Population-based study of rare epilepsy incidence in a US urban population.

OBJECTIVE: This study was undertaken to estimate incidence of rare epilepsies and compare with literature. METHODS: We used electronic health record text search to identify children with 28 rare epilepsies in New York City (2010-2014). We estimated cumulative incidence and compared with literature. RESULTS: Eight of 28 rare epilepsies had five or more prior estimates, and our measurements were within the published range for all. The most common were infantile epileptic spasms syndrome (1 in 2920 live births), Lennox-Gastaut syndrome (1 in 9690), and seizures associated with tuberous sclerosis complex (1 in 14 300). Fifteen of 28 had fewer than five prior estimates, and of these, we provided additional estimates for early infantile developmental and epileptic encephalopathy (1 in 32 700), epilepsy with myoclonic-atonic seizures (1 in 34 100), Sturge-Weber syndrome plus seizures/epilepsy (1 in 40 900), epilepsy in infancy with migrating focal seizures (1 in 54 500), Aicardi syndrome plus seizures/epilepsy (1 in 71 600), hypothalamic hamartoma with seizures (1 in 225 000), and Rasmussen syndrome (1 in 450 000). Five of 28 rare epilepsies had no prior estimates, and of these, we provided a new estimate for developmental/epileptic encephalopathy with spike-and-wave activation in sleep and/or continuous spikes and waves during sleep (1 in 34 100). Data were limited for the remaining 12 rare epilepsies, which were all genetic epilepsies, including PCDH19, CDKL5, Alpers disease, SCN8A, KCNQ2, SCN2A, GLUT1 deficiency, Phelan-McDermid syndrome, myoclonic epilepsy with ragged-red fibers, dup15q syndrome, ring chromosome 14, and ring chromosome 20. SIGNIFICANCE: We estimated the incidence of rare epilepsies using population-based electronic health record data and literature review. More research is needed to better estimate the incidence of genetic epilepsies with nonspecific clinical features. Electronic health records may be a valuable data source for studying rare epilepsies and other rare diseases, particularly as genetic testing becomes more widely adopted.

Mortality and mortality disparities among people with epilepsy in the United States, 2011-2021.

Studies on epilepsy mortality in the United States are limited. We used the National Vital Statistics System Multiple Cause of Death data to investigate mortality rates and trends during 2011-2021 for epilepsy (defined by the International Classification of Diseases, 10th Revision, codes G40.0-G40.9) as an underlying, contributing, or any cause of death (i.e., either an underlying or contributing cause) for U.S. residents. We also examined epilepsy as an underlying or contributing cause of death by selected sociodemographic characteristics to assess mortality rate changes and disparities in subpopulations. During 2011-2021, the overall age-standardized mortality rates for epilepsy as an underlying (39 % of all deaths) or contributing (61 % of all deaths) cause of death increased 83.6 % (from 2.9 per million to 6.4 per million population) as underlying cause and 144.1 % (from 3.3 per million to 11.0 per million population) as contributing cause (P < 0.001 for both based on annual percent changes). Compared to 2011-2015, in 2016-2020 mortality rates with epilepsy as an underlying or contributing cause of death were higher overall and in nearly all subgroups. Overall, mortality rates with epilepsy as an underlying or contributing cause of death were higher in older age groups, among males than females, among non-Hispanic Black or non-Hispanic American Indian/Alaska Native persons than non-Hispanic White persons, among those living in the West and Midwest than those living in the Northeast, and in nonmetro counties compared to urban regions. Results identify priority subgroups for intervention to reduce mortality in people with epilepsy and eliminate mortality disparity.

Creating rare epilepsy cohorts using keyword search in electronic health records.

OBJECTIVE: Administrative codes to identify people with rare epilepsies in electronic health records are limited. The current study evaluated the use of keyword search as an alternative method for rare epilepsy cohort creation using electronic health records data. METHODS: Data included clinical notes from encounters with International Classification of Diseases, Ninth Revision (ICD-9) codes for seizures, epilepsy, and/or convulsions during 2010-2014, across six health care systems in New York City. We identified cases with rare epilepsies by searching clinical notes for keywords associated with 33 rare epilepsies. We validated cases via manual chart review. We compared the performance of keyword search to manual chart review using positive predictive value (PPV), sensitivity, and F-score. We selected an initial combination of keywords using the highest F-scores. RESULTS: Data included clinical notes from 77 924 cases with ICD-9 codes for seizures, epilepsy, and/or convulsions. The all-keyword search method identified 6095 candidates, and manual chart review confirmed that 2068 (34%) had a rare epilepsy. The initial combination method identified 1862 cases with a rare epilepsy, and this method performed as follows: PPV median = .64 (interquartile range [IQR] = .50-.81, range = .20-1.00), sensitivity median = .93 (IQR = .76-1.00, range = .10-1.00), and F-score median = .71 (IQR = .63-.85, range = .18-1.00). Using this method, we identified four cohorts of rare epilepsies with over 100 individuals, including infantile spasms, Lennox-Gastaut syndrome, Rett syndrome, and tuberous sclerosis complex. We identified over 50 individuals with two rare epilepsies that do not have specific ICD-10 codes for cohort creation (epilepsy with myoclonic atonic seizures, Sturge-Weber syndrome). SIGNIFICANCE: Keyword search is an effective method for cohort creation. These findings can improve identification and surveillance of individuals with rare epilepsies and promote their referral to specialty clinics, clinical research, and support groups.

Drivers of US health care spending for persons with seizures and/or epilepsies, 2010-2018.

OBJECTIVE: This study was undertaken to characterize spending for persons classified with seizure or epilepsy and to determine whether spending has increased over time. METHODS: In this cross-sectional study, we pooled data from the Medical Expenditure Panel Survey (MEPS) household component files for 2010-2018. We matched cases to controls on age and sex of a population-based sample of MEPS respondents (community-dwelling persons of all ages) with records associated with a medical event (e.g., outpatient visit, hospital inpatient) for seizure, epilepsy, or both. Outcomes were weighted to be representative of the civilian, noninstitutionalized population. We estimated the treated prevalence of epilepsy and seizure, health care spending overall and by site of care, and trends in spending growth. RESULTS: We identified 1078 epilepsy cases and 2344 seizure cases. Treated prevalence was .38% (95% confidence interval [CI] = .34-.41) for epilepsy, .76% (95% CI = .71-.81) for seizure, and 1.14% (95% CI = 1.08-1.20) for epilepsy or seizure. The difference in annual spending for cases compared to controls was $4580 (95% CI = $3362-$5798) for epilepsy, $7935 (95% CI, $6237-$9634) for seizure, and $6853 (95% CI = $5623-$8084) for epilepsy or seizure, translating into aggregate costs of $5.4 billion, $19.0 billion, and $24.5 billion. From 2010 to 2018, the annual growth rate in total spending incurred for seizures and/or epilepsies was 7.6% compared to 3.6% among controls. SIGNIFICANCE: US economic burden of seizures and/or epilepsies is substantial and warrants interventions focused on their unique and overlapping causes.

Barriers to and Disparities in Access to Health Care Among Adults Aged ≥18 Years with Epilepsy - United States, 2015 and 2017.

Approximately 3 million U.S. adults have active epilepsy (i.e., self-reported doctor-diagnosed history of epilepsy and currently taking epilepsy medication or have had at least one seizure in the past year, or both) (1). One of the most common brain disorders, epilepsy poses a number of challenges for people living with this condition because its treatment can be complex, daily management might be inadequate to achieve seizure control, it limits social participation, and epilepsy is associated with early mortality.† Previous studies indicate that persons with epilepsy are more likely to experience barriers or delays in receipt of certain types of care, including epilepsy specialty care, and that these delays are often associated with individual factors (e.g., seizure type) or social determinants of health (e.g., household income or provider availability) (2-4). To obtain updated estimates of access to health care among U.S. adults aged ≥18 years by epilepsy status, CDC analyzed pooled data from the 2015 and 2017 National Health Interview Survey (NHIS), the most recent years with available epilepsy data. Age-adjusted analyses comparing adults with active epilepsy or inactive epilepsy (i.e., self-reported doctor-diagnosed epilepsy but not currently taking medication for epilepsy and have had no seizure in the past year) with adults without epilepsy indicated that adults with active or inactive epilepsy were more likely to have Medicaid or other public insurance coverage and to report an inability to afford prescription medicine, specialty care, or vision or dental care. Adults with active or inactive epilepsy were more likely to take less medication than prescribed to save money, to be in families having problems paying medical bills, and to report delaying care because of insufficient transportation. Enhancing linkages between clinical and community programs and services by public health practitioners and epilepsy health and social service providers can address gaps in access to health care.

Seizure- or Epilepsy-Related Emergency Department Visits Before and During the COVID-19 Pandemic - United States, 2019-2021.

Seizures, transient signs or symptoms caused by abnormal surges of electrical activity in the brain, can result from epilepsy, a neurologic disorder characterized by abnormal electrical brain activity causing recurrent, unprovoked seizures, or from other inciting causes, such as high fever or substance abuse (1). Seizures generally account for approximately 1% of all emergency department (ED) visits (2,3). Persons of any age can experience seizures, and outcomes might range from no complications for those with a single seizure to increased risk for injury, comorbidity, impaired quality of life, and early mortality for those with epilepsy (4). To examine trends in weekly seizure- or epilepsy-related (seizure-related) ED visits† in the United States before and during the COVID-19 pandemic, CDC analyzed data from the National Syndromic Surveillance Program (NSSP).§ Seizure-related ED visits decreased abruptly during the early pandemic period. By the end of 2020, seizure-related ED visits returned almost to prepandemic levels for persons of all ages, except children aged 0-9 years. By mid-2021, however, this age group gradually returned to baseline as well. Reasons for the decrease in seizure-related ED visits in 2020 among all age groups and the slow return to baseline among children aged 0-9 years compared with other age groups are unclear. The decrease might have been associated with fear of exposure to COVID-19 infection in EDs deterring parents or guardians of children from seeking care, adherence to mitigation measures including avoiding public settings such as EDs, or increased access to telehealth services decreasing the need for ED visits (5). These findings reinforce the importance of understanding factors associated with ED avoidance among persons with epilepsy or seizure, the importance that all eligible persons be up to date¶ with COVID-19 vaccination, and the need to encourage persons to seek appropriate care for seizure-related emergencies** to prevent adverse outcomes.

Mass SARS-CoV-2 Testing in a Dormitory-Style Correctional Facility in Arkansas.

Objectives. To assess SARS-CoV-2 transmission within a correctional facility and recommend mitigation strategies.Methods. From April 29 to May 15, 2020, we established the point prevalence of COVID-19 among incarcerated persons and staff within a correctional facility in Arkansas. Participants provided respiratory specimens for SARS-CoV-2 testing and completed questionnaires on symptoms and factors associated with transmission.Results. Of 1647 incarcerated persons and 128 staff tested, 30.5% of incarcerated persons (range by housing unit = 0.0%-58.2%) and 2.3% of staff tested positive for SARS-CoV-2. Among those who tested positive and responded to symptom questions (431 incarcerated persons, 3 staff), 81.2% and 33.3% were asymptomatic, respectively. Most incarcerated persons (58.0%) reported wearing cloth face coverings 8 hours or less per day, and 63.3% reported close contact with someone other than their bunkmate.Conclusions. If testing remained limited to symptomatic individuals, fewer cases would have been detected or detection would have been delayed, allowing transmission to continue. Rapid implementation of mass testing and strict enforcement of infection prevention and control measures may be needed to mitigate spread of SARS-CoV-2 in this setting.

Sleep duration and quality among U.S. adults with epilepsy: National Health Interview Survey 2013, 2015, and 2017.

BACKGROUND: Epilepsy is associated with a high prevalence of sleep disturbance. However, population-based studies on the burden of sleep disturbance in people with epilepsy are limited. This study assessed sleep duration and sleep quality by epilepsy status in the general U.S. adult population aged ≥ 18 years. METHODS: We pooled data of cross-sectional National Health Interview Surveys in 2013, 2015, and 2017 to compare the prevalence of sleep duration and quality among those without epilepsy (N = 93,126) with those with any epilepsy (a history of physician-diagnosed epilepsy) (N = 1774), those with active epilepsy (those with a history of physician-diagnosed epilepsy who were currently taking medication to control it, had one or more seizures in the past year, or both) (N = 1101), and those with inactive epilepsy (those with a history of physician-diagnosed epilepsy who were neither taking medication for epilepsy nor had had a seizure in the past year) (N = 673). We also compared these measures between those with active and those with inactive epilepsy. The prevalences were adjusted for sociodemographics, behaviors, and health covariates, with multivariable logistic regression. We used Z-tests to compare prevalences of sleep duration and quality at the statistical significance level of 0.05. RESULTS: Adults with any epilepsy reported significantly higher adjusted prevalences of short sleep duration (<7 h) (36.0% vs. 31.8%) and long sleep duration (>9 h per day) (6.7% vs. 3.7%) but a lower prevalence of healthy sleep duration (7-9 h per day) (57.4% vs.64.6%) than those without epilepsy. In the past week, adults with any epilepsy reported significantly higher adjusted prevalences than adults without epilepsy of having trouble falling asleep (25.0% vs. 20.3%), staying asleep (34.4% vs. 26.3%), nonrestorative sleep (adults did not wake up feeling well rested) (≥3days) (50.3% vs. 44.3%), and taking medication to help themselves fall asleep or stay asleep (≥1 times) (20.9% vs. 13.5%). However, adults with active epilepsy did not differ from adults with inactive epilepsy with respect to these sleep duration and quality measures. CONCLUSIONS: Adults with epilepsy reported more short or long sleep duration and worse sleep quality than those without epilepsy. Neither seizure occurrence nor antiepileptic drug use accounted for these differences in sleep duration and quality. Careful screening for sleep complaints as well as identifying and intervening on the modifiable risk factors associated with sleep disturbances among people with epilepsy could improve epilepsy outcomes and quality of life.

CDC-supported epilepsy surveillance and epidemiologic studies: A review of progress since 1994.

To report progress, to identify gaps, and to plan epilepsy surveillance and research activities more effectively, the Centers for Disease Control and Prevention (CDC) Epilepsy Program has summarized findings from selected CDC-supported surveillance and epidemiologic studies about epilepsy from 1994 through 2019. We identified publications supported by CDC funding and publications conducted by the CDC Epilepsy Program alone or with partners. We included only epilepsy surveillance and epidemiologic studies focusing on epilepsy burden, epilepsy-related outcomes, and healthcare utilization. We describe the findings of these studies in the following order: 1)prevalence; 2)incidence; 3)epilepsy-related outcomes by selected demographic characteristics; 4)cysticercosis or neurocysticercosis (NCC); 5)traumatic brain injury (TBI); 6)comorbidity; 7)mortality; 8)access to care; 9)quality of care; and 10) cost. We have characterized these findings in relation to the scope of the first three domains of the 2012 Institute of Medicine report on epilepsy and its relevant first four recommendations. From 1994 through 2019, 76 publications on epilepsy-related epidemiologic and surveillance studies were identified. Over the past 25 years, CDC has expanded community, state, and national surveillance on epilepsy and supported epidemiologic studies by using multiple assessment methods and validated case-ascertainment criteria to identify epilepsy burden, epilepsy-related outcomes, and healthcare utilization in the general population or in population subgroups. Among identified research opportunities, studies on epilepsy incidence and risk factors, mortality, and cost are considered as important surveillance gaps. Other remaining gaps and suggested surveillance strategies are also proposed. Findings from this review may help epilepsy researchers and other stakeholders reference and prioritize future activities for epidemiologic and surveillance studies in epilepsy.

Epilepsy and chronic obstructive pulmonary disease among U.S. adults: National Health Interview Survey 2013, 2015, and 2017.

BACKGROUND: Among U.S. adults, over 4 million report a history of epilepsy, and more than 15 million report a history of chronic obstructive pulmonary disease (COPD); Chronic obstructive pulmonary disease, which includes chronic bronchitis and emphysema, is a common somatic comorbidity of epilepsy. This study assessed the relationship between self-reported physician-diagnosed epilepsy and COPD in a large representative sample of the U.S. adult population and explored possible mechanisms. METHODS: Cross-sectional National Health Interview Surveys for 2013, 2015, and 2017 were aggregated to compare the prevalence of COPD between U.S. respondents aged ≥18 years with a history of physician-diagnosed epilepsy (n = 1783) and without epilepsy (n = 93,126). We calculated prevalence of COPD by age-standardized adjustment and prevalence ratios of COPD overall adjusted for sociodemographic and risk factors, by using multivariable logistic regression analyses. A Z-test was conducted to compare the prevalence between people with and without epilepsy at the statistical significance level of 0.05. Prevalence ratios whose 95% confidence intervals did not overlap 1.00 were considered statistically significant. RESULTS: The overall age-standardized prevalence was 5.7% for COPD and 1.8% for epilepsy. Age-standardized prevalence of COPD among respondents with epilepsy (15.4%) exceeded that among those without epilepsy (5.5%). The association remained significantly different among all sociodemographic and risk factor subgroups (p < .05). In the adjusted analyses, epilepsy was also significantly associated with COPD, overall (adjusted prevalence ratio = 1.8, 95% confidence interval = 1.6-2.1) and in nearly all subgroups defined by selected characteristics. CONCLUSIONS: Epilepsy is associated with a higher prevalence of COPD in U.S. adults. Public health interventions targeting modifiable behavioral and socioeconomic risk factors among people with epilepsy may help prevent COPD and related premature death.

Automated detection of sudden unexpected death in epilepsy risk factors in electronic medical records using natural language processing.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is an important cause of mortality in epilepsy. However, there is a gap in how often providers counsel patients about SUDEP. One potential solution is to electronically prompt clinicians to provide counseling via automated detection of risk factors in electronic medical records (EMRs). We evaluated (1) the feasibility and generalizability of using regular expressions to identify risk factors in EMRs and (2) barriers to generalizability. METHODS: Data included physician notes for 3000 patients from one medical center (home) and 1000 from five additional centers (away). Through chart review, we identified three SUDEP risk factors: (1) generalized tonic-clonic seizures, (2) refractory epilepsy, and (3) epilepsy surgery candidacy. Regular expressions of risk factors were manually created with home training data, and performance was evaluated with home test and away test data. Performance was evaluated by sensitivity, positive predictive value, and F-measure. Generalizability was defined as an absolute decrease in performance by <0.10 for away versus home test data. To evaluate underlying barriers to generalizability, we identified causes of errors seen more often in away data than home data. To demonstrate how small revisions can improve generalizability, we removed three "boilerplate" standard text phrases from away notes and repeated performance. RESULTS: We observed high performance in home test data (F-measure range = 0.86-0.90), and low to high performance in away test data (F-measure range = 0.53-0.81). After removing three boilerplate phrases, away performance improved (F-measure range = 0.79-0.89) and generalizability was achieved for nearly all measures. The only significant barrier to generalizability was use of boilerplate phrases, causing 104 of 171 errors (61%) in away data. SIGNIFICANCE: Regular expressions are a feasible and probably a generalizable method to identify variables related to SUDEP risk. Our methods may be implemented to create large patient cohorts for research and to generate electronic prompts for SUDEP counseling.

Timing of suicide in people with epilepsy: A population-based study from 18 states of the United States, 2003-2014.

Suicide timing varies across several psychiatric disorders, which may share common underlying pathophysiological mechanisms with epilepsy. We investigated suicide timing in people with epilepsy. Using cross-sectional, population-based U.S. National Violent Death Reporting System data from 2003 through 2014 in 18 States, we identified 1310 suicides with epilepsy and 102,582 suicides without epilepsy among those 10 years and older. We compared patterns of suicide mortality ratios between those with and without epilepsy by month of year, week of month, day of week, time of day, and overall by age, sex, and race/ethnicity. As the suicide patterns seen among persons without epilepsy, suicides in persons with epilepsy occurred significantly more often during the morning, afternoon, and evening hours than at night in all subgroups except females. Compared to Sundays, suicides in persons with epilepsy were only significantly increased on Mondays and Tuesdays in those aged ≥45 years and only on Mondays in men. This pattern differs from persons without epilepsy whose suicides significantly increased on Mondays and significantly decreased on Saturdays in nearly all study subgroups. Suicides in persons with epilepsy did not exhibit the timing patterns of persons without epilepsy by week of month (significant decreases from the third to fifth weeks compared to the first week among those aged ≥45 years, males, and Non-Hispanic whites) and month of year (significant increases from January to November peaking from June to September compared to December in all study groups). Compared to the general population or people without epilepsy, previous and current studies suggest that in people with epilepsy, suicide timing differs from and suicide rates significantly exceed those in people without epilepsy. Preventing suicide in people with epilepsy should focus not only on the peak times of occurrence but also across all time periods.

National Association of Medical Examiners position paper: Recommendations for the investigation and certification of deaths in people with epilepsy.

Sudden unexpected death of an individual with epilepsy can pose a challenge to death investigators, as most deaths are unwitnessed, and the individual is commonly found dead in bed. Anatomic findings (eg, tongue/lip bite) are commonly absent and of varying specificity, thereby limiting the evidence to implicate epilepsy as a cause of or contributor to death. Thus it is likely that death certificates significantly underrepresent the true number of deaths in which epilepsy was a factor. To address this, members of the National Association of Medical Examiners, North American SUDEP Registry, Epilepsy Foundation SUDEP Institute, American Epilepsy Society, and the Centers for Disease Control and Prevention constituted an expert panel to generate evidence-based recommendations for the practice of death investigation and autopsy, toxicological analysis, interpretation of autopsy and toxicology findings, and death certification to improve the precision of death certificate data available for public health surveillance of epilepsy-related deaths. The recommendations provided in this paper are intended to assist medical examiners, coroners, and death investigators when a sudden unexpected death in a person with epilepsy is encountered.

Active Epilepsy and Seizure Control in Adults - United States, 2013 and 2015.

Approximately 3 million American adults reported active epilepsy* in 2015 (1). Active epilepsy, especially when seizures are uncontrolled, poses substantial burdens because of somatic, neurologic, and mental health comorbidity; cognitive and physical dysfunction; side effects of antiseizure medications; higher injury and mortality rates; poorer quality of life; and increased financial cost (2). Thus, prompt diagnosis and seizure control (i.e., seizure-free in the 12 months preceding the survey) confers numerous clinical and social advantages to persons with active epilepsy. To obtain recent and reliable estimates of active epilepsy and seizure control status in the U.S. population, CDC analyzed aggregated data from the 2013 and the 2015 National Health Interview Surveys (NHISs). Overall, an annual estimated 2.6 million (1.1%) U.S. adults self-reported having active epilepsy, 67% of whom had seen a neurologist or an epilepsy specialist in the past year, and 90% of whom reported taking epilepsy medication. Among those taking epilepsy medication, only 44% reported having their seizures controlled. A higher prevalence of active epilepsy and poorer seizure control were associated with low family income, unemployment, and being divorced, separated, or widowed. Use of epilepsy medication was higher among adults who saw an epilepsy specialist in the past year than among those who did not. Health care and public health should ensure that adults with uncontrolled seizures have appropriate care and self-management support in order to promote seizure control, improve health and social outcomes, and reduce health care costs.

Suicide among people with epilepsy: A population-based analysis of data from the U.S. National Violent Death Reporting System, 17 states, 2003-2011.

OBJECTIVE: This study analyzed suicide data in the general population from the U.S. National Violent Death Reporting System (NVDRS) to investigate suicide burden among those with epilepsy and risk factors associated with suicide and to suggest measures to prevent suicide among people with epilepsy. METHODS: The NVDRS is a multiple-state, population-based, active surveillance system that collects information on violent deaths including suicide. Among people 10years old and older, we identified 972 suicide cases with epilepsy and 81,529 suicide cases without epilepsy in 17 states from 2003 through 2011. We estimated their suicide rates, evaluated suicide risk among people with epilepsy, and investigated suicide risk factors specific to epilepsy by comparing those with and without epilepsy. In 16 of the 17 states providing continual data from 2005 through 2011, we also compared suicide trends in people with epilepsy (n=833) and without epilepsy (n=68,662). RESULTS: From 2003 through 2011, the estimated annual suicide mortality rate among people with epilepsy was 16.89/100,000 per persons, 22% higher than that in the general population. Compared with those without epilepsy, those with epilepsy were more likely to have died from suicide in houses, apartments, or residential institutions (81% vs. 76%, respectively) and were twice as likely to poison themselves (38% vs. 17%) (P<0.01). More of those with epilepsy aged 40-49 died from suicide than comparably aged persons without epilepsy (29% vs. 22%) (P<0.01). The proportion of suicides among those with epilepsy increased steadily from 2005 through 2010, peaking significantly in 2010 before falling. SIGNIFICANCE: For the first time, the suicide rate among people with epilepsy in a large U.S. general population was estimated, and the suicide risk exceeded that in the general population. Suicide prevention efforts should target people with epilepsy 40-49years old. Additional preventive efforts include reducing the availability or exposure to poisons, especially at home, and supporting other evidence-based programs to reduce mental illness comorbidity associated with suicide.

Cause-specific mortality among children and young adults with epilepsy: Results from the U.S. National Child Death Review Case Reporting System.

We investigated causes of death in children and young adults with epilepsy by using data from the U.S. National Child Death Review Case Reporting System (NCDR-CRS), a passive surveillance system composed of comprehensive information related to deaths reviewed by local child death review teams. Information on a total of 48,697 deaths in children and young adults 28days to 24years of age, including 551 deaths with epilepsy and 48,146 deaths without epilepsy, was collected from 2004 through 2012 in 32 states. In a proportionate mortality analysis by official manner of death, decedents with epilepsy had a significantly higher percentage of natural deaths but significantly lower percentages of deaths due to accidents, homicide, and undetermined causes compared with persons without epilepsy. With respect to underlying causes of death, decedents with epilepsy had significantly higher percentages of deaths due to drowning and most medical conditions including pneumonia and congenital anomalies but lower percentages of deaths due to asphyxia, weapon use, and unknown causes compared with decedents without epilepsy. The increased percentages of deaths due to pneumonia and drowning in children and young adults with epilepsy suggest preventive interventions including immunization and better instruction and monitoring before or during swimming. State-specific and national population-based mortality studies of children and young adults with epilepsy are recommended.

Cytochrome P450 2B1 mediates complement-dependent sublytic injury in a model of membranous nephropathy.

Membranous nephropathy is a disease that affects the filtering units of the kidney, the glomeruli, and results in proteinuria accompanied by loss of kidney function. Passive Heymann nephritis is an experimental model that mimics membranous nephropathy in humans, wherein the glomerular epithelial cell (GEC) injury induced by complement C5b-9 leads to proteinuria. We examined the role of cytochrome P450 2B1 (CYP2B1) in this complement-mediated sublytic injury. Overexpression of CYP2B1 in GECs significantly increased the formation of reactive oxygen species, cytotoxicity, and collapse of the actin cytoskeleton following treatment with anti-tubular brush-border antiserum (anti-Fx1A). In contrast, silencing of CYP2B1 markedly attenuated anti-Fx1A-induced reactive oxygen species generation and cytotoxicity with preservation of the actin cytoskeleton. Gelsolin, which maintains an organized actin cytoskeleton, was significantly decreased by complement C5b-9-mediated injury but was preserved in CYP2B1-silenced cells. In rats injected with anti-Fx1A, the cytochrome P450 inhibitor cimetidine blocked an increase in catalytic iron and ROS generation, reduced the formation of malondialdehyde adducts, maintained a normal distribution of nephrin in the glomeruli, and provided significant protection at the onset of proteinuria. Thus, GEC CYP2B1 contributes to complement C5b-9-mediated injury and plays an important role in the pathogenesis of passive Heymann nephritis.

Cytochrome-P450 2B1 gene silencing attenuates puromycin aminonucleoside-induced cytotoxicity in glomerular epithelial cells.

Previously, we demonstrated that cytochrome P450 2B1 (CYP2B1) can generate reactive oxygen species in puromycin aminonucleoside (PAN)-induced nephrotic syndrome, an animal model of minimal-change disease in humans. In this study we found that overexpression of CYP2B1 in rat glomerular epithelial cells in vitro significantly increased PAN-induced reactive oxygen species generation, cytotoxicity, cell death, and collapse of the actin cytoskeleton. All of these pathological changes were markedly attenuated by siRNA-induced CYP2B1 silencing. The cellular CYP2B1 protein content was significantly decreased whereas its mRNA level was markedly increased, suggesting regulation by protein degradation rather than transcriptional inhibition in the PAN-treated glomerular epithelial cells. This degradation of CYP2B1 was accompanied by the induction of heme oxygenase-1, an important indicator of heme-induced oxidative stress. In PAN-treated CYP2B1-silenced glomerular epithelial cells the induction of heme oxygenase-1 and caspase-3 activity were significantly decreased. Further, cleavage of the stress-induced pro-apoptotic endoplasmic reticulum-specific pro-caspase-12 was prevented in the silenced cells. Our results support a pivotal role of CYP2B1 for reactive oxygen species production in the endoplasmic reticulum in PAN-induced cytotoxicity.

Epidemiology of Sudden Death in a Population-Based Study of Infants and Children.

OBJECTIVE: To describe epidemiologic data from the Sudden Death in the Young (SDY) Case Registry. Understanding the scope of SDY may optimize prevention efforts. STUDY DESIGN: We analyzed sudden, unexpected deaths of infants (<365 days) and children (1-17 years) from a population-based registry of 8 states/jurisdictions in 2015 and 9 in 2016. Natural deaths and injury deaths from drowning, motor vehicle accident drivers, and infant suffocation were included; other injury deaths, homicide, suicide, intentional overdose, and terminal illness were excluded. Cases were categorized using a standardized algorithm. Descriptive statistics were used to characterize deaths, and mortality rates were calculated. RESULTS: Of 1319 cases identified, 92% had an autopsy. We removed incomplete cases, leaving 1132 analyzable deaths (889 infants, 243 children). The SDY rate for infants was 120/100 000 live births and for children was 1.9/100 000 children. Explained Cardiac rates were greater for infants (2.7/100 000 live births) than children (0.3/100 000 children). The pediatric Sudden Unexpected Death in Epilepsy (SUDEP) mortality rate was 0.2/100 000 live births and children. Blacks comprised 42% of infant and 43% of child deaths but only 23% of the population. In all ages, myocarditis/endocarditis was the most common Explained Cardiac cause; respiratory illness was the most common Explained Other cause. SDY occurred during activity in 13% of childhood cases. CONCLUSIONS: Prevention strategies include optimizing identification and treatment of respiratory and cardiac diseases.

Suicide Timing in 18 States of the United States from 2003-2014.

We investigated suicide timing over different time periods by age, sex and race/ethnicity. A total of 122,107 suicide deaths were identified from the population-based U.S. National Violent Death Reporting System in 18 U.S. states from 2003 through 2014. Suicides significantly increased (p < .05) from March to peak in September before falling, the first week of the month, and early in the week. Suicides also significantly increased (p < .05) in the morning, mainly peaking during the afternoon, although suicides in adolescents peaked in the evening and in those 65-years and older peaked in the morning. Comprehensive prevention efforts should focus on those at overall increased suicide risk and at peaks of high suicide frequency, especially among those vulnerable subgroups.