Office Of The Chief Medical Examiner Research Articles

Modeling Changes of Fatal Xylazine-Involved Drug Overdoses in Connecticut Across Time

Background Fatal drug overdoses have involved both xylazine and fentanyl. Xylazine is a non-opioid substance used in veterinary medicine. This study aimed to model changes in fatal xylazine-involved drug overdose deaths from 2019 to 2023 in Connecticut using overdose death data from the Office of the Chief Medical Examiner. Methods Xylazine-involved drug overdose fatality rates were calculated by number of deaths per year per 100,000 population from 2019 to 2023. We used joinpoint regression modeling to evaluate quarterly overdose rates across age, number of drugs, and drug types with a significance level of p < 0.05. Results From 2019 to 2023, there were 1116 xylazine-involved fatal overdoses with a cumulative rate of 31.3 deaths per 100,000. Xylazine-involved overdose death rates were significantly higher in Hispanic populations compared to both non-Hispanic White and Black populations (p < 0.05). The joinpoint analyses showed that xylazine-fentanyl mortality rates significantly increased by 0.18 per 100,000 per quarter from 2019 to 2022. Xylazine-fentanyl overdoses involving at least 4 or 5 substances significantly increased. Windham, Hartford, New London, and New Haven counties had the highest xylazine-involved death rates. Conclusion Xylazine-fentanyl deaths increased from 2019 to 2023, and often involved multiple substances (e.g., cocaine, ethanol, benzodiazepines, and oxycodone). Results show Hispanic populations, those aged 35–49, and 50+ experienced high rates of xylazine-fentanyl overdose deaths. Vulnerable populations in Connecticut for special consideration for future intervention and local resource allocation are recommended.

Selective postmortem arterial angiography of head and neck using digital x-ray or computed tomography: A practical and rapid method to identify vascular injuries.

Identification of vascular injuries is crucial for complete postmortem evaluation and understanding of trauma deaths by the Medical Examiner. Some vascular injuries are difficult to evaluate due to challenging anatomic locations, especially in the head and neck. Documenting injuries of the facial and vertebral arteries is challenging and necessitates time-consuming dissections that can create artifacts and disfigurement. In busy medical examiner offices with a significant number of traumatic injuries, finding a creative solution to employ reliable postmortem angiography is desirable. At the Office of the Chief Medical Examiner for the State of Maryland (OCME), we created and effectively implemented a selective angiography procedure using traditional indwelling Foley catheters and water-soluble barium swallow contrast to evaluate arterial injuries using either digital radiography or computed tomography imaging modalities. This technique and imaging interpretation can be performed by a medical examiner or forensic pathology fellow after basic technical training and basic radiology training. This study outlines the technique, methods, and utilization of the procedure and describes the findings of six deaths due to vascular lesions from different injury mechanisms and disease processes and describes the ease of implementation on a broader scale in busy Medical Examiner's offices.

Lethal Carbon Monoxide Generated from Small Internal Combustion Engines.

Fuel-burning small engines have the potential to emit dangerous and potentially lethal concentrations of carbon monoxide when used in poorly ventilated environments. The North Carolina Office of the Chief Medical Examiner investigated seven cases from 2013 - 2020 involving lethal carbon monoxide from small internal combustion engines. Evaluation of percent carboxyhemoglobin saturation was determined in these case studies as ratios of carboxyhemoglobin to reduced hemoglobin, using HP 8453 and Agilent 8454 UV-Visible Spectrophotometers (Agilent Technologies, Santa Clara, CA). Sources of carbon monoxide included a pressure washer, a propane-powered forklift, an inboard engine boat, a motorcycle, propane and kerosene heaters, and home-use generators. It was demonstrated during one death investigation that the Dräger X-am 2000 electrochemical gas monitor often used by first responders, falsely reacted to acetylene gas, initially misleading investigators to the source of the carbon monoxide. Educating first responders about not only the hazards of these unexpected carbon monoxide sources, but the limitations of their equipment, is a valuable goal of disseminating complete medical examiner case information. The details of these cases will educate first responders, the forensic science community, and public health leaders on potential small engine sources of carbon monoxide in death investigations, responder safety, and the limitations of portable air quality monitoring equipment during death investigation.

Heat-related fatalities in North Carolina 1999-2017.

Research shows the highest rates of occupational heat-related fatalities among farm laborers and among Black and Hispanic workers in North Carolina (NC). The Hispanic population and workforce in NC have grown substantially in the past 20 years. We describe the epidemiology of heat-related fatal injuries in the general population and among workers in NC. We reviewed North Carolina death records and records of the North Carolina Office of the Chief Medical Examiner to identify heat-related deaths (primaryInternational Classification of Diseases, Tenth Revisiondiagnosis code: X30 or T67.0-T67.9) that occurred between January 1, 1999, and December 31, 2017. Decedentage, sex, race, and ethnicity were extracted from both the death certificate and the medical examiner's report as well as determinations of whether the death occurred at work. In NC between 1999 and 2017, there were 225 deaths from heat-related injuries, and 25 occurred at work. The rates of occupational heat-related deaths were highest among males, workers of Hispanic ethnicity, workers of Black, multiple, or unknown race, and in workers aged 55-64. The highest rate of occupational heat-related deaths occurred in the agricultural industry. Since the last report (2001), the number of heat-related fatalities has increased, but fewer were identified as workplace fatalities. Rates of occupational heat-related deaths are highest among Hispanic workers. NC residents identifying as Black are disproportionately burdened by heat-related fatalities in general, with a wider apparent disparity in occupational deaths.

Suspected North Carolina counterfeit pill-involved deaths, 2020-2022.

The NC Office of the Chief Medical Examiner regularly assumes jurisdiction over deaths that are suspicious, unusual or unattended by a medical professional. In recent years, the presence of counterfeit pills is occasionally suggested by investigatory notes and/or scene findings that document reported consumption of prescription drugs, or prescription drugs on scene, which are not reflected in the final autopsy findings after toxicological analysis of the decedent's blood samples. Counterfeit pill consumption is a major public health hazard worthy of attention from the forensic toxicology community. Seventy-five cases from January 2020 to December 2022 serve as a convenience sample of cases where prescription pills including formulations of alprazolam, oxycodone and hydrocodone were specifically referenced during the death scene investigation as recently consumed, yet an unexpected substance was found during toxicological analysis rather than the expected pharmaceutical drug. Of note, novel benzodiazepines detected included flualprazolam, etizolam, clonazolam metabolite (8-aminoclonazolam), bromazolam, flubromazolam and desalkylflurazepam. Decedents' ages ranged from 16 to 69, across 33 different NC counties. Case notes indicated that eight of the decedents obtained pills through direct personal relationships, six decedents obtained them from "the street" and one decedent likely purchased pills online. Pills were largely consumed orally or through insufflation. Seven case reports contained indication that decedents knew or suspected the counterfeit nature of their pills. This study describes the context and characteristics of 2020-2022 suspected counterfeit pill-involved deaths in NC to further the understanding of the forensic science community, law enforcement partners, public health stakeholders and those potentially at risk through the consumption of counterfeit pills.

Increasing Injury Intensity among 6,500 Violent Deaths in the State of Maryland.

Anecdotal evidence strongly suggests there has been a rise in violent crimes. This study sought to examine trends in injury characteristics of homicide victims in Maryland. We hypothesized that there would be an increase in the severity of wound characteristics. The Office of the Chief Medical Examiner is a statewide agency designated by law to investigate all homicides, suicides, or unusual or suspicious circumstances. Using individual autopsy reports, we collected data among all homicides from 2005 to 2017, categorizing them into 3 time periods: 2005 to 2008 (early), 2009 to 2013 (mid), and 2014 to 2017 (late). Primary outcomes included the number of gunshots, stabs, and fractures from assaults. High-violence intensity outcomes included victims having 10 or more gunshots, 5 or more stabs, or 5 or more fractures from assaults. Of 6,500 homicides (annual range 403 to 589), the majority were from firearms (75%), followed by stabbings (14%) and blunt assaults (10%). Most homicide victims died in the hospital (60%). The average number of gunshots per victim was 3.9 (range 1 to 54), stabs per victim was 9.4 (range 1 to 563), and fractures from assaults per victim was 3.7 (range 0 to 31). The proportion of firearm victims with at least 10 gunshots nearly doubled from 5.7% in the early period to 10% (p < 0.01) in the late period. Similarly, the proportion with 5 or more stabbings increased from 39% to 50% (p = 0.02) and assault homicides with 5 or more fractures increased from 24% to 38% (p < 0.01). In Maryland, the intensity of violence increased across all major mechanisms of homicide. Further follow-up studies are needed to elucidate the root causes underlying this escalating trend.

Femicide in the United States: A Study of Connecticut Autopsy and Death Investigation Data.

We examined the records of the Connecticut Office of the Chief Medical Examiner for all female homicides from 2012 to 2021 to ascertain the rate of femicide. The investigative data were subcategorized as femicides and nonfemicides. The records included autopsy, toxicology, and investigators' reports. All underwent autopsy examination. The relationship of the perpetrator, cause of death, and special circumstances were examined in conjunction with the United Nations operational criteria. If the death investigation did not identify the suspected perpetrator, news media were searched for a reported homicide or manslaughter arrest. The total number of homicides was 271, and 259 (96%) could be further categorized, of which 181 (70%) were femicides. Differences between the 2 cohorts included causes of death (P's < 0.001), age at death (P < 0.001), and the involvement of murder-suicide (P < 0.001). No differences were observed for race, and the yearly rate of femicides did not increase during the COVID-19 pandemic.

A Comparative Investigation of Equine-Related and Bovine-Related Human Fatalities in Oklahoma.

This study examined 71 cases, where 45 cases were equine-related and 26 were bovine-related. Data for this study were collected by examining cases between 2000 and 2022 from the Oklahoma Office of the Chief Medical Examiner database.A majority of the equine-related fatality cases involved males aged 0 to 18 and 60 to 69 years, with sustained injuries of the head, neck, and thoracic regions while being mounted. These injuries were most often inflicted by being kicked or resulted from blunt force of impact. A majority of the bovine-related fatality cases involved males aged 60 to 79 years, with sustained injuries of the head, neck, and thoracic regions while being unmounted. These injuries were most often inflicted by being butted, trampled, or resulted from blunt force of impact. Of the total cases, approximately 42% of the causes of death were blunt force trauma of the head/neck and nearly 34% were multiple blunt force injuries. Only 3 mechanisms of death were discussed.There are distinct similarities in the most prominent gender, cause of sustained injury, and location of injury between equine- and bovine-related fatalities in Oklahoma. This study lends significant support to the need for increased awareness of safe handling practices and safety precaution education for both equine and bovine activities.

A Series of 8 Illicit Fentanyl Intoxication Deaths in Infants and Toddlers.

We report 8 children younger than 2 years who died from acute illicit fentanyl intoxications in Connecticut between 2020 and 2022.The Connecticut Office of the Chief Medical Examiner (CT OCME) investigates all unexpected, violent, and suspicious deaths in Connecticut. The CT OCME's electronic database was searched for fentanyl deaths by age. All underwent autopsies and toxicology testing.The ages ranged from 28 days to 2 years (mean age, 12 months). The causes of death involved acute fentanyl intoxications with 1 having xylazine, 1 having para-fluorofentanyl, and 1 having cocaine and morphine. All the manners of death were certified as homicide. The postmortem fentanyl blood concentrations ranged from 0.40 to 46 ng/mL. Most of the children were found unresponsive after being put to sleep. Three were co-sleeping with adults (2 in bed; 1 on a recliner). There was a known history of parental/caregiver drug abuse in 7 of 8 of the fatalities.We summarize the key investigative, autopsy, and toxicological findings. As illicit fentanyl use increases, there is a potential for infant exposure and death. The investigation and certification of these deaths and the role of intentional administration versus inadvertent exposure due to caregiver neglect in the context of the certification of the manner of death are described.

A Year of Deaths Due to or With COVID-19 Under Universal Postmortem Testing in San Francisco.

The Health Officer of the City and County of San Francisco, California, issued the order that all decedents were required to have a documented COVID-19 test effective from June 2020 to June 2021. The justification for the requirement was that complete data on COVID-19 status at the time of death were needed to help protect first responders and funeral home workers, identify missed cases, and characterize the places of death for otherwise unknown COVID-19 cases. To fill the gap in COVID-19 testing for all decedents, particularly among persons dying outside of hospitals, a specialized Decedent Testing Unit was created along with an increased capacity of the Office of the Chief Medical Examiner. From July 1, 2020, to June 30, 2021, the Decedent Testing Unit and Office of the Chief Medical Examiner provided postmortem testing results for 2776 decedents. Of these, 80 tested positive for COVID-19 for a positivity rate of 2.97%. The largest number of COVID-19-positive specimens were collected from persons who died at home (n = 37, 46.3%), followed by those who died in hospice (n = 20, 25.0%), other places outside of homes or facilities (n = 8, 10.0%), and in skilled nursing or long-term care facilities (n = 7, 8.8%). Follow-up of California death records found that 17 of these 80 cases (21.3%) had COVID-19 listed as one of the causes of death, 22 (27.5%) mentioned COVID-19 under "other conditions," and 41 (51.3%) made no mention of COVID-19. In the context of providing the COVID-19 status of decedents not otherwise known to have infection, our data help gauge the likelihood of missing deaths due to or with COVID-19 and inform future public health decisions on whether to require universal postmortem testing with COVID-19 resurgences or with new deadly epidemics.

Validation of an Analytical Method for Quantitation of Metonitazene and Isotonitazene in Plasma, Blood, Urine, Liver and Brain and Application to Authentic Postmortem Casework in New York City.

Starting in 2019, an emerging class of novel opioids causing public health concern was benzimidazole opioids, also known as "nitazenes". Two nitazenes, isotonitazene and metonitazene, were detected in postmortem samples received at the NYC Office of the Chief Medical Examiner. A protein precipitation extraction procedure was developed and validated for metonitazene and isotonitazene using 50 μL of blood, serum, liver, brain, and urine utilizing liquid chromatography-tandem mass spectrometry (LC-MS-MS). The limit of detection for both analytes was 0.10 ng/mL in plasma, blood, and brain, and was 1.0 ng/mL for urine and liver. The developed method was applied to authentic casework in which isotonitazene was detected in 10 cases between 2021 and 2022, with femoral blood concentrations ranging from 0.11 to 12 ng/mL. Metonitazene was detected in four cases in 2022 with concentrations ranging from 0.10 to 1.5 ng/mL in femoral blood. All but one case had the presence of fentanyl and/or fentanyl analogs, and the next most commonly encountered analyte in these cases was xylazine. The manner of death was accidental for all cases with a detected nitazene, and all but one case was attributed to mixed drug intoxications. None of the cases reported the identified nitazene compound as the sole intoxicant responsible for death. The opioid crisis continues to tear apart communities throughout the world, including New York City. Continued research and communication regarding these drugs helps to fight this crisis.

Fentanyl concentrations in ligated femoral blood in the presence and absence of NPS benzodiazepine drugs. A review of over 1250 benzo-dope / fentanyl toxicity cases in Alberta, Canada

The drug combination referred to as ‘benzo dope’ has become prevalent in recent years, with an increasing number of fentanyl-related deaths reporting the concomitant presence of one or more benzodiazepine drug, such as etizolam, flualprazolam and flubromazepam. The central nervous system (CNS) depressant effects of these benzodiazepine drugs can exacerbate respiratory and CNS depressant effects resulting from the use/misuse of potent opioids such as fentanyl. This combined and enhanced drug-induced toxicity can pose a significant threat to life. Over a three-year period (2020–2022), the Office of the Chief Medical Examiner, Edmonton, Alberta, Canada issued 2812 case reports with fentanyl detected; of these cases, approximately 45% (1261) were positive for at least one benzodiazepine drug. This study presents concentrations of both fentanyl and benzodiazepine drugs in post mortem blood collected from a visualized, ligated femoral vein. The study demonstrates that the blood concentration of fentanyl in benzo-dope case reports is considerably higher than in cases where no benzodiazepine drug was detected.The median concentration of fentanyl in femoral blood for cases that also contained a benzodiazepine drug was 12.4 ng/mL (2020), 11.9 ng/mL (2021) and 14.0 ng/mL (2022). The median concentration of fentanyl in femoral blood for cases that did not contain a benzodiazepine drug was 8.5 ng/mL (2020), 7.0 ng/mL (2021) and 7.2 ng/mL (2022). The percent differences between the groups were similar with those observed from quantitative analysis of drug powders from unrelated police seizures in Alberta, Canada, suggesting the observed differences in blood fentanyl concentration may be due to the use of a drug substance with a higher concentration of fentanyl.Furthermore, the reported concentration of the benzodiazepine drug(s) is low, such that the role/contribution, if any, that this drug may have played in the decedents’ death should be questioned and carefully considered by the certifying medical examiner/coroner.

A Rare Case of Fatal Penile Strangulation in a Transgender Woman.

Penile strangulation is a surgical emergency with significant morbidity and potential mortality. It is often associated with psychiatric disorders; objects such as metal rings, plastic bottles, and rubber bands are commonly used. The San Francisco Office of the Chief Medical Examiner was presented with a 50-year-old transgender female decedent with a medical history of psychiatric and substance use disorders. Autopsy revealed external genitalia entrapped by a plastic bottle encircling the penile shaft at the base, causing severe edema and skin blebs of the penile shaft and glans, and evidence of urinary obstruction. We describe the accidental death of an adult transgender female decedent due to penile strangulation, which ultimately led to acute renal failure and death.

The Protective Effect of Clozapine on Suicide: A Population Mortality Study of Statewide Autopsy Records in Maryland.

Objective: Clozapine is the most efficacious antipsychotic medication, but it is underutilized and its mechanism of action is still poorly understood. One aspect of its unique efficacy that requires further study is its effect on suicidality. A randomized controlled trial, the InterSePT study, yielded evidence that clozapine reduces suicidality more than olanzapine, after which it became the only medication indicated for recurrent suicidal behavior in schizophrenia and schizoaffective disorder. We present here the first study of population mortality data to investigate the effect of clozapine on suicide.Methods: We reviewed statewide autopsy records of Maryland's Office of the Chief Medical Examiner, which performs uniquely comprehensive death investigations that include full toxicologic panels with postmortem blood levels of antipsychotics. Our study compared clozapine- and olanzapine-positive decedents across demographic, clinical, and manner-of-death outcomes using contingency table analysis and logistic regression.Results: Of 53,144 decedents from 2003 to 2021, 621 had clozapine or olanzapine detected on autopsy, with the two groups showing no demographic differences. Decedents with clozapine were significantly less likely to have died by suicide than by accident compared to those with olanzapine (odds ratio = 0.47; 95% CI, 0.26-0.84; P = .011).Conclusions: Our study thus adds more naturalistic evidence to the growing literature on the beneficial effect of clozapine on suicidality. Our findings also highlight the utility of statewide autopsy records, an untapped resource for investigating the potential protective effect of psychiatric medications on suicide at a population level.

Trends in fatal occupational injury rates among older workers before and after the Great Recession of 2008

BackgroundOlder workers experience higher rates of fatal occupational injury than younger workers worldwide. In North Carolina, the population of older workers more than doubled between 2000 and 2017. In 2008,...

Concordance between controlled substance receipt and post-mortem toxicology in opioid-detected overdose deaths: A statewide analysis

BackgroundOpioid overdoses are a leading cause of preventable death in the United States. There is limited research linking decedents’ receipt of controlled substances and presence of controlled substances on post-mortem toxicology (PMT). MethodsWe linked data on opioid-detected deaths in Connecticut between May 3, 2016, and December 31, 2017 from the Office of the Chief Medical Examiner, Department of Consumer Protection, and Department of Mental Health and Addiction Services. Exposure was defined as receipt of an opioid or benzodiazepine prescription within 90 days prior to death. Our primary outcome was concordance between medication received and metabolites in PMT. ResultsOur analysis included 1412 opioid-detected overdose deaths. 47 % received an opioid or benzodiazepine 90 days prior to death; 36 % received an opioid and 27 % received a benzodiazepine. Concordance between receipt of an opioid or benzodiazepine and its presence in PMT was observed in 30 % of opioid-detected deaths. Concordance with an opioid was present in 17 % of opioid-detected deaths and concordance with a benzodiazepine was present in 21 % of opioid-detected deaths. Receipt of an opioid or benzodiazepine and concordance with PMT were less common in fentanyl or heroin-detected deaths and more common in pharmaceutical opioid-detected deaths. DiscussionOur results suggest medically supplied opioids and benzodiazepines potentially contributed to a substantial number, though minority, of opioid-detected deaths during the study period. Efforts to reduce opioid and benzodiazepine prescribing may reduce risk of opioid-detected deaths in this group, but other approaches will be needed to address most opioid-detected deaths that involved non-pharmaceutical opioids.

Geographic and temporal trends in fentanyl-detected deaths in Connecticut, 2009–2019

Since 2012 fentanyl-detected fatal overdoses have risen from 4% of all fatal overdoses in Connecticut to 82% in 2019. We aimed to investigate the geographic and temporal trends in fentanyl-detected deaths in Connecticut during 2009-2019. Data on the dates and locations of accidental/undetermined opioid-detected fatalities were obtained from Connecticut Office of the Chief Medical Examiner. Using a Bayesian space-time binomial model, we estimated spatiotemporal trends in the proportion of fentanyl-detected deaths. During 2009-2019, a total of 6,632 opioid deaths were identified. Among these, 3234 (49%) were fentanyl-detected. The modeled spatial patterns suggested that opioid deaths in northeastern Connecticut had higher probability of being fentanyl-detected, while New Haven and its neighboring towns and the southwestern region of Connecticut, primarily Greenwich, had a lower risk. Model estimates also suggested fentanyl-detected deaths gradually overtook the preceding non-fentanyl opioid-detected deaths across Connecticut. The estimated temporal trend showed the probability of fentanyl involvement increased substantially since 2014. Our findings suggest that geographic variation exists in the probability of fentanyl-detected deaths, and areas at heightened risk are identified. Further studies are warranted to explore potential factors contributing to the geographic heterogeneity and continuing dispersion of fentanyl-detected deaths in Connecticut.

The Impact of COVID-19 on Adolescent Suicide Deaths in the State of Maryland

Abstract On March 11, 2020, the World Health Organization officially declared the SARS-CoV-2 virus (COVID-19) a worldwide pandemic. As of December 2021, there have been over 278 million cases and 5.4 million deaths reported. One area of concern regarding the pandemic was its potential impact on mental health, and it was feared that the onset of such a devastating pandemic would lead to increased suicide risks among the general population. With suicide being a leading cause of death in adolescents, it is important to assess the potential mental health consequences that the COVID-19 pandemic may impose. Aim The aim of the study was to analyze the impact of COVID-19 on suicide deaths among adolescents in the state of Maryland from 2019 to 2021. Subjects and Methods This was a retrospective study of adolescent suicide victims, aged 10–19 years, from January 2019 to December 2021 in the state of Maryland. De-identified data were collected from the statewide medical examiner’s office which is responsible for the medicolegal death investigation in Maryland. Results A total of 102 adolescent suicide deaths were investigated statewide by the Maryland Office of the Chief Medical Examiner during these 3 years. The number of adolescent suicide cases stayed relatively stable during the COVID-19 pandemic, with slightly more cases during the pre-COVID-19 pandemic period (2019: n = 37; 2020: n = 31; and 2022: n = 34). Looking at months of incidence, less cases were reported in March–May 2020 (n = 5), which marks the beginning of the pandemic when compared to the same period in 2019 (n = 13). The number was higher for August–November 2020 (n = 15) than for that of 2019 (n = 8) and 2021 (n = 8). The male-to-female suicide ratio was 3.7:1 (n = 80/22). However, the data exhibited a significant increase in the number of female adolescent suicides, from 8.11% in 2019 (n = 3) to 25.81% in 2020 (n = 8) and 32.35% in 2021 (n = 11). Of the cases examined, more than 50% were white and approximately 27% were African-Americans. The two leading causes of death were hanging (47%) and firearm injuries (29%). Maryland consists of 23 countries and Baltimore City. The majority of adolescent suicides occurred in county residents with only 8.8% of cases in Baltimore City.

City streetscapes and neighborhood characteristics of fatal opioid overdoses among people experiencing homelessness who use drugs in New York City, 2017-2019.

While housing is a critical social determinant of nonprescription opioid overdose, little is known about how place impacts fatal overdose for people experiencing homelessness (PEH) who use drugs beyond the public versus private domains. This study investigated patterns of neighborhood environment features at locations of fatal overdoses among PEH. We remotely visited locations of opioid-involved fatal overdoses provided by the New York City Office of the Chief Medical Examiner, 2017-2019 (n=3276), with Google Street View and used systematic social observation to assess characteristics of the street block related to drug exposures. We cross-referenced home address with city shelters and supportive housing to identify PEH (n=503). We used the differences of K functions from the spatial point patterns and kernel ratio function maps to identify geographic clusters. We then used logistic regression to identify significant individual-, block-, and neighborhood-level covariates (neighborhood deprivation, segregation, population density). Over half (55.9%, n=281) of fatal overdoses among PEH occurred in supportive housing or shelters, and 15.5% (n=78) occurred in public spaces (e.g., parks). Spatial analyses identified areas of significant concentrated fatal overdoses among PEH in Manhattan, the South Bronx, and Brooklyn. We identified several significant indicators of physical and social order and disorder associated with increased odds of experiencing homelessness at time of fatal overdose, including construction/renovation, graffiti, traffic calming features, and loitering. Harm reduction services should be co-located in facilities that serve PEH and targeted to street blocks with indicators of physical and social disorder. While supportive housing is a crucial step in preventing fatal opioid overdoses among PEH, identifying neighborhoods for intervention services delivery and harm reduction outreach for PEH is necessary.

Risk Variants in the Exomes of Children With Critical Illness

Diagnostic genetic testing can lead to changes in management in the pediatric intensive care unit. Genetic risk in children with critical illness but nondiagnostic exome sequencing (ES) has not been explored. To assess the association between loss-of-function (LOF) variants and pediatric critical illness. This genetic association study examined ES first screened for causative variants among 267 children at the Morgan Stanley Children's Hospital of NewYork-Presbyterian, of whom 22 were otherwise healthy with viral respiratory failure; 18 deceased children with bronchiolitis from the Office of the Chief Medical Examiner of New York City, of whom 14 were previously healthy; and 9990 controls from the Institute for Genomic Medicine at Columbia University Irving Medical Center. The ES data were generated between January 1, 2015, and December 31, 2020, and analyzed between January 1, 2017, and September 2, 2022. Critical illness. Odds ratios and P values for genes and gene-sets enriched for rare LOF variants and the loss-of-function observed/expected upper bound fraction (LOEUF) score at which cases have a significant enrichment. This study included 285 children with critical illness (median [range] age, 4.1 [0-18.9] years; 148 [52%] male) and 9990 controls. A total of 228 children (80%) did not receive a genetic diagnosis. After quality control (QC), 231 children harbored excess rare LOF variants in genes with a LOEUF score of 0.680 or less (intolerant genes) (P = 1.0 × 10-5). After QC, 176 children without a diagnosis harbored excess ultrarare LOF variants in intolerant genes but only in those without a known disease association (odds ratio, 1.8; 95% CI, 1.3-2.5). After QC, 25 children with viral respiratory failure harbored excess ultrarare LOF variants in intolerant genes but only in those without a known disease association (odds ratio, 2.8; 95% CI, 1.1-6.6). A total of 114 undiagnosed children were enriched for de novo LOF variants in genes without a known disease association (observed, 14; expected, 6.8; enrichment, 2.05). In this genetic association study, excess LOF variants were observed among critically ill children despite nondiagnostic ES. Variants lay in genes without a known disease association, suggesting future investigation may connect phenotypes to causative genes.