SUDEP, the aftermath: supporting the bereaved

Sudden unexpected death in epilepsy is a recurring calamity, yet there is little evidence to guide standards of care for supporting the bereaved. Grief in bereavement includes loss, feelings of guilt, anger and blame. There is also the shock and trauma of the sudden event. How can this be alleviated? This paper focuses on guiding the physician to support the bereaved, while recognising the limited evidence and the varying circumstances that may not always facilitate this. We propose a pathway of care and mode of communication with the deceased's family, with whom contact is currently limited. We suggest timely contact by telephone or in person, followed by ongoing support and referral to voluntary organisations and specialist services, as needed. Clarification and discussion may mitigate inappropriate feelings of guilt and blame, and may help the family with their sudden and unexpected loss

The New Antiepileptic Drugs: The Search for Synergy

Many epileptologists believe that the new antiepileptic drugs as a group constitute a major advance in the treatment of epilepsy. Even their fiercest proponent, however, could not convincingly argue that they are the ideal treatment for all patients with epilepsy. It is widely accepted that if the 'magic bullet' for epilepsy exists, then we have still to find it. Given that the development of new antiepileptic compounds is an expensive, time-consuming gamble, then it may be more beneficial to expend our energies on a quest for better ways of using those compounds already available. Combination therapy is commonplace in other conditions such as hypertension, Parkinsons disease, cardiac failure, or infections such as tuberculosis, and there should be no reason why specific treatments should not be combined with particular efficacy in the treatment of epilepsy. Polypharmacy with antiepileptic drugs (AEDs) has fallen out of favour in recent times. For some years, the prevailing opinion has been that AED combinations merely maximise the incidence of drug-related adverse events while conferring little benefit in terms of seizure control. While this may have been true of the established drugs, phenytoin, carbamazepine, and valproate we should be open to the possibility that the newer AEDs are more suited to use as polypharmacy. We know that the newer AEDs have different mechanisms of action, have fewer pharmacokinetic interactions, and cause less sedation than their older counterparts, while pre-clinical trials would also suggest that they are more specific in their actions. These qualities may suggest that there will be a reduction in the frequency and / or severity of pharmacodynamic interactions when they are used simultaneously. Aside from chance observation, how else can we begin to plan our treatment combinations? The results of basic in-vitro research may suggest certain possibilities, but these will only be relevant in our clinics if we are aware of the key issues involving each new AED. Most importantly: What is/are the relevant mode(s) of action of each drug? To anticipate pharmacodynamic interactions and therapeutic synergy, we need to have a comprehensive view of the actions of each individual drug. For example, vigabatrin is known to inhibit GABA-transaminase, but what changes does it exert on the metabolism of glutamate? Does it have other important effects on GABA? Remacemide, another AED in development was known to be a non-competitive n-methyl-d-aspartate (NMDA) receptor antagonist, but recent evidence has proven its effect on sodium channel conductance. What effect will it have on the GABAergic system? Even once we have a fuller picture of each drug's neurochemical effects (and we cannot even do this convincingly for those drugs that are licensed in the UK!) then how do we proceed in planning the treatment of refractory epilepsy? Should we combine drugs which target the same system (e.g. two GABAergic drugs)? Or should we aim to manipulate two different systems (e.g. one drug acting on the GABAergic system, and one on the excitatory system)? Are there any pharmacodynamic or pharmacokinetic interactions between the two drugs? Are these effects beneficial or deleterious? The answer to this can only be gleaned from proper testing during preliminary clinical trials. Each new AED firstly has to undergo clinical trials as add-on therapy; pharmacokinetic interactions are usually picked up at this relatively early stage of investigation. During each trial, it may also be rational to carry out meta-analyses to investigate which co-therapies are particularly well or poorly tolerated. Despite the relative ease with which this might be accomplished in this age of computerisation, no such analyses have been carried out (or at least not been published!) for any of the emergent treatments, and possible reasons for this will be discussed later. Once both questions are satisfactorily answered, and we suspect that a particular combination of drugs may have some particular merit, then further testing against appropriate controls will be required. The difficulties involved in this will be addressed. The experiments described in this thesis investigate different aspects of some of the newer AEDs. Animal experiments are used to investigate the neurochemical actions of remacemide, gabapentin, tiagabine, and vigabatrin at varying doses with particular emphasis on the GABA shunt. Following the clinical observation of good additive effect with combined tiagabine and vigabatrin, the same parameters were used to look at this particular combination. Culture of rat astrocytes and neurones are used to delineate the dose-related effects of vigabatrin on GABA uptake, a phenomenon previously described in our laboratory. The specific combination of vigabatrin and tiagabine is also used to search for additive or synergistic effects on this system. One set of double-blind clinical studies attempts to investigate interactions between remacemide and the established AEDs, while another investigates the cognitive effects of add-on gabapentin. The issues faced by clinicians in the formation of a rational plan for AED polypharmacy are discussed, and the scope for further investigation is explored

Refractory status epilepticus in adults admitted to ITU in Glasgow 1995-2013 a longitudinal audit highlighting the need for action for provoked and unprovoked status epilepticus

Purpose: Our primary objective was to determine incidence of status epilepticus in adults admitted to 5 ITU settings in Glasgow over 18 years. We wanted to investigate if there are any change in causes and outcomes of SE over last decade. We also compared outcomes of De Novo statuts Epilpeticus (DNSE) and Stauts Epilepticus in patients with previous Epilepsy (SEPE). Methods: The NHS GGC Research Ethics Committee gave permission for this study to continue without a full ethics submission. Between 2013 and 2016, coding records were searched across NHS Greater Glasgow and Clyde for adults over the age of 16 years admitted to an Intensive Care Facility in any of the hospitals in Glasgow. Results: 633 cases were included in study. Cases were separated depending on whether there had been previous epilepsy (SEPE n = 214) or De Novo Status Epilepticus (DNSE, n = 419). Causes in both groups were listed, with 52% of those with DNSE having some contribution from substance misuse. In SEPE, this was felt to play a role in 33.7%. Duration of stay in both groups was similar, but the longest in-patient stays were in the DNSE group. Admission mortality was significantly higher in DNSE than in SEPE (13.8% versus 7.5%). This mortality risk was most closely associated with substance misuse in the group with DNSE. Conclusion: DNSE has a worse prognosis than SEPE. A presentation with DNSE is sign of a system in peril, even where episodes are provoked by alcohol and or drug use. Such episodes should spark off a chain of multispecialty care in order to address this recurring and persisting public health catastrophe

Impact of regulatory safety notices on valproate prescribing and pregnancy outcome among women of child-bearing potential in Scotland: a population-based cohort study

Objective: To examine the impact of Medicines and Healthcare products Regulatory Agency (MHRA) safety alerts on valproate prescribing among women aged 14–45 years in Scotland and examine trends in pregnancies exposed to valproate. Design: Population-based cohort study. Participants: 21 983 women of all ages who received valproate between January 2011 and December 2019. Methods: All valproate prescriptions issued to women in Scotland between January 2011 and December 2019 were identified and prevalence/incidence rates per 10 000 population derived. The impact of regulatory safety alerts on prescribing was analysed using Joinpoint models. Linked pregnancy records for January 2011 to September 2019 were identified and annual rates of pregnancy per 1000 valproate-treated women aged 14–45 years were calculated for each pregnancy outcome: live birth, stillbirth, miscarriage and termination. Results: Annual prevalent and incident rates of valproate prescribing declined in women aged 14–45 years between 2011 and 2019 from 40.5 to 18.3 per 10 000 population (54.8% reduction) and 7.9 to 1.3 per 10 000 population (83.5% reduction), respectively. Statistically significant changes occurred around the times of the MHRA safety alerts. The number of valproate-exposed pregnancies conceived each year fell from 70 in 2011 to 20 in 2018, a 71.4% reduction, and the number of live births fell from 52 to 14, a 73.0% reduction. Expressed as a rate this was a 46.4% decrease from 15.3 to 8.2 per 1000 valproate-treated women aged 14–45 years in 2011 and 2018, respectively. Live birth was the most common pregnancy outcome. Conclusion: This study demonstrates, for the first time, the capabilities of national data sets to identify drug exposure and derive pregnancy outcome at scale across Scotland. Building on this as part of an evolving national/UK surveillance capability will continue efforts to minimise in-utero exposure to valproate; enabling ongoing surveillance to understand better long-term outcomes, and to inform better provision of health and wider support services

Measuring differential attainment:a longitudinal analysis of assessment results for 1,512 medical students at four Scottish medical schools

Funding The Scottish Medical Education Research Consortium (SMERC) provided funding to allow the research project to take place. The funding was used to pay for administrator and researcher time to collate and analyse the data. The funder had no direct input into the analyses chosen or the reporting of the results. The researchers were independent from the funder, and all researchers had access to the data and can take responsibility for the integrity of the data and the accuracy of the data analysis.Peer reviewedPublisher PD

Biomass for thermochemical conversion: targets and challenges

Includes bibliographical references (pages 13-20).Bioenergy will be one component of a suite of alternatives to fossil fuels. Effective conversion of biomass to energy will require the careful pairing of advanced conversion technologies with biomass feedstocks optimized for the purpose. Lignocellulosic biomass can be converted to useful energy products via two distinct pathways: enzymatic or thermochemical conversion. The thermochemical pathways are reviewed and potential biotechnology or breeding targets to improve feedstocks for pyrolysis, gasification, and combustion are identified. Biomass traits influencing the effectiveness of the thermochemical process (cell wall composition, mineral and moisture content) differ from those important for enzymatic conversion and so properties are discussed in the language of biologists (biochemical analysis) as well as that of engineers (proximate and ultimate analysis). We discuss the genetic control, potential environmental influence, and consequences of modification of these traits. Improving feedstocks for thermochemical conversion can be accomplished by the optimization of lignin levels, and the reduction of ash and moisture content. We suggest that ultimate analysis and associated properties such as H:C, O:C, and heating value might be more amenable than traditional biochemical analysis to the high-throughput necessary for the phenotyping of large plant populations. Expanding our knowledge of these biomass traits will play a critical role in the utilization of biomass for energy production globally, and add to our understanding of how plants tailor their composition with their environment.Published with support from the Colorado State University Libraries Open Access Research and Scholarship Fund

Transforming innovation for sustainability

The urgency of charting pathways to sustainability that keep human societies within a "safe operating space" has now been clarified. Crises in climate, food, biodiversity, and energy are already playing out across local and global scales and are set to increase as we approach critical thresholds. Drawing together recent work from the Stockholm Resilience Centre, the Tellus Institute, and the STEPS Centre, this commentary article argues that ambitious Sustainable Development Goals are now required along with major transformation, not only in policies and technologies, but in modes of innovation themselves, to meet them. As examples of dryland agriculture in East Africa and rural energy in Latin America illustrate, such "transformative innovation" needs to give far greater recognition and power to grassroots innovation actors and processes, involving them within an inclusive, multi-scale innovation politics. The three dimensions of direction, diversity, and distribution along with new forms of "sustainability brokering" can help guide the kinds of analysis and decision making now needed to safeguard our planet for current and future generations

Enhancing departmental teaching in the digital age: as easy as 1-3-5

We have recently introduced a new item to our neurology Grand Rounds—the ‘1-3-5 presentation’. The format comprises a presentation on one topic, using three slides and lasting no more than 5 minutes. This a useful way of covering brief single topics and introducing and sparking discussion on more complex ones. ‘1-3-5s’ have proven popular in our department and we have compiled a library of these presentations that is hosted on a YouTube channel. This article discusses the benefits and prospects for this format and encourages other units to provide similar opportunities for teaching and learning among all clinical grades

Drug withdrawal in the epilepsy monitoring unit – The patsalos table

Investigation of possible candidates for epilepsy surgery will usually require inpatient EEG to capture seizures and allow full operative planning. Withdrawal of antiepileptic drugs increases the yield of this valuable diagnostic information and the benefits of this should justify any increase in the risk of harm associated with these seizures This paper outlines our opinion on what would constitute proposed best practice for management of antiepileptic drug (AED) dosing when patients are admitted for monitoring of seizures to an epilepsy monitoring unit (EMU). In the vast majority of cases EMU admissions are safe and, even if seizures occur, will pass off without complication. Previous guidance has concentrated on ensuring practice around technical aspects of EEG monitoring itself and staffing within the unit. In this guidance we aim to outline optimally safe ways of ensuring that EMUs ensure the minimisation of risk to the patients admitted under their care. We propose an algorithm for enhancing the safety of AED withdrawal in VT admissions while ensuring adequate seizure yields. Risk minimisation requires planned management of drug dosing (with reduction if appropriate), provision of adequate rescue medication, and adequate supervision to allow rapid response to generalised seizures. This algorithm is accompanied by a table which uses knowledge of the clinical and pharmacological properties of each AED to ensure dose withdrawal and reduction is timely and safe taking into account the severity and frequency of the individual’s seizures