The impacts of governing agency: A comparison of resources in the patchwork of medicolegal death investigation systems.

In the United States, medical examiners and coroners (MECs) fill critical roles within our public health and public safety systems. These professionals are primarily charged with determining the cause and manner of death as they investigate deaths and respond to associated scenes and mass fatalities and can also help identify trends in public health crises through medicolegal death investigations. Despite their instrumental role, they are organized in disparate systems with varying governing structures, functions, staffing, caseload, budget, and access to resources. This paper examines data from the 2018 Census of Medical Examiner and Coroners to evaluate MEC operations in the United States. The findings show that MEC offices' organizational and operational governance structures greatly influence resources, workloads, and access to information and services. Standalone MEC offices were generally better resourced than those affiliated with law enforcement, public health, forensic science, district attorneys, or other agencies.1.

Mass fatality and disaster response preparedness across medical examiner and coroner offices in the United States.

With the rise of mass fatalities and disasters, access to mass fatality and disaster planning trainings and resources available to medical examiners and coroners (MECs) in the United States should be reviewed. This paper provides a necessary update on the extent of access to these resources by analyzing data from the 2018 Census for Medical Examiner and Coroner Offices (CMEC). Results show that a high percentage of respondents have access to mass fatality and disaster planning trainings/resources; however, the access is disproportionate. Respondents in the Midwest and South-and those with smaller populations-have less access to resources, while agencies with larger budgets and more full-time staff have more access to resources. This paper discusses potential contributing factors for these disparities, but the data only begin to elucidate gaps in access to mass fatality and disaster planning trainings/resources for MECs and where further research should be conducted.

Understanding unidentified human remains investigations through the United States census data.

Each year, thousands of unidentified human remains (UHR) cases are reported in the U.S. Technological advances have greatly enhanced the forensic community's capacity and capability to solve UHR cases, but little is known about the extent to which these resources are used by medical examiners and coroners (MECs). Using public datasets, the study purpose is to describe the current state MEC system with respect to UHR cases, the resources used to investigate these cases, and the evidence retention polices in place. There was an overall decline in UHR cases reported between 2004 and 2018. Less than half of MECs in both study years reported having established written final disposition and evidence retention policies for UHR cases. National missing persons databases were underused. This study provides an important window into the present state of UHRs being handled by our Nation's MEC offices and the resources available to solve these difficult cases.

Reports of Adverse Events Associated with Use of Novel Psychoactive Substances, 2017-2020: A Review.

An important role of modern forensic and clinical toxicologists is to monitor the adverse events of novel psychoactive substances (NPS). Following a prior review from 2013 to 2016, this critical literature review analyzes and evaluates published case reports for NPS from January 2017 through December 2020. The primary objective of this study is to assist in the assessment and interpretation of these cases as well as provide references for confirmation methods. Chemistry, pharmacology, adverse events and user profiles (e.g., polypharmacy) for NPS are provided including case history, clinical symptoms, autopsy findings and analytical results. Literature reviews were performed in PubMed and Google Scholar for publications using search terms such as NPS specific names, general terms (e.g., 'designer drugs' and 'novel psychoactive substances'), drug classes (e.g., 'designer stimulants') and outcome-based terms (e.g., 'overdose' and 'death'). Government and website drug surveillance databases and abstracts published by professional forensic science organizations were also searched. Toxicological data and detailed case information were extracted, tabulated, analyzed and organized by drug category. Case reports included overdose fatalities (378 cases), clinical treatment and hospitalization (771 cases) and driving under the influence of drugs (170 cases) for a total of 1,319 cases providing details of adverse events associated with NPS. Confirmed adverse events with associated toxidromes of more than 60 NPS were reported including synthetic cannabinoid, NPS stimulant, NPS hallucinogen, NPS benzodiazepine and NPS opioid cases. Fifty of these NPS were reported for the first time in January 2017 through December 2020 as compared to the previous 4 years surveyed. This study provides insight and context of case findings described in the literature and in digital government surveillance databases and websites during a recent 4-year period. This review will increase the awareness of adverse events associated with NPS use to better characterize international emerging drug threats.

DNA backlog reduction strategy: Law enforcement agency partnerships for a successful biological screening laboratory.

In 2009, the Palm Beach County Sheriff's Office Forensic Biology Unit developed an innovative DNA backlog strategy to construct and operate a centralized biological processing laboratory (BPL) within a law enforcement agency, the Boca Raton Police Services Department. The BPL became fully operational in 2012 and obtained accreditation in 2017. This coordinated, multi-agency agreement resulted in a streamlined process exemplifying several benefits such as communicating timely testing results, decreasing the case turnaround time, and decreasing the DNA case backlog. This paper provides a summary of the necessary considerations of location, construction, personnel, and services when constructing a BPL, as well as, provides a comparison of initial completion dates and ultimate completion dates over a three-year period from 2016 to 2018. Three LEAs submitted 613 cases to the BPL commensurate with jurisdictional population. Performance metrics such as types and number of criminal cases screened; the number of samples forwarded for PBSO DNA testing; the turnaround time to handle, screen, or analyze a forensic sample; evidentiary samples; and the number of profiles entered into the Combined DNA Index System (CODIS) database are reported. For example, prior to this DNA backlog reduction strategy, the FBU was taking an average of 153 days to handle, screen, or analyze a forensic sample from submission to final report and there was a backlog of 679 cases. From 2016 to 2018, the total average turnaround time for BPL decreased from 30.5 to 19.6 days, (35.8% decrease); and the FBU Request turnaround time decreased from 153 to 80 days (35% decrease). Monitoring laboratory metrics demonstrate the efficacy of the DNA backlog reduction strategy. There are several takeaway lessons from this experience, including (1) engaging legal counsel early to outline necessary legal procedures and the timeline; (2) bringing all stakeholders "to the table" early to discuss expectations, as well as legal and operational responsibilities; and (3) creating a realistic timeline as well as establishing a comprehensive memorandum of understanding by which all parties understand their roles and responsibilities. Understanding laboratory and non-laboratory policy issues is critical to implementation success and the efficacy of a BPL as a DNA backlog reduction strategy.

A Census of Medicolegal Death Investigation in the United States: A Need to Determine the State of our Nation's Toxicology Laboratories and Their Preparedness for the Current Drug Overdose Epidemic.

In 2007, the Bureau of Justice Statistics reported on 2004 data collected from the Census of Medical Examiner and Coroner Offices (CMEC). The CMEC was one of the first comprehensive reports on the state of the medicolegal death investigation system in the United States and included information on administration, expenditure, workload, specialized death investigations, records and evidence retention, and resources. However, the report did not include responses on questions that were related to toxicology such as specimen retention and type of testing. The purpose of this publication is to provide the community with toxicology laboratory-specific responses from nearly 2000 medical examiner and coroner (MEC) offices. Data obtained from a BJS CMEC public use dataset for any remaining information that was not reported in the 2007 BJS report were evaluated specific to the operation of toxicology laboratories within a MEC office or specific to toxicology testing. The CMEC includes information on average operating budget for MEC offices with internal or external toxicology services, budget for toxicology/microbiology services, respondents' routine uses of toxicology analysis, toxicology specimen retention time, average turnaround times, use of computerized information management systems, and participation in federal data collections. These historical data begin to address the present state of our nation's toxicology laboratories within the medicolegal death investigation system and their preparedness for the current drug overdose epidemic.

The Opioid Epidemic: Moving Toward an Integrated, Holistic Analytical Response.

In many jurisdictions, public safety and public health entities are working together to enhance the timeliness and accuracy of the analytical characterization and toxicology testing of novel synthetic opioids. The improved sharing and early detection of these analytical data are intended to inform surveillance, interdiction efforts, patient intervention and treatment, all of which are critical to curbing the opioid epidemic. Forensic practitioners working to identify novel synthetic opioids struggle to provide timely results when encountering new or unknown substances, such as the fentanyl analogs. These compounds, which mimic heroin in pharmacologic effect but can be far more potent, are inconsistently present in chemical identification libraries, and are currently largely unavailable as reference materials for analytical comparison. Additionally, federal, state and local governments as well as nongovernmental organizations require potency, toxicity and potential-for-abuse data to evaluate the potential health risks of emerging drug threats. Subsequent scheduling efforts and criminal prosecutions also require these thorough drug characterization studies. Pilot programs have demonstrated that early communication of real-time drug toxicity and analytical data significantly impacts the successful response to emerging opioids. High-quality, real-time, national-level data on chemical composition, toxicological test data, drug toxicity and overdoses, and analysis of seized materials by law enforcement are needed to track drug trends. However, the USA still lacks a national system to coordinate and communicate toxicology, medical and medical examiner and coroner data with the broader medical and law enforcement communities. Opportunities to address these gaps as well as recent advancements collected through interagency efforts and technical workshops in the toxicology and analytical chemistry communities are presented here. Opportunities for partnership, increased communication and expanding best practices to move toward an integrated, holistic analytical response are also explored.

The hidden costs of the opioid crisis and the implications for financial management in the public sector.

The November 2017 release of the Council of Economic Advisers' White House report on the opioid crisis suggests that prior consideration of expenses severely underestimated the economic costs of the opioid crisis. When corrected for these losses, the annual cost from the opioid crisis leapt nearly 600%. The cost to the criminal justice system was estimated at $8 Billion of which $270 million is borne by crime laboratories. However, laboratory budgets have not grown at a rate capable of meeting this increased demand for forensic science services. The hidden costs of the opioid crisis borne by the forensic crime laboratories comes as funds are diverted in the laboratory to meet the increased demands for services in drug chemistry and toxicology. Dramatic increases in turnaround times across other areas of investigation continue to grow as the crisis accelerates.

The redesigned Forensic Research/Reference on Genetics-knowledge base, FROG-kb.

The Forensic Resource/Reference on Genetics-knowledge base (FROG-kb) web site was introduced in 2011 and in the five years since the previous publication ongoing research into how the database can better serve forensics has resulted in extensive redesign of the database interface and functionality. Originally designed as a prototype to support forensic use of single nucleotide polymorphisms (SNPs), FROG-kb provides a freely accessible web interface that facilitates forensic practice and can be useful for teaching and research. Based on knowledge gained through its use, the web interface has been redesigned for easier navigation through the multiple components. The site also has functional enhancements, extensive new documentation, and new reference panels of SNPs with new curated data. FROG-kb focuses on single nucleotide polymorphisms (SNPs) and provides reference population data for several published panels of individual identification SNPs (IISNPs) and several published panels of ancestry inference SNPs (AISNPs). For each of the various marker panels with reference population data, FROG-kb calculates random match probabilities (RMP) and relative likelihoods of ancestry for a user-entered genotype profile (either completely or partially specified). Example genotype profiles are available and the User's Manual presents interpretation guidelines for the calculations. The extensive documentation along with ongoing updates makes FROG-kb a comprehensive tool in facilitating use of SNPs in forensic practice and education. An overview of the new FROG-kb with examples and material explaining the results of its use are presented here.

Patterns of Marijuana Use in a 6-Month Pain Management Sample in the United States.

This study is a 6-month retrospective analysis of urine drug testing (UDT) data from a pain management population among specimens with clinician-ordered marijuana testing (N = 194 809). Descriptive statistics about the specimen positivity of clinician-ordered marijuana UDT are provided as well as other drug positivity. Specimens from men and adults aged 18 to 34 years had the highest prevalence rates of marijuana positivity. The prevalence of past-month marijuana use among a comparative national population was lower than the prevalence of positive marijuana tests in the UDT specimens by all characteristics. Among the specimens tested for illicit drugs and marijuana, 4.0% were positive for amphetamine, 2.8% were positive for cocaine, and 0.9% were positive for heroin. The most common prescription drugs listed were opioids (64.7%), benzodiazepines (20.5%), and antidepressants (19.9%). In sum, the findings reflect previous research showing high rates of marijuana use, illicit drug use, and prescription drug use in a pain management population.

Reports of Adverse Events Associated with Use of Novel Psychoactive Substances, 2013-2016: A Review.

Novel psychoactive substances (NPS) represent significant analytical and interpretive challenges to forensic and clinical toxicologists. Timely access to case reports and reports of adverse incidents of impairment or toxicity is imperative to clinical diagnosis and treatment, as well as to interpretation of forensic results. Delays in identifying the presence of a novel intoxicating agent have significant consequences for public health and public safety. Adverse effects of intoxications with novel cannabinoids, stimulants, hallucinogens, benzodiazepines and opioids spanning January 2013 through December 2016 as reported in emergency departments, death investigations, impaired driving cases and other forensic contexts are the subject of this review. Discussion of the chemistry, pharmacology and adverse events associated with novel drug classes is summarized and described within. Adverse effects or symptoms associated with ingestion of more than 45 NPS have been abstracted and summarized in tables, including demographics, case history, clinical or behavioral symptoms, autopsy findings and drug confirmations with quantitative results when provided. Based on these findings and gaps in the available data, we provide recommendations for future toxicological testing of these evolving substances. These include development and management of a national monitoring program to provide real-time clinical and toxicological data, confirmed analytically, on emerging drugs and their known toxidromes and side effect profiles. Increased efforts should be made to analytically confirm the agents responsible for clinical intoxications involving adverse events in emergency department admissions or hospitalizations. Evidence-based community preparedness among analytical laboratories gained through active communication and sharing of toxicological findings and trends in NPS is imperative to assist in enabling early detection of new drugs in forensic and clinical populations.

Cocaine analytes in human hair: evaluation of concentration ratios in different cocaine sources, drug-user populations and surface-contaminated specimens.

Hair specimens were analyzed for cocaine (COC), benzoylecgonine (BE), cocaethylene (CE) and norcocaine (NCOC) by liquid chromatography-tandem mass spectrometry. Drug-free hair was contaminated in vitro with COC from different sources with varied COC analyte concentrations. Results were compared to COC analyte concentrations in drug users' hair following self-reported COC use (Street) and in hair from participants in controlled COC administration studies (Clinical) on a closed clinical research unit. Mean ± standard error analyte concentrations in Street drug users' hair were COC 27,889 ± 7,846 (n = 38); BE 8,132 ± 2,523 (n = 38); CE 901 ± 320 (n = 20); NCOC 345 ± 72 pg/mg (n = 32). Mean percentages to COC concentration were BE 29%, CE 3% and NCOC 1%. Concentrations in hair were lower for Clinical participants. COC contamination with higher CE, BE or NCOC content produced significantly higher concentrations (P = 0.0001) of all analytes. CE/COC and NCOC/COC ratios did not improve differentiation of COC use from COC contamination. COC concentrations in illicit and pharmaceutical COC affect concentrations in contaminated hair. Criteria for distinguishing COC use from contamination under realistic concentrations were not significantly improved by adding CE and NCOC criteria to COC cutoff concentration and BE/COC ratio criteria. Current criteria for COC hair testing in many forensic drug-testing laboratories may not effectively discriminate between COC use and environmental COC exposure.

A comparison of the validity of gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry analysis of urine samples II: amphetamine, methamphetamine, (±)-3,4-methylenedioxyamphetamine, (±)-3,4-methylenedioxymethamphetamine, (±)-3,4-methylenedioxyethylamphetamine, phencyclidine, and (±)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol.

On November 25, 2008, the U.S. Department of Health and Human Services posted a final notice in the Federal Register authorizing the use of liquid chromatography-tandem mass spectrometry (LC-MS-MS) and other technologies in federally regulated workplace drug testing (WPDT) programs. To support this change, it is essential to explicitly demonstrate that LC-MS-MS, as a technology, can produce results at least as valid as gas chromatography (GC)-MS, the long-accepted standard in confirmatory analytical technologies for drugs of abuse. A series of manufactured control urine samples (n = 10 for each analyte) containing amphetamine, methamphetamine, (±)-3,4-methylenedioxyamphetamine, (±)-3,4-methylenedioxymethamphetamine, (±)-3,4-methylenedioxyethylamphetamine, phencyclidine, and (±)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol at concentrations ranging from 10% to 2000% of federal cutoffs were analyzed with replication by five federally regulated laboratories using GC-MS and at RTI International using LC-MS-MS. Interference samples as described in the National Laboratory Certification Program 2009 Manual were analyzed by GC-MS and LC-MS-MS as well as previously confirmed urine specimens of WPDT origin. Matrix effects were assessed for LC-MS-MS. Results indicated that LC-MS-MS analysis produced results at least as precise, accurate, and specific as GC-MS for the analytes investigated in this study. Matrix effects, while evident, could be controlled by the use of matrix-matched controls and calibrators with deuterated internal standards.

A comparison of the validity of gas chromatography- mass spectrometry and liquid chromatography- tandem mass spectrometry analysis of urine samples for morphine, codeine, 6-acetylmorphine, and benzoylecgonine.

On November 25, 2008, the U.S. Department of Health and Human Services posted a final notice in the Federal Register authorizing the use of liquid chromatography-tandem mass spectrometry (LC-MS-MS) and other technologies in federally regulated workplace drug testing (WPDT) programs. These rules are expected to become effective in May 2010. To support this change, it is essential to explicitly demonstrate that LC-MS-MS as a technology can produce results at least as valid as gas chromatography-mass spectrometry (GC-MS), the long-accepted standard in confirmatory analytical technologies for drugs of abuse and currently the only confirmatory method allowed for use in support of federally regulated WPDT programs. A series of manufactured control urine samples (n = 10 for each analyte) containing benzoylecgonine, morphine, codeine, and 6-acetylmorphine at concentrations ranging from 10% to 2000% of federal cutoffs were analyzed with replication by five federally regulated laboratories using GC-MS (five replicate analyses per lab) and at RTI International using LC-MS-MS (10 replicate analyses). Interference samples as described in the National Laboratory Certification Program 2009 Manual were also analyzed by both GC-MS and LC-MS-MS. In addition, matrix effects were assessed for LC-MS-MS, and both analytical technologies were used to analyze previously confirmed urine specimens of WPDT origin. Results indicated that LC-MS-MS analysis produced results at least as precise, accurate, and specific as GC-MS for the analytes investigated in this study. Matrix effects, while evident, could be controlled by the use of matrix-matched controls and calibrators with deuterated internal standards. LC-MS-MS data parameters, such as retention time and product ion ratios, were highly reproducible.

External contamination of hair with cocaine: evaluation of external cocaine contamination and development of performance-testing materials.

The National Laboratory Certification Program undertook an evaluation of the dynamics of external contamination of hair with cocaine (COC) while developing performance testing materials for Federal Drug-Free Workplace Programs. This characterization was necessary to develop performance materials that could evaluate the efficacy of hair testing industry's decontamination procedures. Hair locks (blonde to dark brown/black) from five different individuals were contaminated with cocaine HCl. Hair locks were then treated with a synthetic sweat solution and hygienic treatments to model real-life conditions. Hair locks were shampooed daily (Monday through Friday) for 10 weeks, and samples of the hair locks were analyzed for COC, benzoylecgonine (BE), cocaethylene (CE), and norcocaine (NCOC). Three commercial analytical laboratories analyzed samples under three protocols: no decontamination procedure, individual laboratory decontamination, or decontamination by an extended buffer procedure at RTI International. Results indicated substantial and persistent association of all four compounds with all hair types. Hair that was not decontaminated had significantly greater quantities of COC and BE than did hair that was decontaminated. The only hair samples below detection limits for all four compounds were those decontaminated 1 h after contamination. Additionally, BE/COC ratios increased significantly over the 10-week study (regardless of decontamination treatment). From 21 days postcontamination until the end of the study, the mean BE/COC ratio for all hair types exceeded 0.05, the proposed Federal Mandatory Guidelines requirement. The largest variability in results was observed for samples decontaminated by participant laboratories. This suggests that current laboratory decontamination strategies will increase variability of performance testing sample results. None of the decontamination strategies used in the study were effective at removing all contamination, and some of the contaminated hair in this study would have been reported as positive for cocaine use based on the proposed Federal Mandatory Guidelines.

Postmortem tissue distribution of atomoxetine following fatal and nonfatal doses--three case reports.

Atomoxetine (Strattera, Lilly) is a selective norepinephrine reuptake inhibitor (SNRI) prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. It is the first nonstimulant drug-therapy option for ADHD. Three case reports are presented in which atomoxetine was detected in two individuals who died from causes unrelated to the drug and a third from the intentional ingestion of atomoxetine and other drugs. In addition, a brief description of the pharmacokinetics and side effects of atomoxetine are given. Postmortem fluid and tissue concentrations of atomoxetine were as follows: aortic blood, <0.1-8.3 mg/L; femoral blood, 0.33-5.4 mg/L; vitreous humor, 0.1-0.96 mg/L; bile, 1.0-33 g/L; urine, <0.1 mg/L; liver, <0.44-29 mg/kg; and gastric contents, 0.0097-16.8 mg total. Autopsy findings in the two cases in which death was not attributed to drug toxicity included arrhythmogenic right ventricular dysplasia and hypertrophic cardiomyopathy. The analytical method utilized was a modified basic drug, liquid-liquid procedure followed by gas chromatography/mass spectrometry and nitrogen phosphorous detection. Atomoxetine can be considered nontoxic at whole blood and liver concentrations below 1.3 mg/L and 5 mg/kg, respectively.

Postmortem distribution of tramadol, amitriptyline, and their metabolites in a suicidal overdose.

A case report involving a 34-year-old white male who was found dead at home by his roommate is presented. At the time of his death, he was being treated with tramadol/acetaminophen, metaxalone, oxycodone, and amitriptyline. The decedent's mother stated that he had been taking increasing amounts of pain medication in order to sleep at night. There were no significant findings at autopsy; however, toxicology results supported a cause and manner of death resulting from suicidal mixed tramadol and amitriptyline toxicity. This case reports the tissue and fluid distribution of tramadol, amitriptyline, and their metabolites in an acutely fatal ingestion in an effort to document concentrations of these analytes in 12 matrices with respect to one another to assist toxicologists in difficult interpretations.

Metaxalone (Skelaxin)-related death.

The case history and toxicological findings of a fatal multi-drug overdose involving metaxalone (Skelaxin) are presented. Gas-liquid chromatography with flame-ionization detection and gas chromatography-mass spectrometry were used to determine the following drug concentrations (mg/L) in aortic blood: 19 mg/L metaxalone; 190 mg/L acetaminophen; 0.28 mg/L hydrocodone; and < 0.1 mg/L diazepam, nordiazepam, amitriptyline, and nortriptyline. The following concentrations of metaxalone were reported in alternate specimens: 17 mg/L in femoral blood; 44 mg/L in bile; 70 mg/kg in liver; 7 mg/L in urine; 202 mg/kg in gastric contents; and 14 mg/L in vitreous humor. These concentrations were determined using both direct extraction and the method of standard addition. The quantitative results obtained by both procedures were in good agreement. Because of the limited information published on metaxalone toxicity, the pathologist assigned the manner and cause of death as accidental acute hydrocodone intoxication. Four additional cases in which metaxalone was present were analyzed for comparison. Two cases were probable drug-related deaths and had metaxalone aorta blood concentrations of 18 and 11 mg/L. The other two cases had therapeutic metaxalone concentrations in the aortic blood of < 0.75 and 2.1 mg/L.