Epilepsy care in the COVID-19 era

The COVID-19 pandemic will impact on how care for chronic conditions is delivered. We use epilepsy to exemplify how care for patients will be affected, and suggest ways in which healthcare systems can respond to deliver the most effective care. Where face-to-face outpatient appointments have been cancelled, telemedicine can facilitate remote clinical consultations for new and follow-up epilepsy clinic patients while reducing the risk of infection to both patients and healthcare staff. First-seizure patients will need investigation pathways rationalised, while those with chronic epilepsy will need to have reliable alternative avenues to access clinical advice. At the same time, neurologists should support emergency departments and acute medical units, advising on appropriate management of seizures and other acute neurological presentations. Ultimately, the revolution in our clinical practice is unlikely to cease after this pandemic, with reconfiguration of services likely to bring improvements in efficiency and convenience, and a reduced environmental impact

Epilepsy core outcome set for effectiveness trials (EPSET): A systematic review of outcomes measured in registered phase III and IV clinical trials for adults with epilepsy.

At present, little is known about the outcomes measured in studies assessing the effectiveness of treatments for adults with epilepsy. As part of a wider project developing a Core Outcome Set for clinical trials for adults with epilepsy, we summarised the current outcomes and measurement instruments used in completed phase III and IV clinical trials registered in the clinicaltrials.gov and International Standard Randomised Controlled Trial Number (ISRCTN) databases. Of the reviewed studies 104 were deemed eligible. The outcomes that were measured were recorded, and trial registry entries cross referenced against associated peer review publications. In total, 374 unique granular outcome terms were identified, which grouped into 45 outcome concepts across the following domains: seizures, cognitive/behavioural/psychiatric, sleep, general symptom, functional status / disability, emotional functioning, social functioning, delivery of care, life impact, trial processes, side effects / adverse events, pregnancy / offspring, and death. We identified evidence of outcome measurement heterogeneity, with just 10/45 outcome concepts measured in more than half of the identified studies. This association remained when assessing studies grouped by epilepsy chronicity (newly diagnosed vs. chronic/treatment refractory) and epilepsy classification (focal vs. other). These findings highlight the need for a Core Outcome Set for interventional studies for adults with epilepsy to improve consistency of outcome measurement and reporting

How accurate are witnesses of first suspected seizures in recalling semiology at clinically relevant timepoints? A UK experimental study with a pilot intervention

Objective A key diagnostic challenge at “first seizure” clinic appointments is determining whether the reported event was epileptic. Witness accounts are often critical, yet such appointments typically occur weeks after the event. Guidelines recommend review within 2 weeks. Wait times are however often longer, with a median of 7 weeks in countries such as the UK. The accuracy of witness recall at these clinically relevant intervals and whether their confidence predicts accuracy have never been determined. This study addressed these fundamental questions. It also piloted a potential intervention: whether asking witnesses a set of systematic questions immediately after viewing a suspected seizure improves recall at follow-up, compared to the usual free recall approach used by first responders. Methods In this UK-based experimental study, adults (≥18 years old) viewed a video of an epileptic seizure and were randomized into four conditions: A (immediate free recall + 2-week follow-up), B (immediate free recall + 7-week follow-up), C (immediate systematic questions + 2-week follow-up), and D (immediate systematic questions + 7-week follow-up). The primary outcome was accuracy on 15 standardized questions addressing key semiological features, scored against consensus ratings from five neurologists. Results Of a representative sample of 304 participants, 295 (97%) fully viewed the video, and 94.7% completed follow-up. At 2 weeks, participants answered 54.4% of questions correctly—only 3.9% (95% confidence interval [CI] = .52–7.3) more than those at 7 weeks. Confidence was poorly correlated with accuracy. Immediate systematic questioning improved later recall by 6.7% (95% CI = 3.3–10.0). A definitive trial of this intervention would require 926 participants. Significance This is the first evidence on the accuracy of witness recall at clinically relevant intervals. Recall is modest even within recommended timeframes and declines only slightly by 7 weeks. Witness confidence does not predict accuracy. Immediate structured questioning may enhance later recall and thus support seizure diagnoses

Increased Cervical Human Immunodeficiency Virus (HIV) RNA Shedding Among HIV-Infected Women Randomized to Loop Electrosurgical Excision Procedure Compared to Cryotherapy for Cervical Intraepithelial Neoplasia 2/3

Background Treatment of human immunodeficiency virus (HIV)–infected women to prevent cervical cancer may stimulate HIV RNA cervical shedding and risk HIV transmission. Methods From 2011 to 2014, 400 HIV-infected women diagnosed with cervical intraepithelial neoplasia 2/3 in Kenya were randomized to loop electrosurgical excision procedure (LEEP) or cryotherapy. Cervical samples were collected at baseline and 3 weekly intervals. Samples were tested for HIV RNA using the Gen-Probe Aptima HIV assay with a minimum detection level of 60 copies/swab and analyzed using generalized estimating equations. Results Women who received LEEP had significantly higher cervical HIV RNA levels than those who received cryotherapy at weeks 2 (adjusted incident rate ratio [aIRR], 1.07; P = .038) and 3 (aIRR, 1.08; P = .046). Within LEEP, significantly higher cervical shedding was found at weeks 2 (2.03 log10 copies/swab; P < .001) and 3 (2.04 log10 copies/swab; P < .001) compared to baseline (1.80 log10 copies/swab). Cervical HIV RNA was significantly higher following LEEP for up to 3 weeks among women on antiretroviral treatment (ART) (0.18 log10 copies/swab increase; P = .003) and in ART-naive women (1.13 log10 copies/swab increase; P < .001) compared to baseline. Within cryotherapy, cervical shedding increased in ART-naive women (0.72 log10 copies/swab increase; P = 0.004) but did not increase in women on ART. Conclusions Women randomized to LEEP had a larger increase in post-procedural cervical HIV shedding than cryotherapy. Benefits of cervical cancer prevention outweigh the risk of HIV sexual transmission; our findings underscore the importance of risk-reduction counseling

PD222 Balancing Patient Preferences With Feasible Healthcare Delivery: Using Discrete Choice Experiments Alongside Knowledge Exchange To Inform Care Pathways

IntroductionEmergency department (ED) visits for epilepsy are common, costly, and often clinically unnecessary. Configuration of care pathways (CPs) that could divert people away from ED offer an alternative. The aim was to measure patient and carer preferences for alternative CPs and to explore the feasibility of implementing the preferred CPs in the National Health Service (NHS) England with a wider group of stakeholders.MethodsFormative work (provider survey, service-user interviews, knowledge exchange, and think-aloud piloting) informed a discrete choice experiment (DCE) with six attributes: access to care plan, conveyance, time, epilepsy specialist today, general practitioner (GP) notification, and epilepsy specialist follow-up. This was hosted online with random assignment to two of three scenarios (home, public, or atypical). Logistic regression generated preference weights that were used to calculate the utility of CPs. The highest ranked CPs plus a status quo were discussed at three online knowledge exchange workshops. The nominal group technique was used to ascertain stakeholder views on preference evidence and to seek group consensus on optimal feasible alternatives.ResultsA sample of 427 people with epilepsy and 167 friends or family completed the survey. People with epilepsy preferred paramedics to have access to care plan, non-conveyance, one to three hours, epilepsy specialists today, GP notification, and specialist follow-up within two to three weeks. Family and friends differed when considering atypical seizures, favoring conveyance to urgent treatment centers and shorter time. Optimal configuration of services from service users’ perspectives outranked current practice. Knowledge exchange (n=27 participants) identified the optimal CP as feasible but identified two scenarios for resource reallocation: care plan substitutes specialist advice today and times of strain on NHS resources.ConclusionsPreferences differed to current practice but had minimal variation by seizure type or stakeholder. This study clearly identified optimal and feasible alternative CPs. The mixed-methods approach allowed for robust measurement of preferences, whilst knowledge exchange examined feasibility to enhance implementation of optimal alternative CPs in the future. </jats:sec

Clustered ChIP-Seq-defined transcription factor binding sites and histone modifications map distinct classes of regulatory elements

<p>Abstract</p> <p>Background</p> <p>Transcription factor binding to DNA requires both an appropriate binding element and suitably open chromatin, which together help to define regulatory elements within the genome. Current methods of identifying regulatory elements, such as promoters or enhancers, typically rely on sequence conservation, existing gene annotations or specific marks, such as histone modifications and p300 binding methods, each of which has its own biases.</p> <p>Results</p> <p>Herein we show that an approach based on clustering of transcription factor peaks from high-throughput sequencing coupled with chromatin immunoprecipitation (Chip-Seq) can be used to evaluate markers for regulatory elements. We used 67 data sets for 54 unique transcription factors distributed over two cell lines to create regulatory element clusters. By integrating the clusters from our approach with histone modifications and data for open chromatin, we identified general methylation of lysine 4 on histone H3 (H3K4me) as the most specific marker for transcription factor clusters. Clusters mapping to annotated genes showed distinct patterns in cluster composition related to gene expression and histone modifications. Clusters mapping to intergenic regions fall into two groups either directly involved in transcription, including miRNAs and long noncoding RNAs, or facilitating transcription by long-range interactions. The latter clusters were specifically enriched with H3K4me1, but less with acetylation of lysine 27 on histone 3 or p300 binding.</p> <p>Conclusion</p> <p>By integrating genomewide data of transcription factor binding and chromatin structure and using our data-driven approach, we pinpointed the chromatin marks that best explain transcription factor association with different regulatory elements. Our results also indicate that a modest selection of transcription factors may be sufficient to map most regulatory elements in the human genome.</p