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PURPOSEOF REVIEW: Cardiovascular disease is the leading cause of morbidity and mortality among women globally. Numerous studies show ongoing disparities in diagnosis, management, and outcomes of ischemic heart disease in women compared to men. We aim to review the factors contributing to sex-based differential outcomes of percutaneous coronary interventions in women. RECENT FINDINGS: Hormonal influence on coronary arteries and progression of atherosclerosis in women results in distinct coronary plaque characteristics and unique pathological process such as spontaneous coronary artery dissection and myocardial infarction with non-obstructive coronary arteries. During the presentation of acute coronary syndromes, women are older and have higher burden of comorbidities, with higher short- and long-term mortality. Awareness of differences in vascular biology and unique risk factors for cardiovascular disease in women is essential for sustained improvement in cardiovascular mortality. Better representation of women in trials is crucial to address the gaps in knowledge and allow for individualized treatment approaches in women.
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Infarto del Miocardio , Isquemia Miocárdica , Intervención Coronaria Percutánea , Masculino , Humanos , Femenino , Resultado del Tratamiento , Factores Sexuales , Infarto del Miocardio/etiología , Intervención Coronaria Percutánea/efectos adversos , Isquemia Miocárdica/etiología , Factores de RiesgoRESUMEN
OBJECTIVES: Diabetes mellitus (DM) increases the risk of cardiovascular disease and is associated with sudden death. Mental illness among individuals with DM may confound medical care. This study assessed the association of mental illness with DM and poorly controlled DM in sudden death victims. METHODS: We screened out-of-hospital deaths ages 18 to 64 years in Wake County, North Carolina from 2013 to 2015 to adjudicate sudden deaths. We abstracted demographics and clinical characteristics from health records. Mental illness included anxiety, schizophrenia, bipolar disorder, or depression. Poorly controlled DM was defined as a hemoglobin A1c >8 or taking ≥3 medications for glycemic control. Logistic regression assessed the association between DM and mental illness. RESULTS: Among victims with available records, 109 (29.4%) had DM. Of those, 62 (56.9%) had mental illness. Mental illness was present in 53.42% and 63.89% of victims with mild and poorly controlled DM, respectively. Mental illness was associated with DM (adjusted odds ratio 2.46, 95% confidence interval 1.57-3.91). Victims with poorly controlled DM were more likely to have mental illness (adjusted odds ratio 2.66, 95% confidence interval 1.14-6.18). CONCLUSIONS: DM is a common comorbid condition in sudden death victims. Among victims, mental illness is associated with the control of DM. Early management of comorbid mental illnesses may improve the care of patients with DM and reduce the incidence of sudden death.
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Muerte Súbita/epidemiología , Diabetes Mellitus/epidemiología , Trastornos Mentales/epidemiología , Adolescente , Adulto , Comorbilidad , Muerte Súbita/etiología , Femenino , Hemoglobina Glucada/análisis , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , North Carolina/epidemiología , Oportunidad Relativa , Prevalencia , Adulto JovenRESUMEN
BACKGROUND: We assessed patterns of health care utilization to further characterize chronic comorbidities prior to sudden death. METHOD: From March 1, 2013, through February 28, 2015, all out-of-hospital deaths aged 18-64 reported by emergency medical services in Wake County, North Carolina, were screened to adjudicate 399 sudden death victims. Retrospective analysis of clinical records on victims determined health care utilization. Health care utilization frequency was assessed by latent growth curve analysis. RESULTS: Medical records were available for 264 victims (aged 53.5 ± 9.2) who were predominantly male (65%) and white (64%). Of these, 210 (80%) victims had at least one visit within two years of death and 73 (28%) had a visit within one month of death. Over the two years prior to death, there was an increasing frequency of doctor visits (P < .001). Victims averaged 3.7 ± 4.6 yearly visits and were categorized into low (0.4 visits/year), medium (3.3 visits/year), and high (11.4 visits/year) tiers of visit frequency. The high visit tier had a greater prevalence of coronary artery disease (38%), hypertension (80%), diabetes (58%), depression (74%), anxiety (64%), and substance misuse (46%) (P < .001). LIMITATIONS: Those who were non-free-living, minors, without formal medical records, and adults aged 65 and older were excluded from the analysis. CONCLUSIONS: A majority of sudden death victims utilized health care within two years prior to death and had comorbidities that may have contributed to their unexpected death. The increasing frequency of visits prior to death provided an opportunity for health care providers to address potential victims' chronic medical conditions to potentially prevent death.
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Muerte Súbita , Adolescente , Adulto , Muerte Súbita/prevención & control , Servicios Médicos de Urgencia , Femenino , Humanos , Masculino , Registros Médicos , Persona de Mediana Edad , Afecciones Crónicas Múltiples/epidemiología , Afecciones Crónicas Múltiples/terapia , North Carolina/epidemiología , Aceptación de la Atención de Salud/estadística & datos numéricos , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Sudden death is a public health problem with major impact on society. Coronary artery disease (CAD) is believed to underlie 60-80% of these deaths. While deaths from CAD have decreased in the recent decades, sudden death rates remain unacceptably high. OBJECTIVE: We aimed to assess the prevalence of CAD and its risk factors among 18-64-year-old adults in a population-based case registry of sudden deaths and compare them to a living population from the same geographical area. DESIGN: From 2013 to 2015, all sudden deaths among 18-64-year-old adults in Wake County, NC, were identified (n = 371). A comparison group was formed by randomly selecting individuals from an electronic health record repository of a major healthcare system in the area (N = 4218). MAIN MEASURES: Prevalence of CAD and its risk factors among cases of sudden death and living population across sex and age groups. Odds of sudden death associated with atherosclerotic risk factors and comorbidities. KEY RESULTS: CAD was present in 14.8% of sudden death cases. Among sudden death victims, most risk factors and comorbidities were more common in the older age group, except for obesity which was more common in younger cases, and diabetes which was equally prevalent in younger and older cases. Compared to living population, sudden death cases had higher prevalence of atherosclerotic risk factors across all gender and age groups. Sudden death cases had a numerically higher number of risk factors compared to living population, regardless of age group or presence of CAD. CONCLUSIONS: Coronary artery disease is not common among sudden death cases, but risk factors and comorbidities are prevalent. Our findings support the changing etiology of sudden death. In the absence of clinically diagnosed CAD, use of novel imaging modalities and biomarkers may identify high-risk individuals and lead to prevention of sudden death.
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Aterosclerosis , Enfermedad de la Arteria Coronaria , Adolescente , Adulto , Aterosclerosis/epidemiología , Enfermedad de la Arteria Coronaria/epidemiología , Muerte Súbita Cardíaca/epidemiología , Humanos , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Few studies have evaluated the years of life lost (YLL) and productivity loss due to sudden unexpected death (SUD). The burden of SUD on society is undetermined because of lack of population-based studies and comprehensive adjudication methods. OBJECTIVE: We estimated YLL and productivity loss from SUD in working-age adults and compared it with the leading causes of death in the United States. METHODS: We screened all out of hospital deaths among people aged 20-64 in Wake County, NC from 2013 to 2015 to adjudicate SUDs. We extrapolated Wake County incidence to estimate the age-standardized and sex-standardized rate of SUD in the United States. YLL was calculated based on the remaining life expectancy of the victims. Incorporating market and housekeeping value estimated the present value of lifetime productivity loss because of SUD. RESULTS: SUD incidence rates in the US adults aged 20-64 were 49.3 (95% confidence interval, 41.2-58.3) and 21.7 (95% confidence interval, 16.5-27.8) per 100,000 among men and women, respectively. SUD resulted in the loss of 2 million years of life, accounting for 10.0% of YLL from all causes of death. Among natural causes of death, YLL from SUD was only lower than that from all cancers combined and heart disease. Lifetime productivity loss because of SUD was ~$51 billion, exceeding productivity loss from any individual cancer. CONCLUSION: SUD is an important source of YLL and productivity loss among adults aged 20-64. Such a high burden on society justifies prioritizing health policies and interventions toward preventing SUD.
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Muerte Súbita/epidemiología , Eficiencia , Esperanza de Vida/tendencias , Adulto , Causas de Muerte , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , North Carolina/epidemiología , Vigilancia de la Población , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: In Wake County, NC, sudden unexpected death accounts for 10% to 15% of all natural deaths in individuals 18 to 64 years old. Medications such as aspirin, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, and ß-blockers are recommended in guidelines to reduce cardiovascular events and even sudden death (ß-blockers). However, guidelines are often underpracticed, even in high-risk patients, with noted disparities in women. OBJECTIVE: We assessed the relation between prescription of evidence-based medications and sudden unexpected death in Wake County, NC. METHODS: We analyzed 399 cases of sudden unexpected death for the time period March 1, 2013 to February 28, 2015 in Wake County, NC. Medications were assessed from available medical examiner reports and medical records and grouped using the third level of the Anatomical Therapeutic Chemical Classification System (ATC) codes. This study was reviewed and exempt by the University of North Carolina's institutional review board. RESULTS: Among 126 female and 273 male victims, women were prescribed more medications overall than men (6.5 vs 4.3, P = 0.001); however, the use of guideline-directed therapies was not different between genders in the chronic conditions associated with sudden death. Overall, there was remarkably low use of evidence-based medications. CONCLUSIONS: Our findings highlight the need to improve prescribing of evidence-based medications and to further explore the relationship between undertreatment and sudden unexpected death.
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Muerte Súbita/prevención & control , Prevención Primaria/estadística & datos numéricos , Adolescente , Antagonistas Adrenérgicos beta/uso terapéutico , Adulto , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Aspirina/uso terapéutico , Muerte Súbita/epidemiología , Femenino , Mal Uso de los Servicios de Salud , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Persona de Mediana Edad , North Carolina/epidemiología , Adulto JovenRESUMEN
Cell migration and invasion are largely dependent on the complex organization of the various cytoskeletal components. Whereas the role of actin filaments and microtubules in cell motility is well established, the role of intermediate filaments in this process is incompletely understood. Organization and structure of the keratin cytoskeleton, which consists of heteropolymers of at least one type 1 and one type 2 intermediate filament, are in part regulated by post-translational modifications. In particular, phosphorylation events influence the properties of the keratin network. Sphingosylphosphorylcholine (SPC) is a bioactive lipid with the exceptional ability to change the organization of the keratin cytoskeleton, leading to reorganization of keratin filaments, increased elasticity, and subsequently increased migration of epithelial tumor cells. Here we investigate the signaling pathways that mediate SPC-induced keratin reorganization and the role of keratin phosphorylation in this process. We establish that the MEK-ERK signaling cascade regulates both SPC-induced keratin phosphorylation and reorganization in human pancreatic and gastric cancer cells and identify Ser431 in keratin 8 as the crucial residue whose phosphorylation is required and sufficient to induce keratin reorganization and consequently enhanced migration of human epithelial tumor cells.
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Movimiento Celular/efectos de los fármacos , Citoesqueleto/metabolismo , Células Epiteliales/metabolismo , Filamentos Intermedios/metabolismo , Queratina-8/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Citoesqueleto/efectos de los fármacos , Citoesqueleto/genética , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Filamentos Intermedios/efectos de los fármacos , Filamentos Intermedios/genética , Queratina-8/genética , Quinasas Quinasa Quinasa PAM/genética , Quinasas Quinasa Quinasa PAM/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Fosforilación/efectos de los fármacos , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Serina/metabolismo , Transducción de Señal/efectos de los fármacos , Esfingosina/análogos & derivados , Esfingosina/farmacología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologíaRESUMEN
Background: A coronary artery aneurysm is a rare cardiac anomaly that may be incidentally detected on echocardiography. When associated with a coronary cameral fistula, an aneurysm can become symptomatic. We present a unique case of a giant left circumflex coronary aneurysm with a fistula to the left atrium and a large atrial septal defect causing acute heart failure in a young woman during the peripartum period. Case summary: A 32 year-old woman who presented with hypoxia after the delivery of her fourth child was found to have heart failure with severe mitral regurgitation and multiple abnormal intracardiac shunts. Echocardiography showed a large circular structure with Doppler color flow into the left atrium and between the atria. Cardiac computed tomography showed multiple dilated coronary arteries including a left circumflex coronary artery aneurysm measuring >10â cm in diameter with fistulous communication to the left atrium and a large atrial septal defect. A right heart catheterization was performed, and the patient was diagnosed with high-output heart failure. Surgical closure of the coronary cameral fistula was deferred due to the risk of worsening pressure in the coronary aneurysm, and the patient was referred for cardiac transplantation. Discussion: This case illustrates severe heart failure as a complication of a giant coronary artery aneurysm with fistulization to the left atrium and subsequent shunting through a large atrial defect. Echocardiography allows for the detection of a coronary aneurysm and shunting, and cardiac computed tomography provides detailed visualization of a coronary cameral fistula.
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Background: Sudden death accounts for approximately 10% of deaths among working-age adults and is associated with poor air quality. Objectives: To identify high-risk groups and potential modifiers and mediators of risk, we explored previously established associations between fine particulate matter (PM2.5) and sudden death stratified by potential risk factors. Methods: Sudden death victims in Wake County, NC, from 1 March 2013 to 28 February 2015 were identified by screening Emergency Medical Systems reports and adjudicated (n = 399). Daily PM2.5 concentrations for Wake County from the Air Quality Data Mart were linked to event and control periods. Potential modifiers included greenspace metrics, clinical conditions, left ventricular hypertrophy (LVH), and neutrophil-to-lymphocyte ratio (NLR). Using a case-crossover design, conditional logistic regression estimated the OR (95%CI) for sudden death for a 5 µg/m3 increase in PM2.5 with a 1-day lag, adjusted for temperature and humidity, across risk factor strata. Results: Individuals having LVH or an NLR above 2.5 had PM2.5 associations of greater magnitude than those without [with LVH OR: 1.90 (1.04, 3.50); NLR > 2.5: 1.25 (0.89, 1.76)]. PM2.5 was generally less impactful for individuals living in areas with higher levels of greenspace. Conclusion: LVH and inflammation may be the final step in the causal pathway whereby poor air quality and traditional risk factors trigger arrhythmia or myocardial ischemia and sudden death. The combination of statistical evidence with clinical knowledge can inform medical providers of underlying risks for their patients generally, while our findings here may help guide interventions to mitigate the incidence of sudden death.
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Estudios Cruzados , Hipertrofia Ventricular Izquierda , Inflamación , Material Particulado , Humanos , Material Particulado/análisis , Material Particulado/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Hipertrofia Ventricular Izquierda/mortalidad , Factores de Riesgo , Anciano , Contaminación del Aire/efectos adversos , Muerte Súbita/epidemiología , Muerte Súbita/etiología , Contaminantes Atmosféricos/efectos adversos , Exposición a Riesgos Ambientales/efectos adversosRESUMEN
We here identify protein kinase D1 (PKD1) as a major regulator of anchorage-dependent and -independent growth of cancer cells controlled via the transcription factor Snail1. Using FRET, we demonstrate that PKD1, but not PKD2, efficiently interacts with Snail1 in nuclei. PKD1 phosphorylates Snail1 at Ser-11. There was no change in the nucleocytoplasmic distribution of Snail1 using wild type Snail1 and Ser-11 phosphosite mutants in different tumor cells. Regardless of its phosphorylation status or following co-expression of constitutively active PKD, Snail1 was predominantly localized to cell nuclei. We also identify a novel mechanism of PKD1-mediated regulation of Snail1 transcriptional activity in tumor cells. The interaction of the co-repressors histone deacetylases 1 and 2 as well as lysyl oxidase-like protein 3 with Snail1 was impaired when Snail1 was not phosphorylated at Ser-11, which led to reduced Snail1-associated histone deacetylase activity. Additionally, lysyl oxidase-like protein 3 expression was up-regulated by ectopic PKD1 expression, implying a synergistic regulation of Snail1-driven transcription. Ectopic expression of PKD1 also up-regulated proliferation markers such as Cyclin D1 and Ajuba. Accordingly, Snail1 and its phosphorylation at Ser-11 were required and sufficient to control PKD1-mediated anchorage-independent growth and anchorage-dependent proliferation of different tumor cells. In conclusion, our data show that PKD1 is crucial to support growth of tumor cells via Snail1.
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Núcleo Celular/metabolismo , Proliferación Celular , Neoplasias/metabolismo , Proteína Quinasa C/metabolismo , Factores de Transcripción/metabolismo , Transcripción Genética , Transporte Activo de Núcleo Celular/genética , Aminoácido Oxidorreductasas , Núcleo Celular/genética , Ciclina D1/genética , Ciclina D1/metabolismo , Citoplasma/genética , Citoplasma/metabolismo , Células HEK293 , Células HeLa , Histona Desacetilasa 1/genética , Histona Desacetilasa 1/metabolismo , Histona Desacetilasa 2/genética , Histona Desacetilasa 2/metabolismo , Humanos , Proteínas con Dominio LIM/genética , Proteínas con Dominio LIM/metabolismo , Neoplasias/genética , Proteína Quinasa C/genética , Factores de Transcripción de la Familia Snail , Factores de Transcripción/genéticaRESUMEN
Sudden death is a leading cause of deaths nationally. Definitions of sudden death vary greatly, resulting in imprecise estimates of its frequency and incomplete knowledge of its risk factors. The degree to which time-based and coronary artery disease (CAD) criteria impacts estimates of sudden death frequency and risk factors is unknown. Here, we apply these criteria to a registry of all-cause sudden death to assess its impact on sudden death frequency and risk factors. The sudden unexpected death in North Carolina (SUDDEN) project is a registry of out of-hospital, adjudicated, sudden unexpected deaths attended by Emergency Medical Services. Deaths were not excluded by time since last seen or alive or by prior symptoms or diagnosis of CAD. Common criteria for sudden death based on time since last seen alive (both 24 hours and 1 hour) and prior diagnosis of CAD were applied to the SUDDEN case registry. The proportion of cases satisfying each of the 4 criteria was calculated. Characteristics of victims within each restrictive set of criteria were measured and compared to the SUDDEN registry. There were 296 qualifying sudden deaths. Application of 24 hour and 1 hour timing criteria compared to no timing criteria reduced cases by 25.0% and 69.6%, respectively. Addition of CAD criteria to each timing criterion further reduced qualifying cases, for a total reduction of 81.8% and 90.5%, respectively. However, characteristics among victims meeting restrictive criteria remained similar to the unrestricted population. Timing and CAD criteria dramatically reduces estimates of the number of sudden deaths without significantly impacting victim characteristics.
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Enfermedad de la Arteria Coronaria , Servicios Médicos de Urgencia , Humanos , Muerte Súbita/epidemiología , Muerte Súbita/etiología , Factores de Riesgo , Enfermedad de la Arteria Coronaria/complicaciones , North Carolina/epidemiología , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Causas de MuerteRESUMEN
BACKGROUND: Neurotrophic growth factors can stabilize the intestinal barrier by preventing the apoptosis of enteric glial cells (EGCs) and enterocytes. We reasoned that a selective 5-HT1A receptor agonist may have neuroprotective properties in the gut and that topical application of SR57746A might be an effective treatment strategy in inflammatory bowel disease (IBD). METHODS: The therapeutic potential of 5-HT1A receptor agonist SR57746A in IBD was evaluated in vitro (nontransformed NCM460 colonic epithelial cells, SW480 colorectal carcinoma cells) and in vivo (murine dextran sulfate sodium [DSS] colitis and CD4-T-cell transfer colitis). In vitro, we analyzed the effect of SR57746A on apoptosis in intestinal epithelial cells (IECs) and EGCs, and upon proliferation, migration, and intracellular signaling in IECs. In vivo, the effect of topical application of SR57746 on disease activity and on histological and endoscopic findings was compared with intraperitoneal infliximab and placebo, respectively. RESULTS: The SR57746A activates PI3-K/AKT- and ERK-signaling in IECs. Depending on ERK- and AKT activation, SR57746A potently prevents apoptosis of IECs without inducing proliferation or migration in these cells. Moreover, SR57746A prevented apoptosis in EGCs in vitro. Topical SR57746A treatment significantly reduced mucosal injury in 2 experimental murine colitis models and was as effective as intraperitoneal infliximab treatment. CONCLUSIONS: Treatment with SR57746A prevents inflammatory cell damage and apoptosis in IECs and EGCs, similar to the neurotrophic effects of EGCs on IECs. Topical treatment with SR57746A could be a candidate for clinical evaluation in the treatment of IBD.
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Colitis , Agonistas del Receptor de Serotonina 5-HT1 , Animales , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Humanos , Mucosa Intestinal/patología , Ratones , Naftalenos , Neuroglía/metabolismo , Piridinas , Agonistas del Receptor de Serotonina 5-HT1/metabolismoRESUMEN
OBJECTIVE: The authors sought to estimate the prevalence of mental and substance use disorders and psychotropic medication prescriptions among working-age sudden-death victims. METHODS: Using a written protocol, the authors screened for sudden deaths attended by emergency medical services (EMS) in a large metropolitan county in North Carolina from March 1, 2013, to February 28, 2015. Sudden-death cases were adjudicated by three cardiologists. Mental health and chronic disease diagnoses and treatments were abstracted from EMS, medical examiner, toxicology, and autopsy reports and from clinical records for the past 5 years before death. RESULTS: Sudden death was identified for 399 adults ages 18-64 years, 270 of whom had available medical records. Most sudden-death victims were White (63%) and male (65%), had a comorbid condition such as hypertension or respiratory disease, and had a mean±SD age of death of 53.6±8.8 years. Most victims (59%) had at least one mental health or substance use disorder documented in a recent medical record; 76%-78% of victims with a mental disorder had a documented psychotropic medication prescription. However, fewer than one-half (41%) had a documented referral to a mental health professional. The most common diagnostic categories were depressive, anxiety, and alcohol-related disorders. Almost one-half (46%) of the victims had a recent psychotropic prescription, most commonly antidepressants (29%) and benzodiazepines (19%). CONCLUSIONS: Mental illness, substance use disorders, and psychotropic medication prescriptions were prevalent among sudden-death victims. The health care needs of these individuals may be better addressed by collaborative care for general medical and mental disorders.
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Trastornos Mentales , Trastornos Relacionados con Sustancias , Adolescente , Adulto , Muerte Súbita/epidemiología , Prescripciones de Medicamentos , Humanos , Masculino , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/epidemiología , Persona de Mediana Edad , North Carolina/epidemiología , Psicotrópicos/uso terapéutico , Trastornos Relacionados con Sustancias/tratamiento farmacológico , Trastornos Relacionados con Sustancias/epidemiología , Adulto JovenRESUMEN
Out-of-hospital sudden unexpected deaths are non-accidental deaths that occur without obvious underlying causes and may account for 10% of natural deaths before age 65. Short-term exposure to ambient air pollution is associated with all-cause (non-accidental) and cause-specific (e.g., cardiovascular) mortality, and with immediate exposures often yielding the highest magnitude risk estimates. Few studies have focused on short-term exposure to air pollution and sudden unexpected deaths. Using the University of North Carolina Sudden Unexpected Death in North Carolina population, we examine associations between short-term criteria air pollutant exposures with sudden unexpected deaths using a time-stratified case-crossover design, with data on criteria air pollutants from the Environmental Protection Agency's Air Quality System. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression with air pollutant exposures scaled to roughly inter-quartile ranges; models were adjusted for average temperature and relative humidity on event day and preceding 3â¯days. Potential for confounding by co-pollutants were examined in two pollutant models. ORs for PM2.5 at lag day 1 were elevated (adjusted OR for 5⯵g/m3 increase: 1.17 (0.98, 1.40)), and were robust to co-pollutant adjustment. Elevated odds were observed for SO2 at lag day 0, and reduced odds for O3 at lag day 0; however, these associations were somewhat attenuated toward the null (SO2) or were not robust (O3) to co-pollutant adjustment. This analysis in a racially and socioeconomically diverse cohort, with a more inclusive definition of sudden unexpected death than is typically employed offers evidence that PM2.5 may be a clinically relevant trigger of sudden unexpected deaths in susceptible individuals.
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Contaminación del Aire/estadística & datos numéricos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Mortalidad/tendencias , Humanos , North CarolinaRESUMEN
The identification and characterization of sudden unexpected deaths in epilepsy (SUDEP) may be improved, helping to optimize prevention and intervention. We set out to assess the frequency and demographic and clinical characteristics of SUDEP cases in a sudden death cohort. All out-of-hospital deaths were investigated from March 1, 2013 to February 28, 2015 in Wake County, NC, attended by the Emergency Medical Services. Cases were screened and adjudicated by three physicians to identify sudden death cases from any cause among free-living adults, aged 18-64. In total, 399 sudden death victims were identified during this two-year period. Seizure history, demographic and clinical characteristics, and healthcare utilization patterns were assessed from death records, emergency response scene reports, and medical records. Sudden death cases with a history of seizures were summarized by an experienced chart abstractor (SC) and adjudicated by an experienced neurologist (OD). We then compared demographic and clinical characteristics and healthcare utilization patterns of neurologist-identified SUDEP cases to other sudden death victims in our population-based registry of sudden death from any cause. SUDEP accounted for 5.3% of sudden deaths. However, seizures or complications of seizures were only considered the primary cause of death on death certificates in 1.5% of sudden deaths. SUDEP cases were more likely to have a history of alcohol abuse. Mental health disorders and a low level of medication compliance and healthcare utilization were common among SUDEP victims. SUDEP accounts for approximately 5.3% of sudden deaths from any cause in individuals aged between 18 and 64. Death certificates underestimate the burden of sudden death in epilepsy, attributing only 1.5% of sudden deaths to seizures or complications of seizures. Accurate documentation of epileptic disorders on death certificates is essential for the surveillance of SUDEP. Further, interventions that promote better use of medical services and patient engagement with healthy living practices may reduce sudden deaths in epilepsy.
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Muerte Súbita/epidemiología , Documentación/estadística & datos numéricos , Servicios Médicos de Urgencia/estadística & datos numéricos , Epilepsia/mortalidad , Adolescente , Adulto , Certificado de Defunción , Humanos , Persona de Mediana Edad , North Carolina/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: To determine the association between serum lipid measurements and the occurrence of out-of-hospital sudden unexpected death (OHSUD). PATIENTS AND METHODS: We compared 139 OHSUD cases (43 female patients [30.9%]) and 968 controls (539 female patients [55.7%]) from Wake County, North Carolina, from March 1, 2013, through February 28, 2015. Individuals were included if they were aged 18 to 64 years and had lipid measurements in the 5 years before their death (cases) or the most recent health care encounter (controls). Covariates were abstracted from medical records for all subjects, and those with triglyceride (TG) levels greater than 400 mg/dL (to convert to mmol/L, multiply by 0.0259) were excluded for low-density lipoprotein (LDL)-related analyses. RESULTS: By linear regression using age- and sex-adjusted models, cases of OHSUD had lower adjusted mean total cholesterol (170.3±52.2 mg/dL vs 188.9±39.7 mg/dL; P<.001), LDL cholesterol (90.9±39.6 mg/dL vs 109.6±35.2 mg/dL; P<.001), and non-high-density lipoprotein (HDL) (121.6±49.8 mg/dL vs 134.3±39.6 mg/dL; P<.001) levels and a higher adjusted TG/HDL-C ratio (4.7±7 vs 3±2.7; P<.001) than did controls. By logistic regression using age- and sex-adjusted models, the odds of OHSUD were elevated per unit increase in TG/HDL-C ratio (1.08; 95% CI, 1.03-1.12). CONCLUSION: Out-of-hospital sudden unexpected death cases had more favorable levels of total cholesterol, LDL cholesterol, and non-HDL, possibly indicating a lack of association between traditional lipid cardiovascular risk factors and sudden unexpected death. A comparatively elevated TG/HDL-C ratio in cases may corroborate an evolving hypothesis of how vasoactive and prothrombotic remnant-like lipoprotein particles contribute to sudden unexpected death.
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Greenspace has been increasingly recognized as having numerous health benefits. However, its effects are unknown concerning sudden unexpected death (SUD), commonly referred to as sudden cardiac death, which constitutes a large proportion of mortality in the United States. Because greenspace can promote physical activity, reduce stress and buffer air pollutants, it may have beneficial effects for people at risk of SUD, such as those with heart disease, hypertension, and diabetes mellitus. Using several spatial techniques, this study explored the relationship between SUD and greenspace. We adjudicated 396 SUD cases that occurred from March 2013 to February 2015 among reports from emergency medical services (EMS) that attended out-of-hospital deaths in Wake County (central North Carolina, USA). We measured multiple greenspace metrics in each census tract, including the percentages of forest, grassland, average tree canopy, tree canopy diversity, near-road tree canopy and greenway density. The associations between SUD incidence and these greenspace metrics were examined using Poisson regression (non-spatial) and Bayesian spatial models. The results from both models indicated that SUD incidence was inversely associated with both greenway density (adjusted risk ratio [RR]â¯=â¯0.82, 95% credible/ confidence interval [CI]: 0.69-0.97) and the percentage of forest (adjusted RRâ¯=â¯0.90, 95% CI: 0.81-0.99). These results suggest that increases in greenway density by 1â¯km/km2 and in forest by 10% were associated with a decrease in SUD risk of 18% and 10%, respectively. The inverse relationship was not observed between SUD incidence and other metrics, including grassland, average tree canopy, near-road tree canopy and tree canopy diversity. This study implies that greenspace, specifically greenways and forest, may have beneficial effects for people at risk of SUD. Further studies are needed to investigate potential causal relationships between greenspace and SUD, and potential mechanisms such as promoting physical activity and reducing stress.
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Muerte Súbita Cardíaca/epidemiología , Bosques , Análisis Espacial , Ejercicio Físico/fisiología , Humanos , Modelos Estadísticos , North Carolina/epidemiologíaRESUMEN
The incidence of out-of-hospital sudden unexpected death (OHSUD) in a racially and socioeconomically diverse population has been inadequately studied. We collated all OHSUDs over a 24-month period among 18- to 64-year olds in Wake County, North Carolina, to investigate geographic and socioeconomic disparity in incidence of OHSUD. An electronic query of Wake County Emergency Medical Services (EMS) identified all EMS attended out-of-hospital deaths. After excluding trauma, expected deaths, and deaths occurring in non-free-living subjects, medical records and medical examiner's reports were reviewed by a committee of cardiologists to make the determination of OHSUD. Victims were geocoded to census tracts, and demographic and socioeconomic data were obtained from the 2014 American Community Survey and 2010 US Census. Incidence was examined by sociodemographic group with univariate analysis and multivariable regression. There were 397 OHSUDs, and 53% of census tracts had >1 event. The incidence of OHSUD was 64 of 100,000; 107 of 100,000 among blacks; and 60 of 100,000 among whites. Census tracts with >1 OHSUD had a higher population of blacks, a greater proportion unmarried, a lower median household income, and a greater proportion residing in a rural area. Only median household income remained a significant predictor of OHSUD after adjustment in multivariable analysis. Low median household income of a community portends a higher incidence of sudden death. In conclusion, interventions to reduce the incidence of sudden death need to be developed with these specific communities in mind.