The Forensic Perspective of Infectious Endocarditis: A Retrospective Study With Recommendations for the Future.

Increasing rates of infectious endocarditis (IE) are well-described in the United States and worldwide, yet forensic literature regarding IE is sparse. Autopsy databases may help identify subsets of patients at increased risk of mortality. We reviewed all deaths due to IE in our office between 2010 and 2022 (with full autopsy performed) and found 29. The average age was 44 years. Manners of death included natural (69%), accident (28%), and homicide (3%). For all accidental deaths, acute intoxication was included in either part I or II. The aortic valve was most affected (62%), followed by tricuspid (28%) and mitral (24%). Seventy-six percent of affected valves were native, and 24% were prosthetic. Common risk factors included intravenous drug use (48%) and chronic ethanolism (21%). No sustained increase in deaths due to IE was identified. These data show marked differences from clinical literature, including a lower average age and higher incidence of substance use disorders, and it is unlikely selection bias is the sole reason. There was inconsistency in death certification, most notably by not including pertinent IE risk factors. Improving consistency and quality of IE death certification will aid in detecting regional trends and assist multi-institutional collaboration efforts.

The National Association of Medical Examiners Position Paper on the Investigation and Certification of Pediatric Deaths From Environmental Neglect.

ABSTRACT: Pediatric deaths that occur because of environmental neglect often involve 4 common scenarios: (1) hyperthermia due to environmental exposure, (2) ingestion of an accessible drug or poison, (3) unwitnessed/unsupervised drownings, and (4) unsafe sleep practices. Given the same fact pattern, the manner of death will vary from accident to homicide to undetermined based on local custom and/or the certifier's training and experience. Medical examiner/coroner death certifications are administrative public health determinations made for vital statistical purposes. Because the manner of death is an opinion, it is understandable that manner determinations may vary among practitioners. No prosecutor, judge, or jury is bound by the opinions expressed on the death certificate. This position paper does not dictate how these deaths should be certified. Rather, it describes the challenges of the investigations and manner determinations in these deaths. It provides specific criteria that may improve consistency of certification. Because pediatric deaths often are of public interest, this paper provides the medical examiner/coroner with a professional overview of such manner determination issues to assist various stakeholders in understanding these challenges and variations.

The Need to Rethink Harm Reduction for People Using Drugs Alone to Reduce Overdose Fatalities.

Background: During the ongoing opioid epidemic, Cuyahoga County (second largest in Ohio) reported overdose mortality rates (54/per 100,000) higher than the national average. Prior research demonstrates that people who use drugs often use alone but there is minimal research on people who died of overdose while using alone. The objective of this study is to examine sociodemographic, toxicologic, and injury characteristics, and emergency medical response to overdose decedents who died using drugs alone. Method: Data from the Cuyahoga County Medical Examiner's Office (2016-2020, N = 2944) on unintentional overdose deaths in adults was tabulated including socio-demographic, toxicologic, and injury-related information. Decedents using drugs alone were identified and compared to those not using alone via Chi-square and Fisher's exact tests. We further fit a multivariate logistic regression model to evaluate socio-demographic, toxicologic, and injury-related factors associated with increased odds of using alone. All results are reported with 95% confidence intervals. Result: Among decedents, 75% (n = 2205) were using drugs alone. Decedents using alone were more likely to be using drugs at home (p = 0.001) or be found dead at the scene (p < 0.001) and less likely to receive naloxone (p < 0.001) have other person/bystander, not using, present (p = 0.002). Using drugs at home (aOR = 1.61[1.19-2.20]) was associated with higher odds of using alone; and being married (aOR = 0.57[0.38-0.86]), having history of illicit drug use (aOR = 0.25[0.08-0.81]) and other person present, who was not using (aOR = 0.58[0.42-0.79]) were associated with lower odds of using alone. Conclusion: New harm reduction approaches targeting people using drugs alone are needed to reduce overdose deaths.

A case study for local data surveillance in opioid overdose fatalities in Cuyahoga County, OH 2016-2020.

Introduction: Fentanyl and fentanyl analogs have increased the overdose mortality rates in the United States, significantly impacting states like Ohio. We examined carfentanil overdose deaths, other contributing Cause of Death (COD) drugs, and drug seizure trends from 2016 to 2020 in Northeast Ohio. Materials and methods: We studied death investigation data from the Cuyahoga County, Ohio Medical Examiner's Office (CCMEO) of all fatal accidental opioid overdoses as well as drug seizure data from Cuyahoga County Regional Forensic Science Laboratory (CCRFSL). We also compared decedents' race, gender, age, residential locality, drugs contributing to the COD in opioid cases, and for carfentanil, fentanyl, and cocaine seizures in Cuyahoga County from 2016 to 2020 (N = 2948). Results: Decedents' had an average of three different drugs contributing to their COD. A bimodal carfentanil spike was observed in fatal accidental overdoses in Cuyahoga County for the years 2017 and 2019. Decedents in urban residency, who were Non-Hispanic, White and younger, significantly predicted the presence of carfentanil contributing to the COD. In 2020, decedents who were Black and older were significantly associated with cocaine contributing to the COD. Carfentanil and carfentanil-related overdoses were significantly correlated. Discussion: The pervasiveness of illicitly manufactured fentanyl and fentanyl analog (e.g., carfentanil) mixtures with other drugs are changing the demographics of persons who fatally overdose in Cuyahoga County, OH. Significant trending shifts can also be observed for the presence of carfentanil in decedent and seizure county data. Conclusions: Local data of drug-related overdose deaths and drug seizures from a medical examiner's office and affiliated forensic laboratory lab can be used for timely public health surveillance, and informing prevention, and intervention at the county level.

Thoracic Aortic Aneurysm and Dissection: Review and Recommendations for Evaluation.

ABSTRACT: Aortic dissection and rupture (collectively termed "sudden aortic death") are commonly encountered by forensic pathologists, with an estimated incidence at autopsy between 0.6% and 7.7%. Despite this, there is no standard of practice for the evaluation of sudden aortic death at autopsy.Recent studies have shown 20% of patients with thoracic aortic aneurysm or dissection (TAAD) have an identifiable genetic syndrome, and 19% will have an affected first-degree relative. The past 2 decades have seen identification of new culprit genes and syndromes, which can have subtle or nonexistent external phenotypes. A high index of suspicion is warranted to identify possible hereditary TAAD (H-TAAD), allowing family members to obtain screening to avoid catastrophic vascular events. Forensic pathologists need broad knowledge of the spectrum of H-TAAD and awareness of the relative significance of hypertension, pregnancy, substance use, and microscopic changes of aortic architecture.This article reviews the common subtypes of H-TAAD, including Marfan syndrome, vascular Ehlers-Danlos, Loeys-Dietz, and familial thoracic aortic aneurysm and dissection. Recommendations for the evaluation of sudden aortic death at autopsy are presented, including (1) performance of a complete autopsy, (2) documentation of aortic circumference and valve morphology, (3) notifying family of the need for screening, and (4) preservation of a sample for potential genetic testing.

The Public Health Role of Medical Examiner Offices During COVID-19 and Other Mass Fatality Events.

ABSTRACT: The public health role of a medical examiner office (MEO) in a pandemic is largely undefined; however, death data may be useful in strategic planning. Deaths reportable to MEO are defined in statute, with discretion as to the assumption of jurisdiction. We analyzed the daily reported death numbers (DRDNs) in our jurisdiction from March 1, 2020, to March 31, 2021, and compared them with hospital admission and COVID-19 fatality data over the same period. The DRDN from an MEO is easily obtained and may be useful as a supplemental and surrogate metric in certain pandemic mass casualty decisions. Hospital admission data were analyzed in real time and with a 2-week time-shift, as deaths lag hospital admissions as a disease surveillance metric. Moderate correlation was observed between DRDN and hospital admissions (r = 0.570), and this improved to strong correlation (0.645) when the 2-week time-shift was incorporated into the analysis. Both evaluations were statistically significant (P < 0.0001). The DRDN also moderately correlated (r = 0.412) with the number of COVID-19 deaths. Because death certification and hospital diagnosis may be delayed, real-time trend recognition in a pandemic may benefit from use of DRDN from MEO.

Trends in opioid overdose fatalities in Cuyahoga County, Ohio: Multi-drug mixtures, the African-American community and carfentanil.

Background: Ohio's age-adjusted opioid overdose fatality rate is double the national average. In an ever-evolving epidemic, it is crucial to monitor trends to inform public health interventions. Methods: A retrospective study was conducted using the Medical Examiner's decedent case files for all accidental opioid-related adult overdose deaths in Cuyahoga County (Cleveland), Ohio in 2017. Characterization of trends was based on autopsy/toxicology and first responder reports, medical records and death scene investigations. Results: Of 543 accidental opioid-related adult overdose fatalities, 64.1% died from 3+ drugs. The most common cause of death (COD) drugs included fentanyl (63.4%), heroin (44.4%), cocaine (37.0%) and carfentanil (35.0%). There were four times as many African American decedents as two years prior. Three or more COD drugs was >50% more common in those with fentanyl (Prevalence Ratio (PR) = 1.56[1.34-1.70]; p<.001) or carfentanil (PR = 1.51[1.33-1.70]; p<.001) as a COD drug, more common with a history of prescription drug abuse (PR = 1.16[1.02-1.33]; p=.025), but less common in divorced/widowed decedents (PR = 0.83[0.71-0.97]; p=.022). Carfentanil was nearly 4 times as prevalent in those with previous illicit drug use (PR = 3.88[1.09-13.70]; p=.025), and less common in those with previous medical history (PR = 0.72[0.55-0.94]; p=.016) or age 50+ (PR = 0.72[0.53-0.97]; p=.031). Conclusions: Accidental opioid-related overdose fatalities in Cuyahoga County adults were dominated by 3+ COD drugs, with cocaine/fentanyl mixtures driving sharp increases in African American fatalities. Carfentanil was more prevalent in people fitting the profile of recreational drug use. This data can inform harm reduction interventions.

The fentanyl phase of the opioid epidemic in Cuyahoga County, Ohio, United States.

Since late 2014, fentanyl has become the major driver of opioid mortality in the United States. However, a descriptive analysis of fentanyl victims is limited. We studied the 2016 fentanyl and heroin overdose deaths and compared them to previously studied heroin-associated fatalities from 2012 over a wide range of demographic and investigative variables, including overdose scene findings, toxicology results, and prescription drug history. We observed a significant increase in fentanyl-related deaths (n = 421, 2016) versus heroin deaths (n = 160, 2012) but the baseline demographics between both cohorts remained similar. Victims were predominantly of ages 35-64 years (60%-64%), White (83%-85%), and male (73%-76%). 2016 fentanyl decedents were more likely to have naloxone administered upon overdose, and the majority still had a positive prescription history for a controlled substance. Toxicology data showed a decrease in mean morphine and 6-monoacetylmorphine concentrations when cointoxication with fentanyl occurred. Our study emphasizes the medical examiner's role as a public health data source and bridge between different stakeholders combating the opioid epidemic.

Homicide by Unspecified Means: Cleveland 2008 to 2019.

ABSTRACT: The diagnosis homicide by unspecified means (HUM) is used to categorize deaths occurring under suspicious or criminal circumstances, but a specific cause of death cannot be identified. In 2010, Matshes and Lew (Am J Forensic Med Pathol. 2010;31(2):174-177) presented a HUM cases series, from which they derived 5 diagnostic criteria; however, the accuracy of these criteria has not been assessed.To identify a validation cohort, Cuyahoga County Medical Examiner's Office records were searched from 2008 to 2019 for cases certified as HUM. Thirteen cases were identified; on review, all cases fulfilled criteria 1, 4, and 5. Only 1 case had a potential anatomic cause of death identified (criterion 2).However, in 3 cases, toxicologic analyses could not be conducted because of skeletonization; in 2 cases, the decedents tested positive for cocaine/benzoylecgonine but were found in proximity to other victims for whom a specific violent cause of death was determined. By strict reading of criterion 3, these cases would have been excluded from the diagnosis of HUM. Perpetrators confessed to homicide in 7 cases, including the 5 cases that failed the toxicologic criterion. The 2010 diagnostic criteria are a reasonable foundation for the determination of HUM; modification of criterion 3 would provide improved flexibility based on clinical judgment.

Position Paper: Recommendations for the Investigation, Diagnosis, and Certification of Deaths Related to Opioid and Other Drugs.

The National Association of Medical Examiners convened an expert panel to update the association's evidence-based recommendations for investigating and certifying deaths associated with opioids and other misused substances to improve death certificate and mortality data for public health surveillance. The recommendations are as follows:1. Autopsy provides the best information on a decedent's medical condition for optimal interpretation of toxicology results, circumstances surrounding death, medical history, and scene findings. The panel considers autopsy an essential component of investigating apparent overdose deaths.2. Scene investigation includes reconciling prescription information and medication counts. Investigators should note drug paraphernalia or other evidence of using intoxicating substances.3. Retain blood, urine, and vitreous humor whenever available. Blood from the iliofemoral vein is preferable to blood from more central sites.4. A toxicological panel should be comprehensive, including potent depressant, stimulant, and antidepressant medications. Detecting novel substances present in the community may require special testing.5. When death is attributed to a drug or combination of drugs (as cause or contributing factor), the certifier should list the drugs by generic name in the autopsy report and death certificate.6. The best classification for manner of death in an overdose without any apparent intent of self-harm is "accident."

Unique Structural/Stereo-Isomer and Isobar Analysis of Novel Fentanyl Analogues in Postmortem and DUID Whole Blood by UHPLC-MS-MS.

The presented analytical method enabled the Toxicology Department at the Cuyahoga County Medical Examiner's Office to identify 26 and quantitatively report 24 compounds in 500 µL of whole blood, including fentanyl analogues (fentalogues) such as methoxyacetyl fentanyl (MeOAF) and cyclopropyl fentanyl (CPF). This second-generation method (FG2) was developed with the objective to improve the existing analysis (FG1) by decreasing sample size, lowering limits of detection (LOD) and lower limit of quantitation, minimizing ion suppression and resolving chromatographic interferences. Interferences may occur in the analysis of fentanyl, MeOAF, CPF, 3-methylfentanyl (3MF), butyryl fentanyl and isobutyryl fentanyl due to isobars and structural or geometric isomerism with another analogue or metabolite. The isomeric and isobaric fentalogues were grouped into three sets. The LOD established for Set 1 [MeOAF, para-methoxyacetyl fentanyl, para-fluoro acryl fentanyl (isobar), fentanyl carbamate], 2-furanyl fentanyl, Set 2 [CPF, (E)-crotonyl fentanyl] and carfentanil was 0.0125 ng/mL. The LOD established for N-methyl norfentanyl, norfentanyl, norcarfentanil, despropionyl fentanyl (4-ANPP), acetyl fentanyl, ß-hydroxy fentanyl, benzyl fentanyl, acryl fentanyl, alfentanil, fentanyl, para-fluoro fentanyl, Set 3 [(±)-trans-3MF, (±)-cis-3MF, isobutyryl and butyryl fentanyl], para-fluoroisobutyryl fentanyl, sufentanil, phenyl fentanyl and cyclopentenyl fentanyl was 0.0625 ng/mL. Seven-point linear calibration curves were established between 0.025 and 4.0 ng/mL for the 8 analytes with the lower LOD and 0.125 and 20 ng/mL for the 18 analytes with the higher LOD. 4-ANPP and cyclopentenyl fentanyl met qualitative reporting criteria only. The results for five postmortem and two driving under the influence of drugs authentic case samples are presented. To the authors' knowledge, FG2 is the first published method that achieved baseline resolution of the nine structural/stereo isomers and one isobar by ultra-high performance liquid chromatography-MS-MS and provided quantitative validation data for nine compounds. FG2 may be used as the new baseline for future isomers that need to be chromatographically separated.

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.

Homicide-Suicide in Cuyahoga County, Ohio, 1991-2016.

Research on homicides followed by suicides has relied heavily on small samples and relatively short time spans of data. This study helps to fill this gap by examining 26 years of homicide-suicide data from Cuyahoga County, Ohio, between 1991 and 2016. The main data source for the study is medical examiner files. Analyses of the data indicate the rate of homicide-suicide in Cuyahoga County is consistent with other studies but fluctuates considerably across years studied. The majority of victims are female while perpetrators are overwhelmingly male. Black people are overrepresented as victims and offenders. Use of drugs and/or alcohol leading up to the incident is common among perpetrators. Both the homicides and suicides were overwhelming committed with firearms. When comparing our results to the typology of murder-suicides developed by Marzuk, Tardiff, and Hirsch (JAMA 1992;267:3179), we find amorous jealousy is a significant motivating factor in a many cases, including those involving nonintimate partners. Our findings underscore the importance of widespread use of lethality assessment instruments.

An LC-MS-MS Method for the Analysis of Carfentanil, 3-Methylfentanyl, 2-Furanyl Fentanyl, Acetyl Fentanyl, Fentanyl and Norfentanyl in Postmortem and Impaired-Driving Cases.

In July of 2016, carfentanil (CF) emerged in Northeast Ohio resulting in over 25 deaths within a 30-day period. A total of 125 deaths have occurred in Summit County and Cuyahoga County has reported 40 deaths, relating to the presence of CF either alone, or in combinations with heroin and fentanyl. Prior to this surge in CF cases, positive fentanyl enzyme-linked immunosorbent assay (ELISA) screening results were increasing in number. Many were negative for fentanyl confirmation by gas chromatography-mass spectrometry. Fentanyl analogs such as CF, acetyl fentanyl (AF), 2-furanyl fentanyl (2-Fu-F) and 3-methylfentanyl (3-MF) may be present in these cases. Some fentanyl analogs like CF and 3-MF do not cross-react with the Immunalysis ELISA fentanyl assay. With the emergence of potent synthetic fentanyl analogs, questions arose as to how to interpret their very low concentrations or absence in the blood in relation to cause of death. Driving under the influence of drugs (DUID) blood specimens had also tested positive for CF by reference laboratories. A liquid chromatography-tandem mass spectrometry method was developed to identify and quantify fentanyl, norfentanyl (NF) and four analogs: AF, 2-Fu-F, 3-MF and CF. The method has been utilized to quantify these fentanyl analogs in blood and vitreous humor in authentic antemortem and postmortem cases. Calibration curves were established between 0.10-4.0 ng/mL (NF, AF, 3-MF, 2-Fu-F and CF) and 1.0-40 ng/mL for fentanyl. In total, 98 postmortem cases analyzed produced the following blood concentration ranges: CF (0.11-0.88 ng/mL), 3-MF (0.15-1.7 ng/mL), 2-Fu-F (0.15-0.30 ng/mL), AF (0.14-0.16 ng/mL), fentanyl (1.1-15 ng/mL) and NF (0.10-3.7 ng/mL). Only CF, fentanyl and NF were detected in a statistically significant subset DUID population of 26 cases producing concentration ranges between 0.11 and 0.47 ng/mL, 1.0 and 9.8 ng/mL, and 0.11 and 3.5 ng/mL, respectively.

The Evolution of the Opiate/Opioid Crisis in Cuyahoga County.

The United States continues to grapple with an epidemic of opiate/opioid drugs. This crisis initially manifested itself in the use and abuse of opioid pain relievers and has since seen an increase in illicit opiate/opioid drug use mortality. Cuyahoga County (metropolitan Cleveland) has been an area where the crisis has been particularly acute; this paper updates our previous experience. Most notable in the evolution of the drug epidemic has been an increase in mortality associated with fentanyl and an alarming rise in overall deaths, largely attributable to the emergence of fentanyl (a 64% increase in total overdose deaths from 2015 to 2016, with fentanyl increasing 324%). Fentanyl is a synthetic opioid with use in medical analgesia and anesthesia; however, most of the current supply is of clandestinely manufactured origin. Also of concern is the recent appearance of illicit fentanyl analogues, which are briefly described in this report. White males continue to be the most frequent overdose victims in the current crisis. A decrease of age appears to have taken place with the emergence of fentanyl with the most common age group being between 30 and 44 years of age. The majority of decedents are nonurban residents. Educationally, most of these decedents have a high school diploma or less schooling and a significant percentage consists of manual laborers. Medical examiners are an important source of information necessary to develop prevention and interdiction strategies. Challenges faced regarding adequate funding, instrumentation, and staffing are being felt.

Rules for Establishing Causation in Opiate/Opioid Overdose Prosecutions - The Burrage Decision.

As the opiate/opioid crisis has worsened in the United States, one of the law enforcement responses has involved increased efforts to prosecute the individuals responsible for the distribution of illicit drugs that result in overdoses. When mixed intoxications occur, the controlling decision for prosecution is Burrage v. United States (2014), which provides guidance on the types of evidence required for establishment of causation. In many types of legal proceedings, forensic pathologists are called to provide expert testimony, although they may be unaware of the burden of proof that is required in a given case. This paper seeks to elaborate upon the burden of proof in drug overdose prosecutions with the guidance of Burrage and offer insight into the expectations and limitations involved in these cases.