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

Overview: delivery of health care and socioeconomic issues

Current Principles in the Management of Drug-Resistant Epilepsy

Little published information exists about the management of dental treatment procedures for people with epilepsy who, despite their medication, continue to have seizures. This paper draws on relevant literature in neurology and anaesthetics to provide a multi-speciality consensus on methods of assessment and adjunctive treatment options in order to manage the risk of a clinically significant seizure occurring during a procedure. It aims to enhance current guidelines and practice in the provision of specialist care for this diverse group.

/pdf/specialist-management-of-routine-dental-procedures-in-adults-1ruku0nqf5.pdf

Specialist management of routine dental procedures in adults with refractory epilepsy

Epilepsy affects between 5 and 10 people in a 1,000 and carries considerable morbidity and premature mortality. The complex inheritance pattern of a lowered seizure threshold is not fully understood but is likely to be polygenic. In the majority of people with epilepsy, we do not understand the pathophysiology, how a seizure is triggered, and how it can be prevented. In the centennial year of the discovery of the antiepileptic properties of phenobarbital, we have over 20 antiepileptic drugs; however, none have dramatically changed the long-term prognosis of the condition. The cascade of events triggering epilepsy is likely to vary greatly among individuals. The hope for the future is a shift of paradigm away from the symptomatic approach that currently exists. Indeed, once epileptogenesis is fully understood, treatment can be targeted at specific mechanisms, and then we will have truly disease-modifying therapies.

https://www.arquivosdeneuropsiquiatria.org/wp-content/uploads/articles_xml/1678-4227-anp-S0004-282X2013000300180/1678-4227-anp-S0004-282X2013000300180.pdf

Epilepsy treatment: a paradigm shift is urgently need

longer appear. A little packet fell into the box below the screen, together with a card inviting him to go to the optician's counter to have a more detailed visual check and to select a pair of spectacle frames. He felt ill, however, and went home to bed. Three days later, back at home in north Yorkshire, the telephone rang in the evening. \"You haven't been back to a Mediphone booth,\" said the voice from Devon. \"Are you feeling better?\" David felt guilty. \"Much better,\" he said. \"I haven't finished the course of tablets yet, and thought I would leave it until I had since they are obviously working.\" \"OK,\" said the voice at the end of the line. It knew from his family history and from his exam results both in school and university (as recorded by the Central Educational Bureau) that he was intelligent. However, from previous responses to requests to attend the Mediphone booth it knew that he was rather unreliable in this respect. \"Do go back though,\" it said. \"The pills you are on now are only antibiotics designed to get rid of the infection. Once that is dealt with you will need some others to dissolve the gall stones. You could also do with losing some weight.\" It did not mention that the electrocardiogram showed very early signs of ischaemic damage to the heart which would be worth following up, particularly in view of a strong family history of coronary artery disease evident from the genetic record. Luckily there had been no traces of nicotine on David's breath. The computer updated the neural network in the National Databank to pass on all the knowlege it had about David and what treatment it had recommended for him, together with the fact that the abdominal pain had resolved within three days. Further follow up details could be sent in when David next came to the Mediphone. Keeping the central network up to date was important in order to determine which forms of treatment worked best for particular groups of patients. \"OK,\" said David, knowing that he might decide not to go back, but also that he would have to tell the Mediphone of his decision if he did not want to be pestered by one phone call after another. He also knew that his employer might ask him to produce a clean Mediphone \"bill of health\" if …

https://www.bmj.com/content/bmj/307/6919/1624.full.pdf

Josemir W. Sander

Papers

Overview: delivery of health care and socioeconomic issues

Current Principles in the Management of Drug-Resistant Epilepsy

Specialist management of routine dental procedures in adults with refractory epilepsy

Epilepsy treatment: a paradigm shift is urgently need

Consultatio epistulae--the way forward?