RESUMO
Drug overdose death rates are the highest recorded in New York City (NYC). Substance use disorder (SUD) treatment termination can confer increased risk of drug overdose death. Our objective was to determine the probability of, and factors associated with, drug overdose death following SUD treatment termination. Using a retrospective longitudinal cohort design, we identified those who had NYC-based SUD treatment terminated (01/2016-06/2019) using Chief Medical Examiner and SUD treatment data. Using survival analyses, we examined drug overdose deaths ≤ 14 and ≤ 90 days following SUD treatment termination, respectively. Of 51,171 patients with SUD treatment termination, 140 and 342 had a drug overdose death < 14 and ≤ 90 days, respectively. The crude drug overdose death rate was 26.7 per 1000 person-years at-risk in the ≤ 90-day period and was 71.6 per 1000 person-years at-risk in the ≤ 14-day period. In adjusted Cox proportional hazard model examining death ≤ 14 days, those unemployed (compared to employed) and those terminated from residential treatment (compared to medically supervised withdrawal, opioid treatment programs, and outpatient treatment) were more likely to have had a drug overdose death (all p-values < 0.01). In adjusted Cox proportional hazard model examining death ≤ 90 days, non-Hispanic White people (compared to non-Hispanic Black people), those not stably housed (compared to stably housed), those unemployed and those terminated from residential treatment were more likely to have had a drug overdose death (all p-values < 0.01). Strategies to improve retention including the reassessment of program treatment termination criteria along with strategies to promote ongoing OUD treatment, engagement in harm reduction, and distribution of naloxone are needed.
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BACKGROUND: Few reports describe the yield of postmortem genetic testing from medical examiners' offices or correlate genetic test results with autopsy-confirmed phenotypes from a large cohort. OBJECTIVES: To report results from cardiomyopathy- and cardiac arrhythmia-associated genetic testing in conjunction with autopsy findings of cases investigated at the United States' largest medical examiner office. METHODS: Postmortem cases tested from 2015 to 2022 with a cardiomyopathy- and cardiac arrhythmia-associated gene panel were reviewed. American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines were used to classify variant pathogenicity. Correlations of pathogenic/likely pathogenic variants (P/LPVs) with cardiac pathology were evaluated. RESULTS: The cohort included 1107 decedents of diverse ages and ethnicities. P/LPVs were detected in 87 (7.9%) cases, with 73 and 14 variants in cardiomyopathy and cardiac arrhythmia genes, respectively. Variants of uncertain significance were detected in 437 (39.5%) cases. The diagnostic yield (percentage of P/LPV) in decedents with cardiomyopathy (26.1%) was significantly higher than those without (P<.0001). The diagnostic yield was significantly lower in infants (0.7%) than older age groups (ranging from 1 to 74 years old, 5.7%-25.9%), which had no statistical difference between their yields. The diagnostic yields by cardiac autopsy findings were 54.0% for hypertrophic cardiomyopathy, 47.1% for arrhythmogenic cardiomyopathy, 20.0% for myocardial fibrosis, 19.0% for dilated cardiomyopathy, and 11.3% for myocarditis. Most P/LPVs were in MYBPC3, TTN, PKP2, SCN5A, MYH7, and FLNC. Ten P/LPVs were novel. CONCLUSIONS: Our results support the importance of performing postmortem genetic testing on decedents of all ages with cardiomyopathy, cardiac lesions insufficient to diagnosis a specific cardiomyopathy (e.g., myocardial fibrosis), and myocarditis. Combined postmortem cardiac examination and genetic analysis are advantageous in accurately determining the underlying cause of death and informing effective clinical care of family members.
Assuntos
Arritmias Cardíacas , Autopsia , Cardiomiopatias , Estudos de Associação Genética , Predisposição Genética para Doença , Testes Genéticos , Fenótipo , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , Adulto , Adolescente , Criança , Idoso , Adulto Jovem , Lactente , Pré-Escolar , Cardiomiopatias/genética , Cardiomiopatias/patologia , Arritmias Cardíacas/genética , Arritmias Cardíacas/diagnóstico , Idoso de 80 Anos ou mais , Recém-Nascido , Valor Preditivo dos Testes , Causas de Morte , Estados Unidos/epidemiologia , Estudos RetrospectivosRESUMO
Studies of the health impacts of the 11 September 2001 terrorist attacks on New York City's (NYC's) World Trade Center (WTC) towers have been hindered by imprecise estimates of exposure. We sought to identify potential biomarkers of WTC exposure by measuring trace and major metal concentrations in lung tissues from WTC-exposed individuals and less exposed community controls. We also investigated associations of lung tissue metal concentrations with self-reported exposure and respiratory symptoms. The primary analyses contrasted post-mortem lung tissue concentrations obtained from autopsies in 2007-2011 of 76 WTC Health Registry (WTCHR) enrollees with those of 55 community controls. Community controls were frequency-matched to WTCHR decedents by age at death, calendar quarter of death, gender, race, ethnicity and education and resided at death in NYC zip codes less impacted by WTC dust and fumes. We found WTCHR decedents to have significantly higher iron (Fe) lung tissue concentrations than community controls. Secondary analyses among WTCHR decedents adjusted for sex and age showed the log(molybdenum (Mo)) concentration to be significantly associated with non-rescue/recovery exposure. Post hoc analyses suggested that individuals whose death certificates listed usual occupation or industry as the Sanitation or Police Departments had elevated lung tissue Fe concentrations. Among WTCHR decedents, exposure to the WTC dust cloud was significantly associated with elevated lung tissue concentrations of titanium (Ti), chromium (Cr) and cadmium (Cd) in non-parametric univariable analyses but not in multivariable analyses adjusted for age and smoking status. Logistic regression adjusted for age and smoking status among WTCHR decedents showed one or more respiratory symptoms to be positively associated with log (arsenic (As)), log(manganese (Mn)) and log(cobalt (Co)) concentrations, while new-onset wheezing and sinus problems were negatively associated with log(Fe) concentration. Fe concentrations among individuals with wheezing, nonetheless, exceeded those in community controls. In conclusion, these data suggest that further research may be warranted to explore the utility as biomarkers of WTC exposure of Fe in particular and, to a lesser extent, Mo, Ti, Cr and Cd in digestions of lung tissue.
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Sons Respiratórios , Ataques Terroristas de 11 de Setembro , Humanos , Cádmio , Poeira , Sistema de Registros , Pulmão , Biomarcadores , Cadáver , Cidade de Nova Iorque/epidemiologiaRESUMO
BACKGROUND: Sudden deaths due to thoracic aortic dissection or rupture (TADR) are often investigated by forensic pathologists in the United States. Up to a quarter of reported TADR result from a highly penetrant autosomal dominant single gene variant. Testing genes associated with familial TADR provides an underlying etiology for the cause of death and informs effective sudden death prevention for at-risk family members. At the New York City Office of Chief Medical Examiner (NYC-OCME), TADR cases are routinely tested by the in-house, CAP-accredited Molecular Genetics Laboratory. In this retrospective study, TADR and cardiovascular cases were reviewed to understand the burden of TADR in sudden deaths, value of molecular diagnostic testing in TADR, and genotype-phenotype correlations in a demographically diverse TADR cohort. METHODS: Between July 2019 and June 2022, cases with in-house cardiovascular genetic testing at NYC-OCME were retrospectively reviewed. Twenty genes associated with familial TADR were analyzed using high throughput massive parallel sequencing on postmortem tissues or bloodspot cards. Variant interpretation was conducted according to ACMG/AMP guidelines. RESULTS: A total of 1078 cases were tested for cardiovascular genetic conditions, of which 34 (3%) had TADR. Eight of those TADR cases had a pathogenic or likely pathogenic variant (P/LPV), 4 had a variant of uncertain significance (VUS), and 22 cases were negative for variants in TADR genes. The molecular diagnostic yield using the TADR subpanel was 23.5%. The genes with the greatest prevalence of P/LPV were FBN1 (6), followed by TGFBR2 (2), TGFBR1 (1), and MYLK (1). Highly penetrant P/LPV in TGFBR2, FBN1, and TGFBR1 were found in TADR individuals who died younger than 34 years old. Two P/LPV in FBN1 were secondary findings unrelated to cause of death. P/LPV in FBN1 included five truncating variants located in the N-terminal domains and one missense variant involved in the disulfide bonds of the EGF-like domain. All P/LPV in TGFBR1 and TGFBR2 were missense or in-frame deletion variants located in the protein kinase catalytic domain. Three variants were first reported in this study. CONCLUSIONS: Molecular testing of familial TADR-associated genes is a highly effective tool to identify the genetic cause of TADR sudden deaths and benefits surviving at-risk families.
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Dissecção Aórtica , Doenças Cardiovasculares , Dissecção da Aorta Torácica , Humanos , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptor do Fator de Crescimento Transformador beta Tipo I , Estudos Retrospectivos , Dissecção Aórtica/genética , Morte Súbita , Biologia MolecularRESUMO
OBJECTIVE: To determine time trends and distinguishing autopsy findings of sudden unexpected death in epilepsy (SUDEP) in the United States. METHODS: We identified decedents where epilepsy/seizure was listed as cause/contributor to death or comorbid condition on the death certificate among all decedents who underwent medico-legal investigation at 3 medical examiner (ME) offices across the country: New York City (2009-2016), San Diego County (2008-2016), and Maryland (2000-2016). After reviewing all available reports, deaths classified as definite/probable/near SUDEP or SUDEP plus were included for analysis. Mann-Kendall trend test was used to analyze temporal trends in SUDEP rate for 2009-2016. Definite SUDEPs were compared to sex- and age ±2 years-matched non-SUDEP deaths with a history of epilepsy regarding autopsy findings, circumstances, and comorbidities. RESULTS: A total of 1,086 SUDEP cases were identified. There was a decreasing trend in ME-investigated SUDEP incidence between 2009 and 2016 (z = -2.2, S = -42, p = 0.028) among 3 regions. There was a 28% reduction in ME-investigated SUDEP incidence from 2009 to 2012 to 2013-2016 (confidence interval, 17%-38%, p < 0.0001). We found no correlation between SUDEP rates and the month of year or day of week. There was no difference between SUDEP and non-SUDEP deaths regarding neurodevelopmental abnormalities, pulmonary congestion/edema, and myocardial fibrosis. CONCLUSIONS: There was a decreasing monotonic trend in ME-investigated SUDEP incidence over 8 years, with a 28% reduction in incidence from 2009-2012 to 2013-2016. Unlike SIDS and sudden cardiac death, we found no correlation between SUDEP and the season of year or day of week. No autopsy findings distinguished SUDEP from non-SUDEP deaths.
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Morte Súbita/epidemiologia , Epilepsia/epidemiologia , Convulsões/epidemiologia , Morte Súbita Inesperada na Epilepsia/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto JovemRESUMO
OBJECTIVE: To determine the impact of socioeconomic status (SES) on sudden unexpected death in epilepsy (SUDEP) rates. METHODS: We queried all decedents presented for medico-legal investigation at 3 medical examiner (ME) offices across the country (New York City, Maryland, San Diego County) in 2009 to 2010 and 2014 to 2015. We identified all decedents for whom epilepsy/seizure was listed as cause/contributor to death or comorbid condition on the death certificate. We then reviewed all available reports. Decedents determined to have SUDEP were included for analysis. We used median income in the ZIP code of residence as a surrogate for SES. For each region, zip code regions were ranked by median household income and divided into quartiles based on total population for 2 time periods. Region-, age-, and income-adjusted epilepsy prevalence was estimated in each zip code. SUDEP rates in the highest and lowest SES quartiles were evaluated to determine disparity. Examined SUDEP rates in 2 time periods were also compared. RESULTS: There were 159 and 43 SUDEP cases in the lowest and highest SES quartiles. ME-investigated SUDEP rate ratio between the lowest and highest SES quartiles was 2.6 (95% confidence interval [CI] 1.7-4.1, p < 0.0001) in 2009 to 2010 and 3.3 (95% CI 1.9-6.0, p < 0.0001) in 2014 to 2015. There was a significant decline in overall SUDEP rate between the 2 study periods (36% decrease, 95% CI 22%-48%, p < 0.0001). CONCLUSION: ME-investigated SUDEP incidence was significantly higher in people with the lowest SES compared to the highest SES. The difference persisted over a 5-year period despite decreased overall SUDEP rates.
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Disparidades em Assistência à Saúde/economia , Morte Súbita Inesperada na Epilepsia/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Renda , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Classe Social , Estados Unidos/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: Both drowning and sudden unexpected death in epilepsy (SUDEP) are diagnoses of exclusion with predominantly nonspecific autopsy findings. We hypothesized that people with epilepsy found dead in water with no clear sign of submersion could be misdiagnosed as SUDEP. METHODS: All reported seizure-related deaths undergoing medicolegal investigation in three medical examiner's offices (New York City, Maryland, San Diego County) over different time periods were reviewed to identify epilepsy-related drownings and SUDEPs. Drowning cases that fulfilled inclusion criteria were divided into two groups according to the circumstances of death: definite drowning and possible drowning. The SUDEP group included two sex- and age (±2 years)-matched definite SUDEP/definite SUDEP plus cases for each drowning case. RESULTS: Of 1346 deaths reviewed, we identified 36 definite (76.6%) and 11 possible drowning deaths (23.4%), most of which occurred in a bathtub (72.3%). There were drowning-related findings, including fluid within the sphenoid sinuses, foam in the airways, clear fluid in the stomach content, and lung hyperinflation in 58.3% (21/36) of the definite drowning group, 45.5% (5/11) of the possible drowning group, and 4.3% of the SUDEP group (4/92). There was no difference in the presence of pulmonary edema/congestion between the definite drowning group, possible drowning group, and SUDEP group. The definite drowning group had a higher mean combined lung weight than the SUDEP group, but there was no difference in mean lung weights between the possible drowning and SUDEP groups or between the possible drowning and definite drowning groups. SIGNIFICANCE: No distinguishable autopsy finding could be found between SUDEPs and epilepsy-related drownings when there were no drowning-related signs and no clear evidence of submersion. SUDEP could be the cause of death in such possible drowning cases. As most drowning cases occurred in the bathtub, supervision and specific bathing precautions could be effective prevention strategies.
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Morte Súbita , Afogamento/epidemiologia , Epilepsia/epidemiologia , Epilepsia/mortalidade , Adulto , Idoso , Afogamento/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Historically, the duty of the medical examiner in assigning cause and manner of death in drug-related death cases has been fraught with controversial challenges. The lack of standardization in certifying drug-related deaths may involve differences among practicing forensic pathologists in their approach to such cases. The central objectives of the present study include characterization of current drug death patterns and the variability among medical examiners with respect to autopsy performance and death certification practices in one county medical examiner's office. MATERIALS AND METHODS: Death certificates, scene information/investigative reports, autopsy reports, and toxicological laboratory results for each of the 100 cases of drug-related death occurring in 2002 in Fulton County, Georgia were reviewed. Comparison of overall autopsy rates and autopsy rates in drug-related death cases for each medical examiner individually and for the group collectively was performed. In examining cocaine-related deaths (most common), statistical analysis was performed for comparison of drug concentrations (cocaine and benzoylecgonine) between deaths certified as cocaine toxicity (poisoning) versus cocaine-complicating disease or causing an adverse event such as cerebral hemorrhage. RESULTS: Causes of accidental drug deaths included cocaine 40%, mixed drug intoxication 37%, opioids 10%, ethanol 7%, and prescription medication (nonopioid) 5%. Overall total autopsy rates in 2002 for each of the 6 independent medical examiners ranged from 51% to 69% (mean 64%), whereas autopsy rates in drug-related death ranged from 55% to 91% (mean 81%). In review of the subset of 40 cocaine-related deaths, 25% were certified as cocaine toxicity (poisoning), with the remaining 75% certified as cocaine-complicating disease or causing and adverse event. Autopsy rates in cocaine-related deaths were as follows: cocaine toxicity 80%, cocaine-complicating disease 77.3%, and cocaine causing adverse event 62.5%. Thirty-eight percent of cocaine-related deaths were considered to be of "low suspicion" for drug involvement at the time the death was reported to the medical examiner with the remaining 62% being of "high suspicion". Autopsy rates were somewhat lower in the low suspicion group (67%) versus the high suspicion group (72%). Comparison of drug levels between cocaine-related death certification groups was performed. No statistically significant difference was shown in drug levels (cocaine, P > 0.3; benzoylecgonine, P > 0.2) between deaths certified as cocaine toxicity versus those certified as cocaine-complicating disease or causing adverse event. CONCLUSIONS: In Fulton County, accidental drug deaths in 2002 most often involved cocaine either alone or in combination with opiates and/or alcohol. Cocaine, opiates, or both were involved in greater than three-fourths (77%) of all drug-related deaths. The majority of all decedents were black (57%) and male (76%) with an average age of 42.2 years. Cocaine and ethanol were more frequently detected in black decedents, whereas opiates and polydrug abuse were more common in white decedents throughout the period studied. Preliminary investigation showed a high index of suspicion for the specific drug involved in virtually all opiate and alcohol cases, and in 62% of cocaine-related cases. Overall, the 100 accidental drug deaths in 2002 accounted for 7.5% of all deaths investigated and certified by the Fulton County Medical Examiner's Office. Our study provides further evidence to support the lack of correlation between serum drug levels and the mechanism of drug toxicity in cocaine-related deaths. No statistically significant differences were shown in parent cocaine or benzoylecgonine concentrations between those cases certified as toxicities or poisonings versus those cases certified as aggravating underlying disease or causing an adverse event. In addition, 62% of the cocaine-related death cases were considered initially to be of high suspicion for drug-related death, thus emphasizing the strong importance of scene information/investigative reports in evaluating drug-death cases and in formulating plans of action to handle each individual case. Among the drug-death cases handled by 6 staff medical examiners at the Fulton County Medical Examiner's Office, variation existed in autopsy performance and death certification practices. These issues are discussed in the context of the National Association of Medical Examiners' (NAME) Position Paper on Cocaine, NAME Forensic Autopsy Performance Standards, and other relevant literature. Most variations relate to completeness of the cause-of-death statement (whether or not comorbid conditions are included) rather than classification of manner of death within the office. However, specific wording in the cause of death may have significant ramifications regarding drug-related mortality statistics processed by the vital statistics system, with possible under-representation of drug-related deaths in single-cause mortality data.
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Acidentes/mortalidade , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Adolescente , Adulto , Idoso , Autopsia/estatística & dados numéricos , População Negra/estatística & dados numéricos , Depressores do Sistema Nervoso Central/efeitos adversos , Depressores do Sistema Nervoso Central/intoxicação , Criança , Pré-Escolar , Cocaína/efeitos adversos , Cocaína/intoxicação , Médicos Legistas , Inibidores da Captação de Dopamina/efeitos adversos , Inibidores da Captação de Dopamina/intoxicação , Overdose de Drogas/mortalidade , Etanol/efeitos adversos , Etanol/intoxicação , Feminino , Toxicologia Forense , Georgia/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Entorpecentes/efeitos adversos , Entorpecentes/intoxicação , População Branca/estatística & dados numéricosRESUMO
Pulmonary artery aneurysm and pulmonary artery dissection are rare antemortem diagnoses, most often associated with sudden death. These pathologic entities are strongly associated with chronic pulmonary hypertension due to structural cardiac defects, either congenital or acquired. We report the case of a 49-year-old woman who died suddenly due to dissection and rupture of a large pulmonary trunk aneurysm, with subsequent cardiac tamponade. Key historical and physical findings are described. Additionally, we present a discussion of the incidence, clinical presentation, pathogenesis, and pathologic diagnostic features of pulmonary artery dissection.
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Dissecção Aórtica/diagnóstico , Artéria Pulmonar/patologia , Dissecção Aórtica/patologia , Morte Súbita , Diagnóstico Diferencial , Feminino , Patologia Legal , Humanos , Pessoa de Meia-IdadeRESUMO
Sudden death in the setting of sickle cell lung disease (SCLD), is periodically seen in the practice of medical examiners. The goal of the present study was to identify the most common pathologic findings of SCLD associated with sudden or unexpected death. A retrospective/prospective review of 21 autopsy cases from sickle cell patients between 1990 and 2004 was performed. Review of medical records, autopsy reports, and H&E-stained slides of lung tissue was performed. Oil-Red-O and elastic staining of lung tissue were evaluated. All cases were screened for both acute and chronic forms of SCLD. Patients admitted for sickle cell pain crisis ranged in age from 8 months to 65 years. Fifteen out of 21 cases (71.4%) showed significant pulmonary pathology. The most frequent lung findings included pulmonary edema (47.6%), pulmonary thromboembolism (38.1%), fat emboli (33.3%), pulmonary hypertension, grades I-IV (33.3%), and microvascular occlusive thrombi (28.5%). Our study demonstrates higher-than-expected percentages of acute and chronic sickle cell-related lung injury such as fat embolism (33.3%) and pulmonary hypertension (33.3%), with right ventricular hypertrophy (33.3%). Therefore, we propose a simple and high-yield autopsy algorithm of ancillary procedures that should be applied on all known and suspected autopsy cases of sickle cell disease.