Prospective Cohort Study

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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

Remission periods in epilepsy and their relation to long-term prognosis.

The efficacy and tolerability of chewable carbamazepine compared to conventional carbamazepine in patients with epilepsy

Purpose: We evaluated the oral health and dental status of people with epilepsy, and their relationship to seizure frequency, in a community cohort in rural China. Methods: A cross-sectional study of people with epilepsy was carried out in areas in Henan, Shanxi and Ningxia provinces of China. All participants underwent a specially designed “Oral health and Dental status Questionnaire”. Univariate and multivariate analyses were used to explore the relationships between seizure frequency and oral health and dental status. Results: A total of 875 people participated. Almost two thirds (65.8%) reported brushing their teeth at least once a day but 634 (73.0%) brushed their teeth for less than 3 min each time. Only 80 (9.1%) had visited a dental clinic in the previous year. Multivariate logistic regression analysis showed that having 1–4 seizures/month (OR 0.60, 95%CI 0.40-0.90) or >4 seizures/month (OR 0.38, 95%CI 0.22-0.66) was associated with decreased odds of brushing teeth at least once a day, and higher seizure frequency was associated with increased odds of dental injury due to seizures (OR 2.07, 95%CI 1.22–3.50 for 4 seizures/month). Conclusion: Seizure frequency was significantly associated with seizure-related dental injury, and with the lack of good oral health practice. Improvement in the oral health of people with epilepsy in resource-poor areas should be encouraged.

Oral health and dental status in people with epilepsy in rural China.

Long-term prognosis in patients with epilepsy

Sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Patients with refractory epilepsy are at especially high risk of SUDEP. SUDEP occurs predominantly at night and unwitnessed, and can best be regarded as a fatal tonic-clonic seizure. While its pathophysiology is incompletely understood, SUDEP is most probably triggered by a number of predisposing and precipitating factors, including seizure-induced respiratory depression and cardiac arrhythmia. Achieving seizure freedom is the best way to prevent SUDEP. Nocturnal supervision may be another alternative preventive strategy, but this requires further research.

Josemir W. Sander

Papers

Remission periods in epilepsy and their relation to long-term prognosis.

The efficacy and tolerability of chewable carbamazepine compared to conventional carbamazepine in patients with epilepsy

Oral health and dental status in people with epilepsy in rural China.

Long-term prognosis in patients with epilepsy

[Sudden unexpected death in epilepsy: SUDEP].