scholarly journals The Elephant in the Room

2018 ◽  
Vol 8 (3) ◽  
pp. 729-737 ◽  
Author(s):  
Rebecca M. Wilcoxon ◽  
Owen L. Middleton ◽  
Sarah E. Meyers ◽  
Julie Kloss ◽  
Sara A. Love
Keyword(s):  
Substance Abusers ◽  
Forensic Toxicology ◽  
Opioid Overdose ◽  
Definitive Evidence ◽  
Additional Information ◽  
Hennepin County ◽  
Low Concentrations ◽  
Heroin Intoxication ◽  
Drug Paraphernalia ◽  
Medical Examiners

Over a three-month period in early 2017, the Hennepin County Medical Examiner’s Office investigated nine apparent opioid toxicity deaths that occurred in three separate urban, suburban, and rural counties in our jurisdiction. All decedents were known substance abusers and had reportedly recently used heroin; most were found with drug paraphernalia. Complete autopsies variably showed classic stigmata of opioid overdose with no significant injury or natural disease to explain death. Initial toxicology screens failed to identify heroin or other narcotic substances. Several cases were presumptively positive for fentanyl by immunoassay, yet failed to confirm positive for fentanyl. Following American Board of Forensic Toxicology reporting standards, these cases were reported as negative for fentanyl by the laboratory. Due to the discrepant scene and toxicology findings suggestive of an opioid toxicity death, further discussion between the medical examiners and toxicologists prompted additional testing at a referral laboratory. This resulted in quantifiable blood carfentanil in all cases (mean 0.26 ng/mL, range 0.12 – 0.64 ng/mL). Cointoxicants included ethanol (n=2), methamphetamine (n=3), benzodiazepines (n=3), and cocaine (n=1). No case had definitive evidence of acute heroin intoxication, but two cases had low concentrations of morphine present (0.03 and 0.06 ng/mL), and two others had 6-monoacetyl morphine in the urine without morphine in the blood, suggesting recent use. All deaths were certified as accidental acute or mixed carfentanil toxicity. These cases present additional information about carfentanil-related deaths and highlight the importance of collaboration between forensic pathologists and toxicologists.

Microtubule nucleation sequence studied by time-resolved x-ray scattering and electron microscopy

1983 ◽  
Vol 41 ◽  
pp. 766-767
Author(s):  
Eva-Maria Mandelkow ◽  
Eckhard Mandelkow ◽  
Joan Bordas
Keyword(s):  
Electron Microscopy ◽  
Dynamic Equilibrium ◽  
Time Resolved ◽  
X Ray ◽  
Additional Information ◽  
X Ray Scattering ◽  
Low Concentrations ◽  
Microtubule Growth ◽  
Ray Patterns ◽  
Ray Scattering

When a solution of microtubule protein is changed from non-polymerising to polymerising conditions (e.g. by temperature jump or mixing with GTP) there is a series of structural transitions preceding microtubule growth. These have been detected by time-resolved X-ray scattering using synchrotron radiation, and they may be classified into pre-nucleation and nucleation events. X-ray patterns are good indicators for the average behavior of the particles in solution, but they are difficult to interpret unless additional information on their structure is available. We therefore studied the assembly process by electron microscopy under conditions approaching those of the X-ray experiment. There are two difficulties in the EM approach: One is that the particles important for assembly are usually small and not very regular and therefore tend to be overlooked. Secondly EM specimens require low concentrations which favor disassembly of the particles one wants to observe since there is a dynamic equilibrium between polymers and subunits.

scholarly journals Retrieval of ammonia from ground-based FTIR solar spectra

2015 ◽  
Vol 15 (22) ◽  
pp. 12789-12803 ◽  
Author(s):  
E. Dammers ◽  
C. Vigouroux ◽  
M. Palm ◽  
E. Mahieu ◽  
T. Warneke ◽  
...  
Keyword(s):  
Total Error ◽  
High Surface ◽  
Vertical Gradient ◽  
Trace Gas ◽  
Seasonal Cycles ◽  
Random Errors ◽  
Time Resolved ◽  
Additional Information ◽  
Systematic Uncertainties ◽  
Low Concentrations

Abstract. We present a retrieval method for ammonia (NH3) total columns from ground-based Fourier transform infrared (FTIR) observations. Observations from Bremen (53.10° N, 8.85° E), Lauder (45.04° S, 169.68° E), Réunion (20.9° S, 55.50° E) and Jungfraujoch (46.55° N, 7.98° E) were used to illustrate the capabilities of the method. NH3 mean total columns ranging 3 orders of magnitude were obtained, with higher values at Bremen (mean of 13.47 × 1015 molecules cm−2) and lower values at Jungfraujoch (mean of 0.18 × 1015 molecules cm−2). In conditions with high surface concentrations of ammonia, as in Bremen, it is possible to retrieve information on the vertical gradient, as two layers can be distinguished. The retrieval there is most sensitive to ammonia in the planetary boundary layer, where the trace gas concentration is highest. For conditions with low concentrations, only the total column can be retrieved. Combining the systematic and random errors we have a mean total error of 26 % for all spectra measured at Bremen (number of spectra (N) = 554), 30 % for all spectra from Lauder (N = 2412), 25 % for spectra from Réunion (N = 1262) and 34 % for spectra measured at Jungfraujoch (N = 2702). The error is dominated by the systematic uncertainties in the spectroscopy parameters. Station-specific seasonal cycles were found to be consistent with known seasonal cycles of the dominant ammonia sources in the station surroundings. The developed retrieval methodology from FTIR instruments provides a new way of obtaining highly time-resolved measurements of ammonia burdens. FTIR-NH3 observations will be useful for understanding the dynamics of ammonia concentrations in the atmosphere and for satellite and model validation. It will also provide additional information to constrain the global ammonia budget.

Michigan system for opioid overdose surveillance

2021 ◽  
pp. injuryprev-2020-043882
Author(s):  
Jason Goldstick ◽  
Amanda Ballesteros ◽  
Carol Flannagan ◽  
Jessica Roche ◽  
Carl Schmidt ◽  
...  
Keyword(s):  
Surveillance System ◽  
Opioid Overdose ◽  
Web Based ◽  
Fatal Overdose ◽  
Control And Prevention ◽  
User Acceptability ◽  
New Feature ◽  
Medical Examiners ◽  
Data Summaries ◽  
Surveillance System Evaluation

Community rapid response may reduce opioid overdose harms, but is hindered by the lack of timely data. To address this need, we created and evaluated the Michigan system for opioid overdose surveillance (SOS). SOS integrates suspected fatal overdose data from Medical Examiners (MEs), and suspected non-fatal overdoses (proxied by naloxone administration) from the Michigan Emergency Medical Services (EMS) into a web-based dashboard that was developed with stakeholder feedback. Authorised stakeholders can view approximate incident locations and automated spatiotemporal data summaries, while the general public can view county-level summaries. Following Centers for Disease Control and Prevention (CDC) surveillance system evaluation guidelines, we assessed simplicity, flexibility, data quality, acceptability, sensitivity, positive value positive (PVP), representativeness, timeliness and stability of SOS. Data are usually integrated into SOS 1-day postincident, and the interface is updated weekly for debugging and new feature addition, suggesting high timeliness, stability and flexibility. Regarding representativeness, SOS data cover 100% of EMS-based naloxone adminstrations in Michigan, and receives suspected fatal overdoses from MEs covering 79.1% of Michigan’s population, but misses those receiving naloxone from non-EMS. PVP of the suspected fatal overdose indicator is nearly 80% across MEs. Because SOS uses pre-existing data, added burden on MEs/EMS is minimal, leading to high acceptability; there are over 300 authorised SOS stakeholders (~6 new registrations/week) as of this writing, suggesting high user acceptability. Using a collaborative, cross-sector approach we created a timely opioid overdose surveillance system that is flexible, acceptable, and is reasonably accurate and complete. Lessons learnt can aid other jurisdictions in creating analogous systems.

Results of a nine-laboratory survey of forensic toxicology proficiency.

1976 ◽  
Vol 22 (6) ◽  
pp. 843-846 ◽  
Author(s):  
E C Dinovo ◽  
L A Gottschalk
Keyword(s):  
Proficiency Testing ◽  
Forensic Toxicology ◽  
Significant Source ◽  
Limits Of Detection ◽  
Accuracy And Precision ◽  
Laboratory Procedures ◽  
Laboratory Survey ◽  
Drug Death ◽  
Medical Examiners ◽  
Source Of Error

Abstract Toxicological determinations are crucial to coroners' or medical examiners' judgments that drugs are significantly involved in a death. However, differences in laboratory procedures, thoroughness of screening, and limits of detection may result in artifactual differences in the toxicological results and the subsequent interpretations of them. To test this possibility, we conducted a toxicology proficiency-testing survey of nine collaborating laboratories. The results for the proficiency samples point out starting interlaboratory differences in accuracy and precision of detection of drugs. These observed variations in toxicological proficiency may introduce a significant source of error in drug-death statistics and in epidemiological deductions based on these statistics.

A Mechanism-Based Forensic Investigation into the Postmortem Redistribution of Morphine

2019 ◽  
Vol 44 (3) ◽  
pp. 256-262
Author(s):  
Jessica Gleba ◽  
Jonghan Kim
Keyword(s):  
Forensic Toxicology ◽  
Postmortem Interval ◽  
Blood Levels ◽  
Postmortem Redistribution ◽  
Reference Information ◽  
Drug Concentrations ◽  
Liquid Chromatography Tandem Mass ◽  
Heart Blood ◽  
Femoral Blood ◽  
Medical Examiners

Abstract The interpretation of postmortem drug levels is complicated by the change in drug blood levels during the postmortem period, a phenomenon known as postmortem drug redistribution. We investigated the postmortem redistribution (PMR) of morphine, morphine-3-glucuronide and normorphine in the rat. Morphine (10 mg/kg) was intravenously injected into rats, followed by euthanasia 1 h post-injection. The carcasses were placed in a supine position at room temperature, and tissues including heart blood, femoral blood, liver, lung and brain were collected at different time points: 0, 8, 16 or 24 h postmortem. The samples were analyzed with a validated (following modified Scientific Working Group for Forensic Toxicology (SWGTOX) (20) guidelines) liquid chromatography–tandem mass spectrometry method. The use of a mechanism-based approach (involving the used set doses of drug with the study performed in controlled environment) to assess PMR using systematic and statistical analyses provides important information that has not previously been presented in PMR literature. While previous human studies focus on central to peripheral ratios as well as peripheral to tissue ratio, this work focused on the change in morphine and metabolite concentrations over the course of the postmortem interval in relation to each other in addition to the comparison to additional matrices at each postmortem interval. Postmortem redistribution was identified in several tissues across the postmortem interval; however, there was minimal statistical difference observed among each matrix at a given postmortem interval with the exception of normorphine and morphine-3-glucuronide. Combined, our study provides a valuable resource and reference information that can aide toxicologists, medical examiners or coroners when assessing postmortem drug concentrations of morphine and metabolites when they are making determinations of cause of death.

Case Report: Synthetic Cannabinoid Deaths in State of Florida Prisoners

2020 ◽  
Vol 44 (3) ◽  
pp. 298-300 ◽  
Author(s):  
Jessica A Hvozdovich ◽  
Chris W Chronister ◽  
Barry K Logan ◽  
Bruce A Goldberger
Keyword(s):  
Quantitative Methods ◽  
Synthetic Cannabinoids ◽  
Forensic Toxicology ◽  
University Of Florida ◽  
New Methods ◽  
Liquid Chromatography Tandem Mass ◽  
Blood And Urine Samples ◽  
The University ◽  
Medical Examiners ◽  
Emerging Substances

Abstract Between March 2017 and November 2018, 54 prisoner fatal overdose cases submitted to the University of Florida Forensic Toxicology Laboratory involved synthetic cannabinoids including 5F-ADB, FUB-AMB, 5F-AMB, MDMB-FUBINACA and AB-CHMINACA. Analysis of blood and urine samples was performed at NMS Labs (Horsham, PA) by liquid chromatography/tandem mass spectrometry screening, confirmatory and quantitative methods validated according to Scientific Working Group for Forensic Toxicology guidelines. This work highlights the importance of effective communication between toxicologists and medical examiners/coroners, and the value of public-private partnerships to provide coverage while laboratories work to update instrumentation and validate their own new methods to keep up with the challenges of emerging substances.

scholarly journals Coverage with Evidence Development: Applications and issues

2010 ◽  
Vol 26 (1) ◽  
pp. 79-85 ◽  
Author(s):  
Paul Trueman ◽  
David L. Grainger ◽  
Kristen E. Downs
Keyword(s):  
Medical Literature ◽  
New Technology ◽  
Health Technology ◽  
Definitive Evidence ◽  
Additional Information ◽  
Coverage With Evidence Development ◽  
History Of ◽  
Future Negotiation ◽  
Development Applications ◽  
Critical Challenge

Objectives: The aim of this study was to describe the current issues surrounding Coverage with Evidence Development (CED). CED is characterized by restricted coverage for a new technology in parallel with targeted research when the stated goal of the research or data collection is to provide definitive evidence for the clinical or cost-effectiveness impact of the new technology.Methods: Presented here is information summarized and interpreted from presentations and discussions at the 2008 Health Technology Assessment International (HTAi) meeting and additional information from the medical literature. This study describes the differences between CED and other conditional coverage agreements, provides a brief history of CED, describes real-world examples of CED, describes the areas of consensus between the stakeholders, discusses the areas for future negotiation between stakeholders, and proposes criteria to assist stakeholders in determining when CED could be appropriate.Results: Payers could interpret the evidence obtained from a CED program either positively or negatively, and a range of possible changes to the reimbursement status of the new technology may result. Striking an appropriate balance between the demands for prompt access to new technology and acknowledging that some degree of uncertainty will always exist is a critical challenge to the uptake of this innovative form of conditional coverage.Conclusions: When used selectively for innovative procedures, pharmaceuticals, or devices in the appropriate disease areas, CED may provide patients access to promising medicines or technologies while data to minimize uncertainty are collected.

scholarly journals Opioid Drug Death Investigations

2017 ◽  
Vol 7 (1) ◽  
pp. 50-59 ◽  
Author(s):  
Daniel Morgan
Keyword(s):  
Public Health Surveillance ◽  
Health Surveillance ◽  
Steady Increase ◽  
Opioid Overdose ◽  
The Past ◽  
Drug Death ◽  
Death Investigation ◽  
Medical Examiners ◽  
Medicolegal Death Investigation

Opioid-related deaths have transitioned over the past 15 years, beginning with a steady increase in the incidence of fatal prescription overdoses, followed by a dramatic increase in deaths caused by illicit opioids, namely heroin and fentanyl. These trends in drug-related deaths are identified by medical examiners and coroners who serve an important role in public health surveillance. Medicolegal death investigators, being first responders, often recognize spates of drug-related deaths in real time. While few jurisdictions are unaffected by the epidemic, some medicolegal death investigators may have less experience detecting fatal opioid overdoses. This review will outline many of the medical, behavioral, and physical indicators of a deadly prescription or illicit opioid overdose. All aspects of a thorough medicolegal death investigation will be discussed, including the proper documentation of the scene and evidence handling. Investigative questions and follow-up procedures will also be reviewed.

scholarly journals U-47700 and Its Analogs: Non-Fentanyl Synthetic Opioids Impacting the Recreational Drug Market

2020 ◽  
Vol 10 (11) ◽  
pp. 895
Author(s):  
Michael H. Baumann ◽  
Graziella Tocco ◽  
Donna M. Papsun ◽  
Amanda L. Mohr ◽  
Melissa F. Fogarty ◽  
...  
Keyword(s):  
Medicinal Chemistry ◽  
Health And Safety ◽  
Forensic Toxicology ◽  
Drug Market ◽  
Lessons Learned ◽  
Opioid Overdose ◽  
Recreational Drug ◽  
Drug Markets ◽  
Counterfeit Drug ◽  
Synthetic Opioids

The recreational use of opioid drugs is a global threat to public health and safety. In particular, an epidemic of opioid overdose fatalities is being driven by illicitly manufactured fentanyl, while novel synthetic opioids (NSOs) are appearing on recreational drug markets as standalone products, adulterants in heroin, or ingredients in counterfeit drug preparations. Trans-3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700) is a prime example of a non-fentanyl NSO that is associated with numerous intoxications and fatalities. Here, we review the medicinal chemistry, preclinical pharmacology, clandestine availability, methods for detection, and forensic toxicology of U-47700 and its analogs. An up-to-date summary of the human cases involving U-47700 intoxication and death are described. The evidence demonstrates that U-47700 is a potent μ-opioid receptor agonist, which poses a serious risk for overdosing and death. However, most analogs of U-47700 appear to be less potent and have been detected infrequently in forensic specimens. U-47700 represents a classic example of how chemical entities from the medicinal chemistry or patent literature can be diverted for use in recreational drug markets. Lessons learned from the experiences with U-47700 can inform scientists, clinicians, and policymakers who are involved with responding to the spread and impact of NSOs.

Opioid overdoses: Emerging clinical challenges

2020 ◽  
Vol 16 (2) ◽  
pp. 151-154
Author(s):  
Andrea Ramos, BSN, RN, MSPH ◽  
Lina Sarmiento, RN ◽  
Noella Dietz, PhD ◽  
Nelson Cordero, MD ◽  
Ximena Levy, MD-MPH ◽  
...  
Keyword(s):  
Emergency Department ◽  
Medical Records ◽  
Case Series ◽  
Opioid Overdose ◽  
Broward County ◽  
Pain Medications ◽  
Heroin Intoxication ◽  
And Gender ◽  
Percent Female

Objective: Analysis of a large consecutive case series of cases brought to an Emergency Department (ED).Design: Retrospective chart review.Setting: Emergency Department in Broward County, Florida.Patients: Medical records of patients with registered diagnoses of opioid overdose in 2016 and 2017.Outcomes: Demographics, toxicology results, mental-health comorbidities, use/response to naloxone, and hospital disposition.Results: Seven hundred and seventy nine opioid-overdose cases were identified (35 percent female, 65 percent male; age 36.2). Heroin intoxication was registered in 77 percent of discharge diagnoses, and 17.7 percent were prescription pain medications. Urine samples were collected in 39 percent and 81.5 percent of patients received naloxone (mean dose 4.0 mg ± 2.2). Sixty-five percent of cases were discharged home, 17.5 percent left the ED against medical advice, and 17.5 percent were admitted to the hospital/intensive care unit/behavioral unit.Conclusion: There is an alarming number of visits to the ED due to opioid overdoses with differences in age and gender. Clinicians are facing diagnostic, treatment and follow-up challenges for the management of these cases.  

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