrointestinal effects occurred in 4.1% of the patients aged ≤6 years old, 16.6% of the patients aged 7-12 years and 13.8% of the patients aged >12 years. Tachycardia, nausea, vomiting, agitation/irritability, dizziness/vertigo and drowsiness were among the most common clinical effects in all three groups. Overall, 61.4% of the patients aged ≤6 years and 77.5% of the patients aged 7-12 years were managed in a non-health care facility, while 55.8% of the patients aged >12 years were referred to or already in a health care facility. We conclude that the majority of ingestions are benign in both pediatrics and adults. Most symptomatic patients have neurologic, gastrointestinal and cardiovascular effects. Most pediatric patients will be able to be managed in a non-health care facility.

Background: Because the toxicity of arsenic is well known, arsenic-containing compounds have frequently been ingested for suicidal purposes. We report a case of attempted suicide by massive ingestion of arsenic trisulfide, an arsenic mineral of low solubility, which resulted in minimal symptoms., Case Report: An asymptomatic 57-year-old man presented to an Emergency Department 13h after his reported ingestion of approximately 84g of arsenic contained in a mineral specimen of orpiment (arsenic trisulfide) that had been crushed and mixed with an alcoholic beverage and food. His only symptom before presentation was nausea. Physical examination was unremarkable, and diagnostic tests included a normal electrolyte panel, a normal serum lactate, and a normal electrocardiogram. An abdominal radiograph revealed hyper-dense material scattered throughout the large intestine. As per the recommendations of the regional poison center, the patient was managed with whole bowel irrigation with a polyethylene glycol solution, maintenance intravenous hydration, and observation on a telemetry unit. Chelation was not performed. A spot urine specimen collected 12h after admission contained 1490μg of total arsenic per liter (background range<50μg per liter). The patient remained asymptomatic throughout his hospital course. Follow-up studies revealed a diminution in both intra-abdominal radiopacities and urine arsenic concentration. X-ray diffraction analysis of the specimen confirmed its identity as arsenic trisulfide., Conclusions: Our experience demonstrates that massive ingestion of a poorly soluble inorganic arsenic compound can be successfully managed with gastrointestinal decontamination alone without chelation, provided that the patient remains asymptomatic during close clinical monitoring., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Nonmedical use of prescription pain drugs (hereafter "analgesics") has increased substantially in recent years. It is not known whether today's youth are disproportionately driving this increase or, instead, the trend is a general one that has affected cohorts of all ages similarly. To address this question we present the first age-period-cohort analysis of nonmedical use of analgesics., Methods: Data come from the National Survey on Drug Use and Health, a series of annual, nationally representative, cross-sectional surveys of the US civilian, noninstitutionalized population. The analysis focuses on the years 1985-2009 and uses the recently developed "intrinsic estimator" algorithm to disentangle age-period-cohort effects., Results: Substantial increases in the prevalence of nonmedical analgesics use (NAU) have occurred across all cohorts and ages in recent years, but this increase is significantly amplified among today's adolescents. The odds of past-year NAU for today's youngest cohort (born 1980-1994) are higher than would be expected on the basis of their age and broad, historical period influences that have increased use across people of all ages and cohorts. The independent influence of cohort on past-year NAU is about 40% higher for today's youth cohort than any of the cohorts that came before them. This finding is present among men, women, non-Hispanic whites, non-Hispanic blacks, and Hispanics., Conclusions: Although nonmedical use of analgesics is evident among all ages, cohorts, and periods, today's younger cohorts warrant special attention for substance abuse policies and interventions targeted at reversing the increase in NAU., (Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Human glycol ether poisonings are sparsely reported in the medical literature. We describe a healthy 22-month-old boy who accidentally drank up to 330 mL of brake fluid containing a 75% bleed of various glycol ethers (5%-50% polyethylene glycol monomethyl ether, 15%-40% triethylene glycol monoethyl ether, 1%-30% triethylene glycol monomethyl ether, 1%-25% triethylene glycol monobutyl ether, 1%-20% polyethylene glycol, monobutyl ether, 1%-20% triethylene glycol, and <10% of other glycol ethers). Within 4 hours, he became somnolent and developed a persistent metabolic acidosis. Thirty minutes later, he received 1 dose of fomepizole. Neither progression nor improvement in clinical or metabolic status was noted after the fomepizole. He received hemodialysis for 3 hours ∼8 hours after ingestion, and his symptoms resolved resulting in an uneventfully recovery.

Study Objective: To quantify the effect of therapeutic doses of acetaminophen on serum alanine aminotransferase (ALT) levels in subjects who consumed ethanol., Design: Systematic review of six randomized placebo-controlled trials, of which five were included in a meta-analysis., Subjects: Subjects included in the meta-analysis were those who consumed ethanol and received acetaminophen in doses up to 4 g/day (551 subjects) or placebo (350 subjects)., Measurements and Main Results: A comprehensive literature search of the MEDLINE, EMBASE, and International Pharmaceutical Abstracts databases and the Cochrane Central Register of Controlled Trials was performed to identify randomized, placebo-controlled trials that enrolled subjects who consumed ethanol, received acetaminophen in therapeutic doses up to 4 g/day, and had serum ALT level measurements. A total of 184 articles were identified; six articles met all criteria. Five of the six articles reported ALT levels on study day 4 for both groups of subjects who received acetaminophen or placebo. Thus, for the meta-analysis, we used the primary outcome of mean change in serum ALT level from baseline to day 4 in the acetaminophen groups compared with the placebo groups. We found that the difference in mean change from baseline ALT levels between the acetaminophen and placebo groups on day 4 was 0.0 U/L (95% confidence interval -0.2-0.1 U/L). There were no reports of liver dysfunction, liver failure, or death in any of the trials., Conclusion: In randomized, placebo-controlled trials of subjects who consumed ethanol, no elevation of ALT level on study day 4 was noted when subjects ingested up to 4 g/day of acetaminophen., (© 2012 Pharmacotherapy Publications, Inc. All rights reserved.)

Acetylcysteine has been used to treat acetaminophen overdose for nearly 50 years. While no placebo controlled trials have been conducted, the efficacy of acetylcysteine is accepted for the prevention of hepatic injury when administered early after acetaminophen overdose. Acetylcysteine can be administered as an infusion or oral solution. The duration of treatment varies from 21 to 72 hours, depending on the protocol. Acetylcysteine also prevents death when administered to patients with hepatic failure from acetaminophen.