Novel therapies for epilepsy in the pipeline

Despite the availability of many antiepileptic drugs (AEDs) (old and newly developed) and, as recently suggested, their optimization in the treatment of patients with uncontrolled seizures, more than 30% of patients with epilepsy continue to experience seizures and have drug-resistant epilepsy; the management of these patients represents a real challenge for epileptologists and researchers. Resective surgery with the best rates of seizure control is not an option for all of them; therefore, research and discovery of new methods of treating resistant epilepsy are of extreme importance. In this article, we will discuss some innovative approaches, such as P-glycoprotein (P-gp) inhibitors, gene therapy, stem cell therapy, traditional and novel antiepileptic devices, precision medicine, as well as therapeutic advances in epileptic encephalopathy in children; these treatment modalities open up new horizons for the treatment of patients with drug-resistant epilepsy

Dramatic outcomes in epilepsy: depression, suicide, injuries, and mortality

In this narrative review, we will discuss some of the significant risks and dramatic consequences that are associated with epilepsy: depression, suicide, seizure-related injuries, and mortality, both in adults and in children. Considering the high prevalence of depression among people with epilepsy (PWE), routine and periodic screening of all PWE for early detection and appropriate management of depression is recommended. PWE should be screened for suicidal ideation regularly and when needed, patients should be referred for a psychiatric evaluation and treatment. When starting an antiepileptic drug (AED) or switching from one to another AED, patients should be advised to report to their treating physician any change in their mood and existence of suicidal ideation. The risk of injuries for the general epilepsy population is increased only moderately. The risk is higher in selected populations attending epilepsy clinics and referral centers. This being said, there are PWE that may suffer frequent, severe, and sometimes even life-threatening seizure-related injuries. The most obvious way to reduce risk is to strive for improved seizure control. Finally, PWE have a 2–3 times higher mortality rate than the general population. Deaths in PWE may relate to the underlying cause of epilepsy, to seizures (including sudden unexpected death in epilepsy [SUDEP] and seizure related injuries) and to status epilepticus, as well as to other conditions that do not appear directly related to epilepsy. Improving seizure control and patient education may be the most important measures to reduce epilepsy related mortality in general and SUDEP in particular

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population

Dysembryoplastic neuroepithelial tumor and probable sudden unexplained death in epilepsy: a case report

<p>Abstract</p> <p>Introduction</p> <p>This is the first report of the case of a patient with a natural history of dysembryoplastic neuroepithelial tumor associated with probable sudden unexplained death in epilepsy. These tumors are benign, arising within the supratentorial cortex. Over 100 cases have been reported in the literature since the first description by Daumas-Duport in 1988.</p> <p>Case presentation</p> <p>A 24- year-old Caucasian woman had a long period of intractable complex partial seizures, sometimes with tonic-clonic generalization and neuropsychological abnormalities. Magnetic resonance imaging showed a cortico-subcortical parietal tumor with all the characteristics of these types of tumors. After 14 years of evolution, our patient died suddenly during sleep.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first case of probable sudden unexplained death in symptomatic epilepsy due to dysembryoplastic neuroepithelial tumor with natural history. Early and complete excision, with functional studies before and during the surgery, leads to better control of seizures, avoiding neuropsychological changes and the risk of death. Patients with refractory epilepsy should be evaluated for any sleep disorders and should have complete cardiology assessments including electrocardiographic evaluation of cardiac rhythm disturbances.</p

Heat transfer enhancement in a micro-channel cooling system using cylindrical vortex generators.

Three-dimensional conjugate heat transfer under laminar flow conditions within a micro-channel is analysed numerically to explore the impact of a new design of vortex generator positioned at intervals along the base of the channel. The vortex generators are cylindrical with quarter-circle and half-circle cross sections, with variants spanning the whole width of the channel or parts of the channel. Micro-channels with Reynolds number ranging from 100 to 2300 are subjected to a uniform heat flux relevant to microelectronics cooling. To ensure the accuracy of the results, validations against previous microchannel studies were conducted and found to be in good agreement, before the new vortex generators with radii up to 400 µm were analysed. Using a thermal-hydraulic performance parameter expressed in a new way, the VGs described here are shown to offer significant potential in combatting the challenges of heat transfer in the technological drive toward lower weight/smaller volume electrical and electronic devices

Fuel consumption and exhaust emissions of diesel vehicles in worldwide harmonized light vehicles test cycles and their sensitivities to eco-driving factors

Large amounts of fossil fuels are 14 consumed by motor vehicles annually, and hazardous exhaust emissions from the motor vehicles have caused serious problems to environment and human health. Eco-driving can effectively improve the fuel economy and decrease the exhaust emissions, which makes it vital to analyze the fuel consumption and exhaust emissions at given driving cycle, and investigate their sensitivities to eco-driving factors. In this paper, the fuel consumption and exhaust emissions of a Euro-6 compliant light-duty diesel vehicle were tested in Worldwide Harmonized Light Vehicles Test Cycles on a chassis dynamometer; further, the sensitivities of the eco-driving factors that influence the fuel economy and exhaust emissions were analyzed using validated vehicle model. For the vehicle model simulation, the effect of the coolant temperature on fuel consumption and exhaust emission only considered its effect on lubricating oil viscosity. The results showed that vehicle acceleration and velocity dominates the fuel consumption rates in Worldwide Harmonized Light Vehicles Test Cycles, where more than 50% of the exhaust emissions was emitted in the first 300 seconds; also, fuel economy and exhaust emission factors showed a significant dependency on the road grade, coolant temperature, vehicle velocity and mass. For the driver-controllable factors, high vehicle velocity and low road grade (via route-choice) were recommended to achieve low fuel consumption and exhaust emissions

Interpreting outcome following foot surgery in people with rheumatoid arthritis

BACKGROUND: Foot surgery is common in RA but the current lack of understanding of how patients interpret outcomes inhibits evaluation of procedures in clinical and research settings. This study aimed to explore which factors are important to people with RA when they evaluate the outcome of foot and ankle surgery. METHODS AND RESULTS: Semi structured interviews with 11 RA participants who had mixed experiences of foot surgery were conducted and analysed using thematic analysis. Responses showed that while participants interpreted surgical outcome in respect to a multitude of factors, five major themes emerged: functional ability, participation, appearance of feet and footwear, surgeons' opinion, and pain. Participants interpreted levels of physical function in light of other aspects of their disease, reflecting on relative change from their preoperative state more than absolute levels of ability. Appearance was important to almost all participants: physical appearance, foot shape, and footwear were closely interlinked, yet participants saw these as distinct concepts and frequently entered into a defensive repertoire, feeling the need to justify that their perception of outcome was not about cosmesis. Surgeons' post-operative evaluation of the procedure was highly influential and made a lasting impression, irrespective of how the outcome compared to the participants' initial goals. Whilst pain was important to almost all participants, it had the greatest impact upon them when it interfered with their ability to undertake valued activities. CONCLUSIONS: People with RA interpret the outcome of foot surgery using multiple interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than anticipated. These factors can help clinicians in discussing surgical options in patients

The biggest business process management problems to solve before we die

It may be tempting for researchers to stick to incremental extensions of their current work to plan future research activities. Yet there is also merit in realizing the grand challenges in one's field. This paper presents an overview of the nine major research problems for the Business Process Management discipline. These challenges have been collected by an open call to the community, discussed and refined in a workshop setting, and described here in detail, including a motivation why these problems are worth investigating. This overview may serve the purpose of inspiring both novice and advanced scholars who are interested in the radical new ideas for the analysis, design, and management of work processes using information technology.</p

The biggest business process management problems to solve before we die

It may be tempting for researchers to stick to incremental extensions of their current work to plan future research activities. Yet there is also merit in realizing the grand challenges in one’s field. This paper presents an overview of the nine major research problems for the Business Process Management discipline. These challenges have been collected by an open call to the community, discussed and refined in a workshop setting, and described here in detail, including a motivation why these problems are worth investigating. This overview may serve the purpose of inspiring both novice and advanced scholars who are interested in the radical new ideas for the analysis, design, and management of work processes using information technology