Xylazine co-occurrence with illicit fentanyl is a growing threat in the Deep South: a retrospective study of decedent data.

BACKGROUND: Xylazine is a dangerous veterinary sedative found mainly in illicit fentanyl in the Northeast and Midwest. Its role in the Deep South overdose crisis is not well-characterized. METHODS: We conducted a retrospective review of autopsy data in Jefferson County, Alabama to identify trends in xylazine prevalence among people who fatally overdosed from June 2019 through June 2023. RESULTS: 165 decedents met inclusion criteria. While the first identified xylazine-associated overdose was in June 2019, xylazine has become consistently prevalent since January 2021. All cases of xylazine-associated fatal overdoses were accompanied by fentanyl, and most (75.4%) involved poly-drug stimulant use. The average age was 42.2, and most decedents were white (58.8%) and male (68.5%). Overall, 18.2% of people were unhoused at the time of death. DISCUSSION: Xylazine is prevalent in the Deep South. Efforts to promote harm reduction, publicly viewable drug supply trends, and legalization of drug checking and syringe service programs should be prioritized.

Post-mortem formation of ethanol: Is 1-propanol a reliable marker? A proof-of-concept study using an in vitro putrefactive environment setup.

Ethanol is the psychoactive substance identified most frequently in post-mortem specimens. Unfortunately, interpreting post-mortem ethanol concentrations can be difficult because of post-mortem alcohol redistribution and the possibility of post-mortem alcohol neogenesis. Indeed, in the time interval between death and sample collection, the decedent may be exposed to non-controlled environments for an extended period, promoting microbial colonization. Many authors report that in the presence of carbohydrates and other biomolecules, various species of bacteria, yeast, and fungi can synthesize ethanol and other volatile substances in vitro and in vivo. The aim of this study was to study the impact of several variables on microbial ethanol production as well as develop a mathematical model that could estimate the microbial-produced ethanol in correlation with the most significant consensual produced higher alcohol, 1-propanol. An experimental setup was developed using human blood samples and cadaveric fragments incubated under strictly anaerobic conditions to produce a novel substrate, "cadaveric putrefactive blood" mimicking post-mortem corpse conditions. The samples were analyzed daily for ethanol and 1-propanol using an HS-GC-FID validated method. The formation of ethanol was evaluated considering different parameters such as putrefactive stage, blood glucose concentration, storage temperature, and storage time. Statistical analysis was performed using the Mann-Whitney non-parametric test and simple linear regression. The results indicate that the early putrefactive stage, high blood glucose concentration, high temperature, and time of incubation increase microbial ethanol production. In addition, the developed mathematical equation confirms the feasibility of using 1-propanol as a marker of post-mortem ethanol production.

Examining the neighborhood-level socioeconomic characteristics associated with fatal overdose by type of drug involved and overdose setting.

BACKGROUND: Fatal drug overdose in the United States is a public health crisis fueled by increased opioid and polysubstance use. Few studies have compared the neighborhood-level socioeconomic characteristics associated with overdoses of various substance classes and, to our knowledge, no investigation has yet assessed these factors in relation to polysubstance overdoses. Further, no study has determined whether socioeconomic conditions predict other contextually relevant aspects of overdoses such as whether they occur at-home or out-of-home. METHODS: Overdose data (2015-2018) were obtained from the Coroner/Medical Examiner's Office of Jefferson County, Alabama. The toxicology results of decedents with a known overdose locations (N = 768) were assessed for the presence of synthetic opioids, natural and semi-synthetic opioids, heroin, stimulants, benzodiazepines, and alcohol. Socioeconomic characteristics were obtained from the Unites States Census Bureau at the census tract level. RESULTS: Stimulant overdoses occurred in neighborhoods with the highest rates of disadvantage relative to other substance and polysubstance overdose types. The majority of included overdoses occurred at-home (63.7%) and an index of socioeconomic disadvantage predicted overdose rates for both at-home and out-of-home overdoses. Heroin overdose deaths were more likely to occur at-home while polysubstance stimulant-heroin overdoses were more common out-of-home. CONCLUSIONS: An index of socioeconomic disadvantage was generally predictive of overdose, regardless of the setting in which the overdose occurred (in-home vs. out-of-home). The associations between neighborhood-level socioeconomic characteristics and fatal overdose can be tailored by substance type to create targeted interventions. Overdose setting may be an important consideration for future policy efforts, as overdoses were nearly twice as likely to occur at-home.

Pharmacies and features of the built environment associated with opioid overdose: A geospatial comparison of rural and urban regions in Alabama, USA.

BACKGROUND: Elements of the physical environment have been shown to influence health behaviors including drug use and overdose mortality. Throughout the opioid epidemic in the United States, rural regions have been disproportionately affected by opioid overdose. Although the relationship between the urban built environment and opioid overdose has been established, little is known as to how trends may differ in rural areas. METHODS: Risk terrain modeling was used as a spatial analytical approach to assess environmental features that significantly increase the risk of opioid overdose in Jefferson County, Alabama. Spatial risk assessments were conducted for urban and rural regions as well as for the county as a whole. Criminogenic, opioid-related, and community variables were included and compared across spatial risk models. RESULTS: The geographic context, rural or urban, influenced the relationship between environmental features and opioid overdose. In rural areas, community features such as bus stops and public schools were related to the occurrence of opioid overdose. In urban areas, inpatient treatment centers, transitional living facilities, express loan establishments, and liquor vendors were significantly related to the locations of opioid overdose. CONCLUSION: Risk terrain modeling can be used to locate high-risk areas for opioid overdose while identifying factors that are contributing to the risk of events occurring in communities. The patterns of overdose risk differ in rural and urban contexts and may be used to inform the placement of treatment and prevention resources.

Stop the Bleed: gap analysis and geographical evaluation of incident locations.

BACKGROUND: Trauma is a major public health issue. In 2015, the White House launched the "Stop the Bleed" (STB) campaign, which aims to equip would-be bystanders with the ability and equipment to assist in bleeding emergencies. This study sought to estimate the number of patients who might benefit from STB intervention, in an everyday setting, and their spatial injury profile. METHODS: This is a retrospective analysis of trauma registry and medical examiners' data, collected between 2013 and 2017. The majority of patients were male. The median age was 32 years. Incidents were geocoded by ZIP code, and mapped using Quantum Geographic Information System (QGIS). RESULTS: We identified 139 patients from medical examiner records and UAB's trauma registry who might have benefitted from STB intervention. The number of incidents per year ranged from 22 to 35, averaging 2.3 incidents per month. There was no evidence of geographical clustering, although the small number of incidents precluded a formal geostatistical analysis. CONCLUSION: The number of patients who might benefit from STB interventions on a daily basis is small, and incident locations are difficult to predict. Educating the public in how to stop bleeding is appealing, but providing easy and widespread access to STB kits may be difficult. Although there are parallels to the provision of cardiopulmonary resuscitation and defibrillation for cardiac arrest, there are also differences, which should not be overlooked.

Early and prehospital trauma deaths: Who might benefit from advanced resuscitative care?

BACKGROUND: Recent civilian and military data from the United States and the United Kingdom suggest that further reductions in mortality will require prehospital or preoperating room hemorrhage control and blood product resuscitation. The aims of this study were to examine the potential preventability of prehospital and early in-hospital fatalities, and to consider the geographical location of such incidents, to contextualize how the use of advanced resuscitative techniques could be operationalized. METHODS: Retrospective analysis of prehospital and early in-hospital trauma deaths from January to December 2017. Data were obtained from the Coroner/ME's Office. Each death was reviewed by a panel of two trauma surgeons and a forensic pathologist. Anatomical and physiological survivabilities were evaluated separately, and then combined, leading to a holistic assessment of preventability. Incident locations were mapped and analyzed using ArcGIS. RESULTS: Three hundred sixteen trauma deaths were identified. Two hundred thirty-one (73%) were deemed anatomically not survivable; 29 (9%) anatomically survivable, but only with hospital care; 43 (14%) anatomically survivable with advanced prehospital care; and 13 (4%) anatomically survivable with basic prehospital care. Physiologically, 114 (36%) of the patients had been dead for some time when found; 137 (43%) had no cardiorespiratory effort on arrival of Emergency Medical Services (EMS) at the scene; 24 (8%) had cardiorespiratory effort at the scene, but not on arrival at the emergency department; and 41 (13%) had cardiorespiratory effort on arrival at the emergency department, but died shortly after. Combining the assessments, 10 (3%) deaths were deemed probably not preventable, 38 (12%) possibly preventable, and the remaining 278 (85%) not preventable. CONCLUSION: Twelve percent of trauma deaths were potentially preventable and might be amenable to advanced resuscitative interventions. Operationalizing this type of care will be challenging and will require either prehospital doctors, or very highly trained paramedics, nurses, or physician assistants. LEVEL OF EVIDENCE: Epidemiological, level III.

Correctly Identifying Deaths Due to Drug Toxicity Without a Forensic Autopsy.

In 2005, the National Association of Medical Examiners approved the Forensic Autopsy Performance Standards. Standard B3.7 indicates that a forensic pathologist shall perform a forensic autopsy when the death is by apparent intoxication by alcohol, drugs, or poison.The Jefferson County Coroner/Medical Examiner Office has observed an increase in our caseload by 10% per year since 2012. We designed a study to determine if a pathologist could correctly classify the cause of death (COD) and manner of death (MOD) of suspected drug-related deaths without information from the internal examination. The determination of the COD and MOD was then compared with the case file, which includes information from the internal examination and microscopy, to determine agreement between the case file and the reclassification. The percent correct for COD and MOD was calculated, and kappa values were calculated for MOD.The pathologists were able to correctly classify the COD in 73% of cases. For MOD, 2 pathologists achieved substantial agreement between the test cases and the actual case file. The third pathologist had moderate agreement. These findings indicate that a full postmortem examination is necessary to correctly classify the COD/MOD in cases of suspected drug toxicity.Our null hypothesis is that a full autopsy is not necessary to correctly classify the COD and MOD in cases of drug toxicity.

Correcting the Count: Improving Vital Statistics Data Regarding Deaths Related to Obesity.

Obesity can involve any organ system and compromise the overall health of an individual, including premature death. Despite the increased risk of death associated with being obese, obesity itself is infrequently indicated on the death certificate. We performed an audit of our records to identify how often "obesity" was listed on the death certificate to determine how our practices affected national mortality data collection regarding obesity-related mortality. During the span of nearly 25 years, 0.2% of deaths were attributed to or contributed by obesity. Over the course of 5 years, 96% of selected natural deaths were likely underreported as being associated with obesity. We present an algorithm for certifiers to use to determine whether obesity should be listed on the death certificate and guidelines for certifying cases in which this is appropriate. Use of this algorithm will improve vital statistics concerning the role of obesity in causing or contributing to death.

Quantification of Loperamide by Gas Chromatography Mass Spectrometry.

Due to reported pharmacological activity similar to classical opioids at supratherapeutic concentrations, abuse of the anti-diarrheal medication loperamide (Imodium AD™) has become a target in the opioid epidemic. While this phenomenon is not new, published quantitative analytical methods use liquid chromatography tandem mass spectrometry. Described here is an 11 min method for quantification of loperamide in postmortem whole blood by gas chromatography mass spectrometry. Validation studies performed followed SWGTOX guidelines and included: accuracy, specificity, limit of detection (LOD), regression model analysis, stability, and matrix recovery enhancement and/or suppression. The accuracy study consisted of inter-day, intra-day, reproducibility and dilution integrity experiments. Inter-day and intra-day accuracy, precision and coefficient of variation (CV) were measured; normalized results were 1.05 ± 0.09 with 8.87% CV (n = 36) and 1.03 ± 0.09 with 8.53% CV (n = 27), respectively. Reproducibility was evaluated through standard addition with an observed CV of 10.84% (n = 10). Dilution integrity (2× and 4×) resulted in 0.94 ± 0.13 with a CV of 13.9% (n = 5). No interference was observed through analyses of the internal standard (loperamide-d6), endogenous compounds (10 blank matrices) or 60 commonly encountered analytes. The LOD/decision point was 100 ng/mL (CV 8.40%). A linear calibration model was established from 100 to 1,000 ng/mL. Stability was examined; observed analyte-to-internal standard response resulted in 6.59% CV. Recovery was determined for loperamide and loperamide-d6 (31% and 36%, respectively). Neither matrix suppression nor enhancement was observed with loperamide at 750 ng/mL and loperamide-d6 at 300 ng/mL (-6.5% and -4.2%); however, some suppression was exhibited at lower concentrations (-39.8%). The designed method was determined to be sufficient for the analysis of loperamide-related death cases in Alabama (n = 8) and offers postmortem toxicology laboratories an alternative approach that is both highly selective and specific.

Identifying cases of heroin toxicity where 6-acetylmorphine (6-AM) is not detected by toxicological analyses.

PURPOSE: Heroin has a half-life of 2-6 min and is metabolized too quickly to be detected in autopsy samples. The presence of 6-acetylmophine (6-AM) in urine, blood, or other samples is convincing evidence of heroin use by a decedent, but 6-AM itself has a half-life of 6-25 min before it is hydrolyzed to morphine, so 6-AM may not be present in sufficient concentration to detect in postmortem samples. Codeine is often present in heroin preparations as an impurity and is not a metabolite of heroin. Studies report that a ratio of morphine to codeine greater than one indicates heroin use. We hypothesize that the ratio of morphine to codeine in our decedents abusing drugs intravenously will be no different in individuals with 6-AM present than in individuals where no 6-AM is detected, and we report our study of this hypothesis. METHODS: All accidental deaths investigated by the Jefferson County Coroner/Medical Examiner Office from 2010 to 2013 with morphine detected in blood samples collected at autopsy were reviewed. Five deaths where trauma caused or contributed to death were excluded from the review. The presence or absence of 6-AM and the concentrations of morphine and codeine were recorded for each case. The ratio of morphine to codeine was calculated for all decedents. Any individual in whom no morphine or codeine was detected in a postmortem sample was excluded from further study. Absence or presence of drug paraphernalia or evidence of intravascular (IV) drug use was documented in each case to identify IV drug users. The proportion of the IV drug users with and without 6-AM present in a postmortem sample was compared to the M/C ratio for the individuals. RESULTS: Of the 230 deaths included in the analysis, 103 IV drug users with quantifiable morphine and codeine in a postmortem sample were identified allowing for calculation of an M/C ratio. In these IV drug users, the M/C ratio was greater than 1 in 98 % of decedents. When controlling for the absence or presence of 6-AM there was no statistically significant difference in the proportion of IV drug users when compared to non IV drug users with an M/C ratio of greater than 1 (p = 1.000). CONCLUSION: The M/C ratio in IV drug users, if greater than 1, is seen in deaths due to heroin toxicity where 6-AM is detected in a postmortem sample. This study provides evidence that a M/C ratio greater than one in an IV drug user is evidence of a death due to heroin toxicity even if 6-AM is not detected in the blood. Using the M/C ratio, in addition to scene and autopsy findings, provides sufficient evidence to show heroin is the source of the morphine and codeine. Listing heroin as a cause or contributing factor in deaths with evidence of IV drug abuse and where the M/C ratio exceeds 1 will improve identification of heroin fatalities, which will allow better allocation of resources for public health initiatives.

Review of Postmortem Interval Estimation Using Vitreous Humor: Past, Present, and Future.

For decades, forensic scientists have sought a means of estimating the postmortem interval using laboratory analyses. The best known of these attempts uses a linear regression formula based on the increasing concentration of potassium ions in vitreous humor following death. Like all laboratory analyses, the determination of a potassium concentration is subject to pre-analytical, analytical, and post-analytical errors. Any error is magnified when entered into a regression formula that itself is subject to statistical variation, typically with a 95% confidence interval. Estimating the postmortem interval based solely on the concentration of potassium in vitreous humor proved too simplistic for accurate modeling of the myriad factors that influence postmortem changes. Research continues, using more complicated algorithms involving multivariate ion and chemical analyses and genomic sequencing of the postmortem biome. However refined estimates of the postmortem interval based on laboratory analysis become, sound medical practice will still require the integration of scene findings and information concerning the last time that a given decedent was known to be alive with the results of postmortem examination and laboratory analyses into a medical opinion concerning the postmortem interval.

Identifying Errors in Forensic Autopsy Reports Using a Novel Web-Based Program.

INTRODUCTION: Autopsy reports are often complex, with ample opportunity for errors and inconsistencies. These reports are often scrutinized by both families and attorneys. Identification of errors by proofreading physicians or clerical staff can be improved by utilizing a computer program to examine reports for discrepancies. METHODS: A webpage to review demographic consistency, organ descriptions, and pertinent information regarding gunshot wounds was developed to proofread reports. Thirty completed reports were analyzed from the Jefferson County Coroner/Medical Examiner Office. Additionally, a separate individual was instructed to sabotage reports and then determine if the software could detect the alterations. RESULTS: Of the 30 completed reports analyzed, no errors/omissions were identified; however, these reports were accurate upon manual inspection. Rarely, the computer triggered a warning that an organ should be confirmed if the author used a description that differed from the software's vocabulary (e.g., the author discussed "uterine wall" instead of "uterus"). The webpage detected eight out of ten errors supplied to the five sabotaged cases. These errors ranged from inconsistent age, race, and gender, to incomplete gunshot wound descriptions. CONCLUSION: Identification of errors by a computer proofreading program can improve autopsy report quality. The webpage has been designed so that additional modules, such as strangulation proofreading, could easily be added. Furthermore, the ability of the software to detect errors will continue to improve as more words are added to its vocabulary. The webpage is freely available and can be adapted to other medical examiner offices needs from the GitHub website.

Fatal herpes virus type I infection in a newborn.

The authors present a case of environmentally acquired fatal herpes virus type I infection in a newborn after cesarean section and a discussion of the clinical presentation, pathogenesis and diagnosis of herpes simplex type I (HSV-1) at autopsy. Herpes simplex virus, both type I and type II, are well described infectious agents in newborns. Though herpes simplex type II (HSV-2) is commonly associated with fatal neonatal infections, it is important to consider HSV-1 to make the correct diagnosis. Additionally, although HSV infections are typically acquired during parturition, it is possible to be infected postpartum from the environment as occurred in this case. The diagnosis of neonatal HSV must also be communicated by the forensic pathologist to applicable healthcare providers and health care facilities, because of public health and medicolegal issues.

Human organ/tissue growth algorithms that include obese individuals and black/white population organ weight similarities from autopsy data.

Physiologically based pharmacokinetic (PBPK) models need the correct organ/tissue weights to match various total body weights in order to be applied to children and the obese individual. Baseline data from Reference Man for the growth of human organs (adrenals, brain, heart, kidneys, liver, lungs, pancreas, spleen, thymus, and thyroid) were augmented with autopsy data to extend the describing polynomials to include the morbidly obese individual (up to 250 kg). Additional literature data similarly extends the growth curves for blood volume, muscle, skin, and adipose tissue. Collectively these polynomials were used to calculate blood/organ/tissue weights for males and females from birth to 250 kg, which can be directly used to help parameterize PBPK models. In contrast to other black/white anthropomorphic measurements, the data demonstrated no observable or statistical difference in weights for any organ/tissue between individuals identified as black or white in the autopsy reports.

Histologic evidence of repetitive blunt force abdominal trauma in four pediatric fatalities.

In cases of acute fatal child abuse, certain injuries, including cutaneous blunt force trauma, skull fractures, subdural hematomas, intra-abdominal hemorrhage, and retinal hemorrhages are common and well described in the pediatric and forensic literature. These gross findings at autopsy, when taken into consideration with scene investigation and interviews with caregivers, may indicate both a clear manner and cause of death. In such cases, the discovery of additional pathologic changes attributable to older abusive injuries helps support a conclusion of death due to inflicted trauma. We discuss four cases of fatal child abuse in which acute blunt force abdominal trauma was the cause of death. In each of these cases, careful examination with proper sectioning and microscopy of select abdominal tissues revealed that the acute tissue trauma was superimposed on a background of older, healing injury. This older trauma was characterized by classic histologic elements of tissue repair, including fibroblast proliferation, early scar formation, increased vascularity, and hemosiderin-laden macrophages. Iron and trichrome stains were used to confirm the presence of hemosiderin and fibrosis in all four cases, but the recognition of fibroblast proliferation and a reactive vascular pattern was best seen on routine hematoxylin and eosin stains. The gross and microscopic autopsy findings, along with available investigative information, established the diagnosis of chronic physical abuse.