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Trace and Major Element Concentrations in Cadaveric Lung Tissues from World Trade Center Health Registry Decedents and Community Controls

Marmor, Michael; Burcham, Joyce L; Chen, Lung-Chi; Chillrud, Steven N; Graham, Jason K; Jordan, Hannah T; Zhong, Mianhua; Halzack, Elizabeth; Cone, James E; Shao, Yongzhao
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.
PMCID:10606593
PMID: 37887662
ISSN: 1660-4601
CID: 5614362

Predicting accidental drug overdose as the cause of fatality in near real-time using the Suspected Potential Overdose Tracker (SPOT): public health implications

Hochstatter, Karli R; Rastogi, Sonal; Klein, Kathryn; Tait-Ozer, Cameron; El-Bassel, Nabila; Graham, Jason
BACKGROUND:Effective responses to the worsening drug overdose epidemic require accurate and timely drug overdose surveillance data. The objectives of this paper are to describe the development, functionality, and accuracy of the Suspected Potential Overdose Tracker (SPOT) for predicting accidental drug overdose as the cause and manner of death in near real-time, and public health implications of adopting the tool. METHODS:SPOT was developed to rapidly identify overdose deaths through a simple and duplicable process using data collected by death investigators. The tool assigns each death a ranking of 1 through 3 based on the likelihood of it being an unintentional drug overdose, with 1 representing the highest likelihood that the death will be confirmed as an unintentional drug overdose and 3 representing the lowest. We measured the accuracy of the tool for predicting overdose deaths by comparing potential overdose deaths in New York City from 2018-2020 that were identified using SPOT to finalized death certificates. We also calculated the proportion of death certificate-confirmed overdoses that were missed by the SPOT tool and the proportion of type 1 errors. RESULTS:SPOT captured up to 77% of unintentional drug overdose deaths using data collected within 72 h of fatality. The tool predicted unintentional drug overdose from 2018 to 2020 with 93-97% accuracy for cases assigned a ranking of 1, 87-91% accuracy for cases assigned a ranking of 2, and 62-73% accuracy for cases assigned a ranking of 3. Among all unintentional overdose deaths in 2018, 2019, and 2020, 21%, 28%, and 33% were missed by the SPOT tool, respectively. During this timeframe, the proportion of type 1 errors ranged from 15%-23%. CONCLUSIONS:SPOT may be used by health departments, epidemiologists, public health programs, and others to monitor overdose fatalities before death certificate data becomes available. Improved monitoring of overdose fatalities allows for rapid data-driven decision making, identification of gaps in public health and public safety overdose response, and evaluation and response to overdose prevention interventions, programs, and policies.
PMCID:9263436
PMID: 35804334
ISSN: 1471-2458
CID: 5278422

Temporal trends and autopsy findings of SUDEP based on medico-legal investigations in the US

Cihan, Esma; Devinsky, Orrin; Hesdorffer, Dale C; Brandsoy, Michael; Li, Ling; Fowler, David R; Graham, Jason K; Karlovich, Michael W; Yang, Jaclyn E; Keller, Anne E; Donner, Elizabeth J; Friedman, Daniel
OBJECTIVE:To determine time trends and distinguishing autopsy findings of sudden unexpected death in epilepsy (SUDEP) in the U.S. METHODS:We identified the decedents where epilepsy/seizure was listed as cause/contributor to death, or comorbid condition on death certificate among all decedents who underwent medico-legal investigation at three 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:1086 SUDEP cases were identified. There was a decreasing trend in ME-investigated SUDEP incidence between 2009-2016 (z= -2.2 S= -42 p= 0.028) among three regions. There was a 28% reduction in ME-investigated SUDEP incidence from 2009-2012 to 2013-2016 (CI: 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 eight 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.
PMID: 32636323
ISSN: 1526-632x
CID: 4517432

Socioeconomic disparities in SUDEP in the US

Cihan, Esma; Hesdorffer, Dale C; Brandsoy, Michael; Li, Ling; Fowler, David R; Graham, Jason K; Karlovich, Michael; Donner, Elizabeth J; Devinsky, Orrin; Friedman, Daniel
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:< 0.0001). CONCLUSION/CONCLUSIONS: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.
PMID: 32327496
ISSN: 1526-632x
CID: 4397402

Dead in the water: Epilepsy-related drowning or sudden unexpected death in epilepsy?

Cihan, Esma; Hesdorffer, Dale C; Brandsoy, Michael; Li, Ling; Fowler, David R; Graham, Jason K; Donner, Elizabeth J; Devinsky, Orrin; Friedman, Daniel
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/CONCLUSIONS: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.
PMID: 30146719
ISSN: 1528-1167
CID: 3255722

Accidental drug deaths in Fulton County, Georgia, 2002: characteristics, case management and certification issues

Graham, Jason K; Hanzlick, Randy
BACKGROUND AND OBJECTIVES/OBJECTIVE: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/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.
PMID: 18725776
ISSN: 1533-404x
CID: 3544132

Sudden death due to dissecting pulmonary artery aneurysm: a case report and review of the literature [Case Report]

Graham, Jason K; Shehata, Bahig
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.
PMID: 18043023
ISSN: 1533-404x
CID: 3544112

Sickle cell lung disease and sudden death: a retrospective/prospective study of 21 autopsy cases and literature review [Case Report]

Graham, Jason K; Mosunjac, Marina; Hanzlick, Randy L; Mosunjac, Mario
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.
PMID: 17525572
ISSN: 0195-7910
CID: 3544122