Prospective Cohort Study

Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

BACKGROUND: More than 30 percent of patients with epilepsy have inadequate control of seizures with drug therapy, but why this happens and whether it can be predicted are unknown. We studied the response to antiepileptic drugs in patients with newly diagnosed epilepsy to identify factors associated with subsequent poor control of seizures. METHODS: We prospectively studied 525 patients (age, 9 to 93 years) who were given a diagnosis, treated, and followed up at a single center between 1984 and 1997. Epilepsy was classified as idiopathic (with a presumed genetic basis), symptomatic (resulting from a structural abnormality), or cryptogenic (resulting from an unknown underlying cause). Patients were considered to be seizure-free if they had not had any seizures for at least one year. RESULTS: Among the 525 patients, 333 (63 percent) remained seizure-free during antiepileptic-drug treatment or after treatment was stopped. The prevalence of persistent seizures was higher in patients with symptomatic or cryptogenic epilepsy than in those with idiopathic epilepsy (40 percent vs. 26 percent, P=0.004) and in patients who had had more than 20 seizures before starting treatment than in those who had had fewer (51 percent vs. 29 percent, P<0.001). The seizure-free rate was similar in patients who were treated with a single established drug (67 percent) and patients who were treated with a single new drug (69 percent). Among 470 previously untreated patients, 222 (47 percent) became seizure-free during treatment with their first antiepileptic drug and 67 (14 percent) became seizure-free during treatment with a second or third drug. In 12 patients (3 percent) epilepsy was controlled by treatment with two drugs. Among patients who had no response to the first drug, the percentage who subsequently became seizure-free was smaller (11 percent) when treatment failure was due to lack of efficacy than when it was due to intolerable side effects (41 percent) or an idiosyncratic reaction (55 percent). CONCLUSIONS: Patients who have many seizures before therapy or who have an inadequate response to initial treatment with antiepileptic drugs are likely to have refractory epilepsy.

Early Identification of Refractory Epilepsy

The epidemiology and prognosis of typical absence seizures.

People with epilepsy are at higher risk of dying at a younger age than would be expected when compared with the general population, and this has been consistently seen in many studies [1–5]. The ma...

https://www.tandfonline.com/doi/pdf/10.1586/ern.11.72

Premature mortality in epilepsy: is it preventable?

Optimum seizure control and prompt referral to specialist services are essential

People with epilepsy have a higher risk of premature death throughout the course of the condition.1 2 One of the most important causes of mortality is sudden unexpected death in epilepsy (SUDEP), defined as “sudden, unexpected, non-traumatic, and non-drowning death in patients with epilepsy, with or without evidence for a seizure, and excluding documented status epilepticus, in which postmortem examination does not reveal a structural or toxicological cause for death.”3 In practice, all such deaths where an autopsy is performed are classified as definite SUDEP and those in which no autopsy is performed as probable SUDEP.

SUDEP is the most common epilepsy related cause of death in people with chronic epilepsy. Its incidence varies greatly depending on the population studied and the methods used, with a clear increase as the severity of epilepsy increases. Incidence ranges from less than 1 per 1000 person years in people with epilepsy in community based studies, to 2-5 per 1000 person years in people attending tertiary specialist clinics, and 6-9 per 1000 person years in candidates for epilepsy surgery.4 5 Overall, …

Sudden death in epilepsy.

A retrospective audit of the perceived efficacy and tolerability of adjunctive gabapentin (GBT) therapy in patients with intractable epilepsy was carried out. The case-notes of 263 consecutive patients attending a tertiary referral centre in whom GBT had been added to concomitant anti-epileptic drugs were reviewed. There were 119 males (45%); the median age was 35 years (range 15-81 years) and the median duration of epilepsy was 20 years. The median dose of GBT administered was 1,600 mg (range 300-4,800 mg). Twenty-nine patients (11%) had a reduction in seizure frequency of greater than 50% and 7 (3%) achieved seizure freedom of 6 months' duration at least while taking GBT. Side-effects were reported by 169 patients (61%) and in 40 (15%) an increase in seizure frequency of 50% occurred, this being the commonest reason for GBT withdrawal. The median duration of treatment was 4 months (range 0.03-47 months). Ten patients, in whom GBT therapy had proven ineffective in doses of 900-1,800 mg, were rechallenged with doses of 300-4,800 mg. One individual experienced a 50% reduction in seizure frequency and 1 an increase in seizures of at least 50%. GBT was generally well tolerated at high doses and rechallenge of a small number with GBT in doses up to 4,800 mg did not result in further improvement in seizure frequency in the majority.

An Audit of the Perceived Efficacy and Tolerability of Gabapentin Therapy in an Out-Patient Cohort with Chronic Epilepsy

Introduction: The classification of epileptic seizures and the epilepsies has recently been revised by the International League Against Epilepsy (ILAE) and a new classification scheme issued.Areas covered: The new classification scheme has been critically appraised in the light of the previous classifications and subsequent revisions. The purposes of the classification and its potential use have been extensively discussed.Expert commentary: This ILAE classification scheme, the latest of a series of proposals published in the last 30 years, has made progress as it has a multi-level structure (seizure types, epilepsy types, epilepsy syndromes) allowing for differing uses and combines the previously separate seizure types and epilepsies schemes into a single instrument. Seizures and epilepsies can also be classified based on the available diagnostic aids, which may differ substantially between counties with mature economies and resource-poor countries. An intrinsic limitation of the classification, h...

/pdf/the-ilae-classification-of-seizures-and-epilepsies-1ckilexs6u.pdf

Josemir W. Sander

Papers

The epidemiology and prognosis of typical absence seizures.

Premature mortality in epilepsy: is it preventable?

Sudden death in epilepsy.

An Audit of the Perceived Efficacy and Tolerability of Gabapentin Therapy in an Out-Patient Cohort with Chronic Epilepsy

The ILAE classification of seizures and epilepsies: implications for the clinic.