Loperamide-Induced Torsades de Pointes: A Case Series.

BACKGROUND: Loperamide is an over-the-counter, inexpensive, antidiarrheal opioid that can produce life-threatening toxicity at high concentrations. CASE REPORT 1: A 28-year-old man with a history of depression and substance abuse disorder (SUD) presented to the emergency department (ED) with shortness of breath and lightheadedness. He ingested large amounts of loperamide daily. The patient's initial electrocardiogram (ECG) demonstrated sinus rhythm, right axis deviation, undetectable PR interval, QRS 168 ms, and QTc 693 ms. He was administered intravenous sodium bicarbonate and magnesium sulfate and admitted to the intensive care unit, eventually developing Torsades de Pointes (TdP). He was given lidocaine and isoproterenol infusions, and an external pacemaker was placed. He was discharged in stable condition on hospital day (HD) 16. CASE REPORT 2: A 39-year-old woman with a history of hepatitis C, depression, and SUD was transported to the ED after reported seizure-like activity. The patient experienced TdP in the ED and admitted to ingesting large amount of loperamide daily. An ECG demonstrated sinus rhythm, right axis deviation, PR interval 208 ms, QRS interval 142 ms, and QTc 687 ms. She was administered intravenous magnesium, sodium bicarbonate, and isoproterenol. After intensive care unit admission, the patient experienced no further TdP and was discharged on HD 6. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should proceed with caution when treating patients with loperamide toxicity. Even in asymptomatic patients and drug discontinuance, obtain consultation with a medical toxicologist, promptly treat ECG abnormalities aggressively, and admit all patients for further monitoring.

Patterns and trends in accidental poisoning death rates in the US, 1979-2014.

OBJECTIVES: The purpose of this study was to examine US accidental poisoning death rates by demographic and geographic factors from 1979 to 2014, including High Intensity Drug Trafficking Areas. METHODS: Crude and age-adjusted death rates were formed for age group, race, sex, and county for accidental poisonings (ICD 9th revision: E850-E869; ICD 10th revision: X40-X49) from 1979 to 2014 using the Mortality and Population Data System housed at the University of Pittsburgh. Rate ratios were calculated comparing rates from 2014 to 1979, overall, by sex, age group, race, and county. Joinpoint regression detected changes in trends and calculated the average annual percentage change (AAPC) as a summary measure of trend. RESULTS: Drug poisoning mortality rates have risen an average of 6% per year since 1979. Increases are occurring in all ages 15+, and in all race-sex groups. HIDTA counties with the highest mortality rates were in Appalachia and New Mexico. Many of the HIDTA border counties had lower rates of mortality. CONCLUSIONS: The drug poisoning mortality epidemic is continuing to grow. While HIDTA resources are appropriately targeted at many areas in the US most affected, rates are also rapidly rising in some non-HIDTA areas.

Estimating metabolic rate from International Organization for Standardization heart rate method and two walking equations.

Assigning a value for metabolic rate is central to heat stress assessment. ISO 8996 describes a predictive method for walking based on the American College of Sports Medicine (ACSM) method and another generalized method based on average heart rate. In addition, the US Army uses the load carriage decision aid (LCDA) predictive equation to estimate metabolic rate. The purpose of this study was to assess the accuracy/bias and precision of the ISO heart rate method and the ACSM and LCDA equations. The laboratory database included metabolic rate, heart rate, treadmill speed, and grade during a progressive heat stress protocol. Treadmill speed and grade were set to represent one of three metabolic rates. Accuracy and precision were assessed with Bland-Altman plots. All three methods had good accuracy (low bias). For precision, the ISO heart rate method had a root mean square error (RMSE) of 34 W and 11% when adjusted for repeated measures. The RMSE for two equations was 20 W and 7%. Although the heart method had less accuracy, its application is more generalizable. The heart rate method should be used below the occupational exposure limit to avoid a bias toward higher predicted values due to heat strain.

Accidental through and through penetrating injury to the neck.

We present the case of a 24-year-old driver who died when a metal pole entered the front windshield, traveled through the victim's neck, and then exited via the back windshield. This case illustrated an unusual penetration injury and the importance of a thorough and complete death scene investigation.

The Effect of Incomplete Death Certificates on Estimates of Unintentional Opioid-Related Overdose Deaths in the United States, 1999-2015.

OBJECTIVES: A complete and accurate count of the number of opioid-related overdose deaths is essential to properly allocate resources. We determined the rate of unintentional overdose deaths (non-opioid-related, opioid-related, or unspecified) in the United States and by state from 1999 to 2015 and the possible effects of underreporting on national estimates of opioid abuse. METHODS: We abstracted unintentional drug overdose deaths ( International Classification of Diseases, 10th Revision, codes X40-X44) with contributory drug-specific T codes (T36.0-T50.9) from the Mortality Multiple Cause Micro-Data Files. We assumed that the proportion of unspecified overdose deaths that might be attributed to opioids would be the same as the proportion of opioid-related overdose deaths among all overdose deaths and calculated the number of deaths that could be reallocated as opioid-related for each state and year. We then added these reallocated deaths to the reported deaths to determine their potential effect on total opioid-related deaths. RESULTS: From 1999 to 2015, a total of 438 607 people died from unintentional drug overdoses. Opioid-related overdose deaths rose 401% (from 5868 to 29 383), non-opioid-related overdose deaths rose 150% (from 3005 to 7505), and unspecified overdose deaths rose 220% (from 2255 to 29 383). In 5 states (Alabama, Indiana, Louisiana, Mississippi, and Pennsylvania), more than 35% of unintentional overdose deaths were coded as unspecified. Our reallocation resulted in classifying more than 70 000 unspecified overdose deaths as potential additional opioid-related overdose deaths. CONCLUSIONS: States may be greatly underestimating the effect of opioid-related overdose deaths because of incomplete cause-of-death reporting, indicating that the current opioid overdose epidemic may be worse than it appears.

Report of Increasing Overdose Deaths that include Acetyl Fentanyl in Multiple Counties of the Southwestern Region of the Commonwealth of Pennsylvania in 2015-2016.

Acetyl fentanyl is a Schedule I controlled synthetic opioid that is becoming an increasingly detected "designer drug." Routine drug screening procedures in local forensic toxicology laboratories identified a total of 41 overdose deaths associated with acetyl fentanyl within multiple counties of the southwestern region of the state of Pennsylvania. The range, median, mean, and standard deviation of blood acetyl fentanyl concentrations for these 41 cases were 0.13-2100 ng/mL, 11 ng/mL, 169.3 ng/mL, and 405.3 ng/mL, respectively. Thirty-six individuals (88%) had a confirmed history of substance abuse, and all but one case (96%) were ruled multiple drug toxicities. This report characterizes this localized trend of overdose deaths associated with acetyl fentanyl and provides further evidence supporting an alarmingly concentrated opiate and opioid epidemic of both traditional and novel drugs within this region of the United States.

Drug Overdose Surveillance and Information Sharing via a Public Database: The Role of the Medical Examiner/Coroner.

The medical examiner/coroner (ME/C) death scene investigation systems of the United States play a pivotal role in the current public health crisis created by the expanding drug dependency epidemic in the United States. The first point of recognition of a drug-related death in a community is often the local ME/C agency. This circumstance places these entities in an ideal position to provide surveillance data regarding the epidemiology of drug-related deaths occurring within the jurisdiction of the agency. The ability to surveil for the distribution and determinants among drug-related deaths at the first point of contact enhances the capacity to recognize actionable trends at the local, state, and national levels, including the ability to identify secular (longer-term) trends among various drugs and population subgroups, as well as activity spikes (outbreaks) associated with high-potency formulations and drug combinations. In this article, we describe the development and implementation of an online website that provides public access to a wide array of drug-related death surveillance resources and tools. The website gives users access to a detailed dataset that includes information regarding specific drugs, demographic information pertaining to the decedent, and to investigational findings related to the circumstances of the death. A unique aspect of the database is that it is populated by ME/C agencies and accessed by the public with no intermediary agency, so that the lag time between the identification and investigation of the death as drug-related and community knowledge of the circumstances of the death is minimized. Wide dissemination of accurate drug death surveillance information in an easily accessible and customizable format promotes societal awareness of the drug death epidemic, but also provides information to public health, law enforcement, regulatory, and other community-based organizations that can benefit from the most up-to-date knowledge. We envision a national system of surveillance at the regional ME/C level that would allow for optimal information dissemination and sharing. Such a system would likely allow for more efficacious allocation of resources at the regional and national level.

Patterns and Trends in Accidental Poisoning Deaths: Pennsylvania's Experience 1979-2014.

INTRODUCTION: The purpose of this study was to examine county and state-level accidental poisoning mortality trends in Pennsylvania from 1979 to 2014. METHODS: Crude and age-adjusted death rates were formed for age group, race, sex, and county for accidental poisonings (ICD 10 codes X40-X49) from 1979 to 2014 for ages 15+ using the Mortality and Population Data System housed at the University of Pittsburgh. Rate ratios were calculated comparing rates from 1979 to 2014, overall and by sex, age group, and race. Joinpoint regression was used to detect statistically significant changes in trends of age-adjusted mortality rates. RESULTS: Rate ratios for accidental poisoning mortality in Pennsylvania increased more than 14-fold from 1979 to 2014. The largest rate ratios were among 35-44 year olds, females, and White adults. The highest accidental poisoning mortality rates were found in the counties of Southwestern Pennsylvania, those surrounding Philadelphia, and those in Northeast Pennsylvania near Scranton. CONCLUSIONS: The patterns and locations of accidental poisoning mortality by race, sex, and age group provide direction for interventions and policy makers. In particular, this study found the highest rate ratios in PA among females, whites, and the age group 35-44.

Correction: Patterns and Trends in Accidental Poisoning Deaths: Pennsylvania's Experience 1979-2014.

[This corrects the article DOI: 10.1371/journal.pone.0151655.].

Underrepresentation of heroin involvement in unintentional drug overdose deaths in Allegheny County, PA.

Drugs contributing to overdose deaths are listed on death certificates, but their validity is rarely studied. To assess the accuracy of "morphine" and "codeine" listings on death certificates for unintentional overdose deaths in Allegheny County, PA, investigative and laboratory reports were reviewed. Deaths were reclassified as heroin-related if documentation showed 6-monoacetylmorphine in blood or urine, "stamp bags" or drug paraphernalia at scene, history of heroin use, or track marks. Deaths were considered morphine-related if notes indicated morphine use, prescription, or morphine at scene, or codeine-related if the codeine blood level exceeded morphine. Of 112 deaths with morphine but not heroin listed on the death certificate, 74 met heroin criteria and 21 morphine criteria. Of 20 deaths with both morphine and heroin listed, only one met morphine criteria. Of 34 deaths with codeine listed, only five were attributed to codeine. Consideration of patient history, death scene evidence, and expanded toxicology testing may improve the accuracy of death certificate drug listings.

An in vitro chemoresponse assay defines a subset of colorectal and lung carcinomas responsive to cetuximab.

Cetuximab is a chimeric monoclonal antibody for the epidermal growth factor receptor (EGFR) that may provide benefit to select cancer patients; however, identification of the characteristics of those patients who may benefit from its use is not complete. The ChemoFx® drug response marker (DRM) is an in vitro assay that can provide drug response data on tumor specimens before any patient treatment is initiated. We determined the feasibility of using the ChemoFx DRM to test tumor samples for sensitivity to cetuximab. We exposed four non-small cell lung carcinoma (NSCLC) cell lines (H358, H520, HCC827, and H1666) to cetuximab and determined their sensitivity using the ChemoFx DRM and, in parallel, EGFR status using immunocytochemistry, Western blotting, and In-Cell Western (TM) analysis. We used the ChemoFx DRM to determine cetuximab sensitivity of primary NSCLC and colorectal tumor samples. The ChemoFx DRM distinguished between cetuximab-sensitive and -resistant cell lines. Cetuximab sensitivity was not dependent on EGFR mutational status; H358 cells were non-responsive to cetuximab yet contain wild-type EGFR, whereas H1666 cells were intermediately responsive to cetuximab and contain wild-type EGFR. HCC827 (EGFR-mutant) cells were intermediately responsive and, as expected, H520 cells (EGFR-null) were non-responsive to cetuximab. ChemoFx-determined cetuximab sensitivity of primary NSCLC and colorectal tumor samples was 9.0% and 7.5%, respectively. Use of the ChemoFx DRM is feasible for determining cetuximab sensitivity. The ChemoFx-determined cetuximab responses of primary NSCLC and colorectal tumor specimens were similar to published response rates of patients to treatment with cetuximab monotherapy.